Journal of Bone and Mineral Metabolism最新文献

Introduction: Hyperglycemia increases the risk of bone fragility by promoting reactive oxygen species and advanced glycation end products, which disrupt osteoblast activity. Mechanical stress, including osmotic stress from elevated glucose levels, affects bone homeostasis; however, the specific impact of osmotic stress on osteoblast function is not fully understood. The transient receptor potential vanilloid 4 (TRPV4) channel, known to mediate calcium influx in response to mechanical stress, plays a key role in osteoblast differentiation. This study investigated the effects of osmotic stress on osteoblast differentiation and mineralization, as well as the role of TRPV4-mediated calcium influx.

Materials and methods: We investigated the effects of osmotic stress on osteoblast differentiation and mineralization using MC3T3-E1 cells. Mannitol and sorbitol treatments were adjusted to match the osmolality of glucose to assess osmotic stress effects. TRPV4 involvement was examined using the TRPV4 antagonist, HC-067047.

Results: Mineralization was inhibited not only by glucose, but also by treatment with mannitol and sorbitol, which were adjusted to match the osmolality of glucose. Both glucose and mannitol treatments inhibited the nuclear translocation of Runx2 while decreasing the mRNA expression of osteogenic markers such as osteocalcin, ALP, and collagen I. Notably, osmotic stress suppressed calcium influx through TRPV4 channels, which is linked to differentiation induction. Furthermore, HC-067047 inhibited mineralization and osteogenic marker expression.

Conclusion: These findings indicate that osmotic stress impairs osteoblast mineralization by inhibiting TRPV4-mediated calcium influx. TRPV4 may represent a therapeutic target for mitigating bone loss in diabetes, suggesting a novel approach for treating diabetic bone disease.

Introduction: The effects of teriparatide (TPTD) and alendronate (ALN) on health-related quality of life (HRQOL) were evaluated in osteoporotic patients with high fracture risk using data from the JOINT-05 trial.

Materials and methods: JOINT-05 was a randomized, controlled trial comparing the fracture prevention effects of sequential therapy with TPTD for 72 weeks followed by ALN for 48 weeks with those of ALN monotherapy for 120 weeks. This sub-analysis evaluated the effects of TPTD and ALN on HRQOL using data from baseline to 72 weeks. HRQOL was assessed at baseline, 4, 12, 24, 48, and 72 weeks using the EuroQoL-5Dimension (EQ-5D) questionnaire containing five domains (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). Scores were also transformed using utility weights derived from the general Japanese population.

Results: This sub-analysis included 476 patients in the TPTD group and 492 patients in the ALN group. No significant differences in utility scores were observed between groups at all times. Utility scores improved significantly after 12 weeks in the TPTD group and after 24 weeks in the ALN group. Mobility and self-care scores improved significantly in the TPTD group. Significant improvements in usual activity, pain/discomfort, and anxiety/depression scores occurred earlier in the TPTD group.

Conclusion: Although there were no significant differences in utility scores between the TPTD and ALN groups, significant improvements in the utility score and 5 domain scores were observed earlier in the TPTD group. When treating osteoporosis patients with a high risk of fracture, the selecting treatment drugs may be decided with primary consideration of its effect on fracture prevention, followed by its effect on improving HRQOL.

Introduction: The prevalence of osteoporosis (OP) is steadily rising, leading to a higher risk of mortality. This study assessed the impact of the Weight-Adjusted Waist Index (WWI) on osteoporosis-related mortality.

Materials and methods: Data from NHANES 2005-2010, 2013-2014, and 2017-2018 were analyzed to evaluate the relationship between WWI and mortality in osteoporotic patients using weighted proportional hazards model and Kaplan-Meier survival analysis. A subgroup analysis was performed to ensure the stability of the findings.

Results: The study included 1324 participants. The findings indicated a positive correlation between WWI and OP (OR 1.65, 95% CI 1.45-1.89). Among patients with OP, WWI showed a positive association with all-cause mortality (HR 1.28, 95% CI 1.10-1.48). There was no observed correlation between varying WWI levels and mortality due to cardiovascular disease or cancer.

Conclusions: Maintaining a lower WWI is associated with a reduced risk of all-cause mortality among individuals with OP.

Introduction: Patients with rheumatoid arthritis (RA) are at an increased risk of osteoporosis and vertebral fractures. We investigated the risk factors for vertebral fractures and severe vertebral fractures in patients with RA, including comorbidities and urinary pentosidine levels.

Materials and methods: This study included 637 patients with available clinical data on urinary pentosidine levels, vertebral fractures, and comorbidities. Vertebral fractures were evaluated using plain X-ray imaging. Comorbidities considered relevant to osteoporosis were type 2 diabetes mellitus, chronic kidney disease, and lung diseases.

Results: The prevalence of vertebral fractures in this cohort was 30.1%. Patients with vertebral fracture Patients with vertebral fractures were significantly more likely to be older [odds ratio (OR) 1.075; 95% confidence interval (CI) 1.049-1.1.03], had higher prevalence of comorbidities (OR 1.770; 95% CI 1.138-2.753), higher urinary pentosidine levels (OR 1.028; 95% CI 1.013-1.044), higher history of non-vertebral fractures (OR 2.084; 95% CI 1.222-3.557), and lower total hip T-score (OR 0.526; 95% CI 0.329-0.841) than patients without vertebral fractures. Among patients with vertebral fractures, 54.2% had severe vertebral fractures. Patients with severe vertebral fractures were more likely to have lower lumbar spine T-scores (OR 0.768; 95% CI 0.622-0.949) than patients with non-severe vertebral fractures.

