CALCITONIN FOR OSTEOPOROSIS PREVENTION AND TREATMENT NEEDS FURTHER INVESTIGATION, PANEL OF SPECIALISTS MAINTAINS AT NIH SCIENTIFIC WORKSHOP

Calcitonin's safety and ability to reduce bone loss suggest the product has potential in the treatment and prevention of osteoporosis, panel members agreed at a scientific workshop, Research Directions in Osteoporosis, held at the National Institutes of Health on Feb. 9-11. The panel found that "in light of the role of calcitonin as a potent, perhaps physiological inhibitor of bone resorption, [calcitonin] deserves further consideration as an approach to preventing and treating osteoporosis." The chairman of the prevention and treatment session, William Peck, MD, The Jewish Hospital of St. Louis, said calcitonin "is quite unique in its safety, compared to all other medications for osteoporosis with the possible exception of calcium." He noted that the product "could be an alternative prophyaxis with estrogen in the future." The workshop included three days of presentations on the cause, prevention and treatment of osteoporosis, cosponsored by the National Institutes of Health and the National Osteoporosis Foundation. The results of a 1970 study conducted by Stanley Wallach, MD, et al was presented at the workshop. The purpose of the study was to determine calcitonin's effect on total body calcium. A total of 34 osteoporotic patients were treated with calcitonin in doses of 50 units three times a week or as high as 100 units daily. The overall response in the 34 patients was an average increase of three to four percent in total body calcium. On an individual basis the largest increase was a 10% increase in total body calcium over the 24 month treatment period. However, the panel concluded that "there is no substantial evidence of long term benefit, nor of decrease in fracture frequency." Several drawbacks to calcitonin therapy were noted, such as the need for frequent parenteral administration and high cost. Rorer's salmon calcitonin Calcimar, acquired with USV/Armour, is currently the only approved calcitonin product indicated for osteoporosis. Calcimar's labeling notes the product is indicated for postmenopausal osteoporosis "in conjunction with an adequate calcium and vitamin D intake to prevent the progressive loss of bone mass." The indication section adds that efficacy "was based on an increase in total body calcium" and that studies "were not designed to detect differences in fracture rates." Calcimar is also approved for hypercalcemia and Paget's disease. Rorer is understood to be developing an intranasal calcitonin product. In December, Ciba-Geigy launched the first synthetic human calcitonin, Cibacalcin. Approved as an orphan, Cibacalcin is indicated for the treatment of symptomatic Paget's disease in the U.S. and is marketed in Europe for osteoporosis and hypercalcemia. In addition, Sandoz received approval for a salmon calcitonin product, Miacalcin, in November 1985. The specialists agreed that objectives for future investigation should include: an understanding of calcitonin action at the cellular level; discovery of a different delivery system or molecule that would obviate the need for parenteral administration; development of a biosynthesis method; demonstration of calcitonin's safety and efficacy in long term studies; clarification of who responds to the hormone and why; and the demonstration of calcitonin's effect on bone pain and the mechanism of that effect. The panel agreed that low dose estrogen therapy is the most effective way to reduce postmenopausal bone loss. "Oral use of short-acting estrogen preparations reduces postmenopausal bone loss at virtually all skeletal sites examined including the vertebrae, the hip, and the wrist [and] epidemiological evidence indicates reduced fracture frequency in estrogen-treated women," the panel said. The specialists also noted that there is evidence that estrogen treatment reduces cardiovascular mortality in postmenopausal women, however, a protective effect has not been proven. According to the panel, there are 40 mil. women in the U.S. with hormone deficiencies, but only 4-5 mil. women go on estrogen replacement therapy, because of the risks involved. They include endometrial hyperplasia and cancer, as well as abnormal bleeding, which could result in a D&C and/or a hysterectomy. The panel also discussed estradiol transdermal patch treatment (Ciba-Geigy's Estraderm) but noted that its efficacy in reducing bone loss has yet to be determined. Progestins are also used for osteoporosis treatment and "may have independent effects on bone mass, reducing resorption and possibly increasing formation [but] whether these effects are additive to or synergistic with those of estrogen remains to be determined," the panel stated. Physical exercise is a possible preventive and treatment for osteoporosis in that it "may increase peak bone mass at maturity and reduce bone loss thereafter," the panel agreed. From the data, the panel concluded that 3-4 hours per week of weightbearing exercise may be beneficial. The panel said that exercise "deserves strong emphasis in future studies because it may represent a safe, low cost method for maintaining bone mass." Other possible preventive or therapeutic agents that are being studied are fluoride, vitamin D metabolites, lose dose parathyroid hormone, diphosphonates, ADFR, and anabolic steroids. The panel's consensus was that further information was required for all of these agents. Panel members suggested future approaches which may involve osteoblast agonists such as bone growth factors, monoclonal antibodies against resorbing elements and physiological and pharmacological antagonists of osteoblast activity.