Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Meta-Analysis
. 2006 Oct 18;2006(4):CD005326.
doi: 10.1002/14651858.CD005326.pub3.

Strontium ranelate for preventing and treating postmenopausal osteoporosis

S O'Donnell  1 , A Cranney, G A Wells, J D Adachi, J Y Reginster
Affiliations
Meta-Analysis

Strontium ranelate for preventing and treating postmenopausal osteoporosis

S O'Donnell et al. Cochrane Database Syst Rev. .

Abstract

Background: Strontium ranelate is a new treatment for osteoporosis therefore, its benefits and harms need to be known.

Objectives: To determine the efficacy and safety of strontium ranelate for the treatment and prevention of postmenopausal osteoporosis.

Search strategy: We searched MEDLINE (1996 to March 2005), EMBASE (1996 to week 9 2005), the Cochrane Library (1996 to Issue 1 2005), reference lists of relevant articles and conference proceedings from the last two years. Additional data was sought from authors.

Selection criteria: We included randomized controlled trials (RCTs) of at least one year duration comparing strontium ranelate versus placebo reporting fracture incidence, bone mineral density (BMD), health related quality of life or safety in postmenopausal women. Treatment (versus prevention) population was defined as women with prevalent vertebral fractures and/or lumbar spine BMD T score < -2.5 SD.

Data collection and analysis: Two reviewers independently determined study eligibility, assessed trial quality and extracted the relevant data. Disagreements were resolved by consensus. RCTs were grouped by dose of strontium ranelate and treatment duration. Where possible, meta-analysis was conducted using the random effects model.

Main results: Four trials met the inclusion criteria. Three included a treatment population (0.5 to 2 g of strontium ranelate daily) and one a prevention population (0.125 g, 0.5 g and 1 g daily). A 37% reduction in vertebral fractures (RR 0.63, 95% CI 0.56, 0.71) and a 14% reduction in non-vertebral fractures (RR 0.86, 95% CI 0.75, 0.98) were demonstrated over three years with 2 g of strontium ranelate daily in a treatment population. An increase in BMD was shown at all BMD sites after two to three years in both populations. Lower doses of strontium ranelate were superior to placebo and the highest dose demonstrated the greatest reduction in vertebral fractures and increase in BMD. An increased risk of diarrhea with 2 g of strontium ranelate was found; however, adverse events did not affect the risk of discontinuing treatment nor did it increase the risk of serious side effects, gastritis or death. Additional data suggests that the risk of vascular and nervous system side-effects is slightly increased with taking 2 g of strontium ranelate daily over three to four years.

Authors' conclusions: There is silver level evidence (www.cochranemsk.org) to support the efficacy of strontium ranelate for the reduction of fractures (vertebral and to a lesser extent non-vertebral) in postmenopausal osteoporotic women and an increase in BMD in postmenopausal women with/without osteoporosis. Diarrhea may occur however, adverse events leading to study withdrawal were not significantly increased with taking 2 g of strontium ranelate daily. Potential vascular and neurological side-effects need to be further explored.

PubMed Disclaimer

Conflict of interest statement

All four included trials were supported by Servier, the manufacturer of strontium ranelate. Also, J Y Reginster is an author on the four included trials within this review; in addition Dr. Reginster's disclosure of interest is as follows: Consulting fees or paid advisory boards: Servier, Novartis, Negma, Lilly, Wyeth, Amgen, GlaxoSmithKline, Roche, Merckle, Nycomed, NPS, Theramex, UCB.

Lecture fees when speaking at the invitation of a commercial sponsor: 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 Industry: Bristol Myers Squibb, Merck Sharp & Dohme, Rottapharm, Teva, Lilly, Novartis, Roche, GlaxoSmithKline, Amgen, Servier.

Lastly, J Adachi has also received speaker fees from Servier.

