In previous studies regarding the osseointegration of zirconia (ZrO2) implants, a lack of consistency was observed in the surface topographies of the ZrO2 and Ti samples because of the difficult processability of ZrO2 surfaces. To resolve this problem, we used the molecular precursor method (wet process), which is a surface-modifying technique that can easily change the surface chemistry without changing the surface topography. A roughened Ti surface was prepared using sandblasting (large-grit) and acid treatment. We were able to create ZrO2-coated Ti implants with the same topography as that of roughened Ti substrates using the molecular precursor method, which solution contained a Zr complex. The uniform presence of tetragonal Zr was confirmed, and the apparent zeta potential of the surface of the ZrO2-coated Ti implant was higher than that of Ti. In animal experiments, ZrO2-coated Ti implants showed an equivalent or higher bone-to-implant contact ratio compared to that of the non-coated implants inserted into the femur bone defects of the rats. ZrO2 with the same surface topography as that of roughened Ti exhibits a promotion of osteogenesis equivalent to or better than that of Ti in the early stages of bone formation.

Purpose: The aim of the present experimental 3D-finite element study was to evaluate the influence of an augmented sinus lift with an additional inserted bone graft block. The bone graft block stabilizes the implant in addition to conventional augmented bone. We placed the block in three different positions. The implants were loaded with axial force and forces secondary to laterotrusion and protrusion. Material and Methods: A simplified U-shaped 3D finite element model of the upper jaw and a more complex anatomical model of the left maxilla were created. The bone graft block was placed in three positions: in the lower third in contact with the sinus floor, the middle, and the upper third of the implant. Van Mises’ stress distribution was calculated and analyzed for the different models. We also compared the complex anatomical model with the simplified one. Results: The position of the bone graft block significantly influences the magnitude of stress distribution. A bone graft block positioned in the upper third or middle of the implant reduces the quantity of stress compared to the reference model without a bone graft block. The low bone graft block position is clearly associated with lower stress distribution in compact bone. We registered no significant differences in stress in compact bone with regard to laterotrusion or protrusion. Conclusions: Maximum values of von Mises stresses in compact bone can be reduced significantly by using a bone graft block. The reduction of stress is nearly the same for positions in the upper third and the middle of the implant. It is much more pronounced when the bone graft block is in the lower third of the implant near the sinus floor, which appeared to be the best position in the present study.

An 11-month-old castrated male Pomeranian presented with nonunion following a femoral fracture that occurred after femoral head and neck osteotomy. Radiography and computed tomography revealed severe atrophy of the proximal bone fragment and retardation of the ipsilateral distal fragment and tibia. An autogenous bone graft using coccygeal bone was performed, in which three-and-a-half coccyges were placed in series and fixed using an orthogonal locking plate. To promote bone healing and facilitate proper weight bearing and ambulation, bone morphogenetic proteins, biphasic calcium phosphate, platelet-rich plasma, passive range of motion exercises, transcutaneous electrical nerve stimulation, neuromuscular electrical stimulation, and low level laser therapy were applied. During the four-year follow-up, it was observed that the previously engrafted bone healed well and maintained stability over a prolonged period, resulting in the patient being able to walk and trot comfortably with good outcomes. However, some degree of lameness was noted during galloping owing to limb shortening and joint contracture.

There was no significant difference in bacterial adhesion between the 3 bone graft types tested, regardless of the bacterial strain used (p > 0.22). After 72 hours of culture, there was no significant difference between the Fresh and Frozen bone groups, while the number of CFU in the Decellularised group was significantly lower (p < 0.01), averaging -0.72 +/- 0.08 lg, -0.20 +/- 0.01 lg and -0.78 +/- 0.48 lg with S. epidermidis, S. aureus and E. coli respectively. Absolute values differences are low, and considering fresh bone (equivalent to autograft) as the gold standard due to its low infection rates in clinical studies, we can conclude that adhesion and biolfilm development characteristics are similar between Fresh, Frozen and Decellularised bone grafts..

Using polymethylmethacrylate (PMMA) bone cement is widespread in orthopedic surgeries for implant fixation and as a carrier for antibiotic delivery to prevent and treat infections. This review comprehensively evaluates in vitro studies investigating the antibiotic elution profiles and mechanical properties of PMMA bone cement. We explore the kinetics of antibiotic release, factors influencing elution efficiency, and the impact of various antibiotics on the mechanical properties of PMMA composites. At the same time, we examine how the inclusion of antibiotics affects the mechanical integrity of PMMA, including parameters such as compressive strength, tensile strength, and fatigue resistance. Through a detailed analysis of these studies, this review aims to provide insights into optimizing PMMA bone cement formulations for enhanced therapeutic efficacy and structural performance.

Methacrylated silk (Sil-MA) is a chemically modified silk fibroin specifically designed to be crosslinkable under UV light. This allows the structuring of this material throught additive manufacturing techniques and then to easily prototype patient specific construct. In this study we used Sil-MA to produce single layer crosslinked structures that can be withdrawal and ejected recovering their shape after rehydration. A complete chemical and physical characterization of the material has been conducted. Additionally, we tested the material biocompatibility according to the International Standard Organization protocols (ISO 10993) ensuring the possibility to use it in future trials. The material was also tested to verify its ability to support the osteogenesis. Two different additive manufacturing techniques have been tested (a Digital Light Processing (DLP) UV projector and a pneumatic extrusion technique) to develop Sil-MA grid. Finally, we provide a proof-of-concept that the printed Sil-MA structures are injectable.

Different bone bruise patterns observed on magnetic resonance imaging (MRI) after non-contact anterior cruciate ligament (ACL) rupture and lateral patellar dislocation may indicate different injury mechanism of knee. In order to investigate the typical bone bruising patterns after ACL rupture and patellar dislocation. In this study, 77 ACL rupture and 77 patellar dislocation patients’ knee MR images with bone bruises between August 2020 and March 2022at our institution were selected and analyzed, respectively. Sagittal and transverse planes images were used to determine the bone bruise location in the lateral-medial and superior-inferior directions of the MR images. The presence, location, and intensity of the bone bruises within specific compartments of the femur and tibial after ACL rupture and patellar dislocation were recorded. Relative bone bruise patterns of the ACL rupture and patellar dislocation were classified and analyzed. Results showed that there were 4 kinds of bone bruise (1-,2-,3-,4- bone bruises) patterns after ACL rupture. The most common two patterns after ACL rupture were 3- bone bruises (including lateral side of femur and both lateral and medial side of tibia, LF+BT; both lateral and medial side of femur and lateral side of tibia, BF+LT, medial side of femur and both lateral and medial side of tibia, MF+BT) followed by 4- bone bruises (both lateral and medial side of femur and tibia, BF+BT), 2- bone bruises (LF+LT, lateral side of femur and tibia; MF+LT, medial side of femur and lateral side of tibia; LF+MT, lateral side of femur and medial side of tibia; MF+MT, medial side of femur and tibia; 0+BT, both lateral and medial side of tibia;), and 1- bone bruise (0+LT, only lateral side of tibia). There was only 1 pattern bone bruise (latera femur and medial patella bone bruise) of patellar dislocation, the most common pattern of patellar dislocation was in the inferior medial patella and lateral anterior inferior femur. The results suggest that the pattern of bone bruise after ACL rupture and patellar dislocation is completely different. There were 4 kinds of bone bruise patterns after non-contact ACL rupture while there was only 1 kind of bone bruise pattern after patellar dislocation bone bruise patients which was in the inferior medial patella and lateral anterior inferior femur.

Background: Implant surface topography is a key element in achieving osseointegration. Nanostructured surfaces have shown promising results in accelerating and improving bone healing around dental implants. The main objective of the present clinical and histological study is to compare, at 4 and 6 weeks, (w) bone-to-implant contact in implants having either machined surface (MAC), SLA medium roughness surface or a Nanostructured Calcium-Incorporated sur-face (XPEED®). Methods: 35 mini-implants with 3 different surface treatments (XPEED® (n=16) – SLA (n=13) – Machined (n=6), were placed in the posterior maxilla of 11 patients then, retrieved at either 4 or 6w in a randomized split-mouth study design. Results: The BIC rate measured at 4 and 6w respectively, was: 16.8 % (±5.0) and 29.0 % (±3.1) for MAC surface; 18.5 % (±2.3) and 33.7 % (±3.3) for SLA surface; 22.4 % (±1.3) and 38.6 % (±3.2) for XPEED® surface. In all types of in-vestigated surfaces, the time factor appeared to significantly increase the BIC rate (p < .05). XPEED® surface showed a significantly higher values when compared to both SLA and MAC values at 4w (p < .05). Also, at 6w, both roughened surfaces (SLA and XPEED® ) showed signifi-cantly higher values (p < .05) than turned surface (MAC). Conclusion: Nanostructured Calcium titanate coating is able to enhance bone deposition around implants at early healing stages.

Osteoporosis is considered a serious public health problem, particularly affecting the postmenopausal period. In 2018, in the Republic of Kazakhstan the total and primary incidence was 10 and 3.7 cases per 100,000 adults, respectively. The objective is to study osteoporosis prevalence and indicate main factors affecting low bone mineral density by screening adult population of Abay region, Kazakhstan. The target group were 641 respondents aged between 18 and 65 years old, Kazakh population living in Abay region since birth. All participants filled out questionnaire and had a bone mineral density measurement by dual energy X-ray absorptiometry (DXA) between July 15, 2023 and February 29, 2024. Logistic regression analysis was conducted to assess the association between low bone mineral density and key demographic characteristics, aforementioned lifestyle factors and nutrition habits. We identified the prevalence of low bone density and osteoporosis at the level of 34.1% with the highest prevalence in the older population group (50+ years) - 48.3%. Regression analysis revealed a number of indicators associated with the likelihood of bone sparing. However, only 4 of these showed significance in the final multivariate model (R2=22.4%). These included age (AOR 1.05), body mass index (AOR 0.92), fracture history (AOR 1.64), consumption of nuts and dried fruits were associated with lower prevalence of osteoporosis (AOR 0.48). Our study was the first in Kazakhstan that investigates the association of key demographic, behavior and anamnestic factors with low mineral density.

Abstract The aim of the present review is to discuss the roles of vitamin K and vitamin K-dependent proteins, and the combined action of the vitamins K and D, for maintenance of bone health. The most relevant vitamin K-dependent proteins in this respect are osteocalcin and matrix Gla-protein (MGP). When carboxylated these proteins appear to have the ability to chelate and import calcium from the blood to the bone, thereby reducing the risk of osteoporosis. Carboxylated osteocalcin appears to contribute directly to bone quality and strength. Adequate vitamin K status is required for carboxylation of MGP and osteocalcin. In addition, vitamin K acts on bone metabolism by other mechanism, such as a ligand for the nuclear steroid and xenobiotic receptor (SXR). In this narrative review, we examine the evidence for increased bone mineralization through dietary adequacy of vitamin K (phylloquinone or menaquinone). Summarizing the evidence for a synergistic effect of vitamin K and vitamin D3 we find that an adequate supply of vitamin K on top of an optimal vitamin D status seems to add to the benefit for maintaining bone health. More research related to synergism and possible mechanisms of vitamins D3 and K interaction in bone health is needed.

The objective of this study is to clarify the effect of restoring the lowered masticatory muscle functional pressure and correcting the imbalance of bilateral masticatory muscle functional pressure on jawbone growth during growth and development with quantitative evaluation of the changes in micro/nanostructural characteristics of entheses. Male Wistar rats aged 4 weeks were divided into an experimental group injected with a botulinum toxin serotype A (BoNT/A) formulation to reduce muscle function (BTX group) and a control group (CTRL group). They were euthanized after 6, 8, 10, 12, and 16 weeks after measuring the difference between the midline of the upper and lower incisors. The mandibles were harvested for histological examination, second harmonic generation imaging, and quantitative evaluation of biological apatite (BAp) crystal alignment. The midline difference decreased with age in weeks. In rats from 6 weeks after BoNT/A administration to 12 weeks after administration, collagen fibre bundle diameter was significantly smaller in the BTX group; the difference between the two groups decreased with increasing age. BAp crystal alignment was significantly different on the X-axis and the Y-axis on the BTX group from 6 weeks after BoNT/A administration to 10 weeks after administration. Asymmetry of mandibular bone formation caused by load imbalance during growth could be corrected by adjustment of the function of the masseter muscle on either side.

This study aimed to demonstrate the potential role of Dual Energy CT in assessing Bone Mineral Density (BMD) in postmenopausal women. A retrospective study was conducted on 51 postmenopausal female patients who underwent DXA and DECT examinations for other clinical reasons. DECT images were acquired with spectral imaging using a 256-slice system. These images were processed and visualized using an HAP(fat) map. Statistical analysis was performed using the Bland-Altman method to assess agreement between DXA and DECT HAP(fat) measurements. Mean BMD, vertebral and femoral T-scores were obtained. For vertebral analysis, the Bland-Altman plot showed an inverse correlation (R2: -0.042; RMSE: 0.690) between T-scores and DECT HAP(fat) values for measurements from L1 to L4, while a good linear correlation (R2: 0.341; RMSE: 0.589) it was found for measurements at the femoral neck. In conclusion, we demonstrated the enhanced accuracy of BMD calculation through DECT, finding a statistically significant correlation only at the femoral neck where BMD results do not seem to be influenced by the overlap of the measurements on cortical and trabecular bone. This outcome could be beneficial in the future by reducing radiation exposure for patients already undergoing follow-up for chronic conditions.

Percutaneous kyphoplasty (PKP) is a highly successful treatment option for Kümmell's disease (KD). Due to the obstruction of the fibrocartilaginous membrane at the periphery of the intervertebral vacuum cleft (IVC) and inadequate osteointegration of conventional bone cement, there is insufficient locking strength between trabecular bone and bone cement in Kümmell's disease (KD), leading to postoperative displacement of the bone cement and sub-sequent early surgical failure. However, there is no standard strategy managing this complica-tion at present. We reported a rare case of premature bone cement displacement resulting in adjacent vertebra fracture. An 80-year-old male with Kümmell's disease at T10 received per-cutaneous kyphoplasty (PKP) with bone cement leaking into the upper disc. Only 3 days after the surgery, the patient complained of severe back pain again. X-ray and MRI showed bone cement displacement at T10, adjacent vertebra fracture at T9. In consideration of poor toler-ance of open surgery for the old patient, we successfully revised by using percutaneous ky-phoplasty with multi-point anchoring technique (A-PKP). During a 10-month postoperative follow-up, the patient reported pain relief. X-ray and three-dimensional CT scan revealed no obvious progress of bone cement displacement. Although the exact mechanism underlying this rare complication remains unclear, we observed that the premature bone cement dis-placement can result in adjacent vertebra fracture especially when the pattern of bone cement is blocky. Percutaneous kyphoplasty with multi-point anchoring technique (A-PKP) appears effective in managing this complication.

