Role of genetic factors in the pathogenesis of osteoporosis

Osteoporosis is a common disease with a strong genetic component: character ised by low bone mass, microarchitectural deterioration of bone tissue and all increased risk of fracture. Twin and family studies have shown that gen etic factors play an importance rule in regulating bone mineral density and other determinants of osteoporotic fracture risk, such as ultrasound prope rties of bone, skeletal geometry and bone turnover. Osteoporosis is a polyg enic disorder, determined by the effects of several genes, each with relati vely modest effects on bone mass and other determinants of fracture risk. I t is only on rare occasions that osteoporosis occurs as the result of mutat ions in a single gene. Linkage studies in man and experimental animals have defined multiple loci which regulate bone mass but the genes responsible f or these effects remain to be defined. Population-based studies and case-co ntrol studies have similarly identified polymorphisms in several candidate genes that have been associated with bone mass or osteoporotic fracture, in cluding the vitamin D receptor, oestrogen receptor and collagen type I alph a I gene. The individual contribution of these genes to the pathogenesis of osteoporosis is small however, reflected by the fact that the relationship between individual candidate genes and osteoporosis has been inconsistent in different studies. An important aim of future work will be to define how the genes which regulate bone mass, bone turnover and other aspects of bon e metabolism interact with each other and with environmental variables to c ause osteoporosis in individual patients. If that aim can be achieved dim t here is every prospect that preventative therapy could be targeted to those at greatest risk of the osteoporosis, before fractures have occurred.