Figures

1.1
1.1. Analysis
Comparison 1: Fractures, Outcome 1: Verterbral fractures
1.2
1.2. Analysis
Comparison 1: Fractures, Outcome 2: Non‐vertebral fractures
2.1
2.1. Analysis
Comparison 2: BMD, Outcome 1: Lumbar spine BMD not adjusted for strontium content
2.2
2.2. Analysis
Comparison 2: BMD, Outcome 2: Lumbar spine adjusted for strontium content
2.3
2.3. Analysis
Comparison 2: BMD, Outcome 3: Femoral neck
2.4
2.4. Analysis
Comparison 2: BMD, Outcome 4: Total hip
3.1
3.1. Analysis
Comparison 3: Adverse Events, Outcome 1: Total withdrawls
3.2
3.2. Analysis
Comparison 3: Adverse Events, Outcome 2: Withdrawals due to adverse events
3.3
3.3. Analysis
Comparison 3: Adverse Events, Outcome 3: Number of emergent adverse events
3.4
3.4. Analysis
Comparison 3: Adverse Events, Outcome 4: Serious adverse events
3.5
3.5. Analysis
Comparison 3: Adverse Events, Outcome 5: Diarrhea
3.6
3.6. Analysis
Comparison 3: Adverse Events, Outcome 6: Gastritis
3.7
3.7. Analysis
Comparison 3: Adverse Events, Outcome 7: Deaths
See this image and copyright information in PMC

Update of

References

References to studies included in this review

Meunier 2002 {published data only}
    1. Meunier PJ, Slosman DO, Delmas PD, Sebert JL, Brandi ML, Albanese C, Lorenc R, Pors-Nielsen S, Vernejoul MC, Roces A, Reginster JY. Strontium ranelate: Dose-dependent effects in established postmenopausal vertebral osteoporosis - a 2-year randomized placebo controlled trial. Journal of clinical endocrinology and metabolism 2002;87(5):2060-66. - PubMed
Meunier 2004‐1 {published data only}
    1. Meunier PJ, Roux C, Seeman E, Ortolani S, Badurski JE, Spector TD, Cannata J, Balogh A, Lemmel E, Pors-Nielson S, Rizzoli R, Genant HK, Reginster J. The effects of strontium ranelate on the risk of vertebral fracture in women with postmenopausal osteoporosis. New england journal of medicine 2004;350(5):459-68. - PubMed
Reginster 2002‐1 {published data only}
    1. Reginster JY, Deroisy R, Dougados M, Jupsin I, Colette J, Roux C. Prevention of early postmenopausal bone loss by strontium ranelate: The randomized, two-year, double-masked, dose-ranging, placebo-controlled PREVOS study. Osteoporosis international 2002;13:925-31. - PubMed
Reginster 2005 {published data only}
    1. Reginster JY, Seeman E, Vernejoul MC, Adami S, Compston J, Phenekos C, Devogelaer JP, Diaz Curiel M, Sawicki A, Goemaere S, Sorensen OH, Felsenberg D, Meunier PJ. Strontium ranelate reduces the risk of nonvertebral fractures in postmenopausal women with osteoporosis: TROPOS study. Journal of clinical endocrinology and metabolism 2005;90(5):2816-22. - PubMed

