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Purpose: To evaluate a new cultivated coral graft (CCG) in an in vivo experimental guided bone regeneration (GBR) procedure. Materials and Methods: The calvarias of eight rabbits were surgically exposed, and circular defects 8 mm in diameter were prepared. One defect was filled with CCG particles (experimental group); the contralateral defect (control group) was spontaneously filled by blood clot. All defects were covered with a collagen membrane. Subjects were euthanized after 8 weeks. Results: Histologic observations of the defects showed similar bone growth patterns in both experimental and control osteotomies. In the experimental defects, no traces of coral particles were observed. Histometric analysis showed denser bone in the pristine zone (65%-66%) than in the peripheral zone for both the control (50%) and experimental defects (31%) (P = not significant). The new bone percentage was reduced from the peripheral zone toward the middle and the center of the defect (31%, 32%, and 27%, respectively) as the distance from the peripheral pristine bone borders increased. Conclusions: The existing data supports the complete degradation of CCG as a space-maintaining scaffold for GBR procedures. [ABSTRACT FROM AUTHOR]

Fixation and demineralization protocols for bone marrow (BM) across diagnostic laboratories are not standardized. How different protocols affect histomorphology and DNA amplification is incompletely understood. In this study, 2 fixatives and 3 demineralization methods were tested on canine BM samples. Twenty replicate sternal samples obtained within 24 hours of death were fixed overnight in either acetic acid-zinc-formalin (AZF) or 10% neutral-buffered formalin (NBF) and demineralized with formic acid for 12 hours. Another 53 samples were fixed in AZF and demineralized with hydrochloric acid for 1-hour, formic acid for 12 hours, or ethylenediamine tetraacetic acid (EDTA) for 24 hours. Histologic sections were scored by 4 raters as of insufficient, marginal, good, or excellent quality. In addition, DNA samples extracted from sections treated with the different fixation and demineralization methods were amplified with 3 sets of primers to conserved regions of T cell receptor gamma and immunoglobulin heavy chain genes. Amplification efficiency was graded based on review of capillary electrophoretograms. There was no significant difference in the histomorphology scores of sections fixed in AZF or NBF. However, EDTA-based demineralization yielded higher histomorphology scores than demineralization with hydrochloric or formic acid, whereas formic acid resulted in higher scores than hydrochloric acid. Demineralization with EDTA yielded DNA amplification in 29 of 36 (81%) samples, whereas demineralization with either acid yielded amplification in only 2 of 72 (3%) samples. Although slightly more time-consuming and labor-intensive, tissue demineralization with EDTA results in superior morphology and is critical for polymerase chain reaction (PCR) amplification with the DNA extraction method described in this article.

INTRODUCTION: Adjunctive suture augmentation of patellar plate fixation has yet to be investigated. Our biomechanical study sought to evaluate whether suture augmentation improves dorsal patellar locking plate fixation. Our hypothesis was that suture augmentation would improve fixation of this construct. METHODS: A transverse patella fracture in six matched cadaveric pairs was stabilized using a patellar locking plate with or without suture augmentation. Specimens were tested at 60° knee flexion with load placed through quadriceps. Cyclic loading followed by load to failure was done. Stiffness, deformation at peak, and nonrecoverable deformation were calculated. RESULTS: During cyclic loading, suture augmentation demonstrated a higher average stiffness throughout all loads. At the final cycle, deformation was markedly higher without suture augmentation. Average load to failure was higher with suture augmentation. Maximum load to failure occurred at 2500 N in both groups. CONCLUSION: Suture augmentation in a transverse patellar fracture model improved dorsal plate fixation, leading to less fracture displacement at the final load. Although suture augmentation demonstrated higher stiffness and lower deformation, these trends were not statistically significant. In both groups, plate fixation sustained very high loads, which reflects the fixation strength of the dorsal locking plate and screw construct in this fracture model.

Objective: This study aimed to evaluate the effectiveness of biomaterials in bone healing of critical bone defects created by piezoelectric surgery in rat calvaria. Method and materials: Histomorphologic analysis was performed to assess bone regeneration and tissue response. Fifty animals were randomized into five groups with one of the following treatments: Control group (n = 10), spontaneous blood clot formation with no bone fill; BO group (Bio-Oss, Geistlich Pharma; n = 10), defects were filled with bovine medullary bone substitute; BF group (Bonefill, Bionnovation; n = 10), defects were filled with bovine cortical bone substitute; hydroxyapatite group (n = 10), defects were filled with hydroxyapatite; calcium sulfate group (n = 10), defects were filled with calcium sulfate. Five animals from each group were euthanized at 30 and 45 days. The histomorphometry calculated the percentage of the new bone formation in the bone defect. Results: All data obtained were evaluated statistically considering P < .05 as statistically significant. The results demonstrated the potential of all biomaterials for enhancing bone regeneration. The findings showed no statistical differences between all the biomaterials at 30 and 45 days including the control group without bone grafting. Conclusion: In conclusion, the tested biomaterials presented an estimated capacity of osteoconduction, statistically nonsignificant between them. In addition, the selection of biomaterial should consider the specific clinical aspect, resorption rates, size of the particle, and desired bone healing responses. It is important to emphasize that in some cases, using no bone filler might provide comparable results with reduced cost and possible complications questioning the very frequent use of ridge presentation procedures. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the effect of continuous perioperative clopidogrel treatment on the osseointegration of titanium implants. Materials and Methods: A total of 32 New Zealand rabbits were randomly divided between two groups: a clopidogrel group (n = 16) and a control group (n = 16). For 1 week prior to the surgical placement of a titanium implant in their medial femoral condyle, rabbits in the clopidogrel group received 3 mg/kg of clopidogrel daily, and the control group received only the vehicle. This treatment was continued for another 6 weeks postoperatively. At 6 weeks, the rabbits were euthanized and postmortem histologic and histomorphometric evaluation of the implants was performed. Results: The surgical procedures and postoperative period were uneventful and well tolerated by all animals without any surgical wound dehiscence, signs of infection, or other complication. No implant failure was observed in any of the groups. Histomorphometric analysis showed that bone-to-implant contact (BIC) was 48.77% for the clopidogrel group and 34.65% for the control group, with statistically significant difference between them (P < .001). Moreover, clopidogrel group had significantly greater bone tissue density (40.52% vs 28.74%, respectively; P <.001) and mean trabecular thickness (284.7 μm vs 180.7 μm, respectively; P < .001) in proximity to the implant surface than the control group, while the mean trabecular number had no difference between groups (1.56 vs 1.60, respectively; P = .961). Conclusions: The present study showed that continuous clopidogrel treatment does not negatively affect osseointegration, but rather promotes it in terms of BIC and bone density around the titanium implants. Further studies on the effect of the P2Y12 receptor and its antagonists on peri-implant bone homeostasis may provide useful information or applications for long-term success of dental implant therapy. [ABSTRACT FROM AUTHOR]

Scintigraphy and Positron Emission Tomography (PET) are both nuclear medicine imaging techniques, providing functional information of the imaged areas. Scintigraphy is a two-dimensional projected imaging technique that was introduced in equine imaging in the late 1970s. Scintigraphy allows imaging of large body parts and can cover multiple areas, remaining the only technique commonly used in horses for whole body imaging. PET is a cross-sectional imaging technique, first used in horses in 2015, allowing higher resolution three-dimensional functional imaging of the equine distal limb. This manuscript will cover current use and values of these two modalities in equine lameness diagnosis.

The skeletal health of laying hens improves when birds are given opportunities to perform load-bearing movements with elevated structures, such as perches. We investigated how early access to elevated structures varying in complexity and height would affect bone quality and subsequent keel bone fractures in a layer multitiered aviary. Female Dekalb White pullets were reared in floor pens furnished with floor perches (FL), single-tiered aviaries (ST), or 2-tiered aviaries (TT; n = 5 pens/treatment) through 16 wk of age. At 17 wks, all structures were replaced with identical multitiered layer aviaries. The keel, both tibiae, and both humeri were collected from 60 euthanized birds from each rearing treatment at 8, 16 and 30 wk of age, and analyzed with dual X-ray absorptiometry (DEXA) for bone mineral density and length. At 18, 26, 28, and 30 wk of age, 10 focal hens/pen were radiographed repeatedly and the presence, severity of keel bone fractures were assessed with a tagged visual analogue scale. The number of fractures was also recorded. At 16 wk of age, FL pullets had lower BMD of the tibia (P = 0.003), keel (P = 0.013), and humerus (P = 0.004) compared to ST and TT pullets. Most of the observed treatment differences disappeared after pullets were transferred to the aviary. BMD continued to increase for all hens through 30 wk of age. Pullet rearing did not affect the presence or severity of keel bone fractures, or number of new fractures incurred between ages (P > 0.05). The prevalence and severity of keel bone fractures increased between 26 to 28 wk and remained high to 30 wk of age (P < 0.0001). Hens experienced more new fractures between 26 to 30 wk than between 18 to 26 wk of age (P = 0.0046). The effects of pullet housing on bone quality were short-term when hens had access to adult housing with multiple opportunities for load-bearing movements. Keel fractures with minor severity were high in prevalence reflecting the use of radiography to assess this injury.

