The discrepancy between bone mineral density (BMD), the gold standard for bone assessment, and bone strength is a constraint in diagnosing bone function and determining treatment strategies for several bone diseases. Gastric hypochlorhydria induced by clinically used proton pump inhibitor (PPI) therapy indicates a discordance between changes in BMD and bone strength. Here, we used Cckbr-deficient mice with gastric hypochlorhydria to examine the effect of gastric hypochlorhydria on bone mass, BMD, and preferential orientation of the apatite crystallites, which is a strong indicator of bone strength. Cckbr-deficient mice were created, and their femurs were analyzed for BMD and preferential orientation of the apatite c-axis along the femoral long axis. Cckbr-deficient mouse femurs displayed a slight osteoporotic bone loss at 18weeks of age; however, BMD was comparable to that of wild-type mice. In contrast, apatite orientation in the femur mid-shaft significantly decreased from 9 to 18weeks. To the best of our knowledge, this is the first report demonstrating the deterioration of apatite orientation in the bones of Cckbr-deficient mice. Lesions in Cckbr-deficient mice occurred earlier in apatite orientation than in bone mass. Hence, bone apatite orientation may be a promising method for detecting hypochlorhydria-induced osteoporosis caused by PPI treatment and warrants urgent clinical applications.

Bisphosphonate (BF) therapy is strongly related to the occurrence of medication-related osteonecrosis of the jaw (ONJ). However, no previous study has evaluated if there are sex-related differences on the ONJ establishment together with bone biomechanical alterations, and if they could have a synergy with the ZA treatment. This study aimed to analyze the physicochemical properties of mineralized tissues in a zoledronate (ZA)-related osteonecrosis mouse model, by a 2 × 2-factorial design, considering sex (female/male) and treatment (ZA/Saline) factors (n = 8/group). After three ZA (1.0mg/kg) or saline administrations (days 0, 7, 14), the lower left second molar was extracted (day 42). Further ZA administration (day 49) and euthanasia (day 70) were conducted. After confirmation of ZA-induced jaw necrosis (histologic and microtomographic analysis), spectroscopic and mechanical parameters were assessed. ZA-treated groups presented lower bone density due to impaired healing of tooth extraction socket. Sex-related alterations were also observed, with lower bone density in females. Regarding biomechanical parameters, sex and treatment exerted independent influences. ZA, although decreasing flexural modulus and yield stress, increases stiffness mainly due to a higher bone volume. Females show less resistance to higher loads compared to males (considering dimension-independent parameters). Additionally, ZA increases crystallinity in bone and dental structure (p < 0.05). In summary, although strongly related to osteonecrosis occurrence, ZA modifies bone and dental mineral matrix, improving bone mechanical properties. Despite sex-dependent differences in bone biomechanics and density, osteonecrosis was established with no sex influence. No synergistic association between sex and treatment factors was observed in this study.

Many studies have demonstrated the relationship between diet and bone health, but research on the Dietary Approaches to Stop Hypertension (DASH) dietary pattern and bone health across populations is rare. The purpose of this study was to examine associations between the DASH dietary pattern and bone health outcomes in Chinese elders, to verify whether higher adherence to the DASH was associated with better bone health in elderly populations. A total of 839 Chinese adults aged 50years and above participated in this cross-sectional study. Bone mineral density (BMD) at calcaneus was measured via ultrasonic bone densitometer. A semiquantitative food frequency questionnaire (FFQ) was used to assess the usual dietary intake in the past 12months. The DASH score was calculated based on energy-adjusted intakes of nine dietary components, including whole grains, beans, vegetables, fruits, dairy, red meat, total fat, sodium, and sugar-sweetened beverages. In postmenopausal women, DASH score was significantly and positively correlated with BMD T-score after controlling potential covariates (β: 0.027 ± 0.012, P = 0.031) in multivariable linear regression models. In binary logistic regression analysis, male participants in the highest tertile of DASH score had lower risk of osteoporosis than those in the lowest tertile (odds ratio = 0.499; 95% confidence interval, 0.262-0.951; P = 0.035) after adjusting potential covariates. Adherence to the DASH dietary pattern was associated with better bone health in Chinese elderly adults.

The bone metabolism of male endurance runners during a competitive season has been little studied. Furthermore, Japanese runners have a special competitive season. This study aimed to investigate the change of bone turnover markers (BTMs) and other hormones in Japanese male endurance runners. We investigated biochemical markers, bone formation and resorption markers and sex hormones, body composition using dual-energy X-ray absorptiometry (DXA), and training volume during a competitive season. 11 (age: 24.0 ± 4.3years) Japanese male endurance runners were analyzed in this study. They participated in all measurements three times a year: the baseline (BL), the post-track period (PT), and the road race period (RR). Fat mass (FM) and percentage of body fat (% body fat) at RR (p = 0.009, p = 0.009) were lower than at BL. Specific bone alkaline phosphatase (BAP) decreased at PT (p = 0.004) and RR (p = 0.004) compared with BL. However, the bone resorption marker did not change. Free testosterone at PT (p = 0.032) was lower than BL. There was no correlation with blood variables and body composition or training volume. BAP and testosterone in Japanese male endurance runners decreased during the competitive season. However, there was no correlation between blood variables and training volume.

