Abstract
Summary
Adherence is now one of the major issues in the management of osteoporosis. This paper relates the relationship existing between adherence to strontium ranelate and the risk of subsequent nonvertebral fracture among postmenopausal women with osteoporosis.
Introduction
The aim of this study is to investigate compliance to strontium ranelate (SR) therapy and the impact of compliance on the risk of nonvertebral fractures among women with osteoporosis.
Methods
This study was a post-hoc analysis of pooled data from two international, phase III, randomized, placebo-controlled, double-blind studies (the Spinal Osteoporosis Therapeutic Intervention and Treatment Of Peripheral Osteoporosis). A nested case-control study was performed in the strontium ranelate-treated population. Compliance was quantified using the medication possession ratio (MPR).
Results
Two hundred eighty-five nonvertebral fracture cases (hip fx n = 70; major nonvertebral fx n = 213) were identified and matched to 1,425 controls. The mean MPR was 86.8% for controls and 82.6% for cases (p < 0.001). Women who were compliant to SR had a 38% reduction in all nonvertebral fractures compared with those who were not (OR = 0.62; 95%CI[0.47–0.81; p < 0.001). Considering hip fractures only, the risk was reduced by 50% for compliant patients compared to noncompliant patients (OR = 0.50; 95%CI[0.28–0.88]; p < 0.05).
Conclusion
Our analyses emphasize the importance of good compliance to treatment in order to reduce the risk of osteoporotic fractures. In particular, there was a greater reduction in the risk of nonvertebral and hip fractures with increase compliance.
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References
Woolf AD, Plefger B (2003) Burden of major musculoskeletal conditions. Bull WHO 81:646–656
Cummings SR, Melton LJ III (2002) Epidemiology and outcomes of osteoporotic fractures. Lancet 359:1761–1767
Schwenkglenks M, Lippuner K, Hauselmann HJ, Szucs TD (2005) A model of osteoporosis impact in Switzerland 2000–2020. Osteoporos Int 16:659–671
Puffer S, Torgeson DJ, Sykes D et al (2004) Healthcare costs of women with symptomatic vertebral fractures. Bone 35:383–386
Canalis E, Hott M, Deloffre P, Tsouderos Y, Marie PJ (1996) The divalent strontium salt S12911 enhances bone cell replication and bone formation in vitro. Bone 18:517–523
Baron R, Tsouderos Y (2002) In vitro effects of S12911-2 on osteoclast function and bone marrow macrophage differentiation. Eur J Pharmacol 450:11–17
Takahashi N, Sasaki T, Tsouderos Y, Suda T (2003) S 12911-2 inhibits osteoclastic bone resorption in vitro. J Bone Miner Res 18:1082–1087
Meunier PJ, Roux C, Seeman E, Ortolani S, Badurski JE, Spector TD, Cannata J, Balogh A, Lemmel E-M, Pors-Nielsen S, Rizzoli R, Genant HK, Reginster J-Y (2004) The effects of strontium ranelate on the risk of vertebral fracture in women with postmenopausal osteoporosis. N Engl J Med 350:459–468
Reginster J-Y, Seeman E, De Vernejoul MC, Adami S, Compston J, Phenekos C, Devogelaer JP, Diaz Curiel M, Sawicki A, Goemarere S, Sorensen OH, Felsenberg D, Meunier PJ (2005) Strontium ranelate reduces the risk of nonvertebral fractures in postmenopausal women with osteoporosis: treatment of peripheral osteoporosis (TROPOS) study. J Clin Endocrinol Metab 90:2816–2822
Caro JJ, Ishak KJ, Huybrechts KF et al (2004) The impact of compliance with osteoporosis therapy on fracture rates in actual practice. Osteoporos Int 15:1003–1008
McCombs JS, Thibaud P, McLaughlin-Miley C et al (2004) Compliance with drug therapies for the treatment and prevention of osteoporosis. Maturitas 48:271–287
Yood RA, Emani S, Reed JI et al (2003) Compliance with pharmacologic therapy for osteoporosis. Osteoporos Int 14:965–968
Rabenda V, Mertens R, Fabri V, Vanoverloop J, Sumkay F, Vannecke C, Deswaef A, Verpooten GA, Reginster JY (2008) Adherence to bisphosphonates therapy and hip fracture risk in osteoporotic women. Osteoporos Int 19:811–818
Delmas PD, Vrijens B, Eastell R, Roux C, Pols HA, Ringe JD, Grauer A, Cahall D, Watts NB (2007) Improving Measurements of Persistence on Actonel Treatment (IMPACT) investigators effect of monitoring bone turnover markers on persistence with risedronate treatment of postmenopausal osteoporosis. J Clin Endocrinol Metab 92:1296–1304
