Vitamin D Receptor Polymorphisms and Bone Mass Accrual in Indian Girls.

Abstract

Peak bone mass accrual during early adulthood has implications on long term risk of osteoporosis. Two major mechanisms which determine final bone mass and mineral content include peak bonemass accrual during puberty and rate of loss of bone mass during ageing [1, 2]. Bone mineral accretion is dependent on various factors like exercise, nutrition, hormones, gender and genetics [2]. Vitamin D plays a pivotal role in influencing bone mineralization. Studies have shown that bone mass and bone mineral density (BMD) are lower in hypovitaminosis D states. In addition, twin and family studies have shown a strong genetic basis to explain variance in BMD among individuals [1]. Among the genetic factors associated with vitamin D, polymorphisms of vitamin D receptor (VDR) have been most extensively studied [3]. The four common restriction fragment length polymorphisms which have been detected in VDR gene are at Bsm1, Apa1, Taq1 restriction sites and one at the Fok1 restriction site in the translation initiation site [3, 4]. Fok1 has been extensively studied in children and adults in determining bone health and in prognosis of prostate cancer, breast cancer, renal carcinoma and malignant melanoma [3]. Fok1 polymorphism confers a single strand conformational change at the VDR translation initiation site [4]. Most of the earlier studies on VDR polymorphisms had recruited adults or post-menopausal women. Adult studies carry a drawback over studies in children as the former subgroup has higher interference of environmental and ageing processes on BMD. A recent meta-analysis concluded both Fok1 and Bsm1 to be associated with risk of osteoporosis in 60–65 % of studies respectively [5], with poor correlation reported by few other studies [1]. This inconsistency among studies could result from small sample size of different studies, differences in age, pubertal status, dietary calcium intake, physical activity, heterogeneity across the different allele groups in genetic background and lastly, linkage disequilibrium within few ethnic groups [1]. Among studies in children and adolescents, Arabi et al. found significant effect ofBsm1, Taq1 and Apa1 polymorphism in their longitudinal study in adolescent girls whowere randomized to receive supplemental vitamin D [6]. Similarly, Zhang et al. also found significant association between Fok1 and forearmBMD in Chinese children [7]. Contrary to this, Ferrari et al. found no significant interaction between Fok1 polymorphism and BMD among prepubertal girls even after adjusting for age, height and calcium intake [8]. An initial study by Sanwalka et al. evaluated the Bsm1 and Fok1 polymorphism in postmenarchal adolescent Indian girls and reported a significant effect of BB phenotype on total bone mass and lumbar spine BMD and of Ff phenotype on BMD at femur neck [9]. In the current issue of the Journal, Sanwalka et al. have evaluated the association of Fok1 polymorphism with bone mass accrual in 102 Indian girls aged 8–16 y [10]. The study subjects were supplemented with 500 mg calcium daily and 30,000 IU quarterly vitamin D for 1 y; following which a significant increase in bone mineral content and BMD was seen across all genotypesFF, Ff and ff. Subjects with FF phenotype had lower BMD at baseline and after supplementation than Ff and ff phenotypes. The lower BMD with FF genotype in this study is contrary to other reports in children and adolescents reporting higher BMD with FF genotype in Caucasians and Americans [2]. Another study on pre and post * Rajesh Khadgawat rajeshkhadgawat@hotmail.com