Primary bone lymphoma of the spine (PBL) is a rare entity and the most shared type of non-Hodgkin lymphoma (LNH) appearing in bone lesions deprived of nodal or extra-nodal in-volvement and accounting for approximately 2% of all lymphomas. Most PBL are diffuse large B-cell lymphomas (DLBCL) and commonly involve the appendicular skeleton. Due to its atypical location and non-specific clinical imaging features mimicking certain neoplastic or infectious processes, this pathology may be misdiagnosed, thus complicating and delaying diagnosis. Our case reports a patient in her sixties who had been suffering from chronic low back pain for a year, and had gradually started to develop cruralgia and fever. She underwent a blood sample, magnetic resonance imaging (MRI), and positron emission tomography (18F-FDG-PET/CT) which revealed significant inflammatory syndrome, a pattern of spondylodiscitis at the L3-L4 level associated with morphological and metabolic invasion extending posteriorly, raising suspicion of epiduritis. No other lesions were found on the rest of the body. Neurosurgical management was performed and a biopsy was made. Histological results showed aggressive and diffuse large B-cell lymphoma, suggesting a diagnosis of PBL. This case highlights the first case of spondylodiscitis mimicking PBL in the lumbar spine, the intricacies of the diagnostic work-up, and the complexity of discriminating with an infectious process in the spine, as both have a similar, non-specific clinical presentation with different prognosis and therapeutic management.

Plantar fasciitis is one of the most common causes of foot pain; in a significant percentage it is also associated with bone edema of the heel. A prospective randomized clinical trial was designed, in which 48 patients suffering from plantar fasciitis, with or without bone edema, were treated with temperature controlled high energy adjustable multi-mode emission laser and exercises (laser group) or with exercises only (control group). Patients were evaluated at recruitment (T0), at 2 (T1) and 6 months (T2), monitoring pain (with Visual Analogue Scale), functionality (with Foot Function Index) and perception of improvement (with Roles and Maudsley Score) and fascia thickness (with ultrasound examination). In both groups there was a significant improvement in pain, functional recovery, perception of remission and a reduction in plantar fascia thickness at T1 and T2. The laser group presented statistically better values at T2 for the Roles and Maudsley Score (z: 2.21; 0.027). Regression analysis showed that a greater reduction in fascia thickness occurred in the laser group (p-value: 0.047). In conclusion, the two conservative treatments were effective in patients suffering from plantar fasciitis, even in the presence of bone edema, but with lesser results.

Parathyroid-hormone-related protein (PTHrP) is encoded by PTHLH gene which, by alternative promoter usage and splicing mechanisms, can give rise to at least three isoforms of 139, 141 and 173 amino acids with distinct C-terminals. PTHrP is subjected to different post-translational processing that generates smaller bioactive forms, comprising amino terminus, midregion (containing a nuclear/nucleolar targeting signal) and carboxy terminus peptides. Both the full-length protein and the discrete peptides are key controllers of viability, proliferation, differentiation and apoptosis in diverse normal and pathological biological systems via the reprogramming of gene expression and remodulation of PKA or PKC-mediated signalization mechanisms. The aim of this review is to pick up selected studies on PTHrP-associated signatures as revealed by molecular profiling assays, focusing on the available data about exemplary differentiating, differentiated or non-tumoral cell and tissue models. In particular, the data presented relate to adipose, bone, dental, cartilaginous and skin tissues, and also intestinal, renal, hepatic, pulmonary and pancreatic epithelia, with a focus on hepatic fibrosis-, pancreatitis- and diabetes-related changes as diseased states. Whether reported, the biochemical and/or physiological aspects associated with the specific molecular modulation of gene expression and signal transduction pathways in the target model systems under examination will be also briefly commented.

Quantification of bone loss for follow-up comparisons has not been routinely performed in patients with parietal thinning so far. This study compares different methodological approaches including both 2- and 3-dimensional methods in computerized tomographies of a single patient. The 2-dimensional method provides accurate measurements of bone thickness, while the 3-dimensional method allows for a more comprehensive view of the bone's structure, including parameters like shape, size, and thickness. The techniques provided valuable data for the treating physician and suggest a possible effect of corticosteroids in this individual patient. The study concludes that 3-dimensional reconstruction of computerized tomographies with subsequent 2-dimensional analyses appears justified for routine radiological practice to increase clinical awareness of the size of the parietal bone defects and allow for quantification of bone loss during long-term follow-ups. Further validation of the proposed analytical approaches is warranted in larger studies to investigate patterns of bone thinning across the skull and changes in bone volumes over time, with specialized software to be approved for such analyses.

Malnutrition is one of major factors of bone and cartilage disorders. Pacific cod (Gadus macrocephalus) processing waste is a cheap and highly promising source of bioactive substances, including collagen-derived peptides and amino acids, for bone and cartilage structure stabilization. Addition of these substances to a functional drink is one of the ways to achieve their fast intestinal absorption. Collagen hydrolysate was obtained via enzymatic hydrolysis, ultrafiltration, freeze-drying, and grinding to powder. The lyophilized hydrolysate was a light gray powder with high protein content (>90%), including collagen (about 85% of total protein) and a complete set of essential and non-essential amino acids. The hydrolysate was applicable as a protein food supply or a structure-forming food component due to presence of collagen fiber fragments. An isotonic fitness drink (osmolality 298.1 ± 2.1 mOsm/L) containing the hydrolysate and vitamin C as a cofactor in collagen biosynthesis was prepared. Addition of the hydrolysate did not adversely affect its organoleptic parameters. Production of such functional foods and drinks is one of the beneficial ways of fish processing waste utilization.

Current scientific knowledge and guidelines in bone and soft tissue augmentation, suggest the use of
staged surgical workflows as gold standards in regenerative procedures during implant therapy. In this
context, the process is always the same regardless of the techniques applied: an
alternate series of surgical acts is following one another after the completion of a specific period of
osseointegration or graft maturation. As a result, the overall surgical treatment is often long, invasive and
induce scar tissue formation.
This article proposes a novel, fast and less invasive biphasic protocol with the use of a well documented
cortical barrier mounted on stock healing abutments that are further replaced by customised abutments
on an early second stage. 2 cases are reported, one for an upper maxillary edentulous area and the other
for a mandibular, with a total of 4 implants placed.
Results at 4 months post op, showed an optimal soft tissue configuration for both cases with adequate
cervical profile generation and sufficient supracrestal complex height above the implant platforms.
Significant bone gains were also recorded through CBCT data collection either with alveolar width
measurements on axial slices, superposition of preop and postop datasets and 3D visualization after bone
volume segmentation.
Further studies will be needed in the future to evaluate the efficacy of this protocol in both hard and soft
tissue augmentation for edentulous sites in need of implant rehabilitation.

Infrastructure development is rapidly increasing, driving up demand for concrete, a key construction material. Cement and aggregate are essential constituents, with global cement production reaching 4.1 billion metric tons in 2011 and CO2 emissions hitting 1.7 billion metric tons by 2024, a significant contributor to carbon emissions. To address this, alternative constituents like Rice Husk Ash (RHA) and Animal Bone Powder (ABP) are proposed. With rice husk comprising 20% of rice weight and a substantial cattle population in Bangladesh, RHA and ABP offer promising alternatives. This study examines the benefits and limitations of incorporating RHA and ABP into cement, focusing on concrete strength and permeability. By replacing varying percentages of cement with RHA and ABP simultaneously, experiments evaluate their impact on concrete properties after 28 days of curing. The research aims to identify the optimal combination for sustainable concrete production, reducing environmental impact by curbing waste generation and pollution. Results show that compressive strength increases and permeability decreases with up to 5% replacement of RHA and ABP, highlighting their potential for enhancing concrete performance while mitigating environmental concerns.

Background: biophysical stimulation therapy, and in particular Pulsed Electromagnetic Fields (PEMFs) and capacitively coupled electric fields (CCEFs) has significantly increased in the last twenty years. For this, it is necessary to have clear information regarding the efficacy, the therapeutic indication and the expected objectives. Methods: we conducted a narrative review taking into consideration different types of studies with different areas of application. The objective was to take into consideration and analyze the different fields of use and the relevant information present in the literature. Results: There is unanimous opinion regarding the usefulness of applying biophysical therapy on the bone compartment both in terms of the tissue healing process and the symptoms associated with this situation. Differently, but no less importantly, in the joint compartment positive opinions were observed mainly on the inflammatory and catabolic process, however, at present,we did not report evidence regarding cartilaginous tissue regeneration. Conclusion: the effectiveness of PEMFs and CCEFs on the bone healing process in the Orthopedic and Traumatology fields is consolidated evidence in the literature. We have also found positive results on symptoms and patient compliance with rehabilitation therapies. Therefore, notable application can be envisaged in the fields of Prosthetic Surgery and Sports Medicine.

The musculoskeletal system consisting of bones and muscles have been recognized as endocrine organs secreting hormones that are involved in regulating metabolic and inflammatory pathways. Obesity and type 2 diabetes (T2D) are associated with several musculoskeletal system complications. We hypothesized that an interaction exists between adipomyokines namely, irisin and METRNL, and various bone markers in individuals with obesity and T2D. A total of 228 individuals were enrolled in this study, including 124 non-diabetic and 104 T2D. A Multiplex assay was used to assess the level of various bone markers namely Osteoactivin, Syndecan, osteoprotegerin (OPG) and osteonectin/SPARC. Our data shows elevated levels of Osteoactivin, Syndecan, OPG and SPARC in T2D as compared to non-T2D individuals (p ≤ 0.05). Using Spearman’s correlation, irisin was positively correlated only with Osteoactivin and OPG (p &lt; 0.05). Similarly, a positive association was observed between METRNL and Osteoactivin (p &lt; 0.05). The strong positive association shown in our study between irisin, METRNL and various bone markers emphasises the strong interaction between these organs. This suggests that a dysregulation in the functional interaction between these molecules could play a possible role in the development of bone and muscle related complications that are associated with obesity and T2D.

Addressing non-unions involves stabilizing the affected area through osteosynthesis and improving bone biology using bone grafts. However, there is no consensus on the optimal treatment method. This study aims to compare outcomes of non-union revision using conventional treatment methods (metal hardware ± graft) versus osteosynthesis with the human, allogeneic cortical bone screw (Shark Screw®). Thirty-four patients underwent conventional treatment, while 28 cases received Shark Screws®. Patient demographics, bone healing, time to bone healing, and complications were assessed. Results revealed a healing rate of 96.4% for the Shark Screw® group, compared to 82.3% for the conventionally treated group. The Shark Screw® group exhibited a tendency for faster bone healing (9.4±3.2 vs. 12.9±8.5 weeks, p=0.05061). Hardware irritations led to six metal removals in the conventional group versus two in the Shark Screw® group. The Shark Screw® emerges as a promising option for personalized non-union treatment in the foot, ankle, and select lower leg cases, facilitating effective osteosynthesis and grafting within a single construct, promoting high union rates, low complications, and a rapid healing process.

In this study, an optimized multi-material system was designed and developed to print samples in various applications, including biomedical fields (e.g., mandibular bone loss). To improve the mechanical and biological properties of scaffolds utilized for dental bone loss applications, a multi-material setup was devised, which employs digital light processing technology. This setup consists of a linear system comprising two resin vats and one ultrasonic cleaning tank, enabling the integration of diverse materials and structures to optimize the composition of the scaffold. This approach was used to print multi-material PLLA scaffolds containing 20 wt.%. HA on the interior side, and PLLA containing 1 wt.% GO on the exterior surface of the scaffold, which were evaluated mechanically and biologically after printing. The scaffold was designed using a triply periodic minimal surface (TPMS) lattice structure, which is known to possess favorable mechanical and biological properties. Various multi-material samples were successfully printed and evaluated to illustrate the multiple-material setup's potential for ensuring proper function, cleaning, and adequate interface bonding. By numerically evaluating several TMPS structures, a novel Gyroid TPMS scaffold with a nominal porosity of 50% was developed and validated experimentally. The biological properties of the scaffolds were also evaluated, including surface morphology, (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) MTT assay, and cell adhesion. Based on the results, multi-material components with the least contaminations with suitable mechanical and biological properties were successfully printed. By combining PLLA-HA and PLLA-GO, this innovative technique holds tremendous potential for enhancing the effectiveness of regenerative procedures in the field of dentistry.

An increase in plant-sourced (PS) nutrient intake is promoted in support of a sustainable diet. PS dietary minerals and proteins have bioactive properties that can affect bone health and the risk of fracture. In a group randomised, cross-over, design, this study evaluated the post-ingestion, temporal pattern of change in arterialised ionised calcium (iCa), parathyroid hormone (PTH), C-terminal crosslinked telopeptide of type I collagen (CTX) and procollagen type 1 amino-terminal propeptide (P1NP) for 4 hours following ingestion of a novel supplement (SUPP) containing a PS marine multi-mineral + PS protein isolate. A diurnally matched intake of mineral water was used as a control (CON). Compared to baseline, the change in iCa concentration was 0.022 (95%CI, 0.006 to 0.038, p = 0.011) mmol/l greater in SUPP than CON, resulting in a -4.214 (95%CI, -8.244 to -.183, p = 0.042) pg/mL mean reduction in PTH, a -0.64 (95%CI, -0.199 to -0.008, p = .029) ng/mL decrease in the biomarker of bone resorption, CTX, and no change in biomarker of bone formation, P1NP. Used as a dietary supplement, or by incorporation into a food matrix, the promotion of PS marine multi-mineral and PS protein isolates may contribute to a more sustainable diet and overall bone health.

