Journal of Bone and Mineral Metabolism最新文献

Introduction: Despite the increasing number of anti-osteoporotic medications for improving bone mineral density (BMD) and reducing fracture risk, some patients show unsatisfactory responses.

Materials and methods: We retrospectively analyzed 2134 patients who received anti-osteoporotic medications between March 2020 and October 2024. BMD percentage changes at the lumbar spine, femoral neck, and total hip were assessed after 1 year. Patients were categorized as "non-BMD gainers" (<3% increase at all sites) or "BMD gainers" (≥3% increase at any site). Multivariable logistic regression was used to evaluate associations with non-BMD gainer status, including age, body mass index, baseline T-score, and medication class.

Results: 578 patients (27.1%) were classified as non-BMD gainers. The observed rates of non-BMD gainer varied across medication classes in this real-world cohort, with selective estrogen receptor modulators (SERMs) showing the highest non-BMD gain rate (46.0%), followed by bisphosphonates (32.2%), teriparatide (35.1%), denosumab (19.5%), and romosozumab (5.6%). Non-BMD gainers had high baseline BMD and low bone turnover markers, and were more likely to have a history of osteoporosis treatment. In multivariable logistic regression analysis, older age (≥75 years), SERM use, and high baseline BMD T-scores were independently associated with increased risk of non-BMD gainer status. Conversely, low T-scores (≤-3.0) were associated with a significantly reduced likelihood of being a non-BMD gainer.

Conclusion: Approximately 25% of patients did not achieve BMD gain after 1 year of treatment. Older age, higher baseline BMD T-scores, and SERM use were associated with an increased probability of non-BMD gainer status in this observational study.

Introduction: Although bone anabolic agents such as teriparatide are effective for osteoporosis, satisfaction and adherence may vary by regimen. This multicenter study assessed long-term satisfaction, persistence, efficacy, and safety in postmenopausal women with primary osteoporosis treated with alternating daily and twice-weekly teriparatide over 52 weeks, followed by a final free-choice treatment period.

Materials and methods: In a randomized, open-label, crossover study, 358 postmenopausal women at high risk for fracture were assigned to receive once-daily (20 µg) or twice-weekly (28.2 µg) subcutaneous teriparatide for 26 weeks, then crossed over to the alternative regimen for another 26 weeks. Afterwards, 233 patients entered a 52-week free-choice period under their preferred regimen.

Results: Among the 233 patients entering the free-choice period, 162 chose twice-weekly and 71 chose daily teriparatide. Persistence at 104 weeks was 90.1% for twice-weekly and 88.7% for daily groups (p = 0.749). Overall and treatment satisfaction between groups did not differ significantly at 104 weeks (p > 0.05). Fracture incidence was low and similar (2.8% vs. 1.2%, p = 0.758). Patients in both groups showed significant increases in bone mineral density at L2-L4 and the femoral neck (p < 0.05). Adverse events were infrequent and non-severe.

Conclusions: Patient satisfaction and efficacy were maintained with both teriparatide regimens over 104 weeks, and persistence improved during the patient-choice phase. Supporting patient preference may improve adherence to osteoporosis medications.

Clinical trial registration: Japan Registry of Clinical Trials ID: jRCTs031210187.

Introduction: Osteoarthritis and osteoporosis are age-related musculoskeletal disorders characterized by increased oxidative stress and cellular senescence, which contribute to altered metabolism and disease progression. Although research in this field is constantly evolving, the discovery of new molecular targets and drug combinations to counteract musculoskeletal disorders remains a goal of great interest. This study aimed to evaluate the efficacy of a cocktail of trolox, recombinant irisin (r-irisin) and resveratrol in modulation of osteoblastic metabolism by investigating the expression of NADPH oxidase 4 (NOX4), sirtuin 1 (SIRT1) and pentraxin 3 (PTX3).

Materials and methods: 20 male patients undergoing hip arthroplasty were enrolled, including ten patients with coxarthrosis and ten patients with osteoporosis. Femoral head biopsies were taken from each patient to isolate primary osteoblast cultures, which were treated with the cocktail for 6 days.

Results: The cocktail of trolox, r-irisin and resveratrol increased cell viability, and reduced ROS and senescence β-galactosidase activity (SA-β-Gal) levels. In addition, western blotting analysis showed reduced expression of NOX4 and increased expression of SIRT1 and PTX3 in both experimental groups, although with more pronounced effects in osteoarthritic patients, highlighting lower treatment efficacy in the presence of osteoporosis.

Conclusions: The improvement in cell viability and reduction in oxidative stress and cellular senescence observed through treatment-induced modulation of the NOX4-SIRT1 axis and PTX3 suggests a protective role for these biomarkers in bone metabolism. These findings could offer new perspectives in counteracting the effects of aging on the skeletal system by improving bone health and mitigating metabolic alterations.

We appreciate the valuable suggestions and comments that Drs. Caroline Francis, Koyel Roy, and Gujar Anantkumar Jotiram provided regarding this study, "Probability of Achieving Treatment Goals with Twice-Weekly Teriparatide Followed by Bisphosphonate in Japanese Postmenopausal Osteoporosis".

This commentary evaluates the study by Takada et al. on sequential teriparatide bisphosphonate therapy in postmenopausal osteoporosis. While lumbar spine bone mineral density (BMD) targets are frequently met, the clinical validity of total hip BMD thresholds, especially in Asian populations, remains uncertain. We emphasize the need for fracture-based endpoints and caution against over-reliance on surrogate BMD targets in pre-treated patients.

Introduction: Timely surgical intervention for hip fractures is essential for improving outcomes in older adults. Japan's Ministry of Health, Labour and Welfare (MHLW) recently introduced a reimbursement policy to incentivize hip fracture surgery within 48 h. However, the impact and sustainability of this policy remain unclear.

Materials and methods: This retrospective cohort study included 498 patients aged ≥ 75 years with hip fractures at a single Japanese hospital from 2022 (pre-policy) to 2024 (post-policy year 2). We performed univariate and multivariate logistic regression analyses of the rate of early surgery (≤ 48 h) to identify predictors of surgical delay.

Results: The early surgery rate rose from 42.4% in 2022 to 52.7% in 2023 but declined to 45.1% in 2024. The reimbursement policy was associated with reduced surgical delay in its first year (2023; OR = 0.58, p = 0.024), but this effect was not sustained. Key structural and clinical predictors of delay included nursing home residence, refusal at other hospitals, weekend admission, and multi-specialty consultation. The frequency of off-hours surgery decreased in 2024, possibly due to the 'Workstyle Reform for Physicians' policy. Interaction analysis showed a suggestive inverse effect of off-hours surgery on delay.

Conclusion: Japan's reimbursement policy was initially effective, but its impact was transient and ultimately reversed by the competing national workstyle reform policy. Our findings underscore that to achieve sustained improvements in timely surgical care, future strategies must not only ensure coordinated policy design but also address persistent structural barriers, including weekend service gaps and fragmented regional coordination.