Journal of Bone and Mineral Metabolism最新文献

Background: A significant proportion of bone loss per year occurs starting around 1-3 years before menopause. A number of fractures occur in the osteopenic range of bone mineral density (BMD). There are no recommendations for the treatment of osteopenic peri-menopausal women. We conducted this study to explore the utility of zoledronic acid in preserving bone health in this population.

Materials and methods: This is a prospective single-blinded randomized controlled trial. A total of 60 peri-menopausal women and 30 postmenopausal women with osteopenia were enrolled. The peri-menopausal women were randomized to receive either zoledronic acid or placebo in a 1:1 ratio. All postmenopausal osteopenic women received zoledronic acid. Participants were followed up for 12 months. BMD and bone turnover markers (BTM) were assessed.

Results: At the end of 12 months, there was a significant increase in lumbar spine BMD in the peri-menopausal and postmenopausal groups which received zoledronic acid. On further subcategorizing the T-score, the improvement in BMD was statistically significant in the group with a T-score of - 1.75 to - 2.5. In peri-menopausal women with osteopenia with a T-score of - 1.75 to - 2.5, a single infusion of zoledronic acid increased lumbar spine and femoral neck BMD and suppressed the high bone turnover. Zoledronic acid thus could be used for preserving bone density and preventing the risk of osteoporosis and fragility fractures in the future.

Introduction: Osteoclasts and foreign body giant cells (FBGCs) are multi-nuclear cells established by fusion of their mono-nuclear forms. Multi-nucleation via cell-cell fusion is a common characteristic of osteoclasts and FBGCs, and Dendritic Cell-Specific Transmembrane Protein (DC-STAMP) and Osteoclast Stimulatory Transmembrane Protein (OC-STAMP) are both required for the process. Thus, it is thought that DC-STAMP and OC-STAMP interaction likely induces this fusion, but details of these mechanisms are not clear.

Materials and methods: We crossed DC-STAMP knockout (KO) with OC-STAMP KO mice to obtain DC-STAMP/OC-STAMP doubly deficient (DKO) mice. Osteoclasts and FBGC common progenitors were isolated from wild-type (WT), DC-STAMP KO, OC-STAMP KO or DKO mice. We then set up 4 co-culture systems: (1) WT with DC-STAMP KO cells, (2) WT with OC-STAMP KO cells, (3) WT with DKO cells, and (4) DC-STAMP KO with OC-STAMP KO cells to induce osteoclast or FBGC formation. We evaluated osteoclast and FBGC formation by TRAP and May-Gruenwald Giemsa staining, respectively. Finally, we performed bone morphometric analysis of WT, DC-STAMP KO, OC-STAMP KO, and DKO mice.

Results: Cell-cell fusion occurs normally in co-cultures of DC KO with WT cells, OC KO with WT cells, and DKO with WT cells in both osteoclast and FBGC-inducing conditions. By contrast, co-cultures of DC-STAMP KO with OC-STAMP KO cells did not show cell-cell fusion. Bone morphometric analysis revealed enhanced bone formation in DKO mice.

Conclusion: DC-STAMP and OC-STAMP cooperate to promote osteoclast and FBGC cell-cell fusion. DC-STAMP and OC-STAMP doubly deficient mice exhibit increased osteogenesis.

Background: Benign fibro-osseous lesions (BFOLs) are a heterogeneous group of bone-forming pathologies characterized by replacement of normal bone with fibrocellular stroma and mineralized tissue. Their overlapping clinical, radiological, and histopathological features often complicate diagnosis.

Objective: This review summarizes the clinicopathologic characteristics and recent molecular insights of BFOLs to enhance diagnostic accuracy and classification.

Approach: A narrative review of English-language literature available in electronic databases upto 2025 was performed, focusing on key clinical, radiologic, histologic, and molecular findings of BFOLs.

Findings: BFOLs encompass bone dysplasias including fibrous dysplasia and segmental odontomaxillary dysplasia, ossifying fibroma, and cemento-osseous dysplasia, each showing distinct biological behavior. Molecular studies have revealed GNAS mutations in fibrous dysplasia and HRPT2 alterations in ossifying fibroma, providing clues to their pathogenesis.

Conclusion: Integrating molecular data with clinicopathologic assessment refines diagnosis, prevents misclassification, and supports more precise management of BFOLs.

Introduction: Osteoporosis can cause chronic pain, but the mechanisms are unclear. This study investigates pain behaviours in mouse models of osteoporosis and fracture together with nociceptive markers expression in bone and dorsal root ganglia (DRGs). It also quantifies nerve markers in serum of patients with or without osteoporotic fractures and pain.

Material and methods: Ovariectomy (OVX) or Sham surgery (Sham-OVX) of C57/Bl6 mice was performed (n = 10/group) and evoked and spontaneous pain behaviours assessed. In another experiment, OVX or Sham-OVX mice underwent a femoral osteotomy or sham osteotomy (n = 8/group) and pain behaviours measured. Gene expression of pain markers in bone and DRGs was quantified by RT-PCR. Nerve markers were quantified in serum of osteoporotic patients with or without fractures and pain using specific ELISAs.

Results: OVX did not cause changes in pain behaviours nor alter nociceptive gene expression in bone and DRGs. Osteotomy and Sham osteotomy both affected pain behaviours in mice compared to non-operated controls but did not significantly change nociceptive gene expression in bone and DRGs. OVX before osteotomy worsens weight-bearing compared to Sham-OVX. Fracture and pain did not affect nerve markers expression levels in serum of osteoporotic patients.

