Abstract
Summary
The aim of the present study was to determine the efficacy of strontium ranelate as a function of baseline fracture risk. Treatment with strontium ranelate was associated with a significant 31% decrease in all clinical osteoporotic fractures (vertebral fractures included). Hazard ratios for the effect of strontium ranelate on the fracture outcome did not change significantly with increasing fracture probability.
Introduction
Two previous studies have suggested that the efficacy of intervention may be greater in the segment of the population at highest fracture risk as assessed by the FRAX® algorithms. The aim of the present study was to determine whether the anti-fracture efficacy of strontium ranelate was dependent of the level of fracture risk.
Methods
The primary data of the two phase III studies (SOTI and TROPOS) of the effects of strontium ranelate in postmenopausal osteoporosis were combined. Country-specific probabilities were computed using the FRAX® tool (version 2.0). The primary outcome variable comprised all clinical osteoporotic fractures (including clinical vertebral fractures). Interactions between fracture probability and efficacy were explored by Poisson regression.
Results
The 10-year probability of major osteoporotic fractures (with BMD) ranged from 2.5% to 90.8%. FRAX®-based hip fracture probabilities ranged from 0.1% to 90.3%. The incidence of clinical osteoporotic fractures (vertebral fractures excluded) and morphometric vertebral fractures increased with increasing baseline fracture probabilities. Treatment with strontium ranelate was associated with a 31% (95% CI = 20–39%) decrease in osteoporotic clinical fractures and a 40% decrease in vertebral fractures assessed by semiquantitative morphometry (95% CI = 31–48%) Hazard ratios for the effect of strontium ranelate on the fracture outcomes did not change significantly with increasing fracture probability.
Conclusion
Strontium ranelate significantly decreased the risk of osteoporotic clinical fractures, non vertebral fractures and morphometric vertebral fractures in women. Overall, the efficacy of strontium ranelate was not dependent of the level of fracture risk assessed by FRAX
Similar content being viewed by others
References
Chattopadhyay N, Quinn SJ, Kifor O