The gut microbiota (GM) can regulate bone mass, but its association with incident fractures is unknown. We used Cox regression models to determine whether the GM composition is associated with incident fractures in the large FINRISK 2002 cohort (n = 7043, 1092 incident fracture cases, median follow-up time 18 years) with information on GM composition and functionality from shotgun metagenome sequencing. Higher alpha diversity was associated with decreased fracture risk (hazard ratio [HR] 0.92 per standard deviation increase in Shannon index, 95% confidence interval 0.87-0.96). For beta diversity, the first principal component was associated with fracture risk (Aitchison distance, HR 0.90, 0.85-0.96). In predefined phyla analyses, we observed that the relative abundance of Proteobacteria was associated with increased fracture risk (HR 1.14, 1.07-1.20), while the relative abundance of Tenericutes was associated with decreased fracture risk (HR 0.90, 0.85-0.96). Explorative sub-analyses within the Proteobacteria phylum showed that higher relative abundance of Gammaproteobacteria was associated with increased fracture risk. Functionality analyses showed that pathways related to amino acid metabolism and lipopolysaccharide biosynthesis associated with fracture risk. The relative abundance of Proteobacteria correlated with pathways for amino acid metabolism, while the relative abundance of Tenericutes correlated with pathways for butyrate synthesis. In conclusion, the overall GM composition was associated with incident fractures. The relative abundance of Proteobacteria, especially Gammaproteobacteria, was associated with increased fracture risk, while the relative abundance of Tenericutes was associated with decreased fracture risk. Functionality analyses demonstrated that pathways known to regulate bone health may underlie these associations.

Some osteoporosis drug trials have suggested that treatment is more effective in those with low BMD measured by DXA. This study used data from a large set of randomized controlled trials (RCTs) to determine whether the anti-fracture efficacy of treatments differs according to baseline BMD. We used individual patient data from 25 RCTs (103 086 subjects) of osteoporosis medications collected as part of the FNIH-ASBMR SABRE project. Participants were stratified into FN BMD T-score subgroups (≤-2.5, > -2.5). We used Cox proportional hazard regression to estimate treatment effect for clinical fracture outcomes and logistic regression for the radiographic vertebral fracture outcome. We also performed analyses based on BMD quintiles. Overall, 42% had a FN BMD T-score ≤ -2.5. Treatment with anti-osteoporosis drugs led to significant reductions in fractures in both T-score ≤ -2.5 and > -2.5 subgroups. Compared to those with FN BMD T-score > -2.5, the risk reduction for each fracture outcome was greater in those with T-score ≤ -2.5, but only the all-fracture outcome reached statistical significance (interaction P = .001). Results were similar when limited to bisphosphonate trials. In the quintile analysis, there was significant anti-fracture efficacy across all quintiles for vertebral fractures and with greater effects on fracture risk reduction for non-vertebral, all, and all clinical fractures in the lower BMD quintiles (all interaction P ≤ .03). In summary, anti-osteoporotic medications reduced the risk of fractures regardless of baseline BMD. Significant fracture risk reduction with treatment for 4 of the 5 fracture endpoints was seen in participants with T-scores above -2.5, though effects tended to be larger and more significant in those with baseline T-scores

BACKGROUND: Guidelines recommend dual-energy x-ray absorptiometry (DXA) screening to assess fracture risk and benefit from antiresorptive therapy in men with metastatic hormone-sensitive prostate cancer (mHSPC) on androgen deprivation therapy (ADT). However,

Fish oils rank among the world's most popular nutritional supplements and are purported to have numerous health benefits. Previous work suggested that fish oils increase collagen production; however, the effect of fish oils on musculoskeletal health is poorly understood. Further, the divergent effects of omega-3 (Ω3FA) and saturated fatty acids (SFA) remains poorly understood. We tested the effects of Ω3FA and SFAs on in vitro-engineered human ligament (EHL) function. EHLs were treated with bovine serum albumin (BSA)-conjugated eicosapentaenoic acid (EPA, 20:5(n-3)), palmitic acid (PA, 16:0), or a BSA control for 6 days. EPA did not significantly alter, whereas PA significantly decreased EHL function and collagen content. To determine whether this was an in vitro artifact, mice were fed a control or high-lard diet for 14 weeks and musculoskeletal mass, insulin sensitivity, and the collagen content, and mechanics of tendon and bone were determined. Body weight was 40 % higher on a HFD, but muscle, tendon, and bone mass did not keep up with body weight resulting in relative losses in muscle mass, tendon, and bone collagen, as well as mechanical properties. Importantly, we show that PA acutely decreases collagen synthesis in vitro to a similar extent as the decrease in collagen content with chronic treatment. These data suggest that Ω3FAs have a limited effect on EHLs, whereas SFA exert a negative effect on collagen synthesis resulting in smaller and weaker musculoskeletal tissues both in vitro and in vivo.

Risk for transmission of SARS-CoV-2 through allogeneic human tissue transplantation is unknown. To further evaluate the risk of virus transmission, tissues were obtained from deceased donors who had tested positive for SARS-CoV-2 RNA via nasopharyngeal swab. This study evaluated an array of human tissues recovered for transplantation, including bone, tendon, skin, fascia lata, vascular tissues, and heart valves. Tissue samples and plasma or serum samples, if available, were tested for viral RNA (vRNA) using a real time PCR system for the presence of virus RNA. All samples were tested in quadruplicate for both subgenomic (sgRNA) and genomic (gRNA) RNA encoding the SARS-CoV-2 nucleocapsid gene. Amplification of a cellular housekeeping gene served as the positive control for every sample. A total of 47 tissue samples from 17 donors were tested for SARS-CoV-2 RNA. Four donors had plasma or serum available for paired testing. SARS-CoV-2 RNA was not detected from any tissue or plasma/serum sample tested. Based on these findings, risk of transmission through the transplantation of tissue types studied from SARS-CoV-2 infected donors is likely to be low.

There is a common belief that antiosteoporosis medications are less effective in older adults. This study used data from randomized controlled trials (RCTs) to determine whether the anti-fracture efficacy of treatments and their effects on BMD differ in people ≥70 compared to those

PURPOSE: To define the prevalence, characteristics, and treatment approach for proximal junction failure secondary to odontoid fractures in patients with prior C2-pelvis posterior instrumented fusions (PSF). METHODS: A single institutions database was queried for multi-level fusions (6+ levels), including a cervical component. Posterior instrumentation from C2-pelvis and minimum 6-month follow-up was inclusion criteria. Patients who sustained dens fractures were identified; each fracture was subdivided based on Anderson & DAlonzo and Grauers classifications. Comparisons between the groups were performed using Chi-square and T tests. RESULTS: 80 patients (71.3% female; average age 68.1 ± 8.1 years; 45.0% osteoporosis) were included. Average follow-up was 59.8 ± 42.7 months. Six patients (7.5%) suffered an odontoid fracture post-operatively. Cause of fracture in all patients was a mechanical fall. Average time to fracture was 23 ± 23.1 months. Average follow-up after initiation of fracture management was 5.84 ± 4 years (minimum 1 year). Three patients sustained type IIA fractures one of which had a concomitant unilateral C2 pars fracture. Three patients sustained comminuted type III fractures with concomitant unilateral C2 pars fractures. Initial treatment included operative care in 2 patients, and an attempt at non-operative care in 4. Non-operative care failed in 75% of patients who ultimately required revision with proximal extension. All patients with a concomitant pars fracture had failure of non-operative care. Patients with an intact pars were more stable, but 50% required revision for pain. CONCLUSIONS: In this 11-year experience at a single institution, the prevalence of odontoid fractures above a C2-pelvis PSF was 7.5%. Fracture morphology varied, but 50% were complex, comminuted C2 body fractures with concomitant pars fractures. While nonoperative management may be suitable for type II fractures with simple patterns, more complex and unstable fractures likely benefit from upfront surgical intervention to prevent fracture displacement and neural compression. As all fractures occurred secondary to a mechanical fall, inpatient and community measures aimed to minimize risk and prevent mechanical falls would be beneficial in this high-risk group.