References to studies excluded from this review

Boivin 2003 {published data only}
    1. Boivin G. Bone mineralization and mineral status. Therapie 2003;58(5):409-13. - PubMed
Meunier 2003 {published data only}
    1. Meunier PJ, Reginster JY. Design and methodology of the phase 3 trials for the clinical development of strontium ranelate in the treatment of women with postmenopausal osteoporosis. Osteoporosis international 2003;14 Suppl(3):S66-S76. - PubMed
Meunier 2004‐2 {published data only}
    1. Meunier PJ, Roux C, Seeman E, Pagalilauan G, Laya M. Strontium ranelate prevented vertebral fractures in postmenopausal women with osteoporosis. Evidence-based obstetrics and gynecology 2004;6(4):216-7.
Meunier 2004‐3 {published data only}
    1. Meunier PJ, Roux C, Seeman E, Cheung A. Strontium ranelate reduced the risk of vertebral fractures in postmenopausal women osteoporosis. Evidence-based medicine 2004;9(5):149.
Naveau 2004 {published data only}
    1. Naveau B. Strontium: a new treatment for osteoporosis. Joint bone spine 2004;71(4):261-63. - PubMed
Pors 2004 {published data only}
    1. Pors NS. The biological role of strontium. Bone 2004;35(3):583-8. - PubMed
Reginster 2002‐2 {published data only}
    1. Reginster JY. Strontium ranelate in osteoporosis. Current pharmaceutical design 2002;8(21):1907-16. - PubMed
Reginster 2003‐1 {published data only}
    1. Reginster JY, Meunier PJ. Strontium ranelate phase 2 dose-ranging studies: PREVOS and STRATOS studies. Osteoporosis international 2003;14(Suppl 3):S56-S65. - PubMed
Reginster 2003‐2 {published data only}
    1. Reginster JY, Deroisy R, Jupsin I. Strontium ranelate: a new paradigm in the treatment of osteoporosis. Drugs today (Barc ) 2003;39(2):89-101. - PubMed
Reginster 2004 {published data only}
    1. Reginster JY, Devogelaer JP. Treatment of postmenopausal osteoporosis in 2004. Revue medicale de liege 2004;59(11):633-47. - PubMed
Reginster 2004‐1 {published data only}
    1. Reginster JY, Lecart MP, Deroisy R, Lousberg C. Strontium ranelate: a new paradigm in the treatment of osteoporosis. Expert opinion on investigational drugs 2004;13(7):857-64. - PubMed
Sorbera 2003 {published data only}
    1. Sorbera LA, Castan~er J, Leeson PA, Bayes M. Strontium ranelate: Treatment and prevention of osteoporosis bone resorption inhibitor bone formation stimulant. Drugs of the future 2003;28(4):328-35.
Uebelhart 2003 {published data only}
    1. Uebelhart D, Frey D, Frey-Rindova P, Goerres G, Michel BA. Therapy of osteoporosis: bisphosphonates, SERM's, teriparatide and strontium. Zeitschrift für rheumatologie 2003;62(6):512-7. - PubMed

