Elevated serum 1,25-dihydroxyvitamin D in osteopetrotic mutations in three species.

Osteopetrosis is an inherited bone disease in which bone mass accumulates due to a reduction in bone resorption. We have examined serum levels of vitamin D metabolites in seven mutations from three species and found that serum 1,25-dihydroxyvitamin D is markedly elevated in each. In some mutations, these findings cannot be solely explained by the known stimulators of this hormone; namely hypophosphatemia and hyperparathyroidism, and suggest a compensatory adjustment to an end-organ resistance to this hormone. These data, taken together with known alterations in osteoclast structure and function in congenital osteopetrosis and the effects of this hormone on monocyte differentiation and bone resorption, indicate that resistance to 1,25-dihydroxyvitamin D could be a unifying concept to explain the osteoclast heterogeneities in osteopetrosis. Furthermore, this may be an ideal system in which to examine the effects of this hormone on the proliferation, differentiation and function of bone cells.