Immunologic evidence of a bone morphogenetic protein in the milieu intérieur

Eighteen different groups of proteins have been identified in the organic matrix of bone. To date, seven have been identified in circulating blood. Several plasma proteins are found to accumulate in bone matrix. Two bone, carboxyglutamic acid rich proteins (BGP or osteocalcin) and bone morphogenetic protein (BMP) are measured by RIA in serum in the range of ng/ml. Of all matrix groups, the least abundant is BMP. Acting as a paracrine or local hormone, BMP induces perivascular connective tissue cells of bone marrow to differentiate into cartilage and bone. Neither the mechanism of action or target cells, nor the mode of transport of BMP in serum are known, but the immunologic activity demonstrates higher serum BMP RIA levels in growing children and patients with Paget's Disease than in normal adults. Serum BMP is remarkably low in postmenopausal women with severe osteoporosis; serum anti-BMP antibody is correspondingly high. Although these observations are preliminary and based on a relatively small number of patients, the data suggest a working hypothesis that BMP and anti-BMP are bone tissue-specific parameters of normal and pathological bone physiology. The possibility of diagnosis of osteoporosis in the prefracture stage, and the prospects of evidence of an autoimmune response to the products of bone resorption, derived from the serum BMP anti-BMP ratio, warrant special investigation.