The aim of this study was to investigate a recessive genetic component in susceptibility to osteoporosis (OP) by comparing its prevalence in isolated villages of three Croatian islands: Brac, Hvar and Korcula with different levels of inbreeding. A random sample of 20-30% adults from 14 villages was obtained, including a total of 1,389 examinees. The average inbreeding coefficient (F) of examinees from each village population was estimated using Wright's path method (based on genealogical information). The morphometry of the metacarpal bones was performed on hand-wrist radiographs of both hands in all examinees. OP was defined as values of cortical index smaller than 2 standard deviations based on distribution of values in examinees of the same sex under 45 years of age. Mean values of cortical index (CI) and prevalence of OP (both standardized by age and weighted for the sample size) in each village were correlated to the mean inbreeding coefficient (F). The coefficient of correlation (r) between F values and CI was -0.28 in males (p = 0.08) and -0.42 in females (p = 0.005), and between F and OP prevalence 0.32 in males (p < 0.001) and 0.43 in females (p < 0.001). These results indicate a trend of increased susceptibility to osteoporosis with increasing level of inbreeding in isolated communities of Croatian islands.