Journal of Bone and Mineral Metabolism最新文献

Introduction: Articular cartilage is the major affected tissue during the development of osteoarthritis (OA) in temporomandibular joint (TMJ). The core circadian rhythm molecule Bmal1 regulates chondrocyte proliferation, differentiation and apoptosis; however, its roles in condylar cartilage function and in TMJ OA have not been fully elucidated.

Materials and methods: TMJ OA mouse model was induced by unilateral anterior crossbite (UAC) and Bmal1 protein expression in condylar cartilage were examined by western blot analysis. To determine the role of Bmal1 in TMJ OA, we generated cartilage-specific Bmal1 conditional knockout (cKO) mice (Bmal1^Agc1CreER mice) and hematoxylin and eosin staining, toluidine blue and Safranin O/fast green, immunohistochemistry, TUNEL assay, real-time PCR analysis and Western blot assay were followed.

Results: Bmal1 expression was reduced in condylar cartilage in a TMJ OA mouse model induced by UAC. The Bmal1 cKO mice displayed decreased cartilage matrix synthesis, reduced chondrocyte proliferation, increased chondrocyte hypertrophy and apoptosis as well as the upregulation of YAP expression in TMJ condylar cartilage.

Conclusions: We demonstrated that Bmal1 was essential for TMJ tissue homeostasis and loss-of-function of Bmal1 in chondrocytes leads to the development of TMJ OA.

Introduction: To investigate the clinical value of serum albumin to alkaline phosphatase ratio (AAPR) in predicting the risk of osteoporotic vertebral refractures group (OVRFs) after percutaneous vertebral augmentation (PVA) in postmenopausal women.

Materials and methods: This is a retrospective case-control study including a series of postmenopausal women patients with osteoporotic vertebral fracture (OVF) and underwent PVA. Patients were divided into OVRFs and non-OVRFs. COX model was used to evaluate the correlation between preoperative AAPR and OVRFs after PVA. The receiver operating characteristic (ROC) curve and Kaplan-Meier method were used to analyze the predictive value of AAPR for the incidence of OVRFs.

Results: A total of 305 patients were included in the final study, and the incidence of postoperative OVRFs was 28.9%. Multivariate COX analysis showed that advanced age (HRs = 1.062, p = 0.002), low BMI (HRs = 0.923, p = 0.036), low AAPR (HRs = 0.019, p = 0.001), previous fall history (HRs = 3.503, p = 0.001), denosumab treatment (HRs = 0.409, p = 0.007), low L3 BMD (HRs = 0.977, p = 0.001) and low L3 paravertebral muscle density (PMD)value (HRs = 0.929, p = 0.001)) were closely related to the incidence of OVRFs. The area under the curve (AUC) of AAPR for predicting OVRFs was 0.740 (p < 0.001), and the optimal diagnostic cut-off value was 0.49. Kaplan-Meier curve analysis showed that low AAPR group (< 0.49) was significantly associated with lower OVRFs-free survival (p = 0.001; log-rank test).

Conclusion: AAPR is an independent risk factor for OVRFs after PVA in postmenopausal women, and it can be used as an effective index to predict OVRFs.

Introduction: Chemotherapy involves the administration of steroids to prevent nausea and vomiting; however, its effect on bone microstructure remains unknown. This study aimed to evaluate the changes in bone mineral density (BMD) and bone microstructure associated with chemotherapy using high-resolution peripheral quantitative computed tomography (HR-pQCT) in women with early breast cancer.

Materials and methods: This prospective single-arm observational study included non-osteoporotic, postmenopausal women with breast cancer. The patients underwent dual-energy X-ray absorptiometry (DXA), HR-pQCT, and tartrate-resistant acid phosphatase-5b (TRACP-5b) or procollagen type-I N-terminal propeptide (P1NP) measurements at baseline, end of chemotherapy, and 6 months after chemotherapy. The primary endpoint was the change in total volumetric BMD at the distal tibia and radius.

Results: Eighteen women were included in the study (median age: 57 years; range: 55-62 years). At 6 months after chemotherapy, HR-pQCT indicated a significant decrease in total volumetric BMD (median: distal tibia -4.5%, p < 0.01; distal radius -2.3%, p < 0.01), cortical volumetric BMD (-1.9%, p < 0.01;  -0.8%, p = 0.07, respectively), and trabecular volumetric BMD (-1.1%, p = 0.09;  -3.0%, p < 0.01, respectively). The DXA BMD also showed a significant decrease in the lumbar spine (median: -4.5%, p < 0.01), total hip (-5.5%, p < 0.01), and femoral neck (-4.2%, p < 0.01). TRACP-5b and P1NP levels were significantly increased at the end of chemotherapy compared to baseline.

Conclusion: Postmenopausal women undergoing chemotherapy for early breast cancer experienced significant BMD deterioration in weight-bearing bone, which was further reduced 6 months after chemotherapy.

Introduction: Artificial intelligence (AI)-based systems using chest images are potentially reliable for diagnosing osteoporosis.

