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25-08-2010 | Bone health | Article

RANK/RANKL/OPG polymorphisms affect cortical bone mineral density


Free abstract

MedWire News: Genetic variation within the receptor activator of nuclear factor-κB (RANK)/RANK ligand (RANKL)/osteoprotegerin (OPG) system affects cortical bone mineral density (BMDC) in adolescents at a time of peak bone mass attainment, UK research shows.

"Several single-nucleotide polymorphisms (SNPs) have been reliably associated with areal bone mineral density (aBMD) in genome-wide association (GWA) studies of mostly older subjects," observe Lavinia Paternoster (University of Bristol) and colleagues.

It is difficult to determine whether the genetic effects that were reported relate to the control of peak bone acquisition over the first three decades of life or subsequent age-related bone loss, they add.

To investigate, Paternoster and team assessed the relationship between nine SNPs identified as showing associations with aBMD in GWA studies and peripheral quantitative computed tomography (pQCT) parameters measured at the tibia in adolescents and young adults from two different cohorts.

Among participants of the Avon Longitudinal Study of Parents and Children (n=3113), the researchers found a significant association between the RANK SNP rs3018362 and BMDC. However no associations were observed between OPG, RANK, or RANKL markers and other pQCT-derived measures of cortical bone size.

In a second, male only cohort from Sweden (n=935), two SNPs (rs4355801 and rs6993813), which flank the OPG gene showed some evidence of association with BMDC.

Metaanalyses combining the results from both cohorts revealed significant associations between the rs4355801 SNP in the OPG gene, the rs3018362 SNP in the RANK gene, and BMDC.

"The RANK/RANKL/OPG pathway plays an essential role in regulating osteoclast function, and osteoclast activity in turn affects BMDC, for example, by determining the extent of cortical porosity," write Paternoster and co-authors in the Journal of Clinical Endocrinology and Metabolism.

"Based on these findings, we propose that genetic variation within the RANK/RANKL/OPG system influences aBMD in adults at least in part by affecting BMDC during the process of peak bone mass attainment," they conclude.

MedWire ( is an independent clinical news service provided by Current Medicine Group, a trading division of Springer Healthcare Limited. © Springer Healthcare Ltd; 2010

By Laura Dean

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