Journal of Bone and Mineral Metabolism最新文献

Introduction: High + Gz loads, the gravitational forces experienced by the body in hypergravity environments, can lead to bone loss in pilots and astronauts, posing significant health risks.

Materials and methods: To explore the effect of treadmill exercise on bone tissue recovery, a study was conducted on 72 male Wistar rats. These rats were subjected to four weeks of varying levels of periodic high + Gz loads (1G, 8G, 20G) experiments, and were subsequently divided into the treadmill group and the control group. The treadmill group underwent a continuous two-week treadmill experiment, while the control group rested during this period. The mechanical properties, microstructure, and molecular markers of their tibial bone tissue were measured using three-point bending, micro-CT, and PCR.

Results: The results showed that treadmill exercise improved the elastic modulus, ultimate deflection, and ultimate load of rat bone tissue. It also increased the number, density, and volume fraction of bone trabeculae, and decreased their separation. Moreover, treadmill exercise enhanced osteogenesis and inhibited osteoclastogenesis.

Conclusion: This study demonstrates that treadmill exercise can promote the recovery of bone tissue in rats subjected to high + Gz loads, providing a potential countermeasure for bone loss in pilots and astronauts.

Introduction: Low energy availability due to excessive exercise lowers bone mass and impairs various physiological functions, including immunity and hematopoiesis. We focused on Cxcl12 abundant reticular (CAR) cells, which are bone marrow mesenchymal stem cells and are essential for the maintenance of hematopoietic and immune cells in bone marrow. We examine the functional changes in CAR cells resulting from dietary restriction combined with exercise.

Materials and methods: Five-week-old wild-type female mice were divided into an ad libitum group (CON), a 60% dietary restriction group (DR), an ad libitum with exercise group (CON + ex), and a 60% dietary restriction with exercise group (DR + ex). Blood parameters, bone structure parameters, and bone marrow fat volume were evaluated after 5 weeks. In addition, bone marrow CAR cells were isolated by cell sorting and analyzed for gene expression by RT-qPCR.

Results: Bone mineral density (BMD) was significantly decreased in DR and DR + ex compared to CON and CON + ex. Especially, cortical bone mass and thickness were significantly decreased in DR and DR + ex groups, whereas trabecular bone mass was significantly increased. Bone marrow fat volume was significantly increased in DR and DR + ex groups compared to CON and CON + ex. The number of leukocytes in the blood was significantly decreased in the DR + ex group compared to the other three groups. RT-qPCR showed a significant decrease in gene expression of both Foxc1 and Runx2 in CAR cells of the DR + ex group compared to CON.

Conclusion: Dietary restriction combined with exercise promotes CAR cell differentiation into bone marrow adipocyte and suppresses osteoblast differentiation.

Introduction: Patients with multiple sclerosis (MS) commonly present musculoskeletal disorders characterized by lower bone mineral density (BMD) and muscle weakness. However, the underlying etiology remains unclear. Our objective is to identify shared pleiotropic genetic effects and estimate the causal relationship between MS and musculoskeletal disorders.

Materials and methods: We conducted linkage disequilibrium score regression (LDSR), colocalization, and Mendelian randomization (MR) analyses using summary statistics from recent large-scale genome-wide association studies (GWAS), encompassing MS, falls, fractures, and frailty. Additional MR analyses explored the causal relationship with musculoskeletal risk factors, such as BMD, lean mass, grip strength, and vitamin D.

Results: We observed a moderate genetic correlation between MS and falls (RG = 0.10, P-value = 0.01) but not between MS with fracture or frailty in the LDSR analyses. MR revealed MS had no causal association with fracture and frailty but a moderate association with falls (OR: 1.004, FDR q-value = 0.018). We further performed colocalization analyses using nine SNPs that exhibited significant associations with both MS and falls in MR. Two SNPs (rs7731626 on ANKRD55 and rs701006 on OS9 gene) showed higher posterior probability of colocalization (PP.H4 = 0.927), suggesting potential pleiotropic effects between MS and falls. The nine genes are associated with central nervous system development and inflammation signaling pathways.

Conclusion: We found potential pleiotropic genetic effects between MS and falls. However, our analysis did not reveal a causal relationship between MS and increased risks of falls, fractures, or frailty. This suggests that the musculoskeletal disorders frequently reported in MS patients in clinical studies are more likely attributed to secondary factors associated with disease progression and treatment, rather than being directly caused by MS itself.

