Five years treatment with strontium ranelate reduces vertebral and nonvertebral fractures and increases the number and quality of remaining life-years in women over 80 years of age.
Five years treatment with strontium ranelate reduces vertebral and non-vertebral fractures and increases the number and quality of remaining life-years in women over 80 years of age.pdf
Aged, 80 and over; Bone Density/drug effects; Bone Density Conservation Agents/therapeutic use; Bone and Bones/drug effects; Calcium, Dietary/therapeutic use; Female; Hip Fractures/prevention & control; Humans; Intention to Treat Analysis; Organometallic Compounds/therapeutic use; Osteoporosis, Postmenopausal/drug therapy; Quality of Life; Spinal Fractures/prevention & control; Thiophenes/therapeutic use; Treatment Outcome
Abstract :
[en] INTRODUCTION: Longevity has resulted in a greater proportion of the population entering a time of life when increasing bone fragility and falls predispose to fractures, particularly nonvertebral fractures. Women over 80 years of age constitute 10% of the population but contribute 30% of all fractures and 60% of all nonvertebral fractures. Despite this, few studies have examined antifracture efficacy of treatments in this high-risk group and none has provided evidence for benefits beyond 3 years. MATERIALS AND METHODS: To determine whether strontium ranelate reduces the risk of vertebral and nonvertebral fractures during 5 years, we analyzed a subgroup of 1489 female patients over 80 years of age (mean 83.5+/-3.0 years) with osteoporosis from the SOTI (spinal osteoporosis therapeutic intervention) and TROPOS (treatment of peripheral osteoporosis) studies randomized to strontium ranelate 2 g/d or placebo. All received a supplement of calcium plus vitamin D. RESULTS: By intention to treat, vertebral fracture risk was reduced by 31% (relative risk, RR=0.69; 95% confidence interval, CI 0.52-0.92), nonvertebral fracture risk by 27% (RR=0.73; 95% CI 0.57-0.95), major nonvertebral fracture risk by 33% (RR=0.67; 95% CI 0.50-0.89) and hip fracture risk by 24% (RR=0.76; 95% CI 0.50-1.15, not significant). Treatment was cost-saving as it decreased cost and increased QALYs and life-years. DISCUSSION: Strontium ranelate safely produced a significant reduction in vertebral and nonvertebral fracture risk during 5 years in postmenopausal women over 80 years of age and was cost saving.
Disciplines :
General & internal medicine
Author, co-author :
Seeman, Ego
Boonen, Steven
Borgstrom, Frederik
Vellas, Bruno
Aquino, Jean*-Pierre
Semler, Jutta
Benhamou, Claude-Laurent
Kaufman, Jean-Marc
Reginster, Jean-Yves ; Université de Liège - ULiège > Département des sciences de la santé publique > Santé publique, Epidémiologie et Economie de la santé
Language :
English
Title :
Five years treatment with strontium ranelate reduces vertebral and nonvertebral fractures and increases the number and quality of remaining life-years in women over 80 years of age.
Publication date :
2010
Journal title :
BONE
ISSN :
8756-3282
eISSN :
1873-2763
Publisher :
Elsevier Science, New York, United States - New York
Boonen S. Osteoporosis in older persons-pathophysiology and therapeutic approach. Medical treatment of age-related osteoporosis: present and future 2008, 137-152. London. G. Duque, K.D. Springer (Eds.).
Heaney R.P. Is the paradigm shifting?. Bone 2003, 33:457-465.
Garnero P., Hausherr E., Chapuy M.C., Marcelli C., Grandjean H., Muller C., et al. Markers of bone resorption predict hip fracture in elderly women: the EPIDOS Prospective Study. J. Bone Miner. Res. 1996, 11:1531-1538.
Mori S., Harruff R., Ambrosius W., Burr D.B. Trabecular bone volume and microdamage accumulation in the femoral heads of women with and without femoral neck fractures. Bone 1997, 21:521-526.
Black D.M., Delmas P.D., Eastell R., Reid I.R., Boonen S., Cauley J.A., et al. Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis. N. Engl. J. Med. 2007, 356:1809-1822.
Seeman E., Vellas B., Benhamou C., Aquino J.P., Semler J., Kaufman J.M., et al. Strontium ranelate reduces the risk of vertebral and nonvertebral fractures in women eighty years of age and older. J. Bone Miner. Res. 2006, 21:1113-1120.