Purpose: To analyze the process of early oral osseointegration of titanium (Ti) implants in diabetic 129/Sv mice through microCT and histologic and immunohistochemical analysis. Materials and Methods: A group of 30 male 129/Sv mice was equally subdivided into two groups: (1) nondiabetic (ND), in which mice did not undergo systemic alterations and received a standard diet, and (2) diabetic (D), in which mice were provided a high-fat diet from the age of 6 weeks until the conclusion of the study and received two intraperitoneal (IP) injections of streptozotocin (STZ) at a concentration of 100 mg/Kg each. Each mouse underwent extraction of a maxillary first molar, and customized Ti screws (0.50 mm diameter, 1.5 mm length) were placed in the residual alveolar sockets of the palatal roots. At 7 and 21 days after implant placement, the animals were euthanized for maxilla and pancreas collection. Maxillae containing Ti implants were analyzed with microCT, histology, and immunohistochemistry for cells that were positive for F4/80, CD146, runt-related transcription factor 2 (Runx2), and proliferating cell nuclear antigen (PCNA). Pancreata were histologically analyzed. Quantitative data were statistically analyzed with a significance level at 5% (P < .05). Results: ND mice presented successful healing and osseointegration, with a significantly higher fraction of bone volume compared to D mice, both at the alveolar sockets (53.39 ± 5.93 and 46.08 ± 3.18, respectively) and at the implant sites (68.88 ± 7.07 and 44.40 ± 6.98, respectively) 21 days after implant placement. Histologic evaluation revealed that the ND mice showed a significant decrease in inflammatory infiltrate and a significant increase in newly formed bone matrix at 21 days, whereas peri-implant sites in the D mice were predominantly encapsulated by fibrous tissue and chronic inflammatory infiltrate. Immunohistochemical characterization revealed higher Runx2 osteoblast differentiation and higher cell proliferation activity in the ND mice at 7 days, while higher amounts of macrophages were present in D mice at 7 and 21 days. Interestingly, no differences were found in CD146-positive cells when comparing ND and D mice. Conclusions: This study evaluated the effects of immediate dental implant placement in 129/Sv diabetic mice by using specific healing markers to identify changes in cellular events involved in early oral osseointegration. This approach may serve as tool to evaluate new materials and surface coatings to improve osseointegration in diabetic patients. [ABSTRACT FROM AUTHOR]

BackgroundDuring the wars in Afghanistan and Iraq most injuries to service members involved the musculoskeletal system. These wounds often occurred around joints, and in some cases result in traumatic arthrotomy-a diagnosis that is not always clear, especially when there is no concomitant articular fracture. The aim of the present study is to evaluate the diagnosis and treatment of peri-articular blast injuries without fracture.MethodsThe study cohort included 12 consecutive patients (12 involved extremities) who sustained peri-articular blast wounds of the extremities without fractures. The diagnosis of penetrating articular injury was based on clinical examination, radiographic findings, or aspiration. A peri-articular wound was defined as any wound, or radio-opaque blast fragment, within 5 cm of a joint. The New Injury Severity Score (NISS) was calculated for each patient. Four patients had upper, and 8 patients had lower extremity injuries. Nine of 12 patients had joint capsular penetration and underwent joint irrigation and debridement.ResultsTwo patients had retained intra-articular metal fragments. One patient had soft tissue blast wounds within 5 cm of a joint but did not have joint capsule penetration. There were no significant differences (p = 0.23) between the distribution of wounds to upper versus lower extremities. However, there were a significantly greater number of blast injuries attributed to Improvised Explosive Devices (IEDs) than from other blast mechanisms (p = 0.01).ConclusionExtremity blast injuries in the vicinity of joints involving only soft tissues present a unique challenge in surgical management. A high index of suspicion should be maintained for joint capsular penetration so that intra-articular injuries may be appropriately treated.

Over the past two decades Biomedical Engineering has emerged as a major discipline that bridges societal needs of human health care with the development of novel technologies. Every medical institution is now equipped at varying degrees of sophistication with the ability to monitor human health in both non-invasive and invasive modes. The multiple scales at which human physiology can be interrogated provide a profound perspective on health and disease. We are at the nexus of creating avatars (herein defined as an extension of digital twins) of human patho/physiology to serve as paradigms for interrogation and potential intervention. Motivated by the emergence of these new capabilities, the IEEE Engineering in Medicine and Biology Society, the Departments of Biomedical Engineering at Johns Hopkins University and Bioengineering at University of California at San Diego sponsored an interdisciplinary workshop to define the grand challenges that face biomedical engineering and the mechanisms to address these challenges. The Workshop identified five grand challenges with cross-cutting themes and provided a roadmap for new technologies, identified new training needs, and defined the types of interdisciplinary teams needed for addressing these challenges. The themes presented in this paper include: 1) accumedicine through creation of avatars of cells, tissues, organs and whole human; 2) development of smart and responsive devices for human function augmentation; 3) exocortical technologies to understand brain function and treat neuropathologies; 4) the development of approaches to harness the human immune system for health and wellness; and 5) new strategies to engineer genomes and cells.

Purpose To evaluate and report the performance of the winning algorithms of the Radiological Society of North America Cervical Spine Fracture AI Challenge. Materials and Methods The competition was open to the public on Kaggle from July 28 to October 27, 2022. A sample of 3112 CT scans with and without cervical spine fractures (CSFx) were assembled from multiple sites (12 institutions across six continents) and prepared for the competition. The test set had 1093 scans (private test set: n = 789; mean age, 53.40 years ± 22.86 [SD]; 509 males; public test set: n = 304; mean age, 52.51 years ± 20.73; 189 males) and 847 fractures. The eight top-performing artificial intelligence (AI) algorithms were retrospectively evaluated, and the area under the receiver operating characteristic curve (AUC) value, F1 score, sensitivity, and specificity were calculated. Results A total of 1108 contestants composing 883 teams worldwide participated in the competition. The top eight AI models showed high performance, with a mean AUC value of 0.96 (95% CI: 0.95, 0.96), mean F1 score of 90% (95% CI: 90%, 91%), mean sensitivity of 88% (95% Cl: 86%, 90%), and mean specificity of 94% (95% CI: 93%, 96%). The highest values reported for previous models were an AUC of 0.85, F1 score of 81%, sensitivity of 76%, and specificity of 97%. Conclusion The competition successfully facilitated the development of AI models that could detect and localize CSFx on CT scans with high performance outcomes, which appear to exceed known values of previously reported models. Further study is needed to evaluate the generalizability of these models in a clinical environment. Keywords: Cervical Spine, Fracture Detection, Machine Learning, Artificial Intelligence Algorithms, CT, Head/Neck Supplemental material is available for this article. © RSNA, 2024.

Long-duration spaceflight creates a variety of stresses due to the unique environment, which can lead to compromised functioning of the skeletal and immune systems. However, the mechanisms by which organisms respond to this stress remain unclear. The present study aimed to investigate the impact of three different gravitational loadings (microgravity, 1/6 g [lunar gravity], and 1 g) on the behavior, bone, thymus, and spleen of mice housed for 25–35 days in the International Space Station. The bone density reduction under microgravity was mostly recovered by 1 g but only partially recovered by 1/6 g. Both 1 g and 1/6 g suppressed microgravity-induced changes in some osteoblast and osteoclast marker gene expression. Thymus atrophy induced by microgravity was half recovered by both 1 g and 1/6 g, but gene expression changes were not fully recovered by 1/6 g. While no histological changes were observed due to low gravity, alterations in gene expression were noted in the spleen. We found that in bone and thymus, lunar gravity reduced microgravity-induced histological alterations and partially reversed gene expression changes. This study highlighted organ-specific variations in responsiveness to gravity, serving as an animal test for establishing a molecular-level gravity threshold for maintaining a healthy state during future spaceflight. [ABSTRACT FROM AUTHOR]

Background: Few studies focus on the clinical, laboratory, radiological, and biological characteristics of bone and muscle of multiple vertebral fractures, which are associated with a more poor prognosis compared with single fracture. Purpose: To compare the BMD, bone turnover, muscularity, fatty infiltration of muscle, and prevalence of co-morbidities in patients with single and multiple vertebral fractures. Methods: We recruited 100 patients with single fracture (age 66.96 ± 8.24 years) and 100 with multiple fractures (age 69.90 ± 7.80 years); performed dual-energy X-ray absorptiometry of the femoral neck, hip, and lumbar vertebrae; and measured biochemical markers of bone turnover, muscularity, and fatty infiltration. Results: Patients with multiple vertebral fractures had lower hip BMD (p =0.010) than those with single fractures, but there was no difference in femoral neck and lumbar vertebral BMD nor in muscularity. However, fatty infiltration, an indicator of muscle quality, was significantly higher in participants with multiple fractures (p =0.006). Diabetes was significantly more common in patients with multiple fractures (p =0.042). There were no significant differences in markers of bone turnover, and Seperman analyses showed no correlations of CTX-1 or tPINP with the BMD of the hip, femoral neck, or lumbar spine. However, high CTX-1 was associated with high tPINP (r=0.4805; p <0.0001), and marked fatty infiltration was associated with low hip, lumbar vertebral, and femoral neck BMD. Cox regression analyses showed that age (OR 1.057; 95% CI 1.016–1.101; p =0.006) and low hip BMD (OR 0.016; 95% CI, 0.000–0.549; p =0.022) were associated with a higher risk of multiple fractures. Conclusion: Patients with multiple fractures tend to have lower hip BMD, a history of type 2 diabetes, and more substantial fatty infiltration of muscle than in those with single fractures. Age and hip BMD rather than lumbar vertebrae BMD were found to be independent risk factors for multiple vertebral compression fractures, implying that hip BMD may be a more sensitive predictor for multiple vertebral fractures. More improvements in hip BMD and focus on older persons may be useful means of preventing multiple fractures. [ABSTRACT FROM AUTHOR]

