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Introduction: Available evidence on favorable nutritional factors for preventing osteoporosis remains controversial. Considering the recent increases in life expectancy, we investigated the relationship between incident osteoporotic fractures and dietary habits in early and late postmenopausal phase women., Materials and Methods: Subjects were Japanese postmenopausal outpatients recruited at a primary care institution in Nagano Prefecture (Nagano Cohort Study). Patients with critical or acute illness or secondary osteoporosis were not included in this study. In total, 1,071 participants were prospectively followed for a mean of 5.8 years. The cohort was divided into early (≤ 70 years) and late (> 70 years) postmenopausal phases based on median age. Dietary nutrient intake was estimated by the food frequency questionnaire method. According to baseline nutrient intake characteristics, we focused on protein/energy and Ca/NaCl intake ratios, which were also divided by the median values., Results: Kaplan-Meier plots revealed a significantly higher occurrence of fractures for the high protein/energy intake group in early postmenopausal subjects (P = 0.009), whereas the low Ca/NaCl intake group in late postmenopausal subjects exhibited a significantly earlier occurrence of fractures (P = 0.002). Multivariate Cox regression uncovered significant independent risks of higher protein/energy (HR 1.35; 95% CI 1.04-1.74) and lower Ca/NaCl (HR 0.79; 95% CI 0.63-0.99) intake ratios for incident osteoporotic fractures in the early and late postmenopausal cohorts, respectively., Conclusion: Distinct dietary risk factors for osteoporotic fractures were identified in early and late postmenopausal phase women. Appropriate nutritional guidance according to patient age will be important for maintaining bone health and quality of life., (© 2023. The Japanese Society Bone and Mineral Research.)

Although nitric oxide (NO) is a known factor that regulates the bone physiology, few and discordant results have been obtained in human studies evaluating the effect of nitrates on bone health. We investigated for the relationship between serum NOx level and incident osteoporotic fracture rate prospectively in a cohort consisting of Japanese women. A total of 871 subjects (67.5 ± 10.8 y/o) were analyzed. During the observation period (8.8 ± 7.2 yrs), incident osteoporotic fractures occurred in 267 participants (209 vertebral fractures, 57 long-bone fractures, and 1 both types). Hazard ratio, by the Cox proportional hazards model, of serum NOx for incident fracture was 0.64 (95% confidence interval 0.53-0.78, p < 0.001) after adjustment for baseline age (1.13, 1.06-1.21, p < 0.001), lumbar bone mineral density (L-BMD; 0.85, 0.78-0.92, p < 0.001), presence of prevalent fracture (3.27, 2.49-4.32, p < 0.001), and treatment of osteoporosis (0.70, 0.53-0.92, p = 0.010). The relationships between serum level of NOx and bone-related parameters were examined by multiple regression analysis; body mass index (p < 0.001) and L-BMD (p = 0.011) were significantly associated with serum NOx level. These results suggest that the low circulating NOx is one of the independent predictors for osteoporotic fracture occurrence in postmenopausal women., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Shiraki et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The efficacy of romosozumab for severe osteoporosis is uncertain in patients with osteogenesis imperfecta (OI). This report introduced a severe osteoporotic case of OI to examine the effect of romosozumab on bone fragility. A 64-year-old man with OI was referred to our department for finding out the cause of his repeated fractures. He was medicated with alendronate for only 1 year, 8 years ago, but it did not prevent repeated fractures, and thus, he had not received any treatments for osteoporosis since then. However, recently, the frequency of fractures had increased. At presentation, his lumbar and bilateral total hip bone mineral density (BMD) values were severely decreased to 0.546 and 0.209 g/cm2, respectively. Because of his severe osteoporosis, we started romosozumab treatment with eldecalcitol. Romosozumab (210 mg) was injected subcutaneously every month. At 12 months after drug initiation, his lumbar and total hip BMD increased by 22.0% and 136.4% versus pre-treatment levels, respectively. Bone formation markers increased, and bone resorption markers decreased at 12 months of the therapy. Neither hypocalcaemia nor any other severe adverse effects were observed in this severe osteoporotic case. This study revealed good responses of BMD and bone turnover markers to romosozumab treatment, which can be considered as an effective treatment option for osteoporotic OI patients., (© Japan College of Rheumatology 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Peficitinib, a pan-JAK inhibitor, is known to suppress the activation of fibroblast-like synoviocytes (FLSs) and thereby reduces joint inflammation associated with rheumatoid arthritis (RA). However, the effect on osteoporosis in RA remains to be elucidated. In this study, the effect of peficitinib or etanercept on joint inflammation, and consequently decreased bone mineral density (BMD) was evaluated in mice with collagen-induced arthritis (CIA). Additionally, the effect on RANKL production from osteoblasts differentiated from the mesenchymal stem cells of RA patients was evaluated. Administration of peficitinib for established CIA ameliorated arthritis and improved BMD in the femoral metaphysis, but not in the femoral diaphysis. Conversely, etanercept suppressed an increase in synovial inflammatory markers but did not improve arthritic conditions or the reduction of BMD in either region. All elevated bone formation and bone resorption markers were decreased with peficitinib but only partially decreased with etanercept. Furthermore, production of RANKL by human osteoblasts was suppressed by peficitinib but enhanced by etanercept. Unlike etanercept, peficitinib is thought to increase BMD by ameliorating the high bone turnover associated with RA states, resulting in improvement of bone fragility. Our data provide evidence that peficitinib would be expected to show efficacy for osteoporosis associated with RA., (Copyright © 2021 The Authors. Production and hosting by Elsevier B.V. All rights reserved.)

