Abstract
This review examines the evidence on the efficacy of calcitonin and etidronate in the prevention of osteoporosis and osteoporotic fractures. MEDLINE was searched for clinical trials on calcitonin or etidronate and reviews of the treatment of postmenopausal osteoporosis. The reference sections of the papers retrieved were again searched for trials on the treatments of interest. Two people independently collected data from the trials that met the inclusion criteria of the study. Weighted means in the change in bone mineral density (BMD) and differences in vertebral fracture rates were computed for calcitonin and etidronate separately. The existence of publication bias was investigated by funnel plots of effect size against sample size. Eighteen clinical trials and calcitonin and six with etidronate were included in the meta-analysis. The pooled change in vertebral BMD at the end of the studies was 1.97 (95% CI 1.77 to 2.17) with calcitonin and 3.20 (95% CI 2.92 to 3.48) with etidronate. Pooled change in proximal femur BMD was 0.32 (95% CI −0.27 to 0.91) with calcitonin and 2.42 (95% CI 2.16 to 2.68) with etidronate. The aggregated number of vertebral fractures prevented by the treatment was 59.2 per 1000 patient-years (95% CI 55.1 to 63.3) for calcitonin and 28.3 (95% CI 26.2 to 30.4) for etidronate. With the available evidence we cannot establish the superiority of either of the two drugs for the treatment of postmenopausal osteoporosis. The clinical trials are particularly lacking in data on hip fracture, the most important consequence of osteoporosis. In this situation consideration of the relative costs of the drugs is prominent.
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References
Consensus Development Conference. Diagnosis, prophylaxis, and treatment of osteoporosis. Am J Med 1993;94:646–50.
Melton LJ III, O'Fallon WM, Riggs BL. Secular trends in the incidence of hip fractures. Calcif Tissue Int 1987;41:57–64.
Kanis JA, Aaron JE, Evans D, Thavarajah M, Beneton M. Bone loss and age-related fractures. Exp Gerontol 1990;25:289–96.
Cooper C, Campion G, Melton LJ III. Hip fractures in the elderly: a world-wide projection. Osteoporosis Int 1992;2:285–9.
Norris RJ. Medical costs of osteoporosis. Bone 1992;13:S11–6.
New treatments for osteoporosis [editorial]. Lancet 1990;335:1065–6.
Chesnut CH III. Osteoporosis and its treatment. N Engl J Med 1992;326:406–7.
Riggs BL, Melton LJ III. The prevention and treatment of osteoporosis. N Engl J Med 1992;327:620–7.
Sambrock P, Eisman J. Diagnosis and treatment of osteoporosis. Curr Opin Rheumatol 1993,5:346–50.
Patel S, Lyons AR, Hosking DJ. Drugs used in the treatment of metabolic bone disease: clinical pharmacology and therapeutic use. Drugs 1993;46:594–617.
Dempster DW, Lindsay R. Pathogenesis of osteoporosis. Lancet 1993;341:797–801.
Lindsay R. Prevention and treatment of osteoporosis. Lancet 1993;341:801–5.
Peel N, Eastell R. Osteoporosis. BMJ 1995;310:989–92.
Riggs LMD. A new option for treating osteoporosis. N Engl J Med 1990;223:124–5.
Goldman L, Tosteson ANA. Uncertainty about postmenopausal estrogen: time for action, not debate. N Engl J Med 1992;325:800–2.
Marcus R. Cyclic etidronate: has the rose lost its bloom? Am J Med 1993;95:555–6.
Magrini N, Vaccheri A, Montanaro N. The Italian way of osteoporosis. Lancet 1992;339:499–500.
Ettinger B, Gennant HK, Cann CE. Long-term estrogen replacement therapy prevents bone loss and fractures. Ann Intern Med 1985;102:319–24.
Lufkin EG, Wahner HW, O'Fallon WM, et al. Treatment of postmenopausal osteoporosis with transdermal estrogen. Ann Intern Med 1992;117:1–9.
Prince RL, Smith M, Dick IM, Prince RI, Webb PG, Henderson NK, Harris MM. Prevention of postmenopausal osteoporosis: comparative study of exercise, calcium supplementation, and hormone replacement therapy. N Engl J Med 1991;325:1189–95.
Kanis JA, Johnell O, Gullberg B, Allander E, Dilsen G, Gennari C, et al. Evidence for efficacy of drugs affecting bone metabolism in preventing hip fracture. BMJ 1992;305:1124–8.
Wallach S, Farley JR, Baylink DJ, Brenner-Gati L. Effects of calcitonin on bone quality and osteoblastic function. Calcif Tissue Int 1993;52:335–9.