Precise regulation of organ size and position is crucial for optimal organ function. Since the swim bladder is primarily responsible for buoyancy in teleosts, early development and subsequent inflation of the swim bladder should be appropriately controlled with the body growth. However, the underlying mechanism remains unclear. In this study, we show that the size and position of the swim bladder are physically constrained by the surrounding bones in zebrafish. Non‐invasive micro‐CT scanning revealed that the anterior edge of the swim bladder is largely attached to the os suspensorium, which is an ossicle extending medioventrally from the 4th centrum. Additionally, we observed that hoxc6a mutants, which lack the os suspensorium, exhibited an anterior projection of the swim bladder beyond the 4th vertebra. During the swim bladder development, we found that the counterclockwise rotation of the os suspensorium correlates with posterior regression of the swim bladder, suggesting that the os suspensorium pushes the swim bladder posteriorly into its proper position. Furthermore, our results revealed a close association between the posterior region of the swim bladder and the pleural ribs. In hoxaa cluster mutants with additional ribs, the swim bladder expanded posteriorly, accompanied by an enlarged body cavity. Taken together, our results demonstrate the importance of the surrounding bones in the robust regulation of swim bladder size and position in zebrafish. [ABSTRACT FROM AUTHOR]

1. Modern broiler chickens are among the most efficient livestock in terms of resource requirements and production time. To maintain and improve production efficiency and meat quality and account for welfare problems, early interventions, such as incubation temperature, require investigation2. In this study, Ross 308 broiler eggs were incubated at either 36.5°C or 38.5°C on embryonic days (ED) 4–7. The control group eggs were incubated at a constant temperature of 37.5°C. Musculus pectoralis and musculus gastrocnemius samples were taken for the investigation of muscle physiology, and the tibia was sampled for bone strength analysis from chickens aged 35 and 36 d. In addition, meat quality was analysed and gait scoring was performed.3. The performance of chickens in the 36.5°C group was inferior to those in the other groups up to d 10 post-hatch, but compensatory growth was seen by d 35 of age. Meat quality was unaffected, but significant differences between sexes were observed. Males had lighter meat colour than females. Muscle glycogen and intramuscular fat were unaffected by the incubation temperature, but the muscularis pectoralis and gastrocnemius intramuscular fat contents were greater in males than in females, accompanied by the increased expression of enzymes involved in lipolysis. In the 38.5°C group, males had less bone elasticity than females, and the inverse was observed in the other groups. Gait scores were affected by sex but not incubation temperature.4. The results of this study showed a stronger effect of sex than incubation temperature on broiler muscle physiology, bone strength, performance and meat quality. [ABSTRACT FROM AUTHOR]

This review aimed to summarize the current literature on antibiotic distribution in orthopedically relevant tissues and settings where dynamic sampling methods have been used. PubMed and Embase databases were systematically searched. English‐published studies between 2004 and 2024 involving systemic antibiotic administration in orthopedically relevant tissues and settings based on dynamic measurements were included. In total, 5385 titles were identified. After title and abstract screening, 97 eligible studies (43 different antibiotic drugs) were included. The studies covered both preclinical (42%) and clinical studies including healthy and infected tissues (21%) and prophylactic and steady‐state situations (35%). Microdialysis emerged as the predominant sampling method in 98% of the studies. Most of the presented antibiotics (80%) were only assessed once or twice. Among the most extensively studied antibiotics were cefuroxime (18 studies), linezolid (9 studies) and vancomycin (9 studies). This review presents valuable insights into the microenvironmental distribution of antibiotics in orthopedically relevant target tissues and settings and seeks to provide a basis for improving dosing recommendations and treatment outcomes. However, it is important to acknowledge that our findings are limited to the specific drug, dosing regimens, administration method and target tissue, and are crucially linked to the selected PK/PD target. [ABSTRACT FROM AUTHOR]

Summary This study aims to examine and compare the effectiveness of dynamic contrast‐enhanced magnetic resonance imaging (DCE‐MRI) and Digital Subtraction Angiography (DSA) in evaluating hypervascular spinal metastases. A comprehensive literature review was conducted, utilizing top‐tier databases such as PubMed, Scopus and Google Scholar, to compile an authoritative and up‐to‐date overview of the current advancements in the field. We synthesized key studies focusing on the advantages, limitations and efficacy of both imaging techniques. DCE‐MRI provides a non‐invasive method for evaluating tissue morphology, perfusion and vascularity, offering valuable information for cancer diagnosis and treatment monitoring. In contrast, DSA is an invasive procedure primarily used for embolization and diagnosing cerebrovascular events. Both modalities have distinct features regarding image acquisition, contrast agents, resolution and accessibility. DCE‐MRI shows promise for cancer‐related applications, offering advantages over conventional MRI by incorporating anatomical and hemodynamic parameters. While DSA remains important for cases requiring critical vascular information, further research is necessary to explore its potential therapeutic benefits in assessing vessel patency. Continued investigations are crucial to uncover additional insights and therapeutic applications for both DCE‐MRI and DSA in medical imaging. [ABSTRACT FROM AUTHOR]

In recent years, the prevalence of bone diseases is showing an increasing trend, which is mainly attributed to the aging of the global population. However, bone repair and regeneration are still an unsolved problem in the treatment of bone diseases, which include a series of biological events. Photocrosslinked natural hydrogel‐based microspheres (PNHMs) are spherical particles composed of photocrosslinked natural hydrogel components. Due to their morphology, injectability, and biocompatibility, PNHMs are widely used in tissue regeneration, particularly for bone defects. In this article, we review the available photocrosslinked natural materials for PNHMs, and then introduce their preparation methods. After that, we summarize the important advanced functionalities of PNHMs. For example, PNHMs can be loaded with different active ingredients to exert anti‐inflammatory, antibacterial, and antioxidant effects, while also realizing lubrication due to their specific shape and size distribution. In addition, the function of capturing ions can be realized via coordination. When applied in bone tissue engineering, PNHMs can promote angiogenesis and osteogenesis, with great potential in the treatment of bone diseases. Finally, the challenges and prospects of PNHMs for bone repair are discussed. [ABSTRACT FROM AUTHOR]

Context: The beneficial effects of probiotic supplementation on bone health in postmenopausal women require further validation. Objective: This study systematically reviewed and conducted a meta-analysis of randomized controlled trials (RCTs) to assess the relationship between probiotic supplementation and changes in bone mineral density (BMD) and bone turnover markers (BTMs) among postmenopausal women. Methods: A systematic search was conducted across four databases to retrieve data on lumbar spine BMD, hip BMD, collagen type 1 cross-linked C-telopeptide (CTX), receptor activator of nuclear factor-κB ligand (RANKL), osteocalcin (OC), osteoprotegerin (OPG), N-terminal propeptide of type 1 procollagen (P1NP), and bone-specific alkaline phosphatase (BALP) in postmenopausal women. Eligible RCTs were quantitatively analyzed using random-effects meta-analyses. Additional analyses, including subgroup, sensitivity, and meta-regression analyses, were performed. Results: Twelve RCTs involving 1183 postmenopausal women were included. Compared with the control group, postmenopausal women who received probiotic supplementation showed significantly greater BMD in both the lumbar spine (standardized mean difference [SMD] = 0.60, 95% confidence interval [CI] 0.14 to 1.05) and the hip (SMD = 0.74, 95%CI 0.15 to 1.33). Additionally, probiotic supplementation was associated with reduced levels of CTX (SMD = -1.51, 95%CI -1.88 to -0.41) and BALP (SMD = -1.80, 95%CI -2.78 to -0.81). No significant differences were found between the probiotic and control groups in terms of other BTMs. Subgroup analyses revealed that the increase in BMD due to probiotic supplementation was more significant in postmenopausal women with osteopenia than in those with osteoporosis. The meta-analysis results for both lumbar spine and hip BMD remained robust after conducting sensitivity analyses and meta-regressions. Conclusion: Supplementation with probiotics may increase BMD among postmenopausal women, with stronger evidence in women with osteopenia than osteoporosis. Further RCTs are suggested to confirm and refine these findings. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/ , identifier CRD42024576764. [ABSTRACT FROM AUTHOR]

Background: The burden of displacement makes child refugees, asylum seekers, and migrant children less resistant to medical problems. On February 6, 2023, the southeast and the southcentral regions of Türkiye were struck by two sequential large earthquakes. The study aimed to analyze the characteristics of musculoskeletal injuries and the initial orthopedic surgery data resulting from the earthquake and compare the differences between Turkish and displaced children, particularly those who underwent major musculoskeletal interventions at the four state hospitals of the Adana metropolitan region. Methods: The retrospective study analyzed the medical records of the survivors admitted to the four general hospitals run by the government in the Adana, Türkiye metropolitan area between February 06, 2023, and February 13, 2023, the first seven days following the earthquake. The analysis data included age, gender, nationality, time of admission, types and localization of injuries, and treatment methods. Results: The number of cases under 18 years of age requiring orthopedic intervention was 969. The distribution of the cases based on nationality was as follows: there were 517 Turkish (53.35%), 371 Syrian (32.71%), and 81 children of unknown nationality (CUN) (8.36%). The files show that the patients requiring surgery, including fasciotomy, fracture surgery, and amputation (n = 281), were mainly treated at the level I trauma center (n = 171, 60.85%). In terms of the daily distribution of admissions based on the type of musculoskeletal injuries, the admissions of children with foot fractures in the first days were significantly increased (p = 0.0134). Regarding surgery rates, the fracture surgery and fasciotomy rates were significantly higher in cases admitted earlier. (p < 0.0001 and p = 0.0009, respectively). In terms of nationality, there were no significant differences regarding the date of admission, the number of cases who underwent amputations, and the discharge number and types. Conclusion: The study revealed that after the severe earthquake disaster, the state hospitals of the Adana metropolitan region provided unbiased healthcare for all the region's children. Regarding orthopedic care, the response was given accordingly in this particular disaster, highlighting that level I trauma centers should always be ready for such intensity due to the short preparation time in case of a severe disaster. [ABSTRACT FROM AUTHOR]