Boonen S., McClung M.R., Eastell R., El Hajj F.G., Barton I.P., Delmas P. Safety and efficacy of risedronate in reducing fracture risk in osteoporotic women aged 80 and older: implications for the use of antiresorptive agents in the old and oldest old. J. Am. Geriatr. Soc. 2004, 52:1832-1839.
Boonen S., Marin F., Mellstrom D., Xie L., Desaiah D., Krege J.H., et al. Safety and efficacy of teriparatide in elderly women with established osteoporosis: bone anabolic therapy from a geriatric perspective. J. Am. Geriatr. Soc. 2006, 54:782-789.
Lyles K.W., Colon-Emeric C.S., Magaziner J.S., Adachi J.D., Pieper C.F., Mautalen C., et al. Zoledronic acid and clinical fractures and mortality after hip fracture. N. Engl. J. Med. 2007, 357:1799-1809.
Reginster J.Y., Felsenberg D., Boonen S., Diez-Perez A., Rizzoli R., Brandi M.L., et al. Effects of long-term strontium ranelate treatment on the risk of non-vertebral and vertebral fractures in postmenopausal osteoporosis: results of a 5-year, randomized, placebo-controlled trial. Arthritis Rheum. 2008, 58:1687-1695.
Borgstrom F., Jonsson B., Strom O., Kanis J.A. An economic evaluation of strontium ranelate in the treatment of osteoporosis in a Swedish setting: based on the results of the SOTI and TROPOS trials. Osteoporos. Int. 2006, 17:1781-1793.
Meunier P.J., Roux C., Seemar E., Ortolani S., Badurski J.E., Spector T.M., et al. The effects of strontium ranelate on the risk of vertebral fracture in women with postmenopausal osteoporosis. N. Engl. J. Med. 2004, 350:459-468.
Reginster J.Y., Seeman E., De Vernejoul C., Adami S., Compston J., Phenekos C., et al. Strontium ranelate reduces the risk of nonvertebral fractures in postmenopausal women with osteoporosis: treatment of peripheral osteoporosis (TROPOS) study. J. Clin. Endocrinol. Metab. 2005, 90:2816-2822.
Meunier P.J., Reginster J.Y. Design and methodology of the phase 3 trials for the clinical development of strontium ranelate in the treatment of women with postmenopausal osteoporosis. Osteoporos. Int. 2003, 14:S66-S76.
Genant H.K., Wu C.Y., Van Kuijk C., Nevitt M.C. Vertebral fracture assessment using a semiquantitative technique. J. Bone Miner. Res. 1993, 8:1137-1148.
Slosman D.O., Provvedini D.M., Meunier P.J., Delmas P.D., Sebert J.L., De Vernejoul M.C., et al. The use of different dual x-ray absorptiometry brands in a multicenter clinical trial. Consequences and limits. J. Clin. Densitom. 1999, 2:37-44.
Meltzer D. Accounting for future costs in medical cost-effectiveness analysis. J. Health Econ. 1997, 16:33-64.
Woolf A.D., Akesson K. Preventing fractures in elderly people. BMJ 2003, 327:89-95.
Delmas P.D., Rizzoli R., Cooper C., Reginster J.Y. Treatment of patients with postmenopausal osteoporosis is worthwhile. The position of the International Osteoporosis Foundation. Osteoporos. Int. 2005, 16:1-5.
Schousboe J.T., Taylor B.C., Fink H.A., Kane R.L., Cummings S.R., Orwoll E.S., et al. Cost-effectiveness of bone densitometry followed by treatment of osteoporosis in older men. JAMA 2007, 298:629-637.
Black D.M., Cummings S.R., Karpf D.B., Cauley J.A., Thompson D.E., Nevitt M.C., et al. Randomised trial of effect of alendronate on risk of fracture in women with existing vertebral fractures. Fracture Intervention Trial Research Group. Lancet 1996, 348:1535-1541.
Chesnut C.H., Skag A., Christiansen C., Recker R., Stakkestad J.A., Hoiseth A., et al. Effects of oral ibandronate administered daily or intermittently on fracture risk in postmenopausal osteoporosis. J. Bone Miner. Res. 2004, 19:1241-1249.
Ettinger B., Black D.M., Mitlak B.H., Knickerbocker R.K., Nickelsen T., Genant H.K., et al. Reduction of vertebral fracture risk in postmenopausal women with osteoporosis treated with raloxifene. Results from a 3-year randomized clinical trial. JAMA 1999, 282:637-645.