Although there have been reported associations between zinc and bone mineral density (BMD), no reports exist on the effect of zinc treatment in osteoporotic patients. Therefore, we investigated the efficacy and safety of zinc pharmacotherapy in Japanese elderly patients. The present investigation included 122 osteoporotic patients with zinc deficiency, aged ≥65 years, who completed 12 months of follow-up. In addition to standard therapy for osteoporosis in a clinical setting, the subjects received oral administration of 25 mg zinc (NOBELZIN ® , an only approved drug for zinc deficiency in Japan) twice a day. BMD and laboratory data including bone turnover markers were collected at 0 (baseline), 6, and 12 months of zinc treatment. Neither serious adverse effects nor incident fractures were seen during the observation period. Serum zinc levels were successfully elevated by zinc administration. BMD increased significantly from baseline at 6 and 12 months of zinc treatment. Percentage changes of serum zinc showed significantly positive associations with those of BMD. Bone formation markers rose markedly from the baseline values, whereas bone resorption markers displayed moderate or no characteristic changes. Additive zinc supplementation may contribute to BMD augmentation ensuing the prevention of fracture occurrence in elderly osteoporotic patients with zinc deficiency.

The aim of this study was to provide definitive reference values for bone mineral density (BMD) and bone turnover markers in the general elderly population. Registered citizens of 50 to 89 years old were targeted for this survey. After random sampling from the resident registry of Obuse town, we established eight groups based on age (50 s, 60 s, 70 s, and 80 s) and gender. A total of 411 people were enrolled. We used a dual-energy x-ray absorptiometry device to measure and evaluate BMD. The bone formation marker bone alkaline phosphatase (BAP) was measured as a bone turnover marker. Bone quality marker pentosidine, and bone resorption markers including urinary total deoxypyridinoline (DPD), tartrate-resistant acid phosphatase 5b (TRACP-5b), 25-hydroxyvitamin D (25[OH]D), and whole parathyroid hormone (PTH) were also measured as bone turnover markers. Sixty-three people (15.3%) were diagnosed as osteoporosis. BMD decreased with age in the femoral neck and total hip. On the other hand, there was no characteristic change with age in the lumber spine. As for bone markers, pentosidine and DPD increased with aging, although 25(OH)D, whole PTH, and BAP showed no characteristic associations with gender and aging. In terms of the relationship between low BMD and bone markers, there was a significant independent association between low BMD and TRACP-5b in females. In conclusions, hip BMD decreased with aging in men and women. However, there was no characteristic decline with aging in the lumbar spine. All bone markers showed no significant independent characteristics associated with age or gender in a multivariate analysis model, except for a significant association between low BMD and TRACP-5b in females. TRACP-5b was a potentially useful marker for the detection of low BMD.