It is known that complexes based on natural polysaccharides are able to eliminate bone defects. Prolonged hyperglycemia means low bone regeneration and a chronic inflammatory response. The purpose of the study was to increase the efficiency of early bone formation in a cavity of critical size in diabetes mellitus in the experiment. The polyelectrolyte complex contains high molecular ascorbate of chitosan, chondroitin sulfate, sodium hyaluronate, heparin, adgelon serum growth factor, sodium alginate and amorphous nanohydroxyapatite (CH-SA-HA). Studies were conducted on 5 groups of white female Wistar rats: group 1 - regeneration of a bone defect in healthy animals under a blood clot; group 2 - regeneration of a bone defect under a blood clot in animals with diabetes mellitus; group 3 - bone regeneration in animals with diabetes mellitus after filling the bone cavity with a collagen sponge; group 4 - filling of a bone defect with a CH-SA-HA construct in healthy animals; Group 5 - filling of a bone defect CH-SA-HA in animals with diabetes mellitus. Implantation of the CH-SA-HA construct into bone cavities in type I diabetic rats can accelerate the rate of bone tissue repair. The inclusion of modifying polysaccharides and apatite agents in the construction may be a prospect for further improvement of the properties of implants.

Purpose: We aimed to develop a nomogram able to predict treatment failure, skeletal events and overall survival (OS) in patients with castration-resistant prostate cancer with bone metastases (CRPC-BM) treated with Radium-223 dichloride (223Ra). Patients and Methods: Patients from Castilla-La Mancha Spanish region was prospectively included in ChoPET-Rad multicenter study, from January 2015 to December 2022. Patients underwent baseline, interim, and end-of-treatment bone scintigraphy (BS) and 18F-Fluorocholine PET/CT (FCH PET/CT) scans, obtaining multiple imaging radiomics as well as clinical and biochemical variables during follow-up and studying their association with the previously defined end-points. Survival analysis was performed using Kaplan-Meier method and Cox regression. Multivariate logistic and Cox regression models were calculated, and these models were depicted by means of nomograms. Results: Median progression-free survival (PFS) and OS for our population were 4 and 14 months (mo), respectively. The variables that showed the most robust independent significant association with therapeutic failure were baseline alkaline phosphatase (AP) levels (p=0.022) and the characteristics of BM on CT portion of PET/CT (p=0.017). In the case of OS, the significant variables were therapeutic failure (p=0.038), the number of lines received after 223Ra (p

This study aimed to investigate the appearance and frequencies of the booroola polymorphism of the bone morphogenetic protein receptor 1b (BMPR1B) gene (FecB) and the embrapa polymorphism of the growth differentiation factor 9 (GDF9) gene (FecGE) in sheep in Thailand. A total of 454 cross-bred sheep blood samples were collected from four provinces in Thailand during August 2022 to July 2023. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used to identify the FecB and FecGE genotype. The history of ewe birth types was collected from the owners to analyze the association between Fecundity (Fec) genotypes and the history of birth types. The genotypic frequencies of FecB for homozygous genotype (B/B), heterozygous genotype (+/B) and wild-type (+/+) were 0.22%, 1.54%, and 98.24%, respectively. Meanwhile, the genotypic frequencies of FecGE for homozygous genotype (E/E), heterozygous genotype (+/E), and wildtype (+/+) were 0.00%, 2.42%, and 97.58%, respectively. Furthermore, three ewes exhibited both FecB and FecGE genotypes. Fisher’s exact test revealed that the possessor of FecB genotype was associated with multiple births (p&lt;0.01). Both FecB and FecGE mutations were identified in crossbred sheep in Thailand. Sheep containing FecB allele is a better candidate to be selected to improve the prolificacy of crossbred sheep in Thailand.

Background: Xenogenous bone has been proposed as an alternative to overcome the disadvantages of autogenous grafting. The aim of the present study was to study bone dynamics at inlay and onlay xenografts used for bone augmentation applying a ring technique. Methods: The bone at the lateral surface of the mandibular angle of 12 adult male New Zealand White rabbits was exposed bilaterally. The cortical layer received multiple perforations at one side of the mandible and a xenograft block of collagenated cancellous equine bone, 7 mm in diameter and 3 mm in width, was fixed on the prepared surface using an implant (onlay group). On the opposite side, a defect 7 mm in diameter and 3 mm in depth was prepared, the xenograft block was adapted to the defect and fixed with an implant (inlay group). Results: After ten weeks of healing, in the onlay grafts, new bone was mainly formed on the trabeculae surface, reaching in some specimens the most coronal regions of the block. In the inlay grafts, new bone was found arranged on the trabecular surfaces but also occupying the spaces among the trabeculae. The entrance of the defect was often found close at the top of the block by newly formed bone. A higher percentage of new bone was found in the inlay (19.0 ±9.3%) compared to the onlay (10.4 ±7.4%) groups (p=0.031). The mean gain in osseointegration at the implant in relation to the base of the original 3 mm deep defect was 0.95 ±1.05% at the onlay group and 0.78 ±0.71% at the inlay group (p=0.603). Conclusion: The inlay grafts exhibited a higher new bone percentage than the onlay grafts possibly due to the defect conformation that presented more sources for bone formation. The trabecular conformation and the composition of the grafts made possible the expression of the osteoconductive properties of the material used. This resulted, in several specimens, in growth of bone on the graft trabeculae toward the most superior regions in both groups, and in the closure of the coronal entrance of the defects in the inlay group.

Background: Diabetes mellitus (DM) and osteoporosis are two of the most widespread metabolic disease in the world. The aim of this study is to investigate the prevalence of DM among patients affected by osteoporosis and fragility fractures, and to search differences in clinical features. Methods: 713 patients belonging to CTO Bone Unit because of osteoporosis and fragility fractures were divided into two groups, according to the diagnosis of DM. The clinical and bone characteristics of patients were compared. Results: Prevalence of DM was 10.8%. When compared to patients without DM, the median age at the time of first fracture was similar (72 years ± 14 IQR vs 71 years ± 12 IQR); prevalence of combination of vertebral and hip fractures was higher (p=0.039), as well as prevalence of males, although not significantly (p=0.051). Bone mineral density (BMD) at all sites was higher in DM group; Trabecular Bone Score (TBS), instead, was significantly lower (p&lt;0.001). Conclusions: Patients with fragility fractures and DM more frequently show combination of major fractures with higher BMD levels. In these patients, TBS could be a better indicator of bone health than BMD and therefore should be used as a diagnostic tool in clinical practice.

Our results demonstrated that SWT stimulates osteoblastogenesis and increase the cell number of osteoblasts, suggesting positive regulatory effects on osteoblast differentiation. However, the effect of SWT on bone formation need further examination, since the expression of alp gene is downregulated. On the other hand, SWT appears to negatively regulate osteoclast differentiation and bone resorption, as number of osteoclasts and the expression of critical bone resorptive genes are all downregulated. Collectively, SWT might change the equilibrium of bone remodeling and increase the bone mass. Our data provided supportive evidences that this medicine formulation can be applied to treat osteoporosis or bone destructive diseases.

The frequent occurrence of rib fractures in slaughtered lambs results in significant economic loss to producers and processors in South Australia and raises concerns about the welfare of the animals. The prevalence of rib fractures became evident through the Enhanced Abattoir Surveillance (EAS) program introduced in 2007. The present study aimed to investigate the association between rib fracture prevalence in lambs at slaughter and their nutrition and management on the farm of origin. The slaughter of 30,055 lambs from 60 farms was monitored at a South Australian abattoir in November 2016. Rib fracture prevalence was 4% (range 0 - 18% per consignment), with all consignments of more than 240 lambs having at least one with fractured ribs. Traceback investigation on 56 of the 60 farms suggests that rib fractures most probably occur during routine husbandry procedures and, based on soil mineral analysis, are associated with calcium inadequacy. There was substantial variation between lines of lambs from different farms, and factors contributing to the differences included line size, region, and soil characteristics, including available calcium. There is a need to modify sheep husbandry and management practices to improve sheep welfare and reduce the cost of rib fractures to the sheep industry.

In the pursuit of better treatments, the concept of a chemically-active material, responding to local conditions by causing reactions, or reacting to produce substances that are deemed beneficial, seems laudable. Ultimately, the goal appears to be to recruit natural biological processes such that a natural ‘repair’ is effected. This goal seems to be the reason for prefixing “bio-“ to many terms with a view to advertising the desire, yet without presenting evidence that it has occurred, or indeed that it is capable of occurring, relying instead on non-biological processes to justify the claims. The dogma is such that all work where local ‘responsive’ chemistry is involved must receive the label “bioactive” to legitimize and promote. Nevertheless, the primary evidence adduced is flawed, and the claim must fail. A rethink to restore scientific sense and confidence in the endeavour is essential if real progress is to be made.

Thermoplastic molded regenerated silk was proposed as structural material in tissue engineering applications, mainly for application in bone. The protocol allows to obtain a compact non-porous material with a compression modulus in the order of a Giga Pascal starting from silk fibroin by compressing a silk fibroin lyophilized sponge of powder in mold at temperature higher than the glass transition temperature (Tg). The main purpose of the produced resin was the osteofixation and other structural applications in which the lack of porosity was not an issue. In this work, we introduced the use of citric acid in the thermoplastic molding protocol of SF to obtain a porosity inside the structural material. In addition to the previously developed protocols the addition of citric acid allowed us to obtain a structural material. The CA powder during the compression acted as a template for the pore formation. In addition, the CA was able to effectively crosslink the SF chain improving the mechanical strength. This effect was proved both evaluating the compression modulus and by studying the spectra obtained by Fourier infrared spectroscopy (FTIR). This protocol may be applied in the near future to the production of a structural bone scaffold.

Low dietary intake of calcium, vitamin D, vitamin C and magnesium has been associated with increased risk of osteoporosis. The purpose of the study was to evaluate changes in several bone health indicators and metabolic biomarkers in postmenopausal women, with high osteopenia or osteoporosis, followed by a nutritional intervention program. 115 apparently healthy postmenopausal women (52±8 years old) were randomized into four groups: group I (n=40) received daily 1000 mg vitamin C, 100 mcg vitamin D3, 500 mg calcium(Ca) and 300 mg magnesium (Mg); group II (n=42) received daily 100 mcg vitamin D3, 500 mg Ca and 300 mg Mg; group III (n=18) received daily 5 mg bisphosphonates, 100 mcg vitamin D3, 500 mg Ca and 300 mg Mg; and group IV (n=15) received daily about 364 mg polyphenols via an innovative functional food (50 g olive paste enriched with mountain tea extract) along with 100 mcg vitamin D3, 500 mg Ca and 300 mg Mg. Groups I -III received supplementation for a year whereas group IV for 5 months. Changes in bone health indicators and metabolic biomarkers were assessed at the beginning and at the end of the study. Anthropometric indices and whole-body bone mineral density (BMD) were also evaluated at the beginning and at the end of the intervention period. The results revealed improved elevated levels of 25(OH)D3, in groups II, III and IV (+3,71% and +1.45% and +5.62% respectively). Significant positive changes were recorded, for whole-body BMD, in all four study groups. Significant beneficial changes for total cholesterol were observed in group IV (-2.07%, P&lt;0.05) and positive changes in group I for HDL biomarker (+61.62%, P&lt;0.05). Additional larger-scale clinical trials and intervention studies are considered essential, to fully investigate and elucidate associations between dietary components and biochemical indices of bone health.

Abstract. Introduction: BMD study gives partial information on bone health in patients with TSH suppression therapy due to Differentiated Thyroid Cancer (DTC). TBS, a new parameter of bone microarchitecture is propose for bone quality study. This study analyze their long-term use in patients with DTC. Methods: BMD was measured by DXA and TBS with iNsigth software in 145 postmenopausal DTC patients. Vertebral Fractures (VFs) with a semi-quantitative x-ray method. Results: BMD at the end study was not different from initial. TBS decreased from 1.35±0.1 to 1.27±0.1 (p=0.002). PTH, Osteocalcin, and BAP were increased, suggesting increased bone remodeling. There was an increase in osteoporosis and osteopenia (40.6% and 16.5% to 46.6% and 18.6%); 31% had partially degraded and 15.1% degraded TBS changed to 48,9% and 24,8% at the end study. VFs in 30 patients, was not different in age, BMI, calcium and alcohol ingestion, smoking, radioiodine, or thyroid parameters vs. without VFs. Odds ratio for VFs increased with osteopenia (OR 2.63). Combination of TBS plus TBS did not improve discrimination. Conclusions: TBS was lowered while BMD did not differ. Percentage of osteoporosis and osteopenia and of partially degraded and degraded TBS was higher at the end study. Predominant discordance rate was found in partially degraded microarchitecture, in which the proportion of osteopenia was higher than normal or osteoporotic patients. AUC of TBS plus BMD did not improve discrimination. TBS, radioactive iodine, and sedentary lifestyle were the main differential data for patients with DTC and VFs.

Pain in osteoarthritis (OA) results from erosion of joint cartilage, resulting in bone contacting bone without an intervening cushion. The periosteum, including its nociceptive innervation, ends at the border of the cartilage meaning that there is no extrinsic neuronal pathway between the opposing denuded bone surfaces to carry a bone-on-bone pain signal to the brain. The pain signaling pathway must therefore originate in nociceptive sensory endings within the subchondral bone itself. Selective ablation of this intrinsic nerve pathway, using any of a variety of approaches, is expected to permanently eliminate OA pain.

