Journal of Bone and Mineral Metabolism最新文献

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.

Introduction: The association between serum zinc (SZn) concentration and fracture risk in postmenopausal women was investigated.

Materials and methods: Women (n = 851) with a history of natural, premature, or surgical menopause who had completed data, including SZn concentrations at baseline (2009-2011), were included and followed through March 2018 for the incidence of any fracture requiring inpatient care. Potential non-linear and dose-response associations between SZn and fracture risk were assessed using a restricted cubic spline model (RCS) in Cox regression with the likelihood ratio test (LRT). Multivariable Cox proportional hazard models were used to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of fractures across the categories of SZn [< 86, 86-135 (as reference), and ≥ 135 μg/dL].

Results: During a median follow-up period of 8.8 years (interquartile range: 8.1-9.2 years), 4.3% of postmenopausal women (with a mean age of 61.4 ± 8.6 years) experienced a new incident fracture. The mean of baseline SZn concentration was 113 ± 39.3 μg/dL. The LRT indicated no significant non-linear association (P = 0.176) and no evidence of a dose-response relationship (P = 0.448) between SZn and fracture risk. Using the categorical approach, the multivariable-adjusted Cox model showed that postmenopausal women with SZn concentrations below 86 μg/dL had a significantly increased risk of fracture compared to those within the reference range (86-135 μg/dL), with an HR of 2.29 (95% CI = 1.02-5.16, P = 0.044). SZn concentrations exceeding the reference range (≥ 135 μg/dL) were not associated with risk of fractures (HR = 1.47, 95% CI = 0.61-3.58).

Conclusions: Suboptimal SZn levels, indicative of inadequate zinc status, may contribute to an increased risk of bone fractures in postmenopausal women.

Introduction: Administration of an anti-sclerostin antibody enhances Wnt/β-catenin signaling, resulting in a significant increase in bone mass by stimulating bone formation and suppressing bone resorption. Wnt/β-catenin signaling upregulates the expression of osteoprotegerin (Opg), a key regulator that inhibits osteoclast differentiation and suppresses bone resorption. However, sclerostin-knockout (Sost-KO) mice exhibit increased bone formation without a corresponding suppression of bone resorption. Therefore, the role of Opg in Sost deficiency remains unclear.

Materials and methods: To determine whether the osteogenic effects of Sost deficiency depend on the presence of Opg, we compared femoral bone mass among Sost/Opg double-knockout (DKO), Sost-KO, Opg-KO, and C57BL/6 (WT) mice.

Results: High-resolution imaging and histological analysis revealed that cortical bone mass was significantly higher in DKO mice compared with WT and Opg-KO mice. In contrast, trabecular bone mass was reduced in DKO mice compared with WT mice, and the number of TRAP-positive osteoclasts and serum CTX levels, a bone resorption marker, were significantly higher in DKO mice compared with Sost-KO mice. To further examine the role of bone resorption in DKO mice, an anti-RANKL antibody was administered to these mice. This treatment markedly increased both trabecular and cortical bone mass. Bone resorption was almost completely suppressed in antibody-treated DKO mice compared with vehicle-treated mice, while bone formation markers, including the mineral apposition rate, were maintained at approximately one-third the levels of vehicle-treated mice.

Conclusion: These findings indicate that the enhanced bone formation in DKO mice primarily increases cortical bone mass without inhibiting bone resorption. The osteogenic effects of Sost deficiency are independent of Opg.

Introduction: Bone loss is most common around the knee region in spinal cord injury (SCI) population. However, bone mineral density (BMD) measurement and T score in the knee region, which indicate osteoporosis, are not clear. This study aimed to examine BMD, T and Z scores at hip and knee including femoral neck (FN), total hip (TH), proximal tibia (PT), and distal femur (DF) in individuals with SCI, to investigate the relationship between BMD of the knee and hip, and to define DF and PT T scores thresholds that predict osteoporosis at the hip.

Materials and methods: This cross-sectional study used dual-energy x-ray absorptiometry to assess BMD in 94 SCI individuals. The medial and lateral parts of the PT and DF were defined as PT-1 and PT-2, DF-1 and DF-2, respectively. T and Z scores of PT and DF were calculated with a tool recommended by ISCD.

Results: All knee BMD values showed positive correlations with the hip BMD. Applying a PT-1 T-score threshold of - 1.55, the overall specificity was 83.9% and the sensitivity was 84.2% in detecting osteoporosis at FN or TH.

Conclusion: Low hip BMD values are associated with low knee BMD values in SCI individuals. A T score of -1.55 in PT-1 probably indicates osteoporosis of the hip. However, there is a prompt need for standardization of the T-cut off value in the knee region, where the risk of fracture risk is high. Body mass index, time since injury, wheelchair use, and injury severity were associated with bone loss in the PT-1.