Finigan J, Bainbridge PR, Eastell R (2001) Adherence to osteoporosis therapies. Osteoporos Int 12:S48–S49, P110[abstract]
Sebaldt RJ, Shane LG, Pham B et al (2004) Longer term effectiveness outcomes of noncompliance and nonpersitence with daily regimen bisphosphonate therapy in patients with osteoporosis treated in tertiary specialist care. Osteoporos Int 15(Suppl 1):S107 [abstract P391SA]
Huybrechts KF, Ishak KJ, Caro JJ (2006) Assessment of compliance with osteoporosis treatment and its consequences in a managed care population. Bone 38:922–928
Siris ES, Harris ST, Rosen CJ, Barr CE, Arvesen JN, Abbott TA, Silverman S (2006) Adherence to bisphosphonate therapy and fracture rates in osteoporotic women: relationship to vertebral and nonvertebral fractures from 2 US claims databases. Mayo Clin Proc 81:1013–1022
Weycker D, Macarios D, Edelsberg J, Oster G (2007) Compliance with osteoporosis drug therapy and risk of fracture. Osteoporos Int 18:271–277
Wells GA, Cranney A, Peterson J, Boucher M, Shea B, Robinson V, Coyle D, Tugwell P (2008) Risedronate for the primary and secondary prevention of osteoporotic fractures in postmenopausal women. Cochrane Database Syst Rev 1:CD004523
Wells GA, Cranney A, Peterson J, Boucher M, Shea B, Robinson V, Coyle D, Tugwell P (2008) Alendronate for the primary and secondary prevention of osteoporotic fractures in postmenopausal women. Cochrane Database Syst Rev 1:CD001155
Nguyen ND, Eisman JA, Nguyen TV (2006) Anti-hip fracture efficacy of biophosphonates: a Bayesian analysis of clinical trials. J Bone Miner Res 21:340–349
O’Donnell S, Cranney A, Wells GA, Adachi JD, Reginster JY (2006) Strontium ranelate for preventing and treating postmenopausal osteoporosis. Cochrane Database Syst Rev 4:CD005326
Black DM, Cummings SR, Karpf DB, Cauley JA, Thompson DE, Nevitt MC, Bauer DC, Genant HK, Haskell WL, Marcus R, Ott SM, Torner JC, Quandt SA, Reiss TF, Ensrud KE (1996) Randomised trial of effect of alendronate on risk of fracture in women with existing vertebral fractures. Fracture Intervention Trial Research Group Lancet 348:1535–1541
Harris ST, Watts NB, Genant HK, McKeever CD, Hangartner T, Keller M, Chesnut CH 3rd, Brown J, Eriksen EF, Hoseyni MS, Axelrod DW, Miller PD (1999) Effects of risedronate treatment on vertebral and nonvertebral fractures in women with postmenopausal osteoporosis: a randomized controlled trial. Vertebral Efficacy With Risedronate Therapy (VERT) study group. JAMA 282:1344–1352
Reginster J, Minne HW, Sorensen OH, Hooper M, Roux C, Brandi ML, Lund B, Ethgen D, Pack S, Roumagnac I, Eastell R (2000) Randomized trial of the effects of risedronate on vertebral fractures in women with established postmenopausal osteoporosis. Vertebral Efficacy with Risedronate Therapy (VERT) study group. Osteoporos Int 11:83–91
Liberman UA, Weiss SR, Broll J, Minne HW, Quan H, Bell NH, Rodriguez-Portales J, Downs RW Jr, Dequeker J, Favus M (1995) Effect of oral alendronate on bone mineral density and the incidence of fractures in postmenopausal osteoporosis. the Alendronate Phase III Osteoporosis Treatment Study Group. N Engl J Med 333:1437–1443
Ho AY, Kung AW (2005) Efficacy and tolerability of alendronate once weekly in Asian postmenopausal osteoporotic women. Ann Pharmacother 39:1428–1433
Ettinger B, Black DM, Mitlak BH, Knickerbocker RK, Nickelsen T, Genant HK, Christiansen C, Delmas PD, Zanchetta JR, Stakkestad J, Gluer CC, Krueger K, Cohen FJ, Eckert S, Ensrud KE, Avioli LV, Lips P, Cummings SR (1999) Reduction of vertebral fracture risk in postmenopausal women with osteoporosis treated with raloxifene: results from a 3-year randomized clinical trial. Multiple Outcomes of Raloxifene Evaluation (MORE) Investigators. JAMA 282:637–645
Clowes JA, Peel NF, Eastell R (2004) The impact of monitoring on adherence and persistence with antiresorptive treatment for postmenopausal osteoporosis: a randomized controlled trial. J Clin Endocrinol Metab 89:1117–1123
