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.

Introduction: Body size is known to influence bone mass and fracture risk throughout life; however, the critical period at which body size most strongly affects later fracture risk remains unclear. Herein, we investigated whether body size in adolescence or early adulthood is more strongly associated with future fracture risk, hypothesizing a stronger association for adolescence.

Materials and methods: Participants included health examination attendees in the Okazaki region of the Japan Multi-Institutional Collaborative Cohort Study aged 35-79 years. Overall, 2152 males (mean age 58.5 ± 10.9 years) and 1900 females (54.9 ± 10.2 years) were analyzed. In the primary survey (2007-2011), participants recalled body size in junior high school and their 20 s. In the secondary survey, conducted approximately 5 years later, participants self-reported fracture history in the past year. Associations between recalled body size and fracture risk were examined using logistic regression.

Results: Females with a thin body size in junior high school had a higher fracture risk than those with a normal body size (OR 2.29; 95% CI 1.10-4.76). However, a thin body size in the 20 s showed no association (OR 0.83; 95% CI 0.33-2.06). Additionally, no significant associations were observed for overweight females or males in either period.

Conclusion: In females, a thin body size in adolescence may be more strongly associated with future fractures than in early adulthood. Our findings provide a basis for future research confirming these associations with objective measures and longer follow-up.

Introduction: This study aimed to investigate perioperative treatment and postoperative outcomes in osteoporotic patients with vertebral fractures (VFs), categorized by the type of spine surgery.

Materials and methods: Patients aged ≥ 40, diagnosed with VFs and osteoporosis, with initial spine surgery between April 2015 and February 2021, were analyzed using a Japanese claims database. Time-to-event analysis was conducted for postoperative outcome. Outcome-related factors were explored with a multivariable Cox proportional hazards model.

Results: The study population (n = 4870) consisted of 2675 patients in the percutaneous vertebroplasty (PVP) group and 2195 in the spine fusion surgery (SFS) group. Most patients had lumbar VFs, and posterior spinal fusion was common in the SFS group. Approximately 20% of patients did not receive prescriptions for osteoporosis medications during the perioperative period. Most reoperations and subsequent fractures occurred within 90 days after PVP or SFS. In the PVP group, degenerative spine disease (adjusted hazard ratio 1.34 [95% CI, 1.03-1.76]), psychotropic drugs (1.34 [1.03-1.76]), and glucocorticoid prescriptions with a mean dose of ≥ 5 to < 7.5 mg/day (2.35 [1.04-5.34]) (vs. < 1 mg/day) were associated with reoperation. In post hoc subgroup analysis by year of spine surgery, anabolic agents were associated with a lower risk of reoperation (0.48 [0.30-0.75]) in 2019 and later. In the SFS group, hyperparathyroidism and Parkinson's disease were associated with reoperation (2.14 [1.03-4.44] and 2.10 [1.31-3.37], respectively).

Conclusion: Perioperative osteoporosis medication may be suboptimal. Factors associated with postoperative outcomes must be considered, with the strategic goal of improving patient outcomes.

Introduction: Postmenopausal osteoporosis is a critical task in the clinical management of older individuals. Numerous studies have proposed various pathophysiological mechanisms for postmenopausal osteoporosis. Tmem119 is a crucial factor for osteoblastic bone formation, and we previously clarified its contribution to the bone anabolic effects of various osteotropic factors. However, the roles of Tmem119 in postmenopausal osteoporosis and the effects of estrogen on bone remain unknown. Therefore, we herein investigated the roles of Tmem119 in bilateral ovariectomized mice with or without Tmem119 deficiency and/or the administration of estrogen.

Materials and methods: Wild-type and Tmem119-deficient mice underwent bilateral ovariectomy (OVX) and subcutaneous injections of 17β-estradiol for 6 weeks. We measured bone parameters in the femurs of mice using micro-computed tomography.

Results: OVX reduced the uterine weight and trabecular bone parameters, which were increased by estrogen administration. Tmem119 deficiency significantly blunted estrogen-induced increases in uterine weight, trabecular bone volume, and trabecular thickness in OVX mice. Tmem119 deficiency also significantly blunted estrogen-induced increases in alkaline phosphatase activity in mouse osteoblasts.

Conclusion: Our data indicated that Tmem119 is partly involved in the effects of estrogen on trabecular osteopenia induced by estrogen deficiency presumably by affecting osteoblasts in female mice.

Background: Dialysis patients are at increased risk of fractures, particularly in the proximal femur where cortical bone predominates. Effective treatments targeting cortical bone are therefore essential. Romosozumab is a monoclonal antibody that simultaneously promotes bone formation and inhibits bone resorption. It is administered monthly in a clinical setting and continued for one year, offering a treatment regimen acceptable to patients. In dialysis patients, romosozumab has been shown to significantly increase bone mineral density not only in the lumbar spine but also in the proximal femur and femoral neck. However, since dialysis patients are at higher risk of cardiovascular events, the risks and benefits of romosozumab require careful consideration.

Key messages: Romosozumab effectively improves both trabecular and cortical bone mass in dialysis patients. Cardiovascular safety concerns necessitate cautious patient selection. Romosozumab offers medical and economic advantages over teriparatide.