Genetic determination of Colles' fracture and differential bone mass in women with and without Colles' fracture

Osteoporotic fractures (OFs) are a major public health problem. Direct evid ence of the importance and, particularly, the magnitude of genetic determin ation of OF per se is essentially nonexistent. Colles' fractures (CFs) are a common type of OF. In a metropolitan white female population in the midwe stern United States, we found significant genetic determination of CP. The prevalence (K) of CF is, respectively, 11.8% (+/-SE 0.7%) in 2471 proband w omen aged 65.55 years (0.21), 4.4% (0.3%) in 3803 sisters of the probands, and 14.6% (0.7%) in their mothers. The recurrence risk (K-0), the probabili ty that a woman will suffer CF if her mother has suffered CF is 0.155 (0.01 7). The recurrence risk (K-s), the probability that a sister of a proband w oman will suffer CF given that her proband sister has suffered CF is 0.084 (0.012). The relative risk lambda (the ratio of the recurrence risk to K), which measures the degree of genetic determination of complex diseases such as CF, is 1.312 (0.145; lambda(0)) for a woman with an affected mother and 1.885 (0.276; lambda(s)) for a woman with an affected sister. A lambda-val ue significantly greater than 1.0 indicates genetic determination of CF. Th e terms lambda(0) and lambda(s) are related to the genetic variances of CF. These parameters translate into a significant and moderately high heritabi lity (0.254 [0.118]) for CF. These parameters were estimated by a maximum l ikelihood method that we developed, which provides a general tool for chara cterizing genetic determination of complex diseases. In addition, we found that women without CF had significantly higher bone mass (adjusted for impo rtant covariates such as age, weight, etc.) than women with CF.