Patient: Female, 44-year-old Final Diagnosis: Abdominopelvic hematocele with mesenteric contusion * bilateral superior and inferior pubic ramus fractures * bladder wall contusion * Denis type III sacral fractures * L1-5 bilateral transverse process fractures with L4 spinous process fracture * left lateral malleolus avulsion fracture * mild fatty liver * multiple pelvic comminuted fractures (OTA type C-3.3) * multiple skin and soft tissue contusions throughout the body * right 12th costeovertebral joint dislocation * right 2nd, 7th-9th rib fractures * right femoral lateral condyle fracture * right knee dislocation * traumatic wet lung of both lungs with bilateral pleural effusion Symptoms: External rotation and abduction deformity of the right lower limb * movement disorder * persistent dull pain in the chest, abdomen and right knee * right hip pain Clinical Procedure: -- Specialty: Orthopedics and Traumatology Objective: Rare disease Background: Anterior hip dislocation is a rare injury that often occurs following high-energy road traffic accidents and accounts for approximately 7% to 13% of all hip dislocations. This report describes the presentation, diagnosis, and treatment of a 44-year-old woman with anterior hip dislocation and multiple comminuted fractures due to a vehicular crush injury. A PubMed search showed no similar cases have been reported in the English literature. Case Report: A 44-year-old woman was urgently seen at a local hospital after being run over twice by the rear wheel of a reversing truck while walking. Radiographic examination revealed right obturator-type anterior hip dislocation and multiple injuries. Pelvic external fixation and right femoral supracondylar bone traction were performed. Subsequent to hemodynamic stabilization, the patient was transferred to our hospital. Five days later, open reduction internal fixation was performed. Anterior pelvic ring internal fixation was performed after 20 days. The patient was hospitalized for 33 days. At the 5-year postoperative follow-up, the CT image showed healing. There was no lumbar or hip pain, and the patient had returned to normal life and work. Conclusions: Anterior hip dislocation combined with bilateral obturator fractures, sacral fractures, lumbar fractures, and thoraco- abdominal injuries are rare in clinical practice. It is crucial to correctly handle multiple injuries to achieve enhanced recovery after surgery and prevent complications. The aim of this study is to document the clinical presentation, management, and outcomes of this unique case, highlighting the challenges and potential complications associated with femoral head displacement toward the obturator foramen. [ABSTRACT FROM AUTHOR]

ABSTRACT Objectives Methods Results Conclusions This study examined long‐term changes in body composition and bone mineral characteristics among male long‐distance runners from a high‐profile university team, focusing on concerns about impaired musculoskeletal development due to extreme leanness and weight management practices in this population.Trajectory analyses were performed using multilevel modeling of 608 dual‐energy x‐ray absorptiometry datasets from 109 runners (mean age, height, and weight of 18.0 years, 171.4 cm, and 56.8 kg at baseline, respectively) collected biannually over 4 years.Linear increases in total and regional lean mass (LM) were observed on average, with the increase in leg LM being double that of arm LM (0.07 vs. 0.03 kg per occasion, respectively). Similarly, total bone mineral density (BMD) and content (BMC) exhibited linear growth on average, with BMD accrual being greater in the legs than in the arms (0.004 vs. 0.001 g/cm2 per occasion, respectively). However, rib BMD and BMC were predicted to decrease. Individually predicted growth rates in total LM were significantly associated with those in total BMD (r = 0.347, p < 0.001) and BMC (r = 0.424, p < 0.001).These results indicate site‐specific musculoskeletal adaptations to intensive long‐distance running training. Moreover, a random slope model accurately captured the trajectories of most dependent variables, highlighting the heterogeneity of training responses. The predictive models developed in this study offer practical strategies for identifying runners at risk of suboptimal physical development, thereby facilitating the development of personalized conditioning programs. [ABSTRACT FROM AUTHOR]

AMP‐activated protein kinase (AMPK), a crucial regulatory kinase, monitors energy levels, conserving ATP and boosting synthesis in low‐nutrition, low‐energy states. Its sensitivity links microenvironmental changes to cellular responses. As the primary support structure and endocrine organ, the maintenance, and repair of bones are closely associated with the microenvironment. While a series of studies have explored the effects of specific microenvironments on bone, there is lack of angles to comprehensively evaluate the interactions between microenvironment and bone cells, especially for bone marrow mesenchymal stem cells (BMMSCs) which mediate the differentiation of osteogenic lineage. It is noteworthy that accumulating evidence has indicated that AMPK may serve as a hub between BMMSCs and microenvironment factors, thus providing a new perspective for us to understand the biology and pathophysiology of stem cells and bone. In this review, we emphasize AMPK's pivotal role in bone microenvironment modulation via ATP, inflammation, reactive oxygen species (ROS), calcium, and glucose, particularly in BMMSCs. We further explore the use of AMPK‐activating drugs in the context of osteoarthritis and osteoporosis. Moreover, building upon the foundation of AMPK, we elucidate a viewpoint that facilitates a comprehensive understanding of the dynamic relationship between the microenvironment and bone homeostasis, offering valuable insights for prospective investigations into stem cell biology and the treatment of bone diseases. [ABSTRACT FROM AUTHOR]

Background: Hydatid disease is a parasitic infection seen in endemic areas. Musculoskeletal hydatid disease is rarely reported. Purpose: To describe the magnetic resonance imaging (MRI) features of musculoskeletal hydatid disease and to highlight the specific findings in the diagnosis of hydatid cysts. Material and Methods: The MRI scans of 29 cases diagnosed as musculoskeletal hydatid disease between 2000 and 2022 were retrospectively analyzed. The localization, size, appearance (unilocular or multilocular), signal characteristics, rim sign, presence of internal septa and membrane, and gadolinium enhancement pattern of hydatid cysts were evaluated. Results: A total of 29 patients diagnosed with hydatid cyst were included in the study. Of the lesions, 18 were localized in bone and 11 were in soft tissue. The bone hydatid cysts on MRI showed heterogeneous low to intermediate signal intensity on T1-weighted images and high signal intensity on T2-weighted images in the medullary bone. In 15/18 patients, there was also cortical destruction and extension into the adjacent soft tissue planes. In 8/11 cases where the cyst was located in muscle tissue, the "cyst or cysts within a cyst" appearance was observed on MRI. The rim sign was observed in 7/11 cases and the "water lily" sign was noted in 2/11 cases. Conclusion: MRI provides valuable information for the diagnosis of hydatid disease with its distinctive imaging features. Knowledge of the different patterns of hydatid cysts on MRI may be helpful in the diagnosis of this disease. [ABSTRACT FROM AUTHOR]

The development of effective biomaterials for tissue regeneration has led to the exploration of blood derivatives such as leucocyte- and platelet-rich fibrin (L-PRF). A novel variant, Albumin-Enriched Platelet-Rich Fibrin (Alb-PRF), has been introduced to improve structural stability and bioactivity, making it a promising candidate for bone regeneration. This study aimed to evaluate Alb-PRF's capacity for cytokine and growth factor release, along with its effects on the proliferation, differentiation, and mineralization of human osteoblasts in vitro. Alb-PRF membranes were analyzed using histological, scanning electron microscopy, and fluorescence microscopy techniques. Cytokine and growth factor release was quantified over seven days, and osteoinductive potential was evaluated with MG-63 osteoblast-like cells. Structural analysis showed Alb-PRF as a biphasic, highly cellularized material that releases lower levels of inflammatory cytokines and higher concentrations of platelet-derived growth factor (PDGF) and vascular endothelial growth factor (VEGF) compared to L-PRF. Alb-PRF exhibited higher early alkaline phosphatase activity and in vitro mineralization (p < 0.05) and significantly increased the OPG/RANKL mRNA ratio (p < 0.05). These results indicate that Alb-PRF has promising potential as a scaffold for bone repair, warranting further in vivo and clinical assessments to confirm its suitability for clinical applications. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to evaluate the diagnostic performance, image quality, and inter- and intra-observer agreement of the 3D T1 multi-echo fast field echo (mFFE) sequence in cervico-thoraco-lumbar vertebral fractures compared with conventional computed tomography (CT) as the gold standard. Methods: We conducted a prospective single-centre study including 29 patients who underwent spinal magnetic resonance imaging (MRI) at the surgeon's request, in addition to CT for vertebral fracture assessment and classification. A 3D T1 mFFE sequence was added to the standard MRI protocol. Consecutively, two readers analyzed the 3D mFFE sequence alone, the 3D mFFE sequence with the entire MRI protocol, including the STIR and T1 sequences, and, finally, the CT images in random order and 1 month apart. A standardized assessment was performed to determine the presence or absence of a fracture, its location, its classification according to the Genant and AO classifications for traumatic and osteoporotic fractures, respectively, the loss of height of the anterior and posterior walls of the vertebral body, and the presence of concomitant disco-ligamentous lesions. Contingency tables, intraclass correlation coefficients, and Cohen's kappa tests were used for statistical analysis. Results: A total of 25 fractures were recorded (48% cervical, 20% thoracic, and 32% lumbar), of which 52% were classified A, according to the AO classification system. The quality of the 3D mFFE image was good or excellent in 72% of cases. Inter-observer agreement was near perfect (0.81–1) for vertebral body height and for AO and Genant classifications for all modalities. Intra-observer agreement was strong-to-near perfect between CT and the 3D mFFE sequence. Regarding the diagnostic performance of the 3D mFFE sequence, the sensitivity was 0.9200 and 0.9600, the specificity was 0.9843 and 0.9895, and the accuracy was 0.9861 and 0.9769 for Readers 1 and 2, respectively. In addition, up to 40% of intervertebral disc lesions and 33% of ligamentous lesions were detected by the 3D mFFE sequence compared to CT, allowing four AO type A fractures to be reclassified as type B. Conclusions: The 3D mFFE sequence allows accurate diagnosis of vertebral fractures, with superiority over CT in detecting disco-ligamentous lesions and a more precise classification of fractures, which can prompt clinicians to adapt their management despite an image quality that still requires improvement in some cases. Key points: Vertebral fractures and disco-ligamentous lesions can be assessed using CT-like MRI sequences, with 3D T1 mFFE being superior to CT for the detection of disco-ligamentous lesions. CT-like images using the 3D T1 mFFE sequence improve the diagnostic accuracy of bone structures in MRI. [ABSTRACT FROM AUTHOR]

