Objectives: In a mouse model, aldehyde dehydrogenase 2 (ALDH2) knockout resulted in lower bone mineral density; however, higher parathyroid hormone receptor expression than wild-type mice. This study aimed to investigate whether ALDH2 polymorphisms influence efficacy of intermittent parathyroid hormone therapy and bone mineral density changes in humans. Methods: Eighty-two patients with primary osteoporosis treated with parathyroid hormone for > 1 year were divided into wild-type ALDH2 (ALDH2*1) and variant (ALDH2*2) groups. Bone mineral densities were measured by dual-energy X-ray absorptiometry. Changes in bone mineral density, treatment response, bone turnover markers, and new fracture incidence were evaluated. Furthermore, bone mineral density was analyzed using a mixed-effects model. Results: Femoral neck bone mineral density increased by 1.0 ± 7.4% in the ALDH2*1 group and 4.3 ± 8.1% in the ALDH2*2 group (P < 0.05), whereas lumbar spine bone mineral density increased by 5.7 ± 8.2% and 9.4 ± 9.1% without significance. Treatment success rates were higher in ALDH2*2 group (femoral neck 38.7%, lumbar spine 68.8%) compared with ALDH2*1 (16.3%, 51.0%). Statistical significance was observed only at the femoral neck. Bone turnover markers and fracture incidence were comparable between groups. Mixed-effects analysis adjusting for confounders showed a significant ALDH2 genotype × duration interaction for femoral neck, indicating genotype-related differences in the rate of bone mineral density increase over time. For lumbar spine, the genotype main effect was significant, whereas the interaction was not. Conclusions These findings suggest that ALDH2 polymorphisms may influence the therapeutic response to PTH treatment and highlight the need for larger future studies.

Objectives: Physical activity to maintain bone mass and strength is important for hip fracture prevention. We aim to investigate the relationship between physical performance/activity status and bone mineral density (BMD)/hip structural analysis (HSA) parameters among postmenopausal women in Japan. Methods: Sixty-two postmenopausal women diagnosed with osteoporosis (mean age: 72.61 ± 7.43 years) were enrolled in this cross-sectional observational study. They were evaluated for BMD and HSA in the proximal femur by dual-energy X-ray absorptiometry and underwent several physical performance tests, the Geriatric Locomotive Function Scale of 25 questions (GLFS-25). Principal component analysis (PCA) was used to summarize data on the BMD/HSA parameters. Partial correlation analysis, multiple regression analysis, and structural equation modeling (SEM) were performed to investigate the relationship between physical performance/activity status and BMD/HSA parameters of the proximal femur. Results: In a partial correlation analysis adjusted for age and body mass index (BMI), GLFS-25 scores were correlated with HSA parameter (|r| = 0.260–0.396, P < 0.05). Principal component 1 (PC1) calculated by PCA was interpreted as more reflective of bone strength based on the value of BMD/HSA parameters. The SEM results showed that the model created by the 3 questions (Q13, brisk walking; Q15, keep walking without rest; Q20, load-bearing tasks and housework) of the GLFS-25 had the best fit and was associated with the PC1 score (β = −0.444, P = 0.001). Conclusions The GLFS-25 score was associated with the BMD/HSA parameter, which may reflect the bone strength of the proximal femur as calculated by PCA.