Determinants of Peak Bone Mass: Clinical and Genetic Analyses in a Young Female Canadian Cohort

Abstract

Peak bone mass has been shown to be a significant predictor of risk for osteoporosis. Previous studies have demonstrated that skeletal mass accumulation 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 contribution of these factors, genetic and nongenetic, and their interaction in determining peak bone density status have not been delineated. Six hundred and seventy-seven healthy unrelated Caucasian women ages 18-35 years were assessed. A detailed, standardized interview was conducted to evaluate lifestyle factors, menstrual and reproductive history, medical conditions, medication 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) locus at three polymorphic sites (BsmI, ApaI, and TaqI) was performed. In bivariate analyses, BMD at the lumbar spine and hip was positively correlated with weight, height, body mass index (BMI), and level of physical activity, both now and during adolescence, but negatively correlated with a family history of osteoporosis. Hip, but not spine BMD, correlated positively with dietary intake of calcium, and negatively with amenorrhea of more than 3 months, with caffeine intake, and with age. Spine, but not hip BMD, correlated positively with age and with number of pregnancies. VDR haplotype demonstrated significant associations with BMD at the hip, level of physical activity 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 osteoporosis, and VDR genotype (hip only). Weight, age, level of physical activity, and family history are independent predictors of peak BMD. Of these factors, weight accounts for over half the explained variability in BMD. VDR alleles are significant independent predictors of peak femoral neck, but not lumbar spine BMD, even after adjusting for family history of osteoporosis, weight, age, and exercise. However, the overall contribution of this genetic determinant is modest. Taken together, these factors explained ∼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 genetic determinants of BMD. Most importantly, understanding the critical interactive nature between genes and the environment will facilitate development of targeted strategies directed at modifying lifestyle factors as well as earlier intervention in the most susceptible individuals. (J Bone Miner Res 1999;14:633-643)

Dynamic loads are determinants of peak bone mass

“…But even in studies including many of these factors, no more than approximately 20% of the variance in peak bone mass has been explained [18,29]. The present study demonstrated that as much as 40% of the variance in peak BMD at the proximal hip can be explained by including dynamic loading information.…”

“…Previous studies investigating the determinants of peak bone mass [29] have found that approximately 20% or less of the variance in femoral neck BMD has been explained by a combination of genetic and environmental factors. Rubin et al [29] investigated a large cohort of young Caucasian women and found that 21'%, of the variability in femoral neck BMD was explained by a combination of the static factors of height and weight (14'%1), current and past physical activity level (4'%1), age (I%), family history of osteoporosis (I%), and the vitamin D receptor genotype (1%).…”

“…Rubin et al [29] investigated a large cohort of young Caucasian women and found that 21'%, of the variability in femoral neck BMD was explained by a combination of the static factors of height and weight (14'%1), current and past physical activity level (4'%1), age (I%), family history of osteoporosis (I%), and the vitamin D receptor genotype (1%). Similar results were reported in a recent study investigating peak bone mass in young women and men [ 181, reporting that 15'%) of the variance in femoral neck BMD in women and II'%l of the femoral neck BMD in men was explained by a combination of genetic and environmental factors.…”

Effect of acute oral calcium load on serum PTH and bone resorption in young healthy subjects: an overnight study

“…Many randomised control trials show that increasing calcium intake reduces age-related bone loss (Devine et al, 1995). In addition, many observational studies show that calcium intake is positively correlated with bone mass (Aptel et al, 1999;Rubin et al, 1999). There is some evidence that dietary calcium intake is inadequate for optimum bone health in a substantial proportion of some population groups, including adolescent girls (Flynn, 2003).…”

Decreased bone mineral density is common after autologous blood or marrow transplantation

“…[10][11][12][13] Furthermore, multiple myeloma is associated with systemic osteoporosis as a result of increased osteoclastic activity. 14 ABMT patients also may have general risk factors for osteoporosis that include older age, 15 thin body habitus, 16,17 a family history of osteoporosis, 18 smoking, 19,20 and physical inactivity. 16 While survivors of ABMT have significant risks for decreased BMD, little is known about the incidence or predictive variables for osteopenia and osteoporosis in this population.…”