Additional references

1993 Consensus
    1. Consensus Development Conference: Diagnosis, Prophylaxis, and Treatment of Osteoporosis. American journal of medicine. 672 edition. Vol. 94. 1993:561. - PubMed
Alderson 2003
    1. Alderson P, Green S, Higgins JPT. Cochrane Reviewers' Handbook 4.2.2.. http://www.cochrane.org/resources/handbook/hbook.htm 2003.
Blake 2005
    1. Blake GM, Fogelman I. Long-term effect of strontium ranelate treatment on BMD. Journal of bone and mineral research 2005;20(11):1901-4. - PubMed
Brown 2002
    1. Brown JP, Josse RG. 2002 Clinical practice guidelines for the diagnosis and management of osteoporosis in Canada. Canadian medical association journal 2002;167(10 Suppl):S1-34. - PMC - PubMed
Buehler 2001
    1. Buehler J, Chappuis P, Saffar JL, Tsouderos Y, Vignery A. Strontium ranelate inhibits bone resorption while maintaining bone formation in alveolar bone in monkeys (Macaca fascicularis). Bone 2001;29(2):176-9. - PubMed
Burge 2003
    1. Burge RT, King AB, Balda E, Worley D. Methodology for estimating current and future burden of osteoporosis in state populations: application to Florida in 2000 through 2025. Value health 2003;6:574-83. - PubMed
Canalis 1996
    1. Canalis E, Hott M, Deloffre P, Tsouderos Y, Marie PJ. The divalent strontium salt S12911 enhances bone cell replication and bone formation in vitro. Bone 1996;18(6):517-23. - PubMed
Cauley 2000
    1. Cauley JA, Thompson DE, Ensrud KC, Scott JC, Black D. Risk of mortality following clinical fractures. Osteoporosis international 2000;11(7):556-61. - PubMed
Cranney 2002
    1. Cranney A, Guyatt G, Griffith L, Wells G, Tugwell P, Rosen C. Meta-analyses of therapies for postmenopausal osteoporosis. IX: Summary of meta-analyses of therapies for postmenopausal osteoporosis. Endocrine reviews 2002;23(4):570-8. - PubMed
Cummings 2002
    1. Cummings SR. Epidemiology and outcomes of osteoporotic fractures. Lancet 2002;359:1761-7. - PubMed
D'Haese 2000
    1. D'Haese PC, Schrooten I, Goodman WG, Cabrera WE, Lamberts LV, Elseviers MM, Couttenye MM, De Broe ME. Increased bone strontium levels in hemodialysis patients with osteomalacia. Kidney International 2000;57:1107-1114. - PubMed
Eisenberg 1973
    1. Eisenberg E. The biological metabolism of strontium. In: Zipkin I, editors(s). Biological Mineralization. New York: John Wilely & Sons, 1973:435-442.
EMEA 2004
    1. EMEA. PROTELOS. The committee for medicinal products for human use 2004.
Fleiss 1993
    1. Fleiss, JL. Statistical basis of meta-analysis. Statistical methods in medical research 1993;2(2):121-45. - PubMed
Goeree 1996
    1. Goeree R, O'Brien B, Petitt D, Cuddy L, Ferraz M, Adachi JD. An Assessment of the burden of illness due to osteoporosis in Canada. Journal of the society of obstetricians and gynecologists of Canada 1996;(Supplement):15-24.
GRADE Working Group
    1. GRADE Working Group. Grading quality of evidence and strength of recommendations. British medical journal 2005;328.
Higgins 2003
    1. Higgins JPT, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. British medical journal 2003;327:557-60. - PMC - PubMed
Jackson 2000
    1. Jackson SA, Tenenhouse A, Robertson L, the CaMos Study Group. Vertebral fracture definition from population-based data: Preliminary results from the Canadian Multicenter Osteoporosis Study (CaMos). Osteoporosis international 2000;11:680-7. - PubMed
Jadad 1996
    1. Jadad A, Moore RA, Carroll D, Jenkinson D, Reynolds DJ, Gavaghan DJ, McQuay HJ. Assessing the quality of reports of randomized clinical trials: is blinding necessary? Controlled clinical trials 1996;17:1-12. - PubMed
Jagal 1996
    1. Jagal S, Sherry P, Schatzker J. The impact and consequences of hip fracture in Ontario. Canadian journal of surgery 1996;39:105-11. - PMC - PubMed
Jaglal 1998
    1. Jaglal S. Incidence and impact. In: Badley E, Williams JI, editors(s). Patterns of health care in Ontario: Arthritis and related conditions. North York: Institute for Clinical Evaluative Sciences, 1998:Chapter 8.
Johnell 2004
    1. Johnell O, Kanis JA. An estimate of the worldwide prevalence, mortality and disability associated with hip fracture. Osteoporosis international 2004;15(11):897-902. - PubMed
Kanis 2003
    1. Kanis JA, Oden A, Johnell O, De Laet C, Jonsson B, Oglesby AK. The components of excess mortality after hip fracture. Bone 2003;32:468-73. - PubMed
Kanis 2004
    1. Kanis JA, Johnell O. Requirements for DXA for the management of osteoporosis in Europe. Osteoporosis international 2004. - PubMed
Looker 1991
    1. Looker AC, Wahner HW, Dunn WL, Calvo MS, Harris TB, Heyse SP, Johnston CC Jr, Lindsay RL. Proximal femur bone mineral levels of U.S. adults. Osteoporosis international 1995;5:389-409. - PubMed
Marie 1985
    1. Marie PJ, Garba MT, Hott M, Miravet L. Effect of low doses of stable strontium on bone metabolism in rats. Mineral electrolyte and metabolism 1985;11(1):5-13. - PubMed