Breart G, Audran M, Brandi ML, Bröll J, Hamdy ATN, Jakob FJ, McCloskey EV, Palacios S (2009) Good safety and persistence of strontium ranelate in a prospective observational cohort study. Osteoporos Int 20(suppl1):S94, (P273) [abstract]
Lo JC, Pressman AR, Omar MA, Ettinger B (2006) Persistence with weekly alendronate therapy among postmenopausal women. Osteoporos Int 17:922–928
Solomon DH, Avorn J, Katz JN, Finkelstein JS, Arnold M, Polinski JM, Brookhart MA (2005) Compliance with osteoporosis medications. Arch Intern Med 165:2414–2419
Chapuy MC, Pamphile R, Paris E et al (2002) Combined calcium and vitamin D3 supplementation in elderly women: confirmation of reversal of secondary hyperparathyroidism and hip fracture risk: the Decalyos II study. Osteoporos Int 13:257–264
Chapuy MC, Arlot ME, Duboeuf F et al (1992) Vitamin D3 and calcium to prevent hip fractures in the elderly women. N Engl J Med 327:1637–1642
Chapuy MC, Arlot ME, Delmas PD, Meunier PJ (1994) Effect of calcium and cholecalciferol treatment for three years on hip fractures in elderly women. BMJ 308:1081–1082
Dawson-Hughes B, Harris SS, Krall EA, Dallal GE (1997) Effect of calcium and vitamin D supplementation on bone density in men and women 65 years of age or older. N Engl J Med 337:670–376
Larsen ER, Mosekilde L, Foldspang A (2004) Vitamin D and calcium supplementation prevents osteoporotic fractures in elderly community dwelling residents: a pragmatic population-based 3-year intervention study. J Bone Miner Res 19:370–378
Porthouse J, Cockayne S, King C et al (2005) Randomised controlled trial of calcium and supplementation with cholecalciferol (vitamin D3) for prevention of fractures in primary care. BMJ 330:1003–1008
Jackson RD, LaCroix AZ, Gass M et al (2006) Calcium plus vitamin D supplementation and the risk of fractures. N Engl J Med 354:669–683
The RECORD Trial Group (2005) Oral vitamin D3 and calcium for secondary prevention of low-trauma fractures in elderly people (Randomised Evaluation of Calcium Or vitamin D, RECORD): a randomised placebo-controlled trial. Lancet 365:1621–1628
Lips P, Graafmans WC, Ooms ME, Bezemer PD, Bouter LM (1996) Vitamin D supplementation and fracture incidence in elderly persons. A randomized, placebo-controlled clinical trial. Ann Intern Med 124:400–406
Trivedi DP, Doll R, Khaw KT (2003) Effect of four monthly oral vitamin D3 (cholecalciferol) supplementation on fractures and mortality in men and women living in the community: randomised double blind controlled trial. BMJ 326:469–474
Simpson SH, Eurich DT, Majumdar SR, Padwal RS, Tsuyuki RT, Varney J, Johnson JA (2006) A meta-analysis of the association between adherence to drug therapy and mortality. BMJ 333:15
Sikka R, Xia F, Aubert RE (2005) Estimating medication persistency using administrative claims data. Am J Manag Care 11:449–457
Pullar T, Kumar S, Tindall H, Feely M (1989) Time to stop counting the tablets? Clin Pharmacol Ther 46:163–168
Rudd P, Byyny RL, Zachary V, LoVerde ME, Mitchell WD, Titus C, Marshall G (1988) Pill count measures of compliance in a drug trial: variability and suitability. Am J Hypertens 1(3 Pt 1):309–312
Stewart M (1987) The validity of an interview to assess a patient’s drug taking. Am J Prev Med 3:95–100
Acknowledgment
This study has been funded by a research grant from SERVIER.
Conflicts of interest
JYR has received consulting fees or paid advisory boards from Servier, Novartis, Negma, Lilly, Wyeth, Amgen, GlaxoSmithKline, Roche, Merckle, Nycomed, NPS, Theramex; lecture fees when speaking at the invitation of a commercial sponsor from Merck Sharp and Dohme, Lilly, Rottapharm, IBSA, Genevrier, Novartis, Servier, Roche, GlaxoSmithKline, Teijin, Teva, Ebewee Pharma, Zodiac, Analis, Theramex, Nycomed, Novo-Nordisk; grant support from Bristol Myers Squibb, Merck Sharp & Dohme, Rottapharm, Teva, Eli Lilly, Novartis, Roche, GlaxoSmithKline, Amgen, Servier.
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Rabenda, V., Reginster, JY. Positive impact of compliance to strontium ranelate on the risk of nonvertebral osteoporotic fractures. Osteoporos Int 21, 1993–2002 (2010). https://doi.org/10.1007/s00198-009-1155-z
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DOI: https://doi.org/10.1007/s00198-009-1155-z