Aim: In a human pilot case, we used a root formed temporary prosthetical device (Intra-alveolar Device - IAD), to investigate the effect of mechanical stimulation on hard tissue clinically and radiographically. Background: The extraction of a tooth determines the resorption of the alveolar bone. This determines challenge to place an implant and to integrate the prosthesis in soft tissue. Mechanical stimulation is fundamental for bone tropism but is not understood the effect of mechanical stimulation on post-extraction site. Case presentation: A 24 years old woman was enrolled. The IAD’s were used as expected by protocol. Clinical healing was uneventfully. Vertical radiographical bone resorption measured on CBCT was -0,14mm (5,6%) while horizontal bone resorption was -0,21mm (12,36%). Conclusion: This study demonstrated the feasibility of the proposed model. We need clinical prospectical studies enrolling more patients

The purpose of this study was to clarify the attachment types of the tibialis anterior tendon (TAT) in Japanese fixed cadavers and to determine the attachment site area in three dimensions. We examined 100 feet from 50 Japanese cadavers. The TAT was classified according to differences in the number of fiber bundles as: Type I, with one fiber bundle; Type II, with two fiber bundles; and Type III, with three fiber bundles. The attachment site area of the TAT was measured using a three-dimensional scanner. Cases were Type II in 95% and Type III in 5%, with no cases of Type I identified. In Type II, mean attachment site areas were 85.2 ± 18.2 mm2 for the medial cuneiform bone (MCB) and 72.4 ± 19.0 mm2 for the first metatarsal bone (1MB), showing a significantly larger area for MCB than for 1MB. These findings suggest the possibility of ethnic differences in TAT attachment types and suggest that TAT attachments in Japanese individuals are highly likely to be Type II, with rare cases of Type III. Accurate measurement of attachment site areas is possible with appropriate three-dimensional measurements.

Recombinant α1-microglobulin (A1M) is proposed as protector during 177Lu-octreotate treatment of neuroendocrine tumors, which is currently limited by bone marrow and renal toxicity. Co-administration of 177Lu-octreotate and A1M could result in a more effective treatment by protecting healthy tissue, but, the radioprotecting action of A1M is not fully understood. The aim of this study was to examine the proteomic response of kidneys and bone marrow early after 177Lu-octreotate and/or A1M administration. Mice were injected with 177Lu-octreotate and/or A1M, while control mice received saline or A1M vehicle solution. Bone marrow, kidney medulla, and kidney cortex were sampled after 24 hours or 7 days. Differential protein expression was analyzed with tandem mass spectrometry. Dosimetric estimation was based on 177Lu activity in kidney. PHLDA3 was the most prominent radiation responsive protein in kidney tissue. In general, no statistically significant difference in expression of radiation-related proteins was observed between the irradiated groups. Most canonical pathways were identified in bone marrow from the 177Lu-octreotate+A1M group. Altogether, tissue-dependent proteomic response followed exposure to 177Lu-octreotate alone or together with A1M. Combining 177Lu-octreotate with A1M did not inhibit the radiation induced protein expression early after exposure, and late effects should be further studied.

Osteitis fibrosa cystica (OFC) and Brown Tumour are two related but distinct types of bone lesions that result from overactivity of osteoclasts most often associated with chronic kidney disease (CKD). Despite their potential consequences, these conditions are poorly understood because of their rare prevalence and variability in their clinical manifestation. Canonically, OFC and Brown Tumours are caused by secondary hyperparathyroidism in CKD. Recent literature showed that multiple factors such as hyperactivation of the renin-angiotensin-aldosterone system and chronic inflammation may also contribute to the occurrence of these diseases through osteoclast activation. Moreover, hotspot KRAS mutations were identified in these lesions placing them in the spectrum of RAS-MAPK-driven neoplasms, while until recently thought to be reactive lesions. Some risk factors contributed to the occurrence of OFC and Brown Tumour such as age, gender, comorbidities, and certain medications. The diagnosis of OFC and Brown Tumour includes clinical symptoms involving chronic bone pain and laboratory finding of hyperparathyroidism. In radiological imaging, the X-ray and Computed tomography (CT) scan could show lytic or multi-lobular cystic alterations. Histologically both lesions are characterized by clustered osteoclast in a fibrotic hemorrhagic background. Based on the latest understanding of the mechanism of OFC, this review elaborates on the manifestation, diagnosis, and available therapies that can be leveraged to prevent the occurrence of OFC and Brown Tumour.

We investigated the diagnostic capacity of selected circulating biomarkers (CBMs) for the early detection of bone metastasis (BMets) in patients with pancreatic neuroendocrine neoplasms (PanNENs). 115 patients with PanNENs and 40 controls were enrolled. We measured the serum levels of ferritin, cytokeratin 18 (CY18), CA19-9, CA125, AFP, CEA, and beta-2 microglobulin (B2M). 8 PanNENs patients developed BMets, and 107 remained BMets-free. We observed a significantly higher level of CA125 and CY18 in BM-PanNENs patients vs. non-BM-PanNENs patients (p = 0.01 and p = 0.04, respectively). CA125, CY18, and B2M area under receiver operator characteristic (AUROC) analyses differentiated BM-PanNENs from non-BM-PanNENs patients; CA125 area under the curve (AUC) 0.77, p < 0.01; CY18 AUC data were 0.72, p = 0.03, and B2M AUC 0.67, p = 0.02. Based on CBMs metrics in both subgroups, we reached a sensitivity/specificity for CA125 of 75/76%; for CY18 of 75/69%, for B2M of 100/50%, for CA125 and CY18 combination 93/90%, respectively. The useful CBMs for BM-PanNENs patients detection were CA125, CY18, and B2M. They seem to have the diagnostic capacity as a fair single biomarker and CA125&CY18 combination panel for the detection of BMets.

ABSTRACT: Understanding the basis of osteoarthritis (OA) has seen some interesting advancements in recent years. It has been observed that cartilage degeneration is preceded by subchondral bone lesions, suggesting a key role of this mechanism within the pathogenesis and progression of OA, including the formation of ectopic bone and osteophytes. Moreover, low-grade, chronic inflammation of the synovial lining has gained a central role in the definition of OA pathophysiology, and central immunological mechanisms, innate but also adaptive, are now considered crucial in driving inflammation and tissue destruction. In addition, the role of neuroinflammation and central sensitization mechanisms has been characterized as underlying causes of pain chronicity. This has led to a renewed definition of OA, which is now intended as a complex multifactorial joint pathology caused by inflammatory and metabolic factors underlying joint damage. Since this evidence can directly affect the definition of the correct therapeutic approach to OA, an improved understanding of these pathophysiological mechanisms is fundamental. This review provides an overview of the most updated evidence on OA pathogenesis; it presents the most recent insight on the pathophysiology of OA, describing the interplay between immunological and biochemical mechanisms proposed to drive inflammation and tissue destruction, as well as central sensitization mechanisms. Moreover, although the therapeutic implications consequent to the renewed definition of OA are beyond this review scope, some suggestions for intervention have been addressed.

The study aimed to evaluate implant success and bone height variations after transcrestal sinus floor elevation (tSFE) using the osseodensification technique (OD) combined with beta-tricalcium phosphate (β-TCP), as bone graft material and simultaneous implant placement. Thirteen patients requiring the placement of one implant in the upper posterior maxilla, with a residual bone height of

Background: Nutritional rickets is still considered as a global health problem especially in low-resource countries and immigrant societies of developed countries. Generalized skeletal deformities including angular knee deformities as genu varum and genu valgum are prominent features of nutritional rickets. Angular knee deformities can cause gait difficulties. However, the true remodelling potential of the healed knee deformities is largely unknown to the pediatric and orthopedic community. Aims: The primary objective of this study protocol is to investigate the natural history of disease in regard to the remodelling potential of angular knee deformities in children and adolescents with healed nutritional rickets. And determine the potential patient- and deformity-related factors that are associated with a favorable deformity remodelling as age and sex of patients and type, severity, laterality of deformities etc. Methods: This will be a prospective observational analytical cohort natural history of disease study. A minimum of at least 140 knees with healed nutritional rickets and angular knee deformities will be observed at regular three-monthly intervals over a period of at least one year. We will report two outcome variables namely; clinical and radiological tibio-femoral angle. And independent patient and deformity-related variables as age, sex, deformity type, severity and laterality. Inferential statistics namely bivariate and multivariate analysis will be employed accordingly to identify the relation between outcome variables and the different independent variables. Ethics and dissemination: This protocol study has been approved by the institutional research ethics committee. Results will be presented at conferences and submitted to relevant international and society publications. Authors will also communicate the results to their scholarly networks and post them on scholarly networking sites. Conclusions: This study has the potential for improving the decision-making process as to which patients deserve conservative treatment and which deserve surgical deformity correction. Results are expected to have an impact on the clinical practice of pediatricians, orthopedic surgeons and family physicians alike.

Titanium micro-scale topography results in excellent osteoconductivity and bone-implant integration. However, the biological effects of sub-micron topography are unknown. We compared osteoblastic phenotypes and in vivo bone and implant integration abilities between titanium surfaces with micro- (1–5 µm) and sub-micro-scale (0.1–0.5 µm) topographies and machined titanium. Average roughness was 12.5 ± 0.65 nm, 123 ± 6.15 nm, and 24 ± 1.2 nm for machined, micro-rough, and sub-micro-rough surfaces, respectively. The micro-rough surface showed the fewest cells attaching during the initial stage and the lowest proliferation. Calcium deposition and expression of osteoblastic genes were highest on the sub-micro-rough surface and lowest on the machined surface. Bone-to-implant integration was strongest for the micro-rough surface, consistent with it having the greatest ability to retain cells in vitro. Thus, the biological effects of titanium surfaces are not necessarily proportional to the degree of roughness in osteoblastic cultures or in vivo. Sub-micro-rough titanium ameliorates the disadvantage of micro-rough titanium by restoring cell attachment and proliferation and enhances the rate of osteoblastic differentiation over that of micro-rough titanium; however, bone integration and the ability to retain cells are compromised due to its lower interfacial mechanical locking compared to that of micro-rough titanium.

Skeletal metastases of unknown primary (SMUP) represent a clinical challenge dealing with patients diagnosed with bone metastases. The management have improved significantly in the past years, however fraught with lack of evidences, approach to these patients held out hope for more systematic and tailored treatment—and some patients can achieve impressive gains. Nevertheless, in real-life practice the outlook at the beginning of the take in charge of SMUP is decidedly more somber. An incomplete translational relevance of pathological and clinical data on the mortality and morbidity rate has had unsatisfactory consequences for SMUP patients and their physicians. We examined several approaches to confront the available evidences and highlighted three key points that emerge. The characterization of the SMUP biologic profile is essential to drive clinical decisions, integrating genetic and molecular profile into a multi-step diagnostic work-up. Nonetheless, pragmatic investigation plan and therapy of SMUP cannot follow a single template; it must be adapted to different pathophysiological dynamics and coordinated with efforts of a systematic algorithm and high-quality data derived from statistically powered clinical trials within. This review argues that greater efforts are required to face the unmet need dealing with SMUP patients in oncology. Finally, we provide an original functional network analysis, identifying novel therapeutic targets.

Background and Objectives: This study aimed to evaluate the histological and biochemical ef-fects of capsaicin on implant osseointegration and oxidative stress. Materials and Methods: Male Wistar albino rats weighing between 250 and 300 grams were used in this study. Twenty-four rats were randomly divided into three equal groups: implant + control (n= 8), implant + capsai-cin-1 (n= 8), and implant + capsaicin-2 (n= 8). 2.5 mm diameter and 4 mm length titanium im-plants were surgically integrated into the corticocancellous bone parts of the femurs. In the treatment groups, rats were injected intraperitoneally with 25 mg/kg (implant + capsaicin-1) and 50 mg/kg (implant + capsaicin-2) of capsaicin. No additional applications were made in the con-trol group. Three rats in totally were died during and after the experiment, as a result of the an-alyzes performed on 21 animals. Results: The highest total antioxidant status value was found in capsaicin dose 2, according to the analysis. The control group had the highest total oxidant status and oxidative stress index values, while group 2 of capsaicin had the lowest. After analysis, we found that there was no observed positive effect on osteointegration in this study (p> 0.05), alt-hough the bone implant connection was higher in the groups treated with capsaicin. Conclusi-ons: A positive effect on osteointegration was not observed in this study. This may be due to os-teaclast activation. However it was found that it has a positive effect on oxidative stress. Osteo-clast activation may be the cause of this phenomenon. Capsaicin was found to have a positive effect on oxidative stress (p

The phytonutraceutical Ormona® is a product composed of: purified oil of Bixa orellana Linné; dry extract of Myrciaria dubia McVaugh; dry extract of Trifolium pratense L. and dry extract of Euterpe oleracea Mart. obtained using Evolve® technology. This study evaluated the effects of Ormona® on Wistar rats affected by ovariectomy-induced osteoporosis. Pre-treatment was conducted for 15 days before surgery and continued for a further 45 days after the surgical procedure. The experimental design consisted of 5 groups (n=5): OVW: treated with distilled water (1 mL/ kg, p.o); ADS: alendronate sodium (4 mg/ kg p.o); EST: conjugated estrogen (2 ug/ kg, p.o); ORM: Ormona® (20 mg/kg, p.o); ORM + EST: Ormona® (20 mg/kg + conjugated estrogen 2 ug/ kg, p.o. Biochemical and hormonal parameters, along with bone histopathology and trabecular and femoral diaphysis size, were evaluated through Scanning Electron Microscopy (SEM) and bone calcium quantification by atomic absorption spectrophotometry. The results show that ovariectomy caused bone alterations such as loss of femoral microarchitecture, decreased bone homeostasis parameters, and changes in the lipid profile. Estrogen supplementation reduced parameters such as cholesterol, LDL, and Ca2+ concentration. However, Ormona® showed higher serum estradiol levels (p&lt; 0.01), effects on the lipid profile, including parameters that estrogen replacement and alendronate sodium did not affect, with an increase in HDL, and positive modulation of bone metabolism, increasing osteocytes and the presence of osteoblasts. Ormona®, therefore, produced better results than the groups treated with estrogen and alendronate sodium.

Abstract: The centrepiece of this analytical review is the metabolism of hydroxyapatite in its natural, bone, and synthetic forms, where the mitochondria-mediated mechanism may serve as the leading mechanism. The possibility that osteoblast mitochondria play an important role in the initial stages of bone mineralisation is discussed. Furthermore, the paper highlights the key role of mitochondria in the metabolism of synthetic hydroxyapatite.Differences between the results of in vivo and in vitro studies using synthetic hydroxyapatite of different morphologies are also detailed. It is noted that long-term infiltration with immune cells and in vivo studies are necessary to adequately evaluate hydroxyapatite as a bone-plastic material.Particular attention is given to the interaction of hydroxyapatite with immune cells and its ability to affect the ribosomes and mitochondria of cells. Due to its mechanical properties, scalability and potential use for the treatment of extensive bone defects of tumor origin, hydroxyapatite is a promising material.This study also highlights the importance of further development of in vitro research methods in the context of their biomimeticity. Overall, this work offers a theoretical direction for future studies of hydroxyapatite as a bone grafting material and emphasises the value of in vivo studies.

