Gender-related effects of vitamin D metabolites on cartilage and bone

Sex steroid hormones are known to have gender-dependent effects on bone and cartilage in vivo and in vitro. To investigate whether this is a general property of steroids, or is specific to the sex steroid hormones, we examined whether the effects on bone of l,25-(OH)₂D₃ and 24,25(OH)₂D₃, the two active metabolites of vitamin D, are also gender-dependent. One-month-old male and female rats were treated for 1 month with various doses of 1,25-(OH)₂D₃, 24,25-(OH)₂D₃, or a combination of both metabolites. The direct effects of both metabolites on the skeleton of the treated animals were similar in male and female rats. 24,25-(OH)₂D₃ alone or in combination with l,25-(OH)₂D₃ increased bone calcium and phosphorus, while l,25-(OH)₂D₃ slightly decreased bone mineral content. 24,25-(OH)₂D₃ also enhanced the differentiation of cartilage in the growth plate, increasing the size of the hypertrophic zone. In addition, an increased metaphyseal bone volume was observed following 24,25-(OH)₂D₃ treatment in rats of both sexes, but not with l,25-(OH)₂D₃. Vitamin D metabolites affected the weight gain of the experimental animals in a gender-dependent manner; l,25-(OH)₂D₃ increased weight gain of male rats and 24,25-(OH)₂D₃ decreased weight gain of female rats. In addition, l,25-(OH)₂D₃ increased bone weight and ash weight in male animals. These gender-dependent effects of vitamin D metabolites may occur indirectly via effects of sex steroid hormones, the latter being a sex-related effect.