Marie 2001
    1. Marie PJ, Ammann P, Boivin G, Rey C. Mechanisms of action and therapeutic potential of strontium in bone. Calcfied tissue international 2001;69(3):121-9. - PubMed
Marquis 2005
    1. Marquis P, De La Loge C, Diaz-Curiel M, Spector T, Meunier PJ. Beneficial effects of strontium ranelate on the quality of life in patients with vertebral osteoporosis (SOTI Study). Osteoporosis international 2005;16(Suppl 3):S54 (P223).
Marshall 1996
    1. Marshall D, Johnell O, Wedel H. Meta-analysis of how well measures of bone mineral density predict occurence of osteoporotic fractures. British medical journal 1996;312:1254-9. - PMC - PubMed
Melton 1992
    1. Melton LJ, III, Chrischilles EA, Cooper C, Lane AW, Riggs BL. Perspective. How many women have osteoporosis? Journal of bone and mineral research 1992;7(9):1005-10. - PubMed
Neer 2001
    1. Neer RM, Arnaud CD, Zanchetta JR, Prince R, Gaich GA, Reginster JY et al. Effect of parathyroid hormone (1-34) on fractures and bone mineral density in postmenopausal women with osteoporosis. New england journal of medicine 2001;344(19):1434-41. - PubMed
NIH 2001
    1. NIH consensus development panel on osteoporosis prevention and diagnosis. Osteoporosis prevention, diagnosis, prophylaxis and treatment. Journal of american medical association 2001;285:785-95. - PubMed
Ortolani 2006
    1. Ortolani S, Vai S. Strontium ranelate: An increased bone quality leading to vertebral antifracture efficacy at all stages. Bone 2006;38:S19-S22. - PubMed
Oste 2005
    1. Oste L, Bervoets AR, Behets GJ, Dams G, Marijnissen RL, Geryl H, Lamberts LV, Verberckmoes SC, Van Hoof VO, De Broe ME, D'Haese PC. Time-evolution and reversibility of strontium-induced osteomalacia in chronic renal failure rats. Kidney International 2005;67:920-930. - PubMed
Ray 1997
    1. Ray NF, Chan JK, Thamer M, Melton LJ III. Medical expenditures for the treatment of osteoporosis fractures in the United States in 1995: report from the National Osteoporosis Foundation. Journal of bone and mineral research 1997;12:24-35. - PubMed
Riggs 2005
    1. Riggs BL, Parfitt AM. Drugs used to treat osteoporosis: The critical need for a uniform nomenclature based on their action on bone remodeling. Journal of bone and mineral research 2005;20(2):177-84. - PubMed
Robinson 2002
    1. Robinson KA, Dickersin K. Development of a highly sensitive search strategy for the retrieval of reports of controlled trials using PubMed. International journal of epidemiology 2002;31(1):150-3. - PubMed
Schrooten 1998
    1. Schrooten I, Cabrera W, Goodman WG, Dauwe S, Lamberts LV, Marynissen R, Dorrine W, De Broe ME, D'Haese PC. Strontium causes osteomalacia in chronic renal failure rats. Kidney International 1998;54:448-456. - PubMed
Schrooten 2003
    1. Schrooten I, Behets GJ, Cabrera WE, Vercauteren SR, Lamberts LV, Verberckmoes SC, Bervoets AJ, Dams G, Goodman WG, De Broe ME, D'Haese PC. Dose-dependent effects on strontium on bone of chronic renal failure rats. Kidney International 2003;63:927-935. - PubMed
Schulz 1995
    1. Schulz KF, Chalmers I, Hayes RJ, Altman DG. Empirical evidence of bias. Dimensions of methodological quality associated with estimates of treatment effects in controlled trials. Journal of american medical association 1995;273(5):408-12. - PubMed
Seeley 1991
    1. Seeley DG, Browner WS, Nevitt MC, Genant HK, Scott JC, Cummings SR. Which fractures are associated with low appendicular bone mass in elderly women? The Study of Osteoporotic Fractures Research Group. Annals of internal medicine 1991;115(11):837-42. - PubMed
Seeman 2002
    1. Seeman E. Pathogenesis of bone fragility in women and men. Lancet 2002;359(9320):1841-50. - PubMed
Slosman 1999
    1. Slosman D, Provvedini DM, Meunier PJ, Delmas PD, Sebert JL, De Vernejoul MC et al. The use of different dual X-ray absorptiometry brands in a multicenter clinical trial. Journal of clinical densitometry 1999;2:37-44. - PubMed
Tosteson 2001
    1. Tosteson AN, Gabriel SE, Grove MR, Moncur MM, Kneeland TS, Melton LJ, III. Impact of hip and vertebral fractures on quality-adjusted life years. Osteoporosis international 2001;12:1042-9. - PubMed
Tugwell 2004
    1. Tugwell P, Shea B, Boers M, Brooks P, Simon LS, Strand V et al. Evidence-based rheumatology. BMJ Publishing Group, 2004.
US Dept Health 2004
    1. US Department of Health and Human Service. Bone health and osteoporosis: a report of the surgeon general. Office of the Surgeon General, Rockville, and MD. 2004:1-436. - PubMed
WHO 1994
    1. WHO Study Group. Assessment of fracture risk and its application to screening for postmenopausal osteoporosis. Report of a WHO study group. World Health Organization technical report 1994;843:1-129. - PubMed

Publication types

MeSH terms