Estimating age at death is essential to establish a biological profile from human skeletal remains in both forensic and archeological settings. Imaging studies of skeletal age changes in adults have described metamorphosis of trabecular bone structure and bone loss in the proximal femur , as well as changes in morphology during different stages of life. This study aims to assess the utility of a digital representation of conventional X-ray films of the proximal femur for the estimation of age at death in a sample of 91 adult individuals (47 females and 44 males) of the Coimbra Identified Skeletal Collection. The proposed approach showed a root mean squared error (RMSE) of 17.32 years (and mean absolute error of 13.47 years) for females and an RMSE of 14.06 years (mean absolute error of 11.08 years) for males. The main advantage of this approach is the consistency in the feature detection and extraction, as X-ray images projected on the femora space will always produce the same set features to be analyzed for age estimation while more traditional methods rely heavily on operator experience which can lead to inconsistent age estimates among experts.

Forensic anthropologists play a key role in skeletal trauma analysis and commonly use macroscopic features to distinguish between trauma types. However, this approach can be challenging, particularly in cases of highly comminuted or incompletely recovered fractures. Histological analysis of microscopic fracture characteristics in fractured bones may thus help provide additional information on trauma type and bone fracture biomechanics in general. This study analysed the extent of microcrack damage to osteons in long bones with blunt force trauma (BFT) and gunshot trauma (GST), from both traumatic death cases and post-mortem experimental fractures. We identified four types of osteonal damage (OD). In traumatic death cases, OD affecting the inside of the osteon and compromising the Haversian canal (type 1) was found to be indicative of BFT. Moreover, OD affecting the cement line (type 3) and interstitial lamellae (type 4) was more common in the GST samples. OD affecting the inside of the osteon without compromising the Haversian canal (type 2) was not found to be indicative of either trauma type. In cases of experimental fractures, our study revealed that post-mortem fractures in dry bone samples featured the highest amount of OD, particularly of type 4. This study also found that the experimentally produced GST featured similar OD pattern to GST death cases. These findings support our hypothesis that there are distinct osteonal damage patterns in human long bones with BFT and GST, which are of relevant value for trauma analysis in forensic anthropology.

This study aimed to assess the response of 3D printed PLA scaffolds biomimetically coated with apatite on human primary osteoblast spheroids and evaluate the biological response to its association with Bone Morphogenetic Protein 2 (rhBMP-2) in rat calvaria. PLA scaffolds were produced via 3D printing, soaked in simulated body fluid (SBF) solution, and characterized by physical-chemical, morphological, and mechanical properties. The in vitro biological response was assessed with human primary osteoblast (HOb) spheroids. The in vivo analysis was conducted through the implantation of 3D printed PLA scaffolds either alone, covered by apatite (PLA-CaP) or PLA-CaP loaded with rhBMP-2 (PLA-CaP+rhBMP-2) on critical-sized defects (8 mm) of rat calvaria. Increased cell adhesion and in vitro release of growth factors (PDGF, bFGF, VEGF) was observed for PLA-CaP scaffolds when pre-treated with FBS. PLA-CaP+BMP2 presented higher values of newly formed bone (NFB) than other groups at all experimental periods (p&lt;0.05), attaining 44.85% of NFB after 6 months. These findings indicate that functionalization of PLA scaffolds with biomimetic apatite can improve its biological properties in the presence of complex biological media. Its association with BMP2 may enhance bone repair, suggesting this strategy as a promising candidate for bone tissue engineering.

Background: To investigate the safety and efficacy of palliative arterial embolization for metastases of the scapula. Materials and Methods: We studied the files of the patients who underwent palliatrive arterial embolization for metastases of the scapula from January 2016 to January 2023, 15 patients (8 M, and 7 F) with a mean age of 62 years (SD 10.2) with two patients receiving a second procedure, for a total of 17 embolizations. Data on technical and clinical success, as well as changes in tumor size, were collected. All embolization-related complications were evaluated according to the CIRSE classification system for complications. Results: The average follow-up was 18 months (Range 6-36 months). The main primary tumor were renal, lung and breast cancer. The primary arteries embolized were the circumflex scapular artery, the dorsal scapular artery, and the thoracoacromial trunk. A mixture of Glubran and Lipiodol in a 1:2 ratio was used for embolization, with an average of 1.1 mL (Range 0.5-1.5 mL) used per procedure. The efficacy of embolization was measured using the Visual Analogue Scale (VAS), with values recorded at baseline, at 1, 3, 6, and 12 months post-embolization, and at 6-month intervals after. Baseline VAS scores averaged 7.2 (SD 1.5), decreasing to 2.8 (SD 0.9) at one month. Progressive reduction was observed at 3, 6, and 12 months with scores of 2.3 (SD 0.8), 1.9 (SD 0.7), and 1.6 (SD 0.6) respectively. Metastatic tumor size was reduced from a mean of 192.2 cm3 (range 38.7 to 480.1 cm3) pre-embolization to a mean of 177.3 cm3 (range 37.2 to 455.5 cm3) at the 12-month follow-up (p

Exosomes are membrane-bound, biologically active nanovesicles of size 30-200 nm produced by many cell types, such as both mammalian and plant cells. They are wrapped in a phospholipid bilayer and play a significant role in intercellular communications. The ease in their isolation and the ability of plant-derived exosome-like nanovesicles (PDEVs) to efficiently deliver bioactive constituents into mammalian cells have made them popular in contemporary research. PDEVs share many characteristics with mammalian EVs (MEVs), including shape, size, surface charge, and consist of bioactive molecules like lipids, proteins, nucleic acids, and tiny metabolites. However, the chemical composition profile of PDEVs and their biogenesis mechanism differ significantly from those of MEVs. They have been widely explored as potential therapeutic agents and are considered as good alternatives to act as a carrier for drug delivery. The present work elucidates the isolation of exosome-like-nanovesicles (henceforth exosomes) from the culture supernatants of an in vitro cultured callus tissue derived from a bone healing plant known for its osteogenic activity, i.e., Cissus quadrangularis. The physical and biological properties of exosomes were successfully studied using different characterization techniques. To assess their therapeutic potential, we studied the internalisation of calcein-AM labeled exosomes by human derived mesenchymal stromal cells (hMSCs). Additionally, we evaluated the potential of exosomes in the migration of cells in a cell scratch assay with hMSCs and their effect on amelioration of oxidative stress was investigated on preosteoblast MC3T3-E1 cells that were pre-treated with these exosomes. Furthermore, we investigated their proliferation and differentiation to osteoblasts like cells with the help of resazurin assay and alkaline phosphatase assay (ALP). The obtained results provide a primary justification for the use of Cissus quadrangularis-derived exosomes as a nanocarrier for drug molecules for various therapeutic bone applications.

Background: TP53 alterations have a significant prognostic effect in myeloid neoplasms. Our objective was to investigate the TP53 gene mutation status, p53 protein expression, and their re-lationship in dysplasia-related myeloid neoplasms with varying levels of myeloblast counts. Methods: 76 bone marrow biopsy samples with different blast counts were analyzed. Total and strong (3+) p53 expression was determined. Dual immunohistochemical staining was performed to determine the cell population associated with p53 expression. NGS analysis was performed using the Accel-Amplicon Comprehensive TP53 panel. Results: Both p53 expression and TP53 VAF showed a significant correlation with the myeloblast ratio (p<0.0001), however, p53 expres-sion was present in other cell lineages as well. The VAF value exhibited a significant correlation with p53 expression. A high specificity (0.9800) was observed for TP53 mutation using the ≥10% strong (3+) p53 cut-off value, although the sensitivity (0.4231) was low. Conclusion: Strong (3+) p53 expression using a ≥10% cut-off value accurately predicts TP53 mutation but doesn't reveal the allelic state. The p53 expression is significantly influenced by myeloblast count, and histo-logical interpretation should consider the presence of intermixed non-neoplastic marrow cells with varying physiological p53 expression.

Background: Painful spinal bone metastases (PSBMs) patients regularly receive palliative radiation therapy (RT) with response rates in about 2 of 3 patients. In this exploratory study, we evaluated the value of machine learning (ML) models based on radiomic, semantic and clinical features to predict complete pain response. Methods: Gross tumour volumes (GTV) and clinical target volumes (CTV) of 261 PSBMs were segmented on planning computed tomography (CT) scans. Radiomic, semantic and clinical features were collected for all patients. Random forest (RFC) and support vector machine (SVM) classifiers were compared using repeated nested cross-validation.Results: The best radiomic classifier was trained on CTV with an area under the receiver-operator curve (AUROC) of 0.62 ± 0.01 (RFC; 95% confidence interval). The semantic model achieved a comparable AUROC of 0.63 ± 0.01 (RFC), significantly below the clinical model (SVM, AUROC: 0.80 ± 0.01); and slightly lower than the spinal instability neoplastic score (SINS; LR, AUROC: 0.65 ± 0.01). A combined model did not improve performance (AUROC: 0,74 ± 0,01).Conclusions: We could demonstrate that radiomic and semantic analyses of planning CTs allowed for limited prediction of therapy response to palliative RT. ML predictions based on established clinical parameters achieved the best results.

The recent approval of 177Lu PSMA-617 (Pluvicto®) by the United States Food and Drug Administration (FDA) is the culmination of decades of work in advancing the field of targeted radionuclide therapy for metastatic prostate cancer. 177Lu PSMA-617, along with the bone specific radiotherapeutic agent, 223RaCl2, are now commonly used in routine clinical care as a tertiary line of therapy for men with metastatic castrate resistant prostate cancer and for osseus metastatic disease respectively. While these radiopharmaceuticals are changing how metastatic prostate cancer is classified and treated, there is relatively little guidance to the practitioner and patient as to how best utilize these therapies, especially in conjunction with other more well-established regimens including hormonal, immunologic, and chemotherapeutic agents. This review article will go into detail about the mechanism and effectiveness of these radiopharmaceuticals and less well known classes of targeted radionuclide radiopharmaceuticals including alpha emitting prostate specific membrane antigen (PSMA) -, gastrin-releasing peptide receptor (GRPR) -, and somatostatin targeted radionuclide therapeutics. Additionally, a thorough discussion of the clinical approach of these agents is included and required futures studies.

Appropriate supplementation of vitamin D can affect infections, allergy, and mental and behavioral development. This study aimed to assess the effectiveness of monitored vitamin D supplementation in a population of preterm infants. 109 preterm infants (24 0/7–32 6/7 weeks of gestation) were randomized to receive 500 IU vitamin D standard therapy (n=55; approximately 800-1000 IU from combined sources) or monitored therapy (n=54; with an option of dose modification). 25(OH)D concentrations were measured at birth, 4 weeks of age, and 35, 40, and 52±2 weeks of post-conceptional age (PCA). Vitamin D supplementation was discontinued in 23% of infants subjected to standard treatment due to increased potentially toxic 25(OH)D concentrations (&gt;90 ng/mL) at 40 weeks of PCA. A significantly higher infants’ percentage in the monitored group had safe vitamin D levels (20–80 ng/mL) at 52 weeks of PCA (p=0.017). We observed increased vitamin D levels and abnormal ultrasound findings in five infants. Biochemical markers of vitamin D toxicity were observed in two patients at 52 weeks of PCA in the control group. Inadequate and excessive amounts of vitamin D can lead to serious health problems. Supplementation with 800–1000 IU of vitamin D prevents deficiency and should be monitored to avoid overdose.

This study compared the Biodentine (BD) and MTA in repair of furcation perforation (FP) in a dog model in terms of inflammatory cell count and new hard tissue formation through histological and immunohistochemical evaluations. Ninety six teeth in six adult mongrel dogs were divided according to the time of repair into two groups (48 teeth/3 dogs each); immediate and delayed repair of the induced FP. Each group was divided into three subgroups (16 teeth each) according to the evaluation periods; 1, 2, and 3 months. Each subgroup was further subdivided into four subdivisions according to the material used; MTA (6 teeth), Biodentine (6 teeth), negative control (2 teeth) and positive control (2 teeth). In experimental and positive control samples, the teeth were instrumented and obturated then, a FP was performed. The perforations were sealed according to the groups and subdivisions. Histopathology and immunohistochemical analysis using Osteonectin antibodies were performed for assessment of the inflammatory cell count and new hard tissue formation. In all groups and subgroups, there were no significant differences between MTA and BD in the inflammatory cell count and new hard tissue formation (P>0.05). Biodentine can alternate the MTA as a FP repair material.

The most prevalent musculoskeletal disorder of childhood with unclear aetiology is Growing Pains (GPs). Anatomic deformities and factors that change bone turnover are implicated in GPs pathophysiology. Perinatal risk factors alter the bone metabolism affecting the bone mineral density and content. The aim of our study was to analyze the relationship between GPs, knock knees and perinatal factors. The examined population consisted of 276 children aged 3-7 years. Among them 10 pairs of dizygotic twins were evaluated. The data were collected by using a combination of semi-structured questionnaires, clinical examinations and medical charts of the children and the obstetric history of the mothers. 78 children presented GPs meeting Peterson’s criteria. Genu valgum severity was a significant factor for GPs manifestation and for their increased frequency and intensity. Subsequently, perinatal factors regarding gestational age, Apgar score, head circumference (lower than 33cm) and birth length or weight (smaller than 50 cm and 3000gr, respectively) made a remarkable contribution to the development of GPs. Conversely, antenatal corticosteroid treatment, increased maternal age and maternal smoking during pregnancy were not predictive for the disorder. Our data are potentially supportive for the “bone strength” theory and for the contribution of anatomical disturbances in GPs appearance.

