Serum vitamin D metabolites and nuclear uptake of (3H)-1,25-dihydroxyvitamin D3 in monocytes from patients with autosomal dominant osteopetrosis: a study of two radiological types.

The nuclear uptake of (3H)-1,25 dihydroxyvitamin D3 in freshly isolated human monocytes and the serum levels of 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D were investigated in 13 patients with autosomal dominant osteopetrosis and in sex- and age-matched controls. Seven patients had type I osteopetrosis characterized by diffuse, symmetrical osteosclerosis with pronounced sclerosis of the skull and increased thickness of the cranial vault. The other six patients had type II with "Rugger Jersey Spine" and "endobones" as characteristic findings. In type I osteopetrosis the serum 1,25-dihydroxyvitamin D was significantly reduced (p less than 0.05), whereas serum 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D receptor binding were normal. In type II osteopetrosis the serum vitamin D metabolites were normal, as was the maximal binding capacity (Bmax) of 1,25-dihydroxyvitamin D to the nuclear receptor. The dissociation constant (Kd), however, was significantly increased (p less than 0.01) indicating a modest resistance to 1,25-dihydroxyvitamin D. It is concluded that a general end-organ resistance to 1,25-dihydroxyvitamin D at the receptor level does not exist in type I osteopetrosis, but may contribute to some of the radiological and biochemical findings in type II.