Glycogen storage disease (GSD) is the most prevalent inherited disorder of glycogen metabolism for which no causal treatment is available. In recent years, thanks to the improved clinical management, the life expectancy of these patients extended, disclosing previously unidentified adverse conditions in other organs. In this study, we evaluated the clinical bone complications and the cellular responses in 20 patients (aged 14.1 ± 3.4 years) affected by GSD type I. Fragility fractures were reported in 35% of the patients, which were older than unfractured patients. They involved appendicular skeletal segments, while no vertebral deformity was detected. 60% of the patients had a bone mineral density (BMD) "below the expected range for age", and lumbar spine (LS) BMD Z-scores positively correlated with muscle strength. Circulating mineral and bone markers showed reduction in the older subjects, with no increase in the pubertal age. Significant correlations could not be detected between circulating markers and LS BMD Z-scores, except for sclerostin levels, which also correlated with muscle strength. The osteoclasts differentiated from patients' peripheral blood mononuclear cells did not show cell-autonomous alterations. However, circulating osteoclast precursors from healthy individuals cultured in the presence of patients' sera exhibited increased osteoclastogenesis compared to control sera suggesting that GSD type I serum factors could affect osteoclast function in a non-autonomous manner. In contrast, circulating osteoprogenitors were unremarkable. [ABSTRACT FROM AUTHOR]

The effects of androgens on women's bone health are not fully understood. Mendelian randomization (MR) studies using sex-combined data suggest that sex hormone-binding globulin (SHBG) and bioavailable testosterone (BioT) causally affect bone traits. Given significant sex differences in hormone regulation and effects, female-specific MR studies are necessary. In the current study, we explored the causal relationships of SHBG, BioT, and total testosterone (TT) with forearm fracture (FAFx) risk in women using two-sample MR analyses. We utilized a unique female-specific FAFx outcome dataset from three European biobanks (UFO, HUNT, Estonian Biobank) comprising 111,351 women and 8823 FAFx cases, along with female-specific genetic instruments of SHBG, BioT, and TT identified in the UK Biobank. We also assessed bone mineral density (BMD) at the forearm (FA), femoral neck (FN), and lumbar spine (LS) using female-specific GWAS data from the GEFOS consortium. High SHBG (odds ratio per standard deviation increase (OR/SD): 1.53, 95% confidence intervals (CIs): 1.34–1.75), low BioT (OR/SD: 0.77, 0.71–0.84) and low TT (OR/SD 0.90, 0.83–0.98) were causally associated with increased FAFx risk. BioT was positively, and SHBG inversely, causally associated with especially FA-BMD, but also LS-BMD and FN-BMD, while TT was only significantly positively associated with FA-BMD and LS-BMD. We propose that endogenous androgens and SHBG are important for women's bone health at distal trabecular-rich bone sites such as the distal forearm and may serve as predictors for FAFx risk. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the correlation between BMAT and bone quality, describe the long-term effects of ovariectomy on bone, and investigate BMAT's spatial distribution. Fifteen-months-old female Sprague‒Dawley rats were studied, comparing ovariectomized (OVX, n = 22) and sham-operated (SHAM, n = 11) groups at 6 months. Tibias were analyzed for bone microarchitecture, BMAT (microcomputed tomography), mineral parameters (quantitative backscattered electron imaging), and bone composition (Raman microspectroscopy). The OVX tibias showed severe trabecular bone loss (lower bone volume/total volume, p < 0.001) with increased BMAT (higher adipose volume per marrow volume, p < 0.001), decreased mineral content (lower calcium concentration, p < 0.001), and altered organic components (lower mineral/matrix ratio in new bone, p = 0.03 trabecular surface, p < 0.001 trabecular core). When the data are pooled over both groups (SHAM and OVX), the adipose volume/marrow volume ratio was negatively correlated with bone volume/total volume (r = − 0.79, p < 0.001) and mineral/matrix ratio (r = − 0.37, p = 0.04 trabecular surface; r = − 0.65, p < 0.001 trabecular core) and positively correlated with crystallinity (r = 0.55, p = 0.001 trabecular surface; r = 0.49, p = 0.006 trabecular core). The mineral/matrix ratio of trabecular surface new bone was strongly negatively correlated with the adipose compartment nearest to the bone surface. These findings suggest mechanisms underlying BMAT's role in bone resorption. [ABSTRACT FROM AUTHOR]

The lacunocanalicular network (LCN) is an intricate arrangement of cavities (lacunae) and channels (canaliculi), which permeates the mineralized bone matrix. In its porosity, the LCN accommodates the cell network of osteocytes. These two nested networks are attributed a variety of essential functions including transport, signaling, and mechanosensitivity due to load-induced fluid flow through the LCN. For a more quantitative assessment of the networks' function, the three-dimensional architecture has to be known. For this reason, we aimed (i) to quantitatively characterize spatial heterogeneities of the LCN in whole mouse tibial cross-sections of BALB/c mice and (ii) to analyze differences in LCN architecture by comparison with another commonly used inbred mouse strain, the C57BL/6 mouse. Both tibiae of five BALB/c mice (female, 26-week-old) were stained using rhodamine 6G and whole tibiae cross-sections were imaged using confocal laser scanning microscopy. Using image analysis, the LCN was quantified in terms of density and connectivity and lacunar parameters, such as lacunar degree, volume, and shape. In the same tibial cross-sections, the calcium content was measured using quantitative backscattered electron imaging (qBEI). A structural analysis of the LCN properties showed that spatially denser parts of the LCN are mainly due to a higher density of branching points in the network. While a high intra-individual variability of network density was detected within the cortex, the inter-individual variability between different mice was low. In comparison to C57BL/6J mice, BALB/c mice showed a distinct lower canalicular density. This reduced network was already detectable on a local network level with fewer canaliculi emanating from lacunae. Spatial correlation with qBEI images demonstrated that bone modeling resulted in disruptions in the network architecture. The spatial heterogeneity and differences in density of the LCN likely affects the fluid flow within the network and therefore bone's mechanoresponse to loading. [ABSTRACT FROM AUTHOR]

Lipid accumulation product (LAP) has a positive effect on spinal bone mineral density (BMD). However, once LAP levels exceed 27.26, the rate of spinal BMD increase slow down or even decline. This indicates a biphasic relationship between lipid metabolism and BMD, suggesting potential benefits within a certain range and possible adverse effects beyond that range. This study aimed to investigate the potential association between LAP index and BMD in US adults, as well as to explore the presence of a potential saturation effect in this relationship. This study analyzed data from the National Health and Nutrition Examination Survey (NHANES) spanning from 2007 to 2018. A multiple stepwise regression model was employed to examine the association between LAP index and total spinal BMD. Additionally, a generalized additive model and a smooth curve fitting algorithm were utilized to examine the relationship, and saturation effect study was conducted to determine the saturation level. The calculation formula of LAP used in the study was: (LAP = (waist circumstances (WC) (cm) – 58) × triglyceride (TG) (mmol/L)) for women, and (LAP = (WC (cm) – 65) × TG (mmol/L)) for men. The study involved a total of 7913 participants aged 20 years or older. Through multiple stepwise regression analysis, it was found that individuals with higher LAP scores exhibited higher total spinal BMD. In both the crude and partially adjusted models, total spinal BMD was significantly higher in the highest LAP quartile (Q4) compared to the lowest LAP quartile (Q1) (P < 0.05). Utilizing a generalized additive model and smooth curve, a nonlinear relationship between LAP and total spinal BMD was observed. Furthermore, the study identified the saturation value of LAP to be 27.26, indicating a saturation effect. This research highlights a nonlinear relationship between LAP and total spinal BMD, along with the presence of a saturation effect. [ABSTRACT FROM AUTHOR]