Fabrication of scaffolds via 3D printing is a promising approach for tissue engineering. In this study, we combined 3D printing with cryogenic crosslinking to create biocompatible gela-tin/oxidized alginate (Gel/OxAlg) scaffolds with large pore sizes, beneficial for bone tissue re-generation. To enhance the osteogenic effects and mechanical properties of these scaffolds, we evaluated the impact of hydroxyapatite (HAp) on the rheological characteristics of the 2.86% (1:1) Gel/OxAlg ink. We investigated the morphological and mechanical properties of scaffolds with low, 5% and high 10% HAp content, as well as the resulting bio and osteogenic effects. Scanning electron microscopy revealed a reduction in pore sizes from 160-180 µm (HAp-free) to 120-140 µm for both HAp-containing scaffolds. Increased stability and higher Young’s moduli were measured for 5% and 10% HAp (18 and 21 kPa, respectively) compared to 11 kPa for HAp-free constructs. Biological assessments with mesenchymal stem cells indicated excellent cytocompati-bility and osteogenic differentiation in all scaffolds, with high degree of mineralization in HAp-containing constructs. Scaffolds with 5% HAp exhibit improved mechanical characteristics and shape fidelity, demonstrate positive osteogenic impact, and enhance bone tissue formation. Increasing the HAp content to 10% did not show any advantages in osteogenesis, offering a minor increase in mechanical strength at the cost of significantly compromised shape fidelity.

Calcium sulfate (CS) materials containing terbium ions at 0, 1.0, or 2.0 mol.% were obtained by mechanochemical synthesis. According to X-ray diffraction data, the powder materials are characterized by the presence of a CaSO4×0.5H2O phase, while Tb3+ is incorporated into the lattice at ≤1.0 mol.%. Specific surface area enlarged from 2.1 to 22.5 m2/g as crystallite size decreased from 68 to 31 nm and the Tb3+ concentration increased up to 1.0 mol.%. Thermal analysis showed that terbium slightly raises the temperature of CaSO4×2H2O-to-CaSO4 transition. The presence of Tb3+ did not affect the solubility of the CS cements. Furthermore, after 7 days of soaking of the materials in a simulated body fluid, a calcium phosphate layer formed corresponding to a hydroxyapatite phase, in contrast to the pure cements. Luminescent properties were studied by excitation at 276 nm. The recorded emission peaks of the CS materials indicated that the luminescence of the samples is green and blue, with the most intense luminescence observed for samples containing 1.0 mol.% Tb3+. The developed materials can find applications in medicine as bioimplants for the regeneration and restoration of bone tissue with a possibility of noninvasive monitoring of the bone restoration process.

Castration of stallions is traditionally performed after puberty around the age of 2 years old. No studies have focused on the effects of early castration on osteoarticular metabolism. Thus, we sought to compare early castration (3 days after birth) with traditional castration (18 months of age) in horses. Testosterone and estradiol levels were monitored from birth to 33 months in these two groups. We quantified the levels of biomarkers of cartilage and bone anabolism (CPII and N-MID) and catabolism (CTX-I and CTX-II), of osteoarthritis (HA and COMP) and inflammation (IL-6 and PGE2). We revealed a lack of parallelism between testosterone and estradiol syntheses after birth and during puberty in both groups. An extra-gonadal synthesis of steroids was observed around the 28 month-mark, regardless of the castration age. We found the expression of estrogen receptor (ESR1) in cartilage and bone, whereas androgen receptor (AR) expression appeared to be restricted to bone. Nevertheless, with regards to osteoarticular metabolism, steroid hormone deprivation resulting from early castration showed no discernable impact on the levels of biomarkers related to bone and cartilage metabolism, nor on those associated with OA and inflammation. Consequently, our research demonstrated that early castration does not disrupt bone and cartilage homeostasis.

The odontogenic cysts can lead to a bone destruction that can hamper the dental implant place-ment in the ideal 3D position. Different biomaterials and techniques that allow bone regeneration are described in the literature, each with its advantages and disadvantages. This clinical case with 18 months of follow-up shows the enucleation of an odontogenic cyst fol-lowing the guide bone regeneration with fence technique. After 6 months 2, dental implants were placed at the region of tooth 11 and 21, being rehabilitated nine weeks after. The fence technique allowed the recovery of the bone morphology and the placement of the dental implants in the 3D ideal position.

Despite improved knowledge regarding diagnosis and treatment of osteomyelitis of the jaw (OMJ), it remains a clinical challenge for oral and maxillofacial surgeons. This study aimed to identify risk factors associated with severe forms of OMJ, i.e. related to the occurrence of major complications or the refractory course of the disease. A retrospective study was performed based on the medical records of all patients diagnosed with OMJ from the past 20 years. Collected data included demographic information, medical and dental history, clinical, radiological, and bacterial findings as well as treatment modalities. The main outcome variables were the onset of major complications and treatment results. Fifty-four patients were included. Our results showed that alcohol and smoking habits, as well as malnutrition, were significantly associated with the occurrence of major complications. We also established that dental implant–induced OMJ should be considered as an aggressive subtype of OMJ. Finally, clinical bone exposure was significantly associated with unfavorable outcomes, whereas dental causes or radiological evidence of periosteal reaction were predictive of successful outcomes. Identifying such factors could be useful in preventing serious complication and informing patients about the refractory course of the disease based on the presence of these factors.

Biocompatibility of ceramic materials in CaO-P2O5 system was investigated using different methods, including in vitro and in vivo tests. Ceramics based on calcium pyrophosphate Ca2P2O7 were obtained by annealing cement-salt stone from highly concentrated hardening suspensions (HCHS). Cement-salt stone was prepared using powder mixtures of calcium citrate tetrahydrate Ca3(C6H5O7)2·4H2O and monocalcium phosphate monohydrate (MCPM) Ca(H2PO4)2·H2O. These salts were mixed with each other in such a way that calcium pyrophosphate and calcium polyphosphate were present in the final ceramic product in the following weight ratios: Ca(PO3)2/Ca2P2O7 = 0/100; 5/95; 10/90 and 20/80. Distilled water was added to a homogenized powder mixtures of Ca3(C6H5O7)2·4H2O and Ca(H2PO4)2·H2O by a water/solid ratio of 0,5 by weight. The obtained suspensions were shaped using silicon molds and left to dry in air for a week. The phase composition of the obtained samples of cement-salt stone was represented by brushite CaHPO4·2H2O, monetite CaHPO4, calcium citrate tetrahydrate Ca3(C6H5O7)2·4H2O and monocalcium phosphate monohydrate Ca(H2PO4)2·H2O. According to the XRD data, the phase composition of ceramic materials after annealing in the temperature range of 800-1000 0C was mainly represented by the β-Ca2P2O7 phase. In vivo tests shown that obtained ceramic materials can be recommended for regenerative treatments for bone defects.

Osteoarthritis and rheumatoid arthritis are two of the most common chronic inflammatory joint diseases, for which there remains a great clinical need to develop safer and more efficacious pharmacological treatments. The pathology of both osteoarthritis and rheumatoid arthritis involves multiple tissues within the joint, including the synovial joint lining and the bone, as well as the articular cartilage in osteoarthritis. In this review, we discuss the potential for the development of oligonucleotide therapies for these disorders by examining the evidence that oligonucleotides can modulate the key cellular pathways that drive the pathology of the inflammatory diseased joint pathology as well as evidence in preclinical in vivo models that oligonucleotides can modify disease progression.

Sporotrichosis is a subcutaneous mycosis affecting humans and other animals that can be transmitted a zoonosis with cats as the main vector. The conventional anti-fungal therapy is especially inefficient in immunocompromised patients, who tend to develop the most severe forms of the disease, thus prompting the search for alternative therapies. Given their antigen-presenting properties, dendritic cells (DCs) have been used in both prophylactic and therapeutic vaccination strategies. Hence, this study aims to assess the use of DCs as a prophylactic tool in sporotrichosis by evaluating the immune profile induced by Sporothrix schenckii cell wall proteins (SsCWP)-stimulated bone-marrow-derived DCs (BMDCs). Mouse BMDCs were stimulated with SsCWP for 24 hours and analyzed for the surface expression of co-stimulatory molecules and TLR-4, as well as the secretion of proinflammatory cytokines and IL-10. Following that, activated BMDCs were cocultured with splenocytes for 72 hours and had the same cytokines measured in the supernatant. SsCWP-stimulated BMDCs showed higher expression of CD80, CD86, and CD40, but not TLR-4, and higher secretion of IL-6, IL-17A, and TNF. On the other hand, higher levels of IFN-γ, IL-10, and IL-2 were found in the supernatants of the coculture as compared with the BMDCs alone; TNF secretion was almost completely abrogated, whereas IL-6 was only partially inhibited and IL-17A was unaffected. Our results thus suggest SsCWP-stimulated BMDCs are able to induce a Th1-prone cytokine profile, known to be protective against other fungal diseases. This result could lead to evaluate the development of prophylactic and/or therapeutic DC-based tools against sporotrichosis.

The integration of modern technologies like intramedullary fixators and advanced biometallic alloys has revolutionized traumatology and orthopedics. While these innovations have improved treatment, the exploration of new materials for implants persists. Tantalum and niobium, both non-toxic with similar properties, are preferred for titanium-based biomedical alloys due to their exceptional biocompatibility and corrosion resistance. Acting as stabilizers in titanium alloys, they form passive oxide layers resisting corrosion and remain compatible with biological systems. The novel Ti21Nb6Ta (TNT) alloy promises enhanced osteosynthesis outcomes. Our in vivo research on experimental animals evaluated the biocompatibility and osteoinduction of TNT compared to Ti-6Al-4V (BT-6) alloy (control group). The study comprised three experiments across different animal species, assessing acute toxicity, irritant effects, and long-term biocompatibility and osteoinduction through simulated osteosynthesis. Results indicated that aqueous extracts from both alloys were non-toxic and non-irritating. Furthermore, both demonstrated high biocompatibility and active osteoinduction potential after three months of implantation.

In this work we present a versatile, rapid, and low-cost manufacturing technique to develop bioceramic scaffolds that could enhance bone tissue regeneration via microwave preparation using a commercial microwave oven. The scaffolds were prepared combining hydroxyapatite and water glass (sodium trisilicate solution), foamed by using a microwaves oven and then characterized by means of SEM-EDS, mechanical properties, infrared spectroscopy (ATR-FTIR), density and stability test in water. Furthermore, in vitro tests were performed to verify the affinity of osteoclast cells versus the so prepared scaffold. The morphology of the samples showed interconnected pores suitable for promoting tissue regeneration and vascularization while specific mechanical properties were preserved. The physicochemical characterization and the in vitro tests presented promising results for bone regenerative applications.

Few reports exist on the pathologies of the northern bottlenose whale (Hyperoodon ampullatus) and other Ziphiidae. We here describe a large exostosis in the right pterygoid bone of adult female H. ampullatus ANSP-3004 that stranded on the US Atlantic coast in 1867. Images of the skull and 14 cranial measurements were examined and compared with two ‘normal’ adult female H. ampullatus specimens. Surface scans of ANSP-3004 were made with a Faro Design Arm 1.0 scanner at 75µm resolution. The form, structure and width (15.9 cm) of the right pterygoid were found to be abnormal. Its distal extremity was curved in labial direction while its proximal extremity was deformed by a large, bulbous exostosis of 14.3 x 12.5 cm that partially obstructed the right nasal passage. Lytic lesions in the posterior end of the exostosis exposed deep resorption lacunae. The left pterygoid was thin (3.4 cm) and laterally displaced. No diagnosis was possible for lack of histological examination but the osteopathy was consistent with osteoma, a benign bone tumor commonly seen on the jaws and nasal sinuses of bovines, phylogenetical relatives of Cetacea. The partial nasal passage obstruction may have affected respiration to some degree, but since the female was lactating, general fitness appeared stable.

Background: Vitamin D and calcium are important dietary compounds that affect bone mass, even if other minerals (potassium, zinc, etc.) and other vitamins (A, C and K) are also involved. Vitamin D and other minerals, in fact, play an important role in calcium homeostasis and calcium absorption. Hip fractures incidence is higher in western countries, where calcium is frequently included in human diet, while the occurrence of these fractures is lower in developing countries, where diets are often poor in calcium. This situation is known as the “calcium paradox”, and may be partially explained considering phosphate toxicity, that can induce a disorder of mineral metabolism. It is important to maintain adequate dietary calcium-phosphate balance in order to perform a healthy life, reducing the risk of osteoporotic fracture in older people. Vitamin D can also act as a hormone; vitamin D2 (ergocalciferol) is derived from the UV-B radiation of ergosterol, the vitamin D precursor naturally found in plants, fungi, and invertebrates. Vitamin D3 (cholecalciferol) is originated by sunlight exposure from 7-dehydrocholesterol, a precursor of cholesterol that can also act as a provitamin D3. Dietary intake of vitamin D3 is very important when skin is exposed for short times to ultraviolet B light (UV-B) one of the three kinds of invisible light rays together with UV-A and UV-C. This can be considered the usual situation in northern latitudes and in winter season, or the typical condition for older people and/or for people with very white delicate skin. Actually, the recommended daily intake of dietary vitamin D is strictly correlated with age, ranging from 5 μg for infants, children, teen-agers and adults, including women during pregnancy and lactation, to 15 μg for people over 65 years.

Multiple myeloma (MM) is a genetically heterogenous disease that includes a subgroup of 10-15% of patients facing dismal survival despite most intensive treatment. The aim of this review article is to provide an integrated clinical and biological overview on the high-risk MM discussing the novel therapeutic perspectives aimed to target the neoplastic clone and its microenvironment. The dissection of the molecular determinants of the aggressive phenotypes and drug resistance can foster a better tailored clinical management of high-risk profile and refractoriness to therapy. Among the current clinical difficulties in MM, patient’s management manipulating the tumor niche represents a major challenge given the limited knowledge about the MM-milieu interaction. The angiogenesis and bystander infiltrate constitute pivotal mechanisms of mutual collaboration between MM and the non-tumoral counterpart. Immuno-modulatory and anti-angiogenic therapy hold great efficacy but variable and unpredictable responses in high-risk MM. Therefore, it would be worth to better select the population and the MM stage that could profit to a dual immune/vasculogenesis targeting. The comprehensive knowledge of the genetic heterogeneity and MM high-risk ecosystem enforce a systematic bench-to-bedside approach. Despite significant improvements in the biology knowledge, MM is still a chronic and incurable neoplasia and therapeutic options able to overcome the relapsing/refractory behavior represent an unmet clinical need. Here, we corroborate previous biological findings providing a synthetic outlook of novel druggable targets. We also summarize the existing multi-omics-based risk profiling tools, in order to better personalize the patient-oriented clinical management.