Conclusion: This study demonstrates that OVX and subsequent bone loss in mice are insufficient to induce pain behaviours but may intensify pain after fracture. Our clinical analysis does not show a correlation between circulating nerve markers and fracture pain reported by the patients but suggests possible sex differences in pain markers that need to be further investigated.

Introduction: Osteosarcopenia-the coexistence of osteoporosis and sarcopenia-reflects a dual loss of bone and muscle integrity that contributes to frailty, falls, and functional decline in aging populations. While both osteoporosis and sarcopenia have been individually linked to postoperative recovery, their combined effect after major orthopedic procedures remains unclear. This study investigated whether osteosarcopenia independently predicts health-related quality of life after total hip arthroplasty (THA), as a model for older adults with musculoskeletal deficits.

Materials and methods: A retrospective cohort of 214 patients aged ≥ 65 years who underwent unilateral THA was analyzed. Preoperative evaluations included dual-energy X-ray absorptiometry (osteoporosis: lumbar T-score <  - 2.5) and sarcopenia was defined in accordance with the 2019 Asian Working Group for Sarcopenia consensus. Patients were grouped as osteosarcopenia, sarcopenia-only, osteoporosis-only, or normal. Multivariate logistic regression was conducted to identify predictors of achieving the minimum clinically important difference (MCID) in the Hip Disability and Osteoarthritis Outcome Score-Joint Replacement (HOOS-JR) at 24 months postoperatively. Propensity score matching was used to compare patients with osteosarcopenia with matched controls.

Results: Both osteoporosis (OR 0.71, 95%CI 0.60-0.83) and sarcopenia (OR 0.79, 95%CI 0.64-0.97) were independent predictors of failure to achieve MCID (> 18, 154/214). Post-matching, patients with osteosarcopenia (n = 25) had significantly lower HOOS-JR (P < 0.001), EuroQol 5-Dimension (P = 0.029), and satisfaction scores (P < 0.001) than controls (n = 50).

Conclusion: Osteosarcopenia was associated with clinically inferior functional disability after THA. Preoperative identification of bone-muscle deficits could guide interventions-such as osteoporosis treatment and tailored rehabilitation-to enhance outcomes in older adults.

Introduction: To diagnose osteoporosis, assess the risk of fragility fracture, and determine the necessity for treatment, bone mineral density (BMD) is mostly measured from dual energy X-ray absorptiometry (DXA) as a gold standard. Due to the limited resources of DXA, we proposed the deep learning models to screen for osteoporosis and measure its accuracy on osteoporosis detection from lumbar spine radiographs.

Materials and methods: The models were developed from the training data set (2244 anteroposterior and 2368 lateral lumbar spine radiographs). We categorized patients into two groups based on DXA BMD T-score: non-osteoporosis (T >  - 2.5) and osteoporosis (T ≤  - 2.5). A two-class models were trained to classify non-osteoporosis and osteoporosis. Model performance was tested with the test data set (963 AP and 1018 lateral images) to evaluate the accuracy.

Results: The results showed that, for AP images, the ResNet-18 model diagnosing osteoporosis achieved an area under the curve (AUC) of 0.79 (95% confidence interval [CI] 0.76-0.82) with a concomitant sensitivity of 79.7% (95% CI 74.4-85.0%) and specificity of 66.5% (95% CI 63.1-69.9%). For lateral images, the DarkNet-19 model yielded the highest AUC at 0.82 (95% CI 0.80-0.85) with the highest sensitivity for lateral data set at 87.5% (95% CI 83.1-91.9%) and specificity of 79.4% (95% CI 76.6-82.2%).

Conclusions: Deep learning models may have the efficacy to anticipate osteoporosis screening based on lumbar spine radiographs which would be helpful as a readily available tool for assessing the risk and determining treatment.

Introduction: Tendinopathy, a disease that causes inflammation and pain and limits patients' activities of daily living, is considered particularly important to treat during the acute inflammatory phase to prevent the transition to chronic degeneration. Recently, platelet-rich plasma (PRP) has been used to treat tendinopathy; however, it is not clear whether platelets themselves, which are the active component of PRP, could be effective in treating tendinopathy.

Materials and methods: We made rat Achilles tendinopathy models by incision of the calcaneal attachment and administrated platelet-like cells derived from adipose-derived mesenchymal stem cells (ASCL-PLCs) to the injury site and investigated the anti-inflammatory effect.

Results: ASCL-PLCs significantly inhibits the inflammatory cytokine expression and inflammatory cell infiltration in acute tendonitis in a rat Achilles tendon injury model in vivo. Interestingly, we observed no xeno-reaction when human-derived ASCL-PLCs were administered to wild-type rats in vivo. Moreover, IL-6 expression and phosphorylation seen in NIH3T3 fibroblasts treated with IL-6 plus soluble IL-6 receptor were both significantly suppressed by ASCL-PLCs in vitro.

Conclusion: ASCL-PLC has advantages over existing PRP therapies, including the ability to be cryopreserved after quality checks, and homogeneous populations of ASCL-PLCs can be prepared in large quantity. We conclude that in the future ASCL-PLCs may serve as an allogeneic transplant effective to treat tendinopathy.