Objective: Osteoarthritis (OA) is a common and degenerative joint disorder in the elderly. A greater importance of understanding the relationship between genetic factors and OA prevalence has emerged with population aging. We therefore investigated the associations of several bone disease-related genetic variants with the prevalence of OA and osteoporosis in Japanese elderly women from the Obuse study cohort, which was randomly sampled from a basic town resident registry.Methods and Results: In total, 206 female participants (mean ± standard deviation age: 69.7 ± 11.0 years) who completed OA, bone mineral density, and genotype assessments were included. The number of patients diagnosed as having knee/hip OA and osteoporosis was 59 (28.6%) and 30 (14.6%), respectively. Fisher's exact testing revealed significant relationships between the minor T allele of LDL receptor related protein 5 (LRP5) rs3736228 and the prevalence of knee/hip OA and osteoporosis. The respective odds ratios (ORs) of the TT genotype for knee/hip OA and osteoporosis were 7.28 (95% confidence interval [CI] 2.22-28.08) and 5.24 (95% CI 0.95-26.98). An additional subgroup analysis for knee OA revealed that the frequency of the common C allele of methylenetetrahydrofolate reductase (MTHFR) rs1801133 had a statistically significant protective association with the prevalence of knee OA (OR 0.58, 95% CI 0.35-0.97).Conclusion: In sum, the present study demonstrated significant associations of LRP5 rs3736228 and MTHFR rs1801133 with knee/hip OA and osteoporosis prevalences and knee OA prevalence, respectively, in Japanese elderly women. These results will help further the understanding of OA pathogenesis and related genetic risk factors. [ABSTRACT FROM AUTHOR]

Pentosidine (PEN) and carboxymethyl-lysine (CML) are well-recognized advanced glycation end products (AGEs). However, how these AGEs affect the pathophysiology of osteoporosis and osteoporotic fractures remains controversial. This cross-sectional study aimed to investigate the associations of PEN and CML with bone markers, bone mineral density (BMD), and osteoporotic fractures in postmenopausal women from the Nagano Cohort Study. A total of 444 Japanese postmenopausal outpatients (mean ± standard deviation age: 69.8 ± 10.2 years) were enrolled after the exclusion of patients with acute or severe illness or secondary osteoporosis. The relationships among urinary PEN and serum CML levels, various bone markers, lumbar and hip BMD, and prevalent vertebral and long-bone fractures were evaluated. PEN associated significantly with prevalent vertebral fracture after adjustment for other confounders (odds ratio [OR] 1.59, 95% confidence interval [CI] 1.22–2.07; P < 0.001), but not with lumbar BMD. In contrast, a significant negative correlation was found between CML and lumbar BMD (r = − 0.180; P < 0.001), and this relationship was significant after adjustment for confounders (OR 0.84, 95% CI 0.76–0.93; P < 0.01). Although patients with prevalent vertebral fracture had significantly higher CML levels, the association between CML and prevalent vertebral fracture did not reach significance in the multivariate regression model. Both PEN and CML may play important roles in bone health for postmenopausal women, possibly via different mechanisms. [ABSTRACT FROM AUTHOR]

There are no published clinical reports comparing ibandronate (IBN) treatment and zoledronic acid (ZOL) treatment in Japanese postmenopausal osteoporotic patients. This investigation therefore compared the efficacy and safety of the drugs on improving bone metabolism and bone mineral density (BMD) in Japanese postmenopausal women with primary osteoporosis. Eighty-two treatment-naïve primary osteoporotic female patients were randomly divided into IBN-treated or ZOL-treated groups. Bone turnover markers and BMD were examined immediately prior to treatment (baseline) and at 6, 12, 18, 24, and 30 months of therapy. Compared with baseline levels, the values of type 1 procollagen N-terminal propeptide, bone-specific alkaline phosphatase (BAP), urinary type-I collagen amino-terminal telopeptide (NTX), and tartrate-resistant acid phosphatase 5b were all significantly decreased at every time point in both groups apart from BAP at 30 months in the ZOL group, urinary NTX at 12 months in the ZOL group and at 24 and 30 months in both groups. Lumbar BMD values were significantly increased at 6, 12, 18, and 24 months in the IBN group and at 6 and 12 months in the ZOL group compared with pre-treatment levels. Hip BMD values were also significantly increased at 6, 12, 18, and 24 months in the IBN group and at 6, 12, and 18 months in the ZOL group compared with baseline values. The percentage changes of hip BMD at 18 and 24 months in the ZOL group were significantly higher than those in the IBN group (both p < 0.05). No remarkable adverse events were noted in either group. In conclusion, both IBN and ZOL significantly and safely improved bone turnover markers and BMD during 30 months of treatment in Japanese osteoporosis patients. The ZOL group tended to exhibit greater gains in BMD as compared with the IBN group, which merits further investigation. [ABSTRACT FROM AUTHOR]