Magnesium (Mg)-based biomaterials are promising candidates for bone and tissue regeneration. Alloying and surface modifications provide effective strategies for optimizing and tailoring their degradation kinetics. Nethertheless, biocompatibility analyses of Mg-based materials are challenging due to its special degradation mechanism with continous hydrogen release. In this context, the hydrogen release and the related (micro-) milieu conditions pretend to strictly follow in vitro standards based on ISO 10993-5/-12. Thus, special adaptions for the testing of Mg materials are necessary, which have been described in a previous study from our group. Based on these adaptions, further developments of a test procedure allowing rapid and effective in vitro cytocompatibility analyses of Mg-based materials based on ISO 10993-5/-12 are necessary. The following study introduces a new two-step test scheme for rapid and effective testing of Mg. Specimens with different surface characteristcis were produced by means of plasma electrolytic oxidation (PEO) using silicate-based and phosphate-based electrolytes. The test samples were evaluated for corrosion behavior, cytocompatibility and their mechanical and ostogenic properties. Thereby, two PEO ceramics could be identified for further in vivo evaluations.

Most common classifications for acetabular bone defects are based on radiographic two-dimension imaging, with low reliability and reproducibility. With the rise of modern processing techniques based on 3D modelling, methodologies for volumetric quantification of acetabular bone loss are available. Our study aims to describe a new methodology for quantitative assess-ment of acetabular defects, based on 3D modelling, focused on the surface analysis of the integrity of the main anatomical structures of the acetabulum represented by four corresponding sectors (posterior, superior, anterior, and medial). The defect entity is measured as the Area Increase Ra-tio (AIR) detected in all the sectors analyzed on three planes of view (frontal, sagittal and axial) compared to healthy hemipelvises. The analysis was performed on 3D-models from the CT-scan of six exemplary specimens with a unilateral pathological hemipelvis. AIR between the native and the pathological hemipelvis was calculated for each sector, for a total of 48 analysis (range, +0.93% - +171.35%). AIR of >50% were found in 22/48(45.8%) sectors and affected mostly the posterior, medial and superior sectors (20/22, 90.9%). Qualitative analysis showed consistency of the data with the morphological features of the defects. Further studies with larger samples are needed to validate the methodology and potentially develop a new classification scheme.

Osteoporosis is a common problem in orthopedic medicine, and it has become an important medical issue in orthopedics as Taiwan is gradually becoming an aging society. In the diagnosis of osteoporosis, the bone mineral density (BMD) derived from dual-energy X-ray absorptiometry (DXA) is the main criterion for orthopedic diagnosis of osteoporosis, but due to the high cost of this equipment and the lower penetration rate of the equipment compared to the X-ray images, the problem of osteoporosis has not been effectively solved for many people who suffer from osteoporosis, however, at present, in clinical diagnosis, doctors are not yet able to accurately interpret X-ray images for osteoporosis manually, and must rely on the data obtained from DXA. In recent years, with the continuous development of artificial intelligence, especially in machine learning and deep learning, significant progress has been made in image recognition. Therefore, it is worthwhile to revisit whether it is possible to use a convolutional neural network model to read a hip X-ray image and then predict the patient's BMD. In this study, we proposed a hip X-ray image segmentation model and a hip X-ray image recognition classification model. First, we used the U-Net model as a framework to segment the femoral neck, greater trochanter, wards triangle, and the total hip in the hip X-ray images. We then performed image matting and data augmentation. Finally, we constructed a predictive model for osteoporosis using deep learning algorithms. In the segmentation experiments, we used intersection over union (IoU) as the evaluation metric for image segmentation, and both the U-Net and U-Net++ models achieved segmentation results greater than or equal to 0.5. In the classification experiments, using the T-score as the classification basis, the total hip using the DenseNet121 model has the highest accuracy of 74%.

Osteoconductive granulated biopolymers (OGB) are used to restore the lost volume of the jaw bone. OGB is employed as a loose fraction and exhibits physical traits common to bulk mixtures. By removing air bubbles and industrial dust from the OGB fraction through special processing, more accessible spaces are left over for the adsorption of bone growth factors. The recipient site's biological environment alters the OGB fraction's physical characteristics. This is the cause of the OGB fraction's volume changing uncontrollably during the first three weeks following surgery. Predictive indicators for describing the physical processes of osteoconduction include the compaction coefficient and adsorption capacity. Taking into account the prognostic indicators of the dynamics of changes in the physical properties of the OGB fraction in the postoperative period, 3D planning of the bioengineered structure should be done. The OGB fraction's adsorption and drainage properties are optimized by raising the purity of OGB production and preparing the biopolymer for clinical studies.

Age-related disorders of the musculoskeletal system including sarcopenia, osteoporosis and arthritis represent some of the most common chronic conditions worldwide, for which there remains a great clinical need to develop safer and more efficacious pharmacological treatments. Collectively, these conditions involve multiple tissues, including skeletal muscle, bone, articular cartilage and the synovium within the joint lining. In this review, we discuss the potential for oligonucleotide therapies to combat the unmet clinical need in musculoskeletal disorders by evaluating the successes of oligonucleotides to modify candidate pathological gene targets and cellular processes in relevant tissues and cells of the musculoskeletal system. Further, we discuss the challenges that remain for the clinical development of oligonucleotides therapies for musculoskeletal disorders and evaluate some of the current approaches to overcome these.

Celiac disease (CD) is an autoimmune disorder triggered by gluten ingestion in genetically predisposed individuals. In addition to the typical gastrointestinal symptoms such as diarrhea, bloating, or chronic abdominal pain, CD may also present a wide spectrum of manifestations, including low bone mineral density (BMD) and osteoporosis. This review aims to describe the role of CD in the development of skeletal alterations, underlying important clinical aspects and therapeutic implications. The etiopathology of bone lesions in CD is multifactorial and their management is challenging. Here, we provide gastroenterologists and orthopedics with an up-to-date overview on the link between CD and osteoporosis to improve the management of the CD condition.

Denosumab is a human monoclonal antibody that neutralizes RANKL, a cytokine able to interact with the RANK receptor on preosteoclasts and osteoclasts, decreasing their recruitment and differentiation, leading to a decreased bone resorption. The aim of this observational real-life study was to analyze adherence to denosumab therapy, its effectiveness in increasing bone mineral density (BMD) and in modulating biochemical skeletal markers upon previous treatments with bisphosphonates in a group of post-menopausal women affected by osteoporosis. Women were recruited in the specialized center from March 2012 to September 2019. Biochemical markers were recorded at baseline and every six months prior to subsequent drug injection. Dual X-ray Absorptiometry was requested at baseline and after 18/24 months. Comparing BMD at baseline and after denosumab therapy in naive patients and in those previously treated with bisphosphonates, a positive therapeutic effect was observed in both groups. The results of our real-life study demonstrate, as expected, that BMD values significantly increased upon denosumab treatment. Interestingly, denosumab showed an increased effectiveness in patients previously treated with bisphosphonates. Moreover, biochemical markers data indicate that osteoporotic patients, without other concomitant unstable health conditions, could be evaluated once a year, decreasing the number of specialistic center access.

Astronauts are at risk of losing 1.0 to 1.5% of their bone mass for every month they spend in space despite their adherence to high impact exercise training programs and dietary regimens designed to preserve their musculoskeletal system. This loss is the result of microgravity-related impairment of osteocyte and osteoblast function and the consequent upregulation of osteoclast-mediated bone resorption. This review describes the ontogeny of osteoclast hematopoietic stem cells, the contributions of macrophage colony stimulating factor, activator of NFkB and the calcineurin pathways make in osteoclast differentiation, and provides details of bone formation, the osteoclast cytoskeleton, the immune regulation of osteoclasts, and osteoclast mechanotransduction on Earth, in the microgravity of space, and in conditions of simulated microgravity. The article discusses the need to better understand how osteoclasts are able to function in zero gravity and reviews current and prospective therapies that may be used to treat osteoclast-mediated bone disease.

Preterm infants are at significant risk to develop reduced bone mineralization based on inadequate supply of calcium and phosphorus (Ca-P). Biochemical parameters can be used to evaluate the nutritional intake. The direct effect of nutritional intake on changes in biochemical parameters has not been studied. Our objective was to evaluate the effect of Ca-P supplementation on biochemical markers as serum (s)/urinary (u) Ca and P; alkaline phosphatase (ALP); tubular reabsorption of P (TrP) and urinary ratios for Ca/creatinin and P/creatinin in Very-Low-Birth-Weight infants on postnatal day 1, 3, 5, 7, 10, and 14. This observational study compared two groups with High (n = 30) and Low (n = 40) intake of Ca-P. Birth weight: median (IRQ) 948 (772-1225) vs. 939 (776-1163) grams; Gestational age: 28.2 (26.5-29.6) vs. 27.8 (26.1-29.4) weeks. Daily median concentrations of biochemical parameter were not different between the groups but linear regression mixed model analyses showed that Ca intake increased the uCa and TrP (p = 0.04) and decreased ALP (p = 0.00). Phosphorus intake increased sP, uP and uP/creat ratio and ALP (p ≤ 0.02) and caused decrease in TrP (p = 0.00). Protein intake decreased sP (p = 0.000), while low gestational age and male gender increased renal excretion of P (p < 0.03). Standardized repeated measurements showed that biochemical parameters were affected by nutritional intake, gestational age and gender.

Background Popular movement-based injury risk screens have been shown to lack predictive precision, leading to interest in multifactorial models. Furthermore, there is a lack of research regarding injury risk assessment for those currently or planning to be recreationally active. This study aims to provide injury risk insights by analyzing multifactorial injury risk models and as-sociated clinical measures in the U.S. population. Methods Data related to injury, inflammatory markers, physical functioning, body composition, physical activity, and other variables from 21,033 respondents were extracted from NHANES. Odds ratios for self-reported injury were calculated for single predictors and risk models. Case-control and principal component analyses (PCA) were conducted to elucidate confounders and identify risk factor clusters, respectively. Receiver operating characteristic analysis was used to test the precision of a risk factor cluster to identify pain points and functional difficulties. Results Sociodemographic, individual, and lifestyle factors were strongly associated with higher odds of injury. Increases in fibrinogen and C-reactive protein were significantly associated with all risk groups. Membership to the high-risk group (age over 40, obesity, no muscle-strengthening activities, sedentary lifestyle, and low back pain) predicted at least one functional difficulty with 67.4% sensitivity and 87.2% specificity. In the injury group, bone turnover markers were higher, yet confounded by age and there was a significantly higher prevalence of self-reported osteoporosis compared to the control. In males, low testosterone was associated with injury, and higher estradiol was associated with pain and functional difficulties. In females, higher levels of follicle-stimulating hormone were associated with functional difficulties. PCA revealed four high-risk profiles, with markers and activities showing distinct loadings. Conclusion A comprehensive approach to injury risk assessment should consider the nexus of aging, lifestyle, and chronic disease to enhance tailored injury prevention strategies, fostering safe and effective physical activity participation and reducing the burden of musculoskeletal disorders.

Scaffolds for tissue engineering are expected to respond to a challenging combination of physical and mechanical requirements, guiding the research towards the development of novel hybrid materials. This study introduces innovative three-dimensional bioresorbable scaffolds, in which a stiff poly(lactic acid) lattice structure is meant to ensure temporary mechanical support, while a bioactive gelatin-chitosan hydrogel is incorporated to provide a better environment for cell adhesion and proliferation. The scaffolds present a core-shell structure, in which the lattice core is realized by additive manufacturing, while the shell is nested throughout the core by grafting and crosslinking a hydrogel forming solution. After subsequent freeze-drying, the hydrogel network forms a highly interconnected porous structure that completely envelops the poly(lactic acid) core. Thanks to this strategy, it is easy to tailor the scaffold properties for a specific target application, by properly designing the lattice geometry and the core/shell ratio, which are found to significantly affect the scaffold mechanical performance and its bioresorption. Compression stiffness and strength provided by poly(lactic acid) lattices are overall within the range of values displayed by human bone tissue and remain stable after prolonged immersion in water at body temperature for several weeks. On the other hand, the hydrogel undergoes gradual and homogeneous degradation over time, but the core-shell integrity and structural stability are nevertheless maintained during at least 7-week hydrolytic degradation tests. In vitro experiments with human mesenchymal stromal cells reveal that the core-shell scaffolds are biocompatible and their physical-mechanical properties and architecture are suitable to support cell growth and osteogenic differentiation, as demonstrated by hydroxyapatite formation. These results suggest that the bioresorbable core-shell scaffolds can be considered, and further studied, in view of clinically relevant endpoints in bone regenerative medicine.

Background: Glycogen storage diseases (GSDs), known as glycogenoses, belong to inborn metabolic defects in the glycogen metabolism pathway. Several types of GSDs are distinguished, including Ia, Ib, III, VI, and IX. GSDs manifest as excessive glycogen deposition in the liver and muscles, resulting in the dysfunction of these organs. Therefore, the treatment of choice is multitherapy that, due to dietary restrictions, may lead to nutritional deficiencies and organ complications. This study aims to assess anthropometric, body composition, skeletal status, results of selected laboratory tests, dietary, lifestyle and physical capacity analyses in patients with glycogenoses and compare the results between GSD I and GSD III-VI-IX groups. Results: The results indicate that GSD patients were overweight or obese (44% of patients had BMI +1SD or +2SD) with high percentage of fat tissue (50% of patients had above 30% of body fat) and inadequate bone mineralisation (total body less head: median z-score -0.9, L2-L4 segment: median z-score -1.65). GSD I patients had the highest risk of developing obesity (67% of them had above 30% of body fat) and osteoporosis (total body less head: median z-score -1.0, L2-L4 segment: median -1.7). Conclusions: Special attention should be paid to appropriate diet and supplementation in patients with glycogenoses.

