Decreased response to calcitonin in osteopetrotic microphthalmic mouse bone.

Abstract

OSTEOPETROSIS is an autosomal recessive disease characterised by an increase in skeletal mass, often associated with retarded bone growth and a deficiency of marrow cavity development, which is related to a failure of bone resorption to keep pace with bone formation1,2. The disease has been studied in man and in several genetic mouse and rat mutants1. These mutants generally have diminished osteoclast function in the skeleton based on a lack of ruffled borders1,3, lowered acid phosphatase activity4 and a lower level of parathormone-induced resorption in vivo3,5 and in vitro6. It seems that osteo-petrosis has a cellular basis as it can be cured by parabiosis with a normal littermate7 or by administration of spleen or bone marrow cells8. However, the only report examining bone cell metabolism in osteopetrosis indicates that in the calvarium of the osteopetrotic incisor-absent rat, parathormone affects adenylate cyclase activity and lactic acid production to the same extent as in the bone from normal littermates9. Recently, specific hormone-sensitive biochemical activities in intact bone in culture10,11 or in cultured bone cells12,13 have been associated with the functions of osteoclasts and osteoblasts. Based on these biochemical parameters we show here that in osteopetrotic (micropthalmic) bone there is a defect in calcitonin response attributable to osteoclast function whereas osteoblast activity is apparently normal.