Determinants of peak bone mass: Clinical and genetic analyses in a young female Canadian cohort

Peak bone mass has been shown to be a significant predictor of risk for ost eoporosis. Previous studies have demonstrated that skeletal mass accumulati on is under strong genetic control, and efforts have been made to identify candidate loci. Determinants of peak bone mass also include diet, physical activity, hormonal status, and other clinical factors. The overall contribu tion of these factors, genetic and nongenetic, and their interaction in det ermining peak bone density status have not been delineated. Six hundred and seventy-seven healthy unrelated Caucasian women ages 18-35 years were asse ssed. A detailed, standardized interview was conducted to evaluate lifestyl e factors, menstrual and reproductive history, medical conditions, medicati on use, and family history of osteoporosis. Bone mineral density (BMD) was measured at the lumbar spine (L2-L4) and the femoral neck (hip) using dual- energy X-ray absorptiometry. Genotyping of the vitamin D receptor (VDR) loc us at three polymorphic sites (BsmI, ApaI, and TaqI) was performed. In biva riate analyses, BMD at the lumbar spine and hip was positively correlated w ith weight, height, body mass index (BMI), and level of physical activity, both now and during adolescence, but negatively correlated with a family hi story of osteoporosis. Hip, but not spine BMD, correlated positively with d ietary intake of calcium, and negatively with amenorrhea of more than 3 mon ths, with caffeine intake, and with age. Spine, but not hip BMD, correlated positively with age and with number of pregnancies. VDR haplotype demonstr ated significant associations with BMD at the hip, level of physical activi ty currently, and BMI. In multivariate analysis, independent predictors of greater BMD (at the hip or spine) were: age (younger for the hip, older for the spine), greater body, weight, greater height (hip only), higher level of physical activity now and during adolescence, no family history of osteo porosis, and VDR genotype (hip only). Weight, age, level of physical activi ty, and family history are independent predictors of peak BMD. Of these fac tors, weight accounts for over half the explained variability in BMD. VDR a lleles are significant independent predictors of peak femoral neck, but not lumbar spine BR;ID, even after adjusting for family history of osteoporosi s, weight, age, and exercise. However, the overall contribution of this gen etic determinant is modest. Taken together, these factors explained similar to 17% and 21% of the variability in peak spine and hip BMD, respectively, in our cohort. Future research should be aimed at further evaluation of ge netic determinants of BR ID. Most importantly, understanding the critical i nteractive nature between genes and the environment will facilitate develop ment of targeted strategies directed at modifying lifestyle factors as web as earlier intervention in the most susceptible individuals.