Polymorphisms in the gene coding for low-density lipoprotein receptor-related protein 5 (LRP5) contribute to variation in bone mass in the general population. Whether this is due to influence on bone mass acquisition or on bone loss thereafter has not been established.
We studied the association of LRP5 polymorphisms with peak bone mass in young men. The study included 235 Finnish men, aged 18.3 to 20.6 years. Lifestyle factors and fracture history were recorded. Bone mineral content (BMC), density (BMD) and scan area were measured for the lumbar spine and proximal femur by dual energy X-ray absorptiometry (DXA). Blood and urine were collected for determination of bone turnover markers, serum 25-OHD and PTH. Genomic DNA was extracted from peripheral blood for genetic analysis of LRP5. Ten single nucleotide polymorphisms in LRP5 were analyzed and correlated with bone parameters.
Only the A1330V polymorphism of LRP5 significantly associated with bone parameters. In comparison with subjects with the AlaAla genotype (n=215), those with AlaVal genotype (n=20) had lower femoral neck BMC (P=0.029) and BMD (P=0.012), trochanter BMC (P=0.0067) and BMD (P=0.015), and total hip BMC (P=0.0044) and BMD (P=0.0089). Fracture history was similar for the genotypes.
The polymorphic valine variant at position 1330 of LRP5 was significantly associated with reduced BMC and BMD values in healthy young Finnish men. The results provide evidence for the crucial role of LRP5 in peak bone mass acquisition.
The data on of alimentary risk factors of osteoporosis have been observed. The frequency of decreased bone mineral density, vitamin and calcium diet content and sufficiency with vitamins evaluated by means of blood serum level determination among patients suffering from chronic diseases (of cardiovascular system, gastrointestinal tract, osteopenia and osteoporosis).
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 approximately 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.