Although associations among obesity, adipocytokines, and bone mineral density have been reported, the influence of adipocytokines on osteoporotic fractures remains unclear. This study aimed to assess the impact of the adipocytokines leptin and adiponectin on the risk of incident vertebral and long-bone fractures in postmenopausal women. Clinical data were obtained from the retrospective Nagano Cohort Study of outpatients followed at a single primary care institute in Nagano Prefecture, Japan, between 1993 and 2018. The primary outcome was the occurrence of incident vertebral or long-bone fractures. In total, 1167 Japanese postmenopausal women (mean age: 65.9 years) completed the follow-up and the average observation period was 7.2 years. The subjects were divided into 4 groups (quartile 1 to 4) based respective leptin and adiponectin values. Kaplan–Meier analysis demonstrated a significantly lower incident long-bone fracture rate in the higher quartiles of serum leptin levels (p = 0.002). A significantly higher and more rapid occurrence of incident vertebral fractures, but not long-bone fractures, was found in the highest adiponectin quartile (p < 0.001). A Cox proportional hazards model adjusted for confounders including age, body weight, and either leptin or adiponectin revealed lower leptin levels and higher adiponectin levels as significant independent risk factors for incident long-bone fractures (hazard ratio [HR] 0.70, 95% confidence interval [CI] 0.50–0.96; p = 0.03) and vertebral fractures (HR 1.18, 95% CI 1.02–1.37; p = 0.02), respectively. Therefore, serum leptin and adiponectin may be independent risk factors for osteoporotic fractures affecting different bone types and sites. Determining patient adipocytokine levels may help predict the occurrence of specific osteoporotic fractures, thereby enabling optimal treatment for osteoporosis and improving quality of life. • The influence of adipocytokines on osteoporotic fractures remains controversial. • Serum leptin and adiponectin are independent osteoporotic fracture risk factors. • Serum adipocytokine levels may predict the occurrence of osteoporotic fractures. [ABSTRACT FROM AUTHOR]

Study Design: Retrospective observational study from the Nagano Cohort Study.Objective: Clarify the association between spinal osteoarthritis and loss of stature in postmenopausal women.Summary Of Background Data: Loss of stature with aging is known to deteriorate health-related quality of life and has been implicated with increased mortality. Although the association of vertebral fracture with height loss has been well documented, the relationship between stature loss and spinal osteoarthritis remains unclear.Methods: We retrospectively investigated Japanese postmenopausal women recruited from the Nagano Cohort Study. The participants were outpatients at a primary care institute in Nagano prefecture, Japan. A total of 977 postmenopausal patients (mean age: 65.8 yr) completed a minimum of 1 year of follow-up, with an average observation period of 7.6 years. Quartile analysis on the prevalence of spinal osteoarthritis and occurrence of incident fracture was performed based on the rate of stature change per year (Δ cm/yr). Multiple regression analysis was also conducted to identify the determinants of stature change.Results: The lower quartiles of stature change rate (i.e., more rapid stature loss) displayed a significantly higher prevalence of spinal osteoarthritis (P < 0.001) and incident vertebral fracture (P < 0.001). A statistically significant independent negative association for spinal osteoarthritis prevalence with change in stature was revealed by multiple regression analysis after adjusting for confounders including incident vertebral fracture. The partial regression coefficient for spinal osteoarthritis was -0.18 (95% confidence interval -0.33 to -0.03; P = 0.016).Conclusion: This study demonstrated an independent association of spinal osteoarthritis with stature loss in postmenopausal women. Adequate understanding of this relationship and appropriate treatment approaches will help improve health-related quality of life in elderly patients.Level Of Evidence: 3. [ABSTRACT FROM AUTHOR]