Methods: We performed a systematic review and meta-analysis to assess the diagnostic accuracy of chest X-ray and computed tomography (CT) scans using AI for osteoporosis in accordance with the diagnostic test accuracy guidelines. We included any type of study investigating the diagnostic accuracy of index test for osteoporosis. We searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, and IEEE Xplore Digital Library on November 8, 2023. The main outcome measures were the sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) for osteoporosis and osteopenia. We described forest plots for sensitivity, specificity, and AUC. The summary points were estimated from the bivariate random-effects models. We summarized the overall quality of evidence using the Grades of Recommendation, Assessment, Development, and Evaluation approach.

Results: Nine studies with 11,369 participants were included in this review. The pooled sensitivity, specificity, and AUC of chest X-rays for the diagnosis of osteoporosis were 0.83 (95% confidence interval [CI] 0.75, 0.89), 0.76 (95% CI 0.71, 0.80), and 0.86 (95% CI 0.83, 0.89), respectively (certainty of the evidence, low). The pooled sensitivity and specificity of chest CT for the diagnosis of osteoporosis and osteopenia were 0.83 (95% CI 0.69, 0.92) and 0.70 (95% CI 0.61, 0.77), respectively (certainty of the evidence, low and very low).

Conclusions: This review suggests that chest X-ray with AI has a high sensitivity for the diagnosis of osteoporosis, highlighting its potential for opportunistic screening. However, the risk of bias of patient selection in most studies were high. More research with adequate participants' selection criteria for screening tool will be needed in the future.

In the management of osteoporosis, anti-resorptive agents serve as a primary therapeutic approach. However, in cases where individuals exhibit an increased susceptibility to fractures, such as those characterized by severe low bone mass or a history of vertebral or hip fractures that markedly diminish life expectancy, the immediate reduction of fracture risk through the administration of osteoanabolic agents could be beneficial. Teriparatide, available in daily, once-weekly, or twice-weekly dosages, along with abaloparatide and romosozumab, constitutes a trio of such agents. Each of these medications is defined by unique characteristics, distinct efficacy profiles, and specific adverse effects. There is growing evidence to suggest that these agents have a superior effect on enhancing bone mineral density and reducing fracture incidence when compared to traditional bisphosphonate therapies. Nonetheless, their employment demands thorough consideration of clinical indications, which includes evaluating economic factors, the frequency of injections required, and the potential for adverse effects. The objective of this review is to consolidate the current evidence focusing primarily on the efficacy of these agents, with the goal of enhancing understanding and aiding in making more informed treatment decisions, particularly for those individuals who are at an elevated risk of fractures.

Chronic obstructive pulmonary disease (COPD) is a lifestyle-related disease that develops in middle-aged and older adults, often due to smoking habits, and has been noted to cause bone fragility. COPD is a risk factor for osteoporosis and fragility fracture, and a high prevalence of osteoporosis and incidence of vertebral fractures have been shown in patients with COPD. Findings of lung tissue analysis in patients with COPD are primarily emphysema with a loss of alveolar septal walls, and the severity of pulmonary emphysema is negatively correlated with thoracic spine bone mineral density (BMD). On the other hand, epidemiological studies on COPD and fracture risk have reported a BMD-independent increase in fracture risk; however, verification in animal models and human bone biopsy samples has been slow, and the essential pathogenesis has not been elucidated. The detailed pathological/molecular mechanisms of musculoskeletal complications in patients with COPD are unknown, and basic research is needed to elucidate the mechanisms. This paper discusses the impacts of COPD on bone strength, focusing on findings in animal models in terms of bone microstructure, bone metabolic dynamics, and material properties.

Various diseases and conditions cause joint disorders. Osteoarthritis (OA) is characterized by the degeneration of articular cartilage, synovitis, and anabolic changes in surrounding bone tissues. In contrast, rheumatoid arthritis (RA) and hemophilic arthropathy (HA) display marked destruction of bone tissues caused by synovitis. RA is a representative autoimmune disease. The primary tissue of RA pathogenesis is the synovial membrane and involves various immune cells that produce catabolic cytokines and enzymes. Hemophilia is a genetic disorder caused by a deficiency in blood clotting factors. Recurrent intra-articular bleeding leads to chronic synovitis through excessive iron deposition and results in the destruction of affected joints. Although the triggers for these two joint diseases are completely different, many cytokines and enzymes are common in the pathogenesis of both RA and HA. This review focuses on the similarities between joint and bone destruction in RA and HA. The insights may be useful in developing better treatments for hemophilia patients with arthropathy and osteoporosis by leveraging advanced therapeutics for RA.

Chronic obstructive pulmonary disease (COPD) is a disease characterized by chronic respiratory symptoms due to inflammatory and destructive changes of the lung leading to progressive airflow obstruction. Fragility fractures associated with osteoporosis are among major comorbidities and have significant impacts on quality of life and prognosis of patients with COPD. Evidence suggests that both decreased bone mineral density (BMD) and impaired bone quality contribute to bone fragility and resultant fractures in COPD. Although various clinical risk factors of osteoporosis have been described, mechanisms of COPD-associated osteoporosis are still largely unknown. In addition, its specific treatment has not been established, either. Previous studies have suggested involvement of low BMI and sarcopenia in the pathogenesis of COPD-associated osteoporosis. In this narrative review, we will propose critical roles of vitamin D deficiency and inflammation, both of which are often present in COPD and may underlie the development of osteosarcopenia and impaired bone quality, ultimately causing fractures in COPD patients.