Vitamin K is a fat-soluble vitamin discovered as an essential factor for blood coagulation. It is suggested that vitamin K can benefit several aging-related diseases, including osteoporosis, osteoarthritis, and dementia. We previously reported the cross-sectional association of vitamin K insufficiency with frailty in community-dwelling older adults. In October 2020, a health examination of community-dwelling older adults (The Otassha Study) was performed, including frailty evaluation and blood tests. We used a ucOC and OC ratio (ucOC/OC) to indicate vitamin K insufficiency. One year later, we conducted a follow-up evaluation of frailty on 518 people who were not frail at baseline. The serum ucOC/OC at the baseline examination was divided into quartiles (Q1, Q2, Q3, and Q4). Odds ratio (OR) and 95% confidence interval (CI) were calculated using multivariate binary logistic regression for each quartile of ucOC/OC to determine the risk of incident frailty in the follow-up study, with the lowest quartile (Q1) as the reference. Among the 518 older adults who were not frail at baseline, 66 people (12.7%) became frail in the follow-up study. In the multivariate binary logistic regression analysis, setting the lowest quartile of ucOC/OC (Q1) as a reference, the OR of the incident frailty in the highest quartile (Q4) was 2.53 (95% CI 1.07, 4.92) which was significantly different from Q1. The findings of this longitudinal study suggest that vitamin K insufficiency has nutritional importance in predicting the future incidence of frailty in the Japanese older adult population.

A 2015 survey of the Japan Osteoporosis Society (JOS) on medication-related osteonecrosis of the jaw (MRONJ) revealed that cooperation between physicians and dentists was poor. Discontinuation of antiresorptive agents before tooth extraction was found to increase adverse events without preventing MRONJ. We compared this 2015 survey with a new survey conducted in 2022 to investigate cooperation between physicians and dentists for MRONJ. A web-based structured questionnaire including 13 key queries was sent to 3813 physicians who were members of JOS, and 1227 (32.2%) responses were received. Of the 1227 respondents, 909 (74.1%) had complied with a discontinuation request from a dentist before tooth extraction, although 25.4% of medications were not related to the incidence of MRONJ. Of these, 177 respondents reported 252 adverse events including 10 (1.3%) cases of MRONJ. The prevalence of fractures increased from 4.8% in 2015 to 8.2% in 2022. The rates of respondents who requested oral health care by a dentist before antiresorptive agent therapy and reported cooperation between physicians and dentists were 72.7% and 42.4% in 2022 compared with 32.9% and 24.8% in 2015, respectively. The rates of cooperation among the 47 prefectures in Japan were significantly different, ranging from 10.0 to 83.3% (p = 0.02). This study confirmed increased cooperation between physicians and dentists for MRONJ in Japan. However, a more equal distribution of cooperation across Japan is necessary to optimally manage MRONJ. Discontinuation of antiresorptive agents is no longer necessary because fractures during discontinuation continue to increase in Japan.

Observational studies demonstrated that the relationship between bone mineral density and oral diseases is mixed. To access the association between heel bone mineral density and various oral diseases, we conducted the Mendelian randomization analysis to explore the association. Two-sample bidirectional Mendelian analysis was used to explore the relationship between heel bone mineral density and various oral diseases. The inverse-variance weighted (IVW) was used as the primary effect estimate, and various methods were applied to test the reliability and stability of the results, namely MR-Egger, weighted median, simple mode, and weighted mode. This study showed that there was a negative relationship between heel BMD and periodontitis when heel BMD was used as an exposure factor and periodontitis as an outcome factor (IVW OR = 0.85; 95% CI, 0.75-0.95; p = 0.005). Bidirectional Mendelian randomization showed that there was no statistically significant association between periodontitis and heel bone mineral density when chronic periodontitis was the exposure factor (p > 0.05). And there was no significant relationship between heel bone mineral density and other oral diseases (dental caries, diseases of pulp and periapical tissues, impacted teeth, cleft lip, and cleft palate, oral and oropharyngeal cancer) (p > 0.05). This study showed that there was a negative relationship between heel bone density and periodontitis, and the decrease in heel bone density could promote the occurrence of periodontitis. In addition, there was no statistically significant relationship between heel bone density and other oral diseases.

This study aimed to determine the efficacy of abaloparatide in increasing bone mineral density (BMD) and its safety in postmenopausal Japanese women with osteoporosis. Randomized, double-blind, placebo-controlled, dose-finding study of abaloparatide in postmenopausal Japanese women at high fracture risk. The primary endpoint was the change in lumbar spine (LS) BMD from baseline at the last visit after daily subcutaneous injections of placebo or 40 or 80µg abaloparatide. Other endpoints included time-course changes in LS BMD at 12, 24, and 48weeks, in total hip (TH) and femoral neck (FN) BMDs, and in bone turnover markers. Increases in LS BMD with 40 and 80µg abaloparatide were significantly higher than that with placebo (6.6% and 11.5%, respectively), with significant between-group differences for the abaloparatide groups (4.9%). TH BMD increased by 0.4%, 1.6%, and 2.9% and FN BMD increased by 0.6%, 1.5%, and 2.4% in the placebo and 40and 80µg abaloparatide groups, respectively. Serum PINP rapidly increased by 67.3% and 140.7% and serum CTX slowly increased by 16.4% and 34.5% in the 40and 80µg abaloparatide groups, respectively. Although more adverse events were observed in the abaloparatide groups, they were mild to moderate and not dose dependent. In postmenopausal Japanese women with osteoporosis at high fracture risk, abaloparatide for 48weeks dose-dependently increased LS, TH, and FN BMDs, supporting further investigation with 80μg abaloparatide for the treatment of osteoporosis in this population. JapicCTI-132381.