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 formation^1,2. 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 borders^1,3, lowered acid phosphatase activity⁴ and a lower level of parathormone-induced resorption in vivo^3,5 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 culture^10,11 or in cultured bone cells^12,13 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.