Introduction: Osteoporosis and related fractures are major public health problems in the elderly. It is well known that low bone-mineral density (BMD) is the most important determinant of osteoporosis. Recently, some studies have suggested that genetic factors regulate the response of BMD to lifestyle factors such as physical activity. However, little is known about the effect of gene polymorphism on the association between muscle function and bone loss in the community-dwelling population.
Purpose: The purpose of the current study was to assess the interaction between single nucleotide polymorphisms (SNPs) of the vitamin D receptor gene (VDR), muscle strength, and longitudinal changes in BMD among postmenopausal Japanese women.
Methods: The data for the current study were derived from baseline, and data were collected for the subsequent three biennial follow-ups as part of the survey of the National Institute for Longevity Sciences-Longitudinal Study of Aging (NILS-LSA). The subjects consisted of 507 postmenopausal women (age 62.5 ± 8.2 years at baseline) who had completed the following examination and analysis. BMD was measured by a dual-energy X-ray absorptiometry (DXA; Hologic QDR-4500A). Measurement site was the right femoral neck (FN). The VDR SNPs (G/A) were genotyped using an automated fluorescent allele-specific DNA primer assay system (Toyobo Gene Analysis), and the polymorphisms were divided into two genotype groups (GG vs. GA/AA). Knee-extension strength was measured by an adjustable straight-back chair with the pelvis, knee, and ankle fixed at 90° (KES; Takei Co.). The interactive effect of VDR genotype and KES on BMD changes was investigated using a mixed-effect model analysis, which is a type of statistical analysis commonly used for repeated measurements, controlled for age, body-mass index (BMI), and age of last menses. Significant probability levels were less than .05. Statistical testing was performed using the Statistical Analysis System (SAS, release 9.1.).
Results: The mean BMD at the FN was 0.660 g/cm2 at baseline. The annual change in BMD was -0.007 g/cm2/year. Bone loss in the early postmenopausal years (<10 years since menopause) was observed to be greater than that in the later postmenopausal years. The result of analysis with the mixed-effect models indicated that there was a significant interaction between the VDR polymorphism and KES on BMD changes (p < .05). Bone loss at the low level of KES was greater than the higher levels of KES among carriers of the GA/AA polymorphism, whereas this difference was not observed for GG polymorphism. Estimated bone loss of carriers of GA/AA polymorphism at 20 kg, 24 kg, and 30 kg of KES (setting at age = 80 years, BMI = 22 and last menses age = 50 years) was about -0.266, -0.238 and -0.197 g/cm2, respectively. As for GG polymorphism, estimated bone loss at all levels of KES was about -0.193 g/cm2.
Conclusion: The results suggested that strong knee-extension strength may contribute to preservation of further bone loss for the carriers of GA/AA polymorphism in postmenopausal Japanese women.