Studies on the pathophysiology and therapy of osteoporosis

Etiologic and pathologic factors in clinical osteoporosis are reviewed. Techniques were developed to determine total skeletal calcium content with in vivo neutron activation analysis and to induce osteoporosis (in about three months) with low calcium diet, corticosteroid or heparin treatment in experimental animals. Genetic influence was demonstrated: C3H/St (Ha) mice were more susceptible to osteoporosis by all three modalities than C57B1/6 (J) mice. Fluoride was ineffective in preventing osteoporosis induced by either of these three modalities. Heparin induced osteoporosis was prevented by conjugated estrogens, progestins or their combinations. Progestins were shown in other studies to inhibit estrogen induced metaplasia and neoplasia. Combining estrogens with progestin may result in an increased therapeutic index for the prevention of postmenopausal osteoporosis. Human and salmon calcitonin, Deca - Durabolin, an anabolic steroid, Mopidamole, a pyrimidopyrimidine derivative, Trental, a methylxanthine derivative, certain 2-thiophene carboxylic acid derivatives and imidazoquinazolines exhibited anti-osteoporotic effects.