Burckhardt P, Burnand B. The effect of treatment with calcitonin on vertebral fracture rate in osteoporosis. Osteoporosis Int 1993;3:24–30.
Jackson RD. Cyclic etidronate for postmenopausal osteoporosis. Adv Endocrinol Metab 1991;2:1–21.
Sacks HS, Berrier J, Reitman D, Ancona-Berk VA, Chalmers TC. Meta-analysis of randomized controlled trials. N Engl J Med 1987;316:450–5.
Jenicek M. Méta-analyse en medicine. Québec: Edisem, 1987.
Andersen B. Methodological errors in medical research. Oxford: Blackwell Scientific, 1990.
Detsky AS, Naylor CD, O'Rourke K, McGeer AJ, L'Abbé KA. Incorporating variations in the quality of individual randomized trials into meta-analysis. J Clin Epidemiol 1992;45:255–65.
Wolf FM. Meta-analysis: quantitative methods for research synthesis. Quantitative applications in the social sciences. Newbury Park, CA: Sage Publications, 1986.
Chalmers TC, Frank CS, Reitman D. Minimising the three stages of publication bias. JAMA 1990;263:1392–5.
Dickersin K. The existence of publication bias and risk factors for its occurrence. JAMA 1990;263:1385–9.
Easterbrook PJ, Berlin JA, Gopalan R, Matthews DR. Publication bias in clinical research. Lancet 1991;337:867–72.
Felson DT. Bias in meta-analytic research. J Clin Epidemiol 1992;45:885–92.
Gennari C, Chierichetti SM, Bigazzi S, et al. Comparative effects on bone mineral content of calcium and calcium plus salmon calcitonin given in two different regimes in postmenopausal osteoporosis. Curr Ther Res 1985;38:455–64.
Mazzuoli GF, Passeri M, Gennari C, et al. Effects of salmon calcitonin in postmenopausal osteoporosis, a controlled, double-blind clinical study. Calcif Tissue Int 1986;38:3–8.
Maclntyre I, Stevenson JC, Whitehead MI, Wimalawansa SJ, Banks LM, Henakey MJR. Calcitonin for prevention of postmenopausal bone loss. Lancet 1988;1:900–2.
Overgaard K, Riis BJ, Christiansen C, Hansen MA. Effect of salcatonin given intranasally on early postmenopausal bone loss. BMJ 1989;299:477–9.
Overgaard K, Riis BJ, Christiansen C, Podenphant J, Johansen JS. Nasal calcitonin for treatment of established osteoporosis. Clin Endocrinol (Oxf) 1989;30:43S-42.
Mazzuoli GF,Tabolli S, Bigi F, Valtorta C, Minisola S, Diacinti D, et al. Effects of salmon calcitonin on the bone loss induced by ovariectomy. Calcif Tissue Int 1990;47:209–14.
Ljunghall S, Gardsell P, Johnell O, Larsson K, Lindh E, Obrant K, Sernbo I. Synthetic human calcitonin and postmenopausal osteoporosis: a placebo-controlled, double-blind study. Calcif Tissue Int 1991;49:17–9.
Gennari C, Agnusdei D, Montagnani M, Gonnelli S, Civitelli R. An effective regimen of intranasal salmon calcitonin in early postmenopausal bone loss. Calcif Tissue Int 1992;50:381–3.
Rico H, Hernandez ER, Revilla M, Gomez Castresana F. Salmon calcitonin reduces vertebral fracture rate in postmenopausal crush fracture syndrome. Bone Miner 1992;16:131–8.
Overgaard K, Hansen MA, Jensen SB, Christiansen C. Effect of salcatonin given intranasally on bone mass and fracture rates in established osteoporosis: a dose-response study. BMJ 1992;305:556–61.
Meunier PJ. Calcitonina intranasal para la prevencion de la osteoporosis post-menopausica. Rev Med Univ Navarra 1992;37:200–4.
Meschia M, Brincat M, Barbacini P, Crossignani PG, Albisetti W. A clinical trial on the effects of a combination of calcitonin (carbocalcitonin) and conjugated estrogens on vertebral bone mass in early postmenopausal women. Calcif Tissue Int 1993;53:17–20.
Kollerup G, Hermann AP, Brixen K, Lindblad BE, Mosekilde L, Sorensen OH. Effects of salmon calcitonin suppositories on bone mass and turnover in established osteoporosis. Calcif Tissue Int 1994;54:12–5.
Mango D, Ricci S, Manna P, Natili G, Dell' Acqua S. Preventive treatment of cortical bone loss with salmon nasal calcitonin in early postmenopausal women. Minerva Endocrinol 1993;18:115–21.
Overgaard K. Effect of intranasal salmon calcitonin therapy on bone mass and bone turnover in early postmenopausal women: a dose-response study. Calcif Tissue Int 1994;55:82–6.
