Bone mass and strength: Phenotypic and genetic relationship to alcohol preference in P/NP and HAD/LAD rats

Background: The association between moderate alcohol intake and elevated bone mineral density observed in several epidemiologic studies might result from common genetic pathway regulating both phenotypes. In this study, we determined whether there is a relationship between alcohol preference and high bone mass or strength and whether bone mass-regulating genes segregate during selective breeding of alcohol preferring rats. Methods: Six different lines of male rats with high or low preference for alcohol consumption were used in this study. The high alcohol preference lines are alcohol-preferring (P), high-alcohol-drinking 1 (HAD1), and high-alcohol-drinking 2 (HAD2), and their corresponding low alcohol preference lines are alcohol-nonpreferring (NP), low-alcohol-drinking 1 (LAD1), and low-alcohol-drinking 2 (LAD2). Bone mass phenotypes were determined using dual energy x-ray absorptiometry (DYA), peripheral quantitative computed tomography (pQCT), and biornechanics in long bones and lumbar vertebrae from rats at 3 and 6 months of age. Results: P rats had significantly higher bone mass and strength compared with NP rats, mainly due to higher cortical bone in long bones and lumbar vertebrae. HAD2 rats also had significantly higher bone mass compared with LAD2 rats, but mostly due to increased trabecular bone leading to increased strength only in lumbar vertebra. Conversely, HAD1 rats had significantly lower bone mass and strength compared with LAD1 rats in long bones. The vertebral bone mass and strength did not differ between HAD1 and LAD1 rats. Conclusions: This study demonstrated that preference for alcohol consumption had no consistent relationship with high bone mass or strength, as each alcohol-preferring rat line had their unique bone mass phenotypes. However, genes regulating bone mass and strength appear to segregate with alcohol preference genes in P and HAD rat lines, suggesting that alcohol preferring rat lines may be useful for identifying genes that regulate bone mass and structure.