Purpose: Metastatic castration-resistant prostate cancer (mCRPC) patients harbor reduced life expectancy after first-line treatment progression. Currently, no information is available regarding the influence of metastatic sites and osseous burden on progression-free (PFS) and overall survival (OS) of mCRPC patients. Methods: We relied on the Frankfurt Metastatic Cancer Database of the Prostate (FRAMCAP) database to select patients progressing to mCRPC and stratified them according to lymph node vs. osseous vs. visceral metastatic sites. Moreover, we stratified osseous mCRPC patients regarding the number of metastatic lesions. Endpoints were PFS and OS in uni- and multivariable Cox regression models. Results: Of 363 patients, 9.4% harbored M1a vs. 78% M1b vs. 12% M1c mCRPC with significantly higher PSA in M1b (9 vs. 22 vs. 8ng/ml). Rates of DeNovo (15% vs. 60% vs. 56%) were significantly lower in the M1a mCRPC group, compared to M1b and M1c (p < 0.001). In PFS analyses, a median of 12.7 vs. 10.1 vs. 15.9 months for M1a vs. M1b vs. M1c mCRPC was observed (p > 0.05). In multivariable Cox regression models, M1c mCRPC was independently at higher risk for progression (hazard ratio [HR]: 5.93, p = 0.048), relative to M1a. Regarding OS, significant differences were observed (p = 0.002), with median OS of 58 vs. 42 vs. 25 months for M1a vs. M1b vs. M1c mCRPC and corresponding HRs of 1.54 (p = 0.11) and 2.76 (p < 0.01). In multivariable models M1c mCRPC was associated with higher risk of death (HR: 3.56, p = 0.049), relative to M1a. No differences were observed after stratification according to number of bone lesions (all p ≥ 0.05). Conclusion: M1c mCRPC patients are independently at higher risk for progression and death, while M1a patients harbor best cancer-control outcomes. [ABSTRACT FROM AUTHOR]

Patients with bone metastasis are prevalent among those receiving palliative radiotherapy (RT), with approximately 20 % requiring reirradiation (reirradiation). The goal of bone reirradiation may be local control (oligoreoccurrence or oligoprogression of a previously treated lesion or in a previous treatment field) or symptomatic (threatening or painful progression). Published data on bone reirradiation indicate almost two-thirds of overall pain response. The primary organ at risk (especially for spine treatment) is the spinal cord. The risk of radiation myelitis is < 1 % for cumulative doses of < 50 Gy. Intensity-modulated RT (IMRT) and stereotactic RT (SRT) appear to be safer than three-dimensional RT (3DRT), although randomized trials comparing these techniques in reirradiation are lacking. Reirradiation requires multidisciplinary assessment. Alternative treatments for bone metastases (surgery, interventional radiology, etc.) must be considered. Patients should have a performance status ≤ 2, with at least a 1-month interval between treatments. The planning process involves reviewing previous RT plans, cautious dose adjustments, and precise target delineation and dose distribution to minimize toxicity. Cumulative dosimetry, patient consent, and vigilant post-treatment monitoring and dose reporting are crucial. [ABSTRACT FROM AUTHOR]

Aim: To assess the possibility of vertical alveolar ridge augmentation by means of activation of the periosteum. Materials and Methods: Six adult male Beagle dogs were used for the study. All premolars and first molars were extracted, and one vertical saucer‐shaped bony defect was created on each side of the mandible. After 3 months of healing, full‐thickness muco‐periosteal flaps were elevated, and one distraction device was placed on each side of the mandible. The distraction plate was left submerged, and the activation mechanism connected to the distraction rod was exposed intra‐orally. The protocol of periosteal activation (PP: periosteal 'pumping') was initiated after a latency of 7 days. The alternation of activation and relaxation at the rate of 0.35 mm/12 h during 5 days was followed by the sole activation of 0.35 mm/12 h for 5 days (PP group). Devices were left inactivated on the contralateral control side of the mandible (C group). All animals were euthanized after 8 weeks of consolidation. Samples were analysed histologically and by means of micro‐CT. Results: New mature lamellar bone was formed over the pristine bone in all groups. More intensive signs of bone modelling and remodelling were observed in the PP group compared to the C group. Mean new bone, bone marrow, connective tissue and total volumetric densities were greater in the PP group (p < 0.001, p = 0.001, p = 0.003 and p < 0.001, respectively). No differences were observed in the relative area parameters. Total tissue volume and bone volume were higher in the PP group (p = 0.031 and p = 0.076, respectively), while the bone mineral densities were higher in the C group (p = 0.041 and p = 0.003, respectively). Trabecular number, trabecular thickness and trabecular separation values were similar between the two groups. Conclusions: Regeneration of vertical alveolar bone ridge defects may be enhanced by activation of the periosteum, without the application of bone grafting materials. [ABSTRACT FROM AUTHOR]

Proximal junctional kyphosis and failure is a common complication of adult spinal deformity surgery, with osteoporosis as a risk factor. This retrospective study investigated the influence of long thoracolumbar fusion with pelvic fixation on regional bone density of adjacent vertebrae (Hounsfield units on computed tomography) and evaluated the association between bone loss and the incidence of proximal junctional kyphosis and failure. Patients who underwent long thoracolumbar fusion (pelvis to T10 or above) or single‐level posterior lumbar interbody fusion (control group) between 2016 and 2022 were recruited. Routine computed tomography preoperatively and within 1–2 weeks postoperatively was performed. Postoperative changes in Hounsfield unit values in the vertebrae at one and two levels above the uppermost instrumented vertebrae (UIV + 1 and UIV + 2) were evaluated. Overall, 127 patients were recruited: 45 long fusion (age, 73.9 ± 5.6 years) and 82 proximal junctional kyphosis and failure (age, 72.5 ± 9.3 years). Postoperative computed tomography was performed at a median [interquartile range] of 3.0 [1.0–7.0] and 4.0 [1.0–7.0] days, respectively. In both groups, Hounsfield unit values at UIV + 2 were significantly decreased postoperatively. In the long‐fusion group, Hounsfield unit values at UIV + 1 and UIV + 2 were significantly lower in patients with proximal junctional kyphosis and failure (within 18 months postoperatively) than in those without proximal junctional kyphosis and failure. Proximal junctional kyphosis and failure and long thoraco‐pelvic fusion negatively affect regional Hounsfield unit values at adjacent levels immediately after surgery. Patients with subsequent proximal junctional kyphosis and failure show greater postoperative bone loss at adjacent levels than those without. [ABSTRACT FROM AUTHOR]

Recombinant human growth hormone therapy, which was introduced in the 1980s, is now routine for children with advanced chronic kidney disease (CKD) who are exhibiting growth impairment. Growth hormone usage remains variable across different centers, with some showing low uptake. Much of the focus on growth hormone supplementation has been on increasing height because of social and psychological effects of short stature. There are, however, numerous other changes that occur in CKD that have not received as much attention but are biologically important for pediatric growth and development. This article reviews the current knowledge about the multisystem effects of growth hormone therapy in pediatric patients with CKD and highlights areas where additional clinical research is needed. We also included clinical data on children and adults who had received growth hormone for other indications apart from CKD. Ultimately, having robust clinical studies which examine these effects will allow children and their families to make more informed decisions about this therapy. [ABSTRACT FROM AUTHOR]

• Identification of a novel role for type IV collagen in bone biology. • Col4a1 mutant mouse models of Gould syndrome exhibit skeletal abnormalities. • Elevated TGFβ signaling contributes to skeletal pathogenesis in Col4a1 mutant mice. • Phenotypic and mechanistic overlap between Gould syndrome and other collagen-related ECM disorders. Skeletal defects are hallmark features of many extracellular matrix (ECM) and collagen-related disorders. However, a biological function in bone has never been defined for the highly evolutionarily conserved type IV collagen. Collagen type IV alpha 1 (COL4A1) and alpha 2 (COL4A2) form α1α1α2 (IV) heterotrimers that represent a fundamental basement membrane constituent present in every organ of the body, including the skeleton. COL4A1 and COL4A2 mutations cause Gould syndrome, a variable and clinically heterogenous multisystem disorder generally characterized by the presence of cerebrovascular disease with ocular, renal, and muscular manifestations. We have previously identified elevated TGFβ signaling as a pathological insult resulting from Col4a1 mutations and demonstrated that reducing TGFβ signaling ameliorate ocular and cerebrovascular phenotypes in Col4a1 mutant mouse models of Gould syndrome. In this study, we describe the first characterization of skeletal defects in Col4a1 mutant mice that include a developmental delay in osteogenesis and structural, biomechanical and vascular alterations of mature bones. Using distinct mouse models, we show that allelic heterogeneity influences the presentation of skeletal pathology resulting from Col4a1 mutations. Importantly, we found that TGFβ target gene expression is elevated in developing bones from Col4a1 mutant mice and show that genetically reducing TGFβ signaling partially ameliorates skeletal manifestations. Collectively, these findings identify a novel and unsuspected role for type IV collagen in bone biology, expand the spectrum of manifestations associated with Gould syndrome to include skeletal abnormalities, and implicate elevated TGFβ signaling in skeletal pathogenesis in Col4a1 mutant mice. [ABSTRACT FROM AUTHOR]