Conclusions: This study identified factors associated with vertebral fractures and severe vertebral fractures in patients with RA. Notably, vertebral fractures were associated with comorbidities and urinary pentosidine levels. In patients with RA and vertebral fractures, low BMD in the lumbar spine was a significant factor associated with severe vertebral fractures.

Introduction: This study aimed to evaluate fracture incidence in patients with rheumatoid arthritis (RA) over 13 years in the Institute of Rheumatology Rheumatoid Arthritis (IORRA) cohort study.

Materials and methods: The IORRA is a prospective observational cohort study of Japanese patients with RA. Between 2011 and 2023, 10,257 patients with RA were enrolled. Clinical parameters and data on fractures were collected biannually using self-reported questionnaires. The fracture incidence, standardized by sex, age, and Japanese Health Assessment Questionnaire score, was calculated for each two-year period.

Results: From 2011 to 2023, the proportions of patients achieving Disease Activity Score in 28 joints remission, using biologic disease-modifying antirheumatic drugs, and taking osteoporosis medications increased (38.0% to 64.7%, 14.2% to 42.2%, and 31.6% to 38.3%, respectively), while the proportion of glucocorticoid use decreased (38.3% to 22.2%). The incidence of all and non-vertebral fractures increased from 47.2 and 36.7/1000 person-years in 2011 to 52.8 and 43.0/1000 person-years in 2023, respectively. Using 2023 as the reference, the standardized incidence ratios for all and non-vertebral fractures were: 2011-2012, 0.90 [95% confidence interval (CI) 0.82-0.98] and 0.86 (95% CI 0.78-0.95); 2013-2014, 0.88 (95% CI 0.81-0.96) and 0.84 (95% CI 0.76-0.93); 2015-2016, 0.94 (95% CI 0.86-1.02) and 0.89 (95% CI 0.80-0.98); 2017-2018, 0.97 (95% CI 0.88-1.07) and 0.94 (95% CI 0.84-1.05); 2019-2020, 0.95 (95% CI 0.84-1.07) and 0.93 (95% CI 0.81-1.06); 2021-2022, 1.00 (95% CI 0.89-1.13) and 0.99 (95% CI 0.86-1.13).

Conclusion: Despite advancements in RA management over 13 years, fracture incidence may have increased in patients with RA.

Aim: This study aimed to evaluate the effects of Limosilactobacillus reuteri (LR) and its combination with menaquinone-7 (MK-7; K) on ovariectomy-induced bone loss in mice and on bacterial growth in vitro.

Methods: In the in vivo study, animals were divided into five groups: sham-operated (SHAM); ovariectomy (OVX); OVX-LR; OVX-K; OVX-LR-K. After 4 weeks of treatment, femur cortical biomechanical properties, vertebral microarchitecture, osteocalcin levels, Occludin and Jam3 expression, and intestinal histomorphometry were evaluated. In vitro, microbial growth was assessed by incubating L. reuteri with MK-7. After incubation, optical densities were measured, and bacteria were cultured on MRS agar for the colony-forming unit (CFU/ml) counting.

Results: L. reuteri, MK-7, and their combination significantly improved femur intrinsic biomechanical properties and cortical vertebral thickness. The combined treatment exhibited a synergistic effect on the modulus of elasticity, and increased cortical vertebral volume and the villus/crypt ratio in comparison to OVX. L. reuteri and its combination with MK-7 restored vertebral trabecular microarchitecture values to SHAM levels. However, no significant differences were observed in serum levels of osteocalcin, Occludin or Jam3 expression among groups. In vitro, a significant increase in optical density and viable cell count was observed after 4 h of incubation.

Conclusion: L. reuteri and its combination with MK-7 improved bone biomechanical and microarchitecture properties. We propose a synergistic preventive action of L. reuteri and MK-7 in estrogen-deficient mice. Additionally, the enhanced survival of L. reuteri in the presence of MK-7 may partially explain the observed benefits of the combined treatment in vivo.

Introduction: The increase in the older population is a serious concern in developed countries, and how to maintain independence of these individuals is now an urgent issue. Various factors are known to put older people at risk for needing long-term care, but it is not clear to what extent each factor is associated with that need.

Materials and methods: In a cohort of 1577 community-dwelling older persons, we excluded 40 persons whose long-term care insurance certification was unknown and then divided the remaining 1537 into two groups: dependent group (134 persons) certified as requiring assistance or long-term care, and an independent group (1403 persons). We extracted 7 factors and created a scoring system from these factors based on regression coefficients.

Results: Among 92 factors initially evaluated, 7 were significantly associated with the need for assistance or long-term care, namely walking speed, age, grip strength, mobility (EQ5D), ability to use public transportation by oneself (IADL), ability to perform usual activities (EQ5D), and serum albumin levels. Based on these 7, we constructed a scoring system and calculated a cutoff value of 8 points with an area under curve as high as 0.949.

Conclusion: We determined the cutoff value for dependency risk to be 8, but no single factor scored 8 or higher, suggesting that a combination of these factors promotes the need for nursing care in older people.