Reginster JY, Meurmans L, Deroisy R, Juspin I, Biquet I, Albert A, Franchimont P. A 5-year controlled randomized study of prevention of postmenopausal trabecular bone loss with nasal salmon calcitonin and calcium. Eur J Clin Invest 1994:24:565–9.
Rico H, Revilla M, Hernandez ER, Villa LF, Alvarez de Buergo M. Total and regional bone mineral content and fracture rate in postmenopausal osteoporosis treated with salmon calcitonin: a prospective study. Calcif Tissue Int 1995;56:181–5.
Reginster JY, Deroisy R, Lecart MP, Sarlet N, Zegels B, Juspin I, et al. A double-blind, placebo controlled, dose-finding trial of intermittent nasal salmon calcitonin for prevention of postmeno-pausal lumbar spine bone loss. Am J Med 1995;98:452–8.
Smith ML, Fogelman I, Hart DM, et al. Effects of etidronate disodium on bone turnover following surgical menopause. Calcif Tissue Int 1989;44:143–8.
Storm T, Thamsborg G, Steiniche T, Genant HK, Sorensen OH. Effect of intermittent cyclical etidronate therapy on bone mass and fracture rate in women with postmenopausal osteoporosis. N Engl J Med 1990;322:1265–71.
Watts NB, Harris ST, Genant HK, Wasnich RD, Miller PD, Jackson RD, et al. Intermittent cyclical etidronate treatment of postmenopausal osteoporosis. N Engl J Med 1990;323:73–9.
Evans RA, Somers NM, Dunstan CR, Royle H, Kos S. The effect of low-dose cyclical etidronate and calcium on bone mass in early postmenopausal women. Osteoporosis Int 1993;3:71–5.
Harris St, Watts NB, Jackson RD, Genant HK, Wasnich RD, Ross P, et al. Four-year study of intermittent cyclic etidronate treatment of postmenopausal osteoporosis: three years of blinded therapy followed by one year of open therapy. Am J Med 1993;95:557–67.
Wimalawansa SJ. Combined therapy with estrogen and etidronate has an additive effect on bone mineral density in the hip and vertebrae: four-year randomized study. Am J Med I995;99:36–42.
Pacifici R, McMurtry C, Vered I, et al. Coherence therapy does not prevent axial bone loss in osteoporotic women: a preliminary comparative study. J Clin Endocrinol Metab 1988;66:747–53.
Mallette LE, LeBlanc AD, Pool JL, Mechanick JI. Cyclic therapy of osteoporosis with neutral phosphate and brief, high-dose pulses of etidronate. J Bone Miner Res 1989;4:143–8.
Miller PD, Neal BJ, McIntyre DO, Yanover MJ, Anger MS, Kowalski L. Effect of cyclical therapy with phosphorus and etidronate on axial bone mineral density in postmenopausal osteoporotic women. Osteoporosis Int 1991;1:171–6.
Silberstein EB, Schnur W. Cyclic oral phosphate and etidronate increase femoral and lumbar bone mineral denisty and reduce lumbar spine fracture rate over three years. J Nucl Med 1992;33:1–5.
Cristallini S, Pedetti M, Donatelli C, Gregorio F, Filipponi P. Effetto di differenti schemi terapeutici di tipo “coerente” sulla densita minerale ossea e sull'incidenza delle fratture vertebrali nell'osteoporosi avanzata. Recenti Prog Med 1993:84:336–45.
Franceschini R, Bottaro P, Panopoulos C, Messina V. Long-term treatment with salmon calcitonin in postmenopausal osteoporosis. Curr Ther Res Clin Exp 1983;34:795–800.
Palmieri GM, Pitcock JA, Brown P, Karas JG, Roen LJ. Effect of calcitonin and vitamin D in osteoporosis. Calcif Tissue Int 1989;45:137–41.
Steiniche T, Hasling C, Charles P, Eriksen EF, Mel sen F, Mosekilde L. The effects of etidronate on trabecular bone remodeling in postmenopausal spinal osteoporosis: a randomized study comparing intermittent treatment and an ADFR regime. Bone 1991;12:155–63.
Perrone G, Galoppi P, Valente M, Capri O, D'Ubaldo C, Anelli G, Zichella L. Intranasal salmon calcitonin in postmenopausal osteoporosis, effect of different therapeutic regimes on vertebral and peripheral bone density. Gynecol Obstet Invest 1992;33:168–71.
Overgaard K, Hansen MA, Dirksen KL, Christianen C. Rectal salmon calcitonin for the treatment of postmenopausal osteoporosis. Calcif Tissue Int 1992;51:184–8.