Hochberg M.C., Thompson D.E., Black D.M., Quandt S.A., Cauley J.A., Geusens P., et al. Effect of alendronate on the age-specific incidence of symptomatic osteoporotic fractures. J. Bone Miner. Res. 2005, 20:971-976.
Morin S., Rahme E., Behlouli H., Tenenhouse A., Goltzman D., Pilote L. Effectiveness of antiresorptive agents in the prevention of recurrent hip fractures. Osteoporos. Int. 2007, 18:1625-1632.
Bruyere O., Roux C., Badurski J., Isaia G., De Vernejoul M.C., Cannata J., et al. Relationship between change in femoral neck bone mineral density and hip fracture incidence during treatment with strontium ranelate. Curr. Med. Res. Opin. 2007, 23:3041-3045.
Bruyere O., Roux C., Detilleux J., Slosman D.O., Spector T.D., Fardellone P., et al. Relationship between bone mineral density changes and fracture risk reduction in patients treated with strontium ranelate. J. Clin. Endocrinol. Metab. 2007, 92:3076-3081.
Zethraeus N., Strom O., Borgstrom F., Kanis J.A., Jonsson B. The cost-effectiveness of the treatment of high risk women with osteoporosis, hypertension and hyperlipidaemia in Sweden. Osteoporosis International 2007, 19(6):819-827.
Breart G., Cooper C., Meyer O., Speirs C., Deltour N., Reginster J.Y. Osteoporosis and venous thromboembolism: a retrospective cohort study in the UK General Practice Research Database. Osteoporos. Int. 2009.
Mellstrom D.D., Sorensen O.H., Goemaere S., Roux C., Johnson T.D., Chines A.A. Seven years of treatment with risedronate in women with postmenopausal osteoporosis. Calcif. Tissue. Int. 2004, 75:462-468.
Siris E.S., Harris S.T., Eastell R., Zanchetta J.R., Goemaere S., Diez-Perez A., et al. Skeletal effects of raloxifene after 8 years: results from the Continuing Outcomes Relevant to Evista (CORE) Study. J. Bone Miner. Res. 2005, 20:1514-1524.
Cummings S.R., Black D.M., Thompson D.E., Applegate W.B., Barrett-Connor E., Musliner T.A., et al. Effect of alendronate on risk of fracture in women with low bone density but without vertebral fractures: results from the Fracture Intervention Trial. JAMA 1998, 280:2077-2082.
Sorensen O.H., Crawford G.M., Mulder H., Hosking D.J., Gennari C., Mellstrom D.D., et al. Long-term efficacy of risedronate: a 5-year placebo-controlled clinical experience. Bone 2003, 32:120-126.
Delmas P.D., Ensrud K.E., Adachi J.D., Harper K.D., Sarkar S., Gennari C., et al. Efficacy of raloxifene on vertebral fracture risk reduction in postmenopausal women with osteoporosis: four-year results from a randomized clinical trial. J. Clin. Endocrinol. Metab. 2002, 87:3609-3617.
Odvina C.V., Zerwekh J.E., Rao D.S., Maalouf N., Gottschalk F.A., Pak C.Y. Severely suppressed bone turnover: a potential complication of alendronate therapy. J. Clin. Endocrinol. Metab. 2005, 90:1294-1301.
Neviaser A.S., Lane J.M., Lenart B.A., Edobor-Osula F., Lorich D.G. Low-energy femoral shaft fractures associated with alendronate use. J. Orthop. Trauma 2008, 22:346-350.
Kwek E.B., Goh S.K., Koh J.S., Png M.A., Howe T.S. An emerging pattern of subtrochanteric stress fractures: a long-term complication of alendronate therapy?. Injury 2008, 39:224-231.
Dodson T.B., Raje N.S., Caruso P.A., Rosenberg A.E. Case records of the Massachusetts General Hospital. Case 9-2008. A 65-year-old woman with a nonhealing ulcer of the jaw. N. Engl. J. Med. 2008, 358:1283-1291.
Migliorati C.A., Siegel M.A., Elting L.S. Bisphosphonate-associated osteonecrosis: a long-term complication of bisphosphonate treatment. Lancet Oncol. 2006, 7:508-514.
Rizzoli R., Burlet N., Cahall D., Delmas P.D., Eriksen E.F., Felsenberg D., et al. Osteonecrosis of the jaw and bisphosphonate treatment for osteoporosis. Bone 2008, 42:841-847.