Tissue bioengineering has been assuming a pivotal role in implementing alternatives to conven-tional ossicular middle ear replacement prostheses to overcome extrusion while preserving acoustic properties. This in vitro study aims to explore for the first time in current literature the feasibility of a biohybrid middle ear prosthesis composed of titanium surrounded by bone ex-tracellular matrix as bio-coating. We have hereby studied the adhesion and proliferation of human adipose-derived mesenchymal stem cells (hASC) on titanium scaffolds in vitro. Moreover, we identified the osteogenic differentiation of hASC using immunofluorescence assay to analyze osteoblasts gene expression profile (Alp, Runx2, Col1a1, Osx, and Bglap) and we accounted the presence of collagen as a marker of hASC ability to secrete extracellular matrix. We utilized scanning electron microscopy to evaluate the presence of extracellular matrix on the scaffolds. Our preliminary data demonstrated the titanium ability to support human adipose-derived mesenchymal stem cell colonization, proliferation, and osteoblastic differentiation, to obtain a biohybrid device. Our experience seems encouraging, we advocate further in vivo research to corroborate our results towards bone transplantation.

nutrition, macro and micronutrients, bone health, exercise, exogenous and endogenous microRNA, epigenetics

Total Hip Arthroplasty is one of the most successful surgery. However, due to the worldwide growing population life expectancy and the related incidence of age-dependent bone diseases, a growing number of cases of intra-operative fractures lead to revision surgery with high rates of morbidity and mortality. Surgeons choose the type of the implant, either cemented or cementless prosthesis, on the basis of the age, the quality of the bone and the general medical conditions of the patients. Generally, no quantitative measures are available to assess the intra-operative fracture risk. Consequently, the decision-making process is mainly based on medical operators’ expertise and qualitative information obtained by imaging. Motivated by this scenario, we here propose a mechanical-supported strategy to assist surgeons in their decisions, by giving intelligible maps of the risk fracture which take into account the interplay between actual strength distribution inside the bone tissue and its response to the forces exerted by the implant. To this end, we produce charts and patient-specific synthetic “traffic-light” indicators of fracture risk, by making use of ad hoc analytical solutions to predict the stress levels in the bone by means of CT-based mechanical and geometrical parameters of the patient. We felt that, if implemented in a friendly software or proposed as an app, the strategy could constitute a practical tool to help the medical decision-making process, in particular with respect to the choice of adopting cemented or cementless implant

Background: The receptor activator of the nuclear factor-kB (RANK)/RANK ligand (RANKL)/osteoprotegerin (OPG) pathway is a determining pathway in the balance between bone formation and resorption; disruptions in this complex can affect bone metabolism. Methods: This study analyzed the changes in RANKL, OPG and 25(OH)D levels, the RANKL/OPG ratio, and other bone turnover markers (BTM) from diagnosis to complete remission in children with acute lym-phoblastic leukemia (ALL). This is a prospective observational cohort study. This study was carried out in the Instituto Mexicano del Seguro Social in Mexico City. Thirty-three patients (4-17 years) with newly diagnosed B-cell ALL were included. The patients were treated with the HP09 chemotherapy protocol. Children who had previously been treated with corticosteroids were excluded. A pe-ripheral blood sample at diagnosis and remission was collected to determine the 25(OH)D and BTM concentrations. Results: Increased RANKL (p=0.001) and osteocalcin (p

Oral bone defects occur as a result of trauma, cancer, infections, periodontal diseases, and caries. Autogenic and allogenic grafts are the gold standard used to treat and regenerate damaged or defective bone segments. However, these materials do not possess the antimicrobial properties necessary to inhibit the invasion of the numerous deleterious pathogens present in the oral microbiota. In the present study poly(ε-caprolactone) (PCL), nano-hydroxyapatite (nHAp), and a commercial extract of Humulus lupulus L. (hops) were electrospun into polymeric matrices to assess their po-tential for drug delivery and bone regeneration. The fabricated matrices were analyzed by scanning electron microscopy (SEM), tensile analysis, thermogravimetric analysis (TGA), FT-IR assay, and in vitro hydrolytic degradation. The antimi-crobial properties were evaluated against the oral pathogens Streptococcus mutans, Porphyromonas gingivalis, and Aggregatibacter actinomycetemcomitans. The cytocompatibility was proved by the MTT assay. SEM analysis proved the nanostructured matrices have suitable fiber size. The present research provides new information about the interaction of natural compounds with ceramic and polymeric biomaterials. The hop extract and other natural or synthetic medicinal agents can be effectively loaded into PCL fibers and has the potential to be used in biomedical applications.

People are increasingly encouraged to reduce animal food consumption and shift towards plant-based diets, however the implications for children’s health are unclear. In this narrative review of research in high-income settings, we summarize evidence on the increasing consump-tion of plant-based diets in children, and update an earlier systematic review regarding their associations with children’s health outcomes. The evidence indicates that vegan but not vege-tarian diets can restrict growth relative to omnivorous children, and increase the risk of being stunted and underweight although the percentage affected is relatively small. Bone mineral content is reduced in vegetarian and especially vegan children, compared to omnivores. Both vegetarian and vegan children who do not use vitamin B12 supplements manifest with B12 defi-ciency, however supplementation rectifies this problem. Both vegetarians and vegans have lower concentrations of 25 (OH)D if unsupplemented, and lower body iron stores, but usually have normal iron metabolism markers. Both groups are at risk of iodine deficiency and this might affect thyroid health. Children consuming a vegan diet have more favorable lipid profile than omniv-orous children, however the results for vegetarian diet are inconsistent and vary by outcome. Based on the same scientific evidence, national and international dietary recommendations are heterogeneous, with some countries supporting plant-based diets among infants, children and adolescents, and others discouraging them. We offer a research roadmap, highlighting what is needed to provide adequate evidence to harmonize dietary recommendations for plant-based diets in children. A number of measures should urgently be introduced at international and na-tional levels to improve the safety of their use in children.

: For a long time, atherosclerosis has been regarded as a mere lipid deposit in the blood vessels. However, in the recent years a growing body of experimental and clinical evidence have highlighted the role of inflammation and immunity as a central mechanism of disease. Moreover, in the last decade the coming of next-generation sequencing and its application to large human population has broken the barrier between inflammation and cancer. Indeed, acquired mutation in key genes related to the control of hematopoiesis and myeloproliferation have paved the way to establish the new concept of clonal hematopoiesis of indeterminate potential. This phenomenon is being considered not such “indeterminate”, but as an emerging cardiovascular risk factor. Thus, this may explain the mechanisms of myeloproliferation and inflammation in atherosclerosis. And in a bidirectional journey, it has helped to explain the extremely high cardiovascular risk in cancer survivors, in particular in myeloprolfierative neoplasm patients. A deeper understanding of these mechanisms may pave the way for the future early diagnosis and potential preemptive treatments of the leading worldwide cause of death.

Fibrodysplasia Ossificans Progressiva (FOP) is an enigmatic, ultra-rare genetic disorder characterized by progressive heterotopic ossification, wherein soft connective tissues undergo pathological transformation into bone structures. This incapacitating process severely limits patient mobility and poses formidable challenges for therapeutic intervention. Predominantly caused by missense mutations in the ACVR1 gene, the disorder has hitherto defied comprehensive mechanistic understanding and effective treatment paradigms. This write-up offers a comprehensive overview of the contemporary understanding of FOP's complex pathobiology, underscored by advances in molecular genetics and proteomic studies. We shed light on targeted therapy, spanning genetic therapeutics, enzymatic and transcriptional modulation, stem cell therapies, and innovative immunotherapies. We also focused on the intricate complexities surrounding clinical trial design for ultra-rare disorders like FOP, addressing fundamental statistical limitations, ethical conundrums, and methodological advancements essential for the success of interventional studies. We advocate for the adoption of a multi-disciplinary approach that converges bench-to-bedside research, clinical expertise, and ethical considerations to tackle the challenges of ultra-rare diseases like FOP and comparable ultra-rare diseases. Overall, this article serves a dual role: as a definitive scientific resource for ongoing and future FOP research and as a call to action for innovative solutions to address methodological and ethical challenges that impede progress in the broader field of medical research for ultra-rare conditions.

Introduction: Osteosarcomas of the jaw (OSJ) are rare tumors with a different behavior from osteosarcomas of other bones. This study aims to analyze the clinical, pathological, and therapeutic characteristics of this type of sarcoma. Methods: a retrospective observational study of cases diagnosed with OSJ registered at the “La Paz” University Hospital (Madrid). Results: Eight cases with a diagnosis of OSJ were obtained in a study period of 22 years (2000-2022). The mean age was 41 years. The distribution was 1:1 between the maxilla and mandible. Painful inflammation was the most frequent clinical manifestation. Conventional osteoblastic osteosarcoma was the most common. Survival at 5 years was 50%, while at 10 years, it decreased to 25%. Conclusions: OSJ differs from conventional osteosarcomas of long tubular bones. Surgery continues to be the mainstay of treatment; more studies are needed in which more standardized protocols can be proposed for adjuvant therapeutic management.

Previous research has shown that propolis has immunomodulatory activity. Extracts from two UK propolis samples were assessed for their anti-inflammatory activities by investigating their ability to alter the production of the cytokines tumour necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-6 and IL-10 from mouse bone marrow derived macrophages co-stimulated with lipopolysaccharide (LPS). The propolis extracts suppressed secretion of IL-1β and IL-6 with less effect on TNFα. In addition, propolis reduced the levels of nitric oxide formed by LPS-stimulated macrophages. Metabolomic profiling was carried out by liquid chromatography (LC) coupled with mass spectrometry (MS) on a ZIC-pHILIC column. LPS increased the levels of intermediates involved in nitric oxide biosynthesis; propolis lowered many of these. Also, LPS produced an increase in itaconate and citrate and propolis treatment increased itaconate still further while greatly reducing citrate levels. Moreover, LPS treatment increased levels of GSH and intermediates in its biosynthesis while propolis treatment boosted these still further. In addition, propolis treatment greatly increased levels of UDP-sugar conjugates. Overall, the results showed that propolis extracts exert an anti-inflammatory effect by inhibition of pro-inflammatory cytokines and by metabolic reprogramming of LPS activity in macrophages.

The hypothesis that consumption of Aronia melanocarpa berries (chokeberries) extract, recently reported by us to improve bone metabolism in female rats at low-level and moderate chronic exposure to cadmium (1 and 5 mg Cd/kg diet for up to 24 months), may increase the bone resistance to fracture was investigated. Biomechanical properties of the neck (bending test with vertical head loading) and diaphysis (three-point bending test) of the femur of rats administered 0.1% aqueous chokeberry extract (65.74% of polyphenols) or/and Cd in the diet (1 and 5 mg Cd/kg) for 3, 10, 17, and 24 months were evaluated. Moreover, procollagen I was assayed in the bone tissue. The low-level and moderate exposure to Cd decreased procollagen I concentration in the bone tissue and weakened biomechanical properties of the femoral neck and diaphysis. Chokeberry extract administration under the exposure to Cd improved the bone collagen biosynthesis and femur biomechanical properties. The results allow for the conclusion that consumption of chokeberry products under exposure to Cd may improve the bone biomechanical properties and protect from fracture. This study provides support for Aronia melanocarpa berries being a promising natural agent for the skeleton protection under low-level and moderate chronic exposure to Cd.

Some studies have demonstrated that in vivo degradation processes are influenced by the material’s physico-chemical properties. The present study compares two hydroxyapatites manufactured on an industrial scale, deproteinized at low and high temperatures, and how physico-chemical properties can influence the mineral degradation process of material performance in bone biopsies retrieved 6 months after maxillary sinus augmentation. Residual biomaterial particles were examined by field scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy (EDX) to determine the composition and degree of degradation of the bone graft substitute material. According to the EDX analysis, the Ca/P ratio significantly lowered in the residual biomaterial (1.08±0.32) compared to the initial composition (2.22±0.08) for the low-temperature sintered group, which also presented high porosity, low crystallinity, low density, a large surface area, and poor stability and a high resorption rate compared to the high-temperature sintered material. This demonstrates that variations in the physico-chemical properties of bone substitute material clearly influence the degradation process. Further studies are needed to determine whether the resorption of deproteinized bone particles proceeds slowly enough to allow sufficient time for bone maturation to occur.

Background: The main objective of this study is to develop a customized metatarsophalangeal implant for the treatment of various conditions affecting this specific joint. This approach involves replacing the joint with a custom implant designed specifically to fit each patient's unique anatomical structure. The need for custom implants stems from the obvious lack of size variety available, which presents a major challenge when, the search for the ideal size implant can be a hard task, also when considering the possibility of extensive modification of the bone to adapt it to the available implant. This adaptation, often synonymous with bone reduction, can cause significant post-operative pain for the patient and impact healing time. Methods: A comparative study of modeling software was carried out to select the perfect software, by defining and comparing the relevant criteria. Similarly, the different biomaterial options were examined and compared to select the one best suited to this project, mentioning the imaging modality used to determine the types of images used for our approach. Finally, the 3D printers used in this work were represented, highlighting their technical characteristics. Findings: A resin metatarsophalangeal implant prototype was created using 3D modeling and reconstruction software and tools. Interpretation: Reconstruction and 3D modeling techniques are revolutionizing implant creation, offering customized solutions for patients suffering from metatarsophalangeal joint disorders caused by a wide range of diseases. These results have significant implications for disability management and rehabilitation, encouraging further exploration and progress.

Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary kidney disorder but kidneys are not the only organs involved in this systemic disorder. Individuals with the condition may display additional manifestations beyond the renal system, involving liver, pancreas and brain in the con-text of cystic manifestations, while vascular system, gastrointestinal tract, bones, and cardiac valves in the context of non-cystic manifestations. Despite kidney involvement remain the main feature of the disease, thanks to new generation therapies, early diagnosis and better management of kidney related problems, a new wave of complications must be faced from clinicians who treated polycystic patients. Involvement of the liver represents the most prevalent extrarenal manifestation and grows importance in symptom burden and quality of life. Vascular abnormalities are a key factor for patients’ life expectancy and there’s still de-bate whether to screen or not to screen all patients. Arterial hypertension is often the earliest onset among polycystic patients leading to frequent cardiovascular complications. Although cardiac valvular abnormali-ties is a frequent complication, it rarely leads to relevant problems in the clinical history of polycystic pa-tients. One of the new relevant aspects concern bone disorders, that can exert a considerable influence on the clinical course of these patients. This review aims to provide the “state of art” among extrarenal mani-festation of ADPKD.