Szucs J, Horvath C, Kollin E, Szathmari M, Hollo I. Three-year calcitonin combination therapy for postmenopausal osteoporosis with crush fractures of the spine. Calcif Tissue Int 1992;50:7–10.
Ryan PJ, Fogelman I. Clinical experience with etidronate in osteoporosis. Clin Rheumatol 1994;13:455–8.
Gruber HE, Ivey JL, Baylink DJ, Matthews M, Nelp WB, Sisom K, et al. Long-term calcitonin therapy in postmenopausal osteoporosis. Metabolism 1984;33:295–303
Harjue E, Punnonen R, Tuimala R, Salmi J, Paronen I. Vitamin D and calcitonin treatment in patients with femoral neck fracture: a prospective controlled clinical study. J Int Med Res 1989;17:226–42.
Agnusdei D, Gonnelli S, Camporeale A, Batignani T, Nardi P, lanes A, Gennari C. Efficacia clinica di un trattamento con calcitonina di salmone, somministrata per via endonasale per un anno, nell'osteoporosi postmenopausale stabilizzata. Minerva Endocrinol 1989;14:169–76.
Ringe JD. Behandlung der primaren Osteoporose mit Calcium und Lachscalcitonin. Dtsch Med Wochenschr 1990;115:1176–82.
Villareal DT, Rupich RC, Pacifici R, Griffin MG, Maggio D, Avioli LV, Civitelli R. Effect of estrogen and calcitonin on vertebral bone density and vertebral height in osteoporotic women. Osteoporosis Int 1992;2:70–3.
Peyron R, Serrurier D, Edouard C, Ghozlan R, Mayoux-Benhamou A, Meunier PJ, CIGOP. Treatment of high remodeling vertebral osteoporosis with human calcitonin: a two year double-blind placebo-controlled trial in 93 patients. In: Christiansen C, Overgaard K, editors. Osteoporosis 1990. Copenhagen: Osteo-press, 1990:1430–3.
Abellan Perez M, Bayina Garcia FJ, Calabozo M, et al. Estudio comparativo multicentrico de la calcitonina sintetica de salmon administrada por via nasal en el tratamiento de la osteoporosis postmenopausica establecida. An Med Interna 1995;12:12–6.
Reginster JY, Denis D, Albert A, et al. 1-Year controlled randomised trial of prevention of early postmenopausal bone loss by intranasal calcitonin. Lancet 1987;2:1481–3.
Reginster JY, Denis D, Deroisy R, Lecart MP, De Longueville M, Zegels B, et al. Long-term (3 years) prevention of trabecular postmenopausal bone loss with low-dose intermittent nasal salmon calcitonin. J Bone Miner Res 1994;9:69–73.
Overgaard K, Hansen MA, Nielsen VA, Riis BJ, Christiansen C. Discontinuous calcitonin treatment of established osteoporosis-effects of withdrawal of treatment. Am J Med 1990;89:1–6.
Overgaard K, Christiansen C. Long-term treatment of established osteoporosis with intranasal calcitonin. Calcif Tissue Int 1991;Suppl 49:S60–3.
Parfitt AM. Implications of architecture for the pathogenesis and prevention of vertebral fracture. Bone 1992;13:S41–7.
Wimalawansa SJ. Long- and short-term side effects and safety of calcitonin in man: a prospective study. Calcif Tissue Int 1993;52:90–3.
Altman DG. Practical statistics for medical research. London: Chapman & Hall, 1991:472–3.
Kanis JA, Geusens P, Christiansen C. Guidelines for clinical trials in osteoporosis. Osteoporos Int 1991;1:182–8.
Heaney RP. How can we tell if a treatment works? Further thoughts on the randomized controlled trial. Osteoporosis Int 1991;1:215–7.
Heaney RP. Interpreting trials of bone-active agents. Am J Med 1995;98:329–30.
Cooper C, Kanis JA, Compston J. How to assess drug efficacy in osteoporosis. Lancet 1995;345:743–4.
Epstein S, Bryce G, Hinman JW, et al. The influence of age on bone mineral regulating hormones. Bone 1986;7:421–5.
Avioli LV. Osteoporosis syndromes: patient selection for calcitonin therapy. Geriatrics 1992;47:58,61–4,67
Avioli LV. Heterogeneity of osteoporotic syndromes and the response to calcitonin therapy. Calcif Tissue Int 1991;49(Suppl 2):S16–9
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Cardona, J.M., Pastor, E. Calcitonin versus etidronate for the treatment of postmenopausal osteoporosis: A meta-analysis of published clinical trials. Osteoporosis Int 7, 165–174 (1997). https://doi.org/10.1007/BF01622285
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DOI: https://doi.org/10.1007/BF01622285