genetics

Last reviewed 07/2021

Genetic factors are known to play an important part in the pathogenesis of osteoporosis (1).

Twin and family based studies have revealed that bone mineral density (BMD) is determined genetically while other known risk factors such as reduced bone quality, femoral neck geometry and bone turn over have also been shown to be heritable (1,2)

The genetic element in osteoporosis appears to control the peak bone mass achieved during early adulthood.

Polymorphisms have been identified in several genes that are associated with BMD, bone loss or osteoporotic fractures. Some of the important candidate genes which play a role in regulating BMD are (1):

• vitamin D receptor gene
• type I collagen gene (COLIA1)
• oestrogen receptor gene (ESR1)
• lipoprotein receptor–related protein 5 (LRP5)
• variation in the gene coding for LRP5 has also been implicated in bone mass accrual and susceptibility to osteoporosis.
• study evidence revealed that common LRP5 variants are consistently associated with BMD and fracture risk across different white populations (1)

However, the magnitude of the effect of these polymorphisms is modest and probably accounts for less than 5% of the heritable contribution to BMD (2).

Reference:

• (1) Ralston SH. Genetics of osteoporosis. Proc Nutr Soc. 2007;66(2):158-65
• (2) Williams FM, Spector TD. Recent advances in the genetics of osteoporosis. J Musculoskelet Neuronal Interact. 2006;6(1):27-35.  
• (3) van Meurs JB et al. Large-scale analysis of association between LRP5 and LRP6 variants and osteoporosis. JAMA. 2008 Mar 19;299(11):1277-90