Objectives: To determine whether adherence to hip fracture clinical care quality indicators influences mortality among people who undergo surgery after hip fracture in New South Wales, both overall and by individual indicator. Study design: Retrospective population‐based study; analysis of linked Australian and New Zealand Hip Fracture Registry (ANZHFR), hospital admissions, residential aged care, and deaths data. Setting, participants: People aged 50 years or older with hip fractures who underwent surgery in 21 New South Wales hospitals participating in the ANZHFR, 1 January 2015 – 31 December 2018. Main outcome measures: Thirty‐day (primary outcome), 120‐day, and 365‐day mortality (secondary outcomes) by clinical care indicator adherence level (low: none to three of six indicators achieved; moderate: four indicators achieved; high: five or six indicators achieved) and by individual indicator. Results: Registry data were available for 9236 hip fractures in 9058 people aged 50 years or older during 2015–2018; the mean age of patients was 82.8 years (standard deviation, 9.3 years), 5510 patients were women (69.4%). Complete data regarding adherence to clinical care indicators were available for 7951 fractures (86.1%); adherence to these indicators was high for 5135 (64.6%), moderate for 2249 (28.3%), and low for 567 fractures (7.1%). After adjustment for age, sex, comorbidity, admission year, pre‐admission walking ability, and residential status, 30‐day mortality risk was lower for high (adjusted relative risk [aRR], 0.40; 95% confidence interval [CI], 0.30–0.52) and moderate indicator adherence hip fractures (aRR, 0.61; 95% CI, 0.46–0.82) than for low indicator adherence hip fractures, as was 365‐day mortality (high adherence: aRR, 0.59 [95% CI, 0.51–0.68]; moderate adherence: aRR, 0.74 [95% CI, 0.63–0.86]). Orthogeriatric care (365 days: aRR, 0.78; 95% CI, 0.61–0.98) and offering mobilisation by the day after surgery (365 days: aRR, 0.74; 95% CI, 0.67–0.83) were associated with lower mortality risk at each time point. Conclusions: Clinical care for two‐thirds of hip fractures attained a high level of adherence to the six quality care indicators, and short and longer term mortality was lower among people who received such care than among those who received low adherence care. [ABSTRACT FROM AUTHOR]

Stress fractures, including both fatigue and insufficiency types, are frequently encountered in clinical practice as a source of pain in a variety of patients (athletes, older patients, and patients with predisposing conditions). Radiography is the imaging modality of choice for baseline diagnosis. MRI has greatly improved our ability to diagnose radiographically occult stress fractures. Nuclear medicine scintigraphy and CT may also be useful as diagnostic tools. Although fatigue and insufficiency fractures can be self-limited and go on to healing even without diagnosis, there is usually value in initiating prompt therapeutic measures as incomplete stress fractures have the potential to progress to completion, necessitating surgery. This is particularly important in the setting of stress fractures of the femoral neck. Accuracy in the identification of these injuries is also relevant because the differential diagnosis includes entities that would otherwise be treated differently (ie, metastatic disease). The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where peer reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation. [ABSTRACT FROM AUTHOR]

Chronic nonbacterial osteomyelitis (CNO) is an autoinflammatory bone disease that primarily affects children and young people. It can cause significant pain, reduced function, bone swelling, and even (vertebral body) fractures. Because of a limited understanding of its pathophysiology, the treatment of CNO remains empiric and is based on relatively small case series, expert opinion, and personal experience. Several studies have linked pathological NOD-kike receptor (NLR) family pyrin domain containing 3 (NLRP3) inflammasome activation and the resulting imbalance between pro- and anti-inflammatory cytokine expression with CNO. This agrees with elevated pro-inflammatory (mostly) monocyte-derived protein signatures in the blood of CNO patients that may be used as future diagnostic and/or prognostic biomarkers. Recently, rare variants in the P2RX7 gene, encoding for an ATP-dependent transmembrane channel, were linked with increased NLRP3 inflammasome assembly and prolonged monocyte/macrophage survival in CNO. Although the exact molecular mechanisms remain unclear, this will inform future target-directed and individualized treatment. This manuscript reviews most recent developments and their impact on diagnostic and therapeutic strategies in CNO. [ABSTRACT FROM AUTHOR]

Metabolic syndromes (eg, obesity, type 2 diabetes (T2D), atherosclerosis, and neurodegenerative diseases) and aging, they all have a strong component of carbonyl and reductive-oxidative (redox) stress. Reactive carbonyl (RCS) and oxidant (ROS) stress species are commonly generated as products or byproducts of cellular metabolism or are derived from the environment. RCS and ROS can play a dual role in living organisms. Some RCS and ROS function as signaling molecules, which control cellular defenses against biological and environmental assaults. However, due to their high reactivity, RCS and ROS inadvertently interact with different cellular and extracellular components, which can lead to the formation of undesired posttranslational modifications of bone matrix proteins. These are advanced glycation (AGEs) and glycoxidation (AGOEs) end products generated in vivo by non-enzymatic amino-carbonyl reactions. In this review, metabolic processes involved in generation of AGEs and AGOEs within and on protein surfaces including extracellular bone matrix are discussed from the perspective of cellular metabolism and biochemistry of certain metabolic syndromes. The impact of AGEs and AGOEs on some characteristics of mineral is also discussed. Different therapeutic approaches with the potential to prevent the formation of RCS, ROS, and the resulting formation of AGEs and AGOEs driven by these chemicals are also briefly reviewed. These are antioxidants, scavenging agents of reactive species, and newly emerging technologies for the development of synthetic detoxifying systems. Further research in the area of in vivo glycation and glycoxidation should lead to the development of diverse new strategies for halting the progression of metabolic complications before irreversible damage to body tissues materializes. Graphical Abstract [ABSTRACT FROM AUTHOR]

Recently, cellular materials made by the repetition of unit cells, that is, iron lattices have become appealing to mimic the structure of bone. The aim of the study is to choose the most adequate lattice structures, which have the compressive mechanical properties closer to the ones of bone, in the perspective of their use as temporary implants. Five types of unit cells were selected, such as, cubic (C), truncated octahedron (TO), truncated cubic (TC), rhombicuboctahedron (RCO), and rhombitrucated cuboctahedron (RTCO). The mechanical properties were assessed by numerical simulations with a finite-element analysis. The size effect was studied with the comparison of results among samples with different numbers of unit cells. Simulations covered a wide range of relative densities. Graded dense-in and dense-out configurations were constructed with lattices of types RTCO and TO, being the unit cells, themselves graded. Lattice structures RTCO and TO were found to be stable at every relative density studied, while C, TC and RCO lattices are unstable at low densities. The evaluation of size effects was not conclusive, which could be biased by other factors. The Young's modulus of RTCO and TO lattices enable to reproduce the properties of both trabecular and cortical bone, with an appropriate choice of the relative density. To mimic trabecular bone, only RTCO and TO structures with low relative densities, can be used, while arrangements of C, TC and RCO cells can only replicate the properties of cortical bone. Graded cells may have the same properties as non-graded with lower density. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate fattening performance, carcass traits, meat quality, and leg bone traits in geese reared under an intensive production system, depending on genotypes. In the study, a total of 210 goslings (70 goslings for each genotype such as Linda, Toulouse, and Mast) were obtained from 168-week-old breeders. The geese were fed ad libitum with the same feeds during 12 weeks. Then, 5 males and 5 females from each goose genotype (30 birds in total) were slaughtered to determine the carcass, meat, and bone properties. The fattening performance, carcass properties, relative organ weights, and proximate analyses of breast and thigh meats did not differ among the genotype groups. The relative abdominal fat percentage weight was the highest in the Mast geese among the examined genotypes. Dry matter and crude protein values in meat were affected by genotype. The liver compositions, such as dry matter, crude fat, and crude protein, was significantly different from breast and thigh meat. It was found that the meat of Toulouse and Linda genotypes had lower SFA, n6/n3, and TI values, but higher MUFA, UFA, and crude protein values, making them superior to the meat of the Mast genotype. In the thigh meat, it was determined that lower SFA, AI, and TI values, and higher MUFA and UFA values, made it superior to the breast meat. In goose liver, DFA, NF and TI values were higher than the other tissues. Interactions were observed in the chemical composition and some fatty acids (P < 0.05). The femur and metatarsus bones of the Linda genotype were more durable than those of the Mast genotype due to their lower Robusticity indexes of femur and metatarsus bones. These results show that Linda and Toulouse geese are superior to the Mast genotype in terms of valuable fatty acids under intensive fattening. Additionally, the superior bone strength of Linda geese indicates that bone-related problems will be less common when this genotype is raised under intensive conditions. [ABSTRACT FROM AUTHOR]