Introduction: Glucocorticoids delay fracture healing and induce osteoporosis. Angiogenesis plays an important role in bone repair after bone injury. Plasminogen activator inhibitor-1 (PAI-1) is the principal inhibitor of plasminogen activators and an adipocytokine that regulates metabolism. However, the mechanisms by which glucocorticoids delay bone repair remain unclear.

Materials and methods: Therefore, we herein investigated the roles of PAI-1 and angiogenesis in glucocorticoid-induced delays in bone repair after femoral bone injury using PAI-1-deficient female mice intraperitoneally administered dexamethasone (Dex).

Results: PAI-1 deficiency significantly attenuated Dex-induced decreases in the number of CD31-positive vessels at damaged sites 4 days after femoral bone injury in mice. PAI-1 deficiency also significantly ameliorated Dex-induced decreases in the number of CD31- and endomucin-positive type H vessels and CD31-positive- and endomucin-negative vessels at damaged sites 4 days after femoral bone injury. Moreover, PAI-1 deficiency significantly mitigated Dex-induced decreases in the expression of vascular endothelial growth factor as well as hypoxia inducible factor-1α, transforming growth factor-β1, and bone morphogenetic protein-2 at damaged sites 4 days after femoral bone injury.

Conclusion: The present results demonstrate that Dex-reduced angiogenesis at damaged sites during the early bone-repair phase after femoral bone injury partly through PAI-1 in mice.

Purpose: Transmission electron microscopy (TEM) is widely used to study the ultrastructure of bone. The mineral of bone occurs as polycrystalline mineral plates about 3 to 6 nm in thickness. A problem in using TEM to make quantitative analyses of bone is that the orientation of the plates with respect to the plane of the section being imaged is expected to affect their apparent thickness. The purpose of this study was to test if this was true, if the apparent thickness of plates changed substantially as a result of tilt of the section.

Methods: We prepared TEM sections of samples of cortical human bone by ion beam milling, orienting one section parallel to the collagen fibril axes and one perpendicular to them. We obtained TEM bright field and HAADF images of these sections, tilting the sections up to ± 20° at 2° intervals and measuring the apparent thickness of individual mineral platelets at each angle of tilt.

Results: Thickness appears to double as section is tilted ± 20°. True thickness of plates is determined by tilting the section along an axis parallel to the plate orientation and determining the minimum apparent thickness. However, as plates are tilted away from minimum-thickness orientation, they become less well-resolved, disappearing when tilted more than 20°. We therefore also measured apparent thickness of only the darkest (most electron scattering) plate images in an untilted section and obtained the same average thickness as that obtained by tilting.

Conclusion: We conclude that tilting of the section is not necessary to obtain an accurate measurement of the thickness of mineral plates.

Introduction

Osteosarcopenia is an age-related syndrome characterized by the coexistence of osteoporosis and sarcopenia. Little is known about the clinical implications of osteosarcopenia among patients undergoing hemodialysis. This study investigated the prevalence of osteosarcopenia and its association with all-cause mortality and fractures in this population.

Materials and methods

This retrospective cohort study included outpatients undergoing hemodialysis in Japan. Sarcopenia was defined according to the recommendations of the Asian Working Group for Sarcopenia 2019. Osteoporosis was defined as a T-score of the calcaneus bone < – 2.5. We divided patients into three groups: robust (no osteoporosis or sarcopenia), osteoporosis or sarcopenia alone (osteoporosis without sarcopenia or sarcopenia without osteoporosis), and osteosarcopenia (osteoporosis and sarcopenia). Cox proportional-hazard and negative binomial regression models were used to estimate the associations between osteosarcopenia and all-cause mortality and fractures.

Results

Among the 328 patients (mean age, 65.5 ± 11.3 years; men, 59.1%), the prevalence of osteosarcopenia was 22.9%. During the follow-up period (1972 person-years), 131 deaths and 113 fractures occurred. Patients with osteoporosis or sarcopenia alone (hazard ratio 1.36; 95% confidence interval 0.85–2.18) and osteosarcopenia (hazard ratio 2.13; 95% confidence interval, 1.23–3.68) showed a higher risk of all-cause mortality than the robust group. Similar results were observed for the risk of fractures in patients with osteosarcopenia.

Conclusions

Patients undergoing hemodialysis showed a high prevalence of osteosarcopenia, and osteosarcopenia was associated with a poor prognosis in this patient population. Assessing osteosarcopenia may be useful for accurate prognostic stratification of patients undergoing hemodialysis.

Abstract

Introduction: The purpose of this study was to clarify the relationship between seasonal variation and distal radius fractures using diagnosis procedure combination data in Japan.

Materials and methods: The participants were hospitalized patients who underwent surgical treatment for distal radius fracture as the primary injury at hospitals that introduced the diagnosis procedure combination system between April 2011 and March 2016. We obtained a summary table of the month of admission, region of residence, age at admission, and sex of the patients from the Ministry of Health, Labour and Welfare and evaluated it by month, region, age group, and sex.

Results: The total number of patients for the 5 years from 2011 to 2016 was 105,025. There were 29,224 male and 75,801 female participants, with a female-to-male ratio of 2.6. The mean age was 60.2 (standard deviation, 20.8) years. Distal radius fractures occurred more frequently in the winter, especially among female individuals in eastern Japan. Female participants aged ≥ 50 years tended to have a higher incidence of distal radius fracture in winter. The incidence of distal radius fracture among male participants aged 0-19 years was higher from spring to autumn.

Conclusion: Surgically treated distal radius fractures occur frequently during the winter months among female individuals in eastern Japan or those aged ≥ 50 years and increase from school age to adolescence, especially in male individuals from spring to autumn. We should be aware of the high incidence of distal radius fractures in winter, especially in regions with snowfall and cold temperatures.

Introduction: Although synthetic glucocorticoids (GCs) are commonly used to treat autoimmune and other diseases, GC induced osteoporosis (GIOP) which accounts for 25% of the adverse reactions, causes fractures in 30-50% of patients, and markedly decreases their quality of life. In 2014, the Japanese Society for Bone and Mineral Research (JSBMR) published the revised guidelines for the management and treatment of steroid-induced osteoporosis, providing the treatment criteria based on scores of risk factors, including previous fractures, age, GC doses, and bone mineral density, for patients aged ≥18 years who are receiving GC therapy or scheduled to receive GC therapy for ≥3 months.

Materials and methods: The Committee on the revision of the guidelines for the management and treatment of GIOP of the JSBMR prepared 17 clinical questions (CQs) according to the GRADE approach and revised the guidelines for the management and treatment of GIOP through systematic reviews and consensus conferences using the Delphi method.

Results: Bisphosphonates (oral and injectable formulations), anti-RANKL antibody teriparatide, eldecalcitol, or selective estrogen receptor modulators are recommended for patients who has received or scheduled for GC therapy with risk factor scores of ≥3. It is recommended that osteoporosis medication is started concomitantly with the GC therapy for the prevention of fragility fractures in elderly patients.

Conclusion: The 2023 guidelines for the management and treatment of GIOP was developed through systematic reviews and consensus conferences using the Delphi method.

Introduction: Exercise intensity determines the benefits of aerobic exercise. Our objectives were, in aerobic exercise at different intensities, to determine (1) changes in bone metabolism-related genes after acute exercise and (2) changes in bone mass, strength, remodeling, and bone formation-related proteins after long-term exercise.

Materials and methods: Total 36 male C57BL/6J mice were divided into a control group and exercise groups at 3 different intensities: low, moderate, or high group. Each exercise group was assigned to acute- or long-term exercise groups. Tibias after acute exercise were evaluated by real-time PCR analysis. Furthermore, hindlimbs of long-term exercise were assessed by micro-CT, biomechanical, histological, and immunohistochemical analyses.

Results: Acute moderate-intensity exercise decreased RANKL level as bone resorption marker, whereas low- and high-intensity exercise did not alter it. Additionally, only long-term exercise at moderate intensity increased bone mass and strength. Moderate-intensity exercise promoted osteoblast activity and suppressed osteoclast activity. After low- and high-intensity exercise, osteoblast and osteoclast activity were unchanged. An increase in the number of β-catenin-positive cells and a decrease in sclerostin-positive cells were observed in the only moderate group.

Conclusion: These results showed that moderate-intensity exercise can inhibit bone resorption earlier, and long-term exercise can increase bone mass and strength through promoted bone formation via the Wnt/β-catenin activation. High-intensity exercise, traditionally considered better for bone, may fail to stimulate bone remodeling, leading to no change in bone mass and strength. Our findings suggest that moderate-intensity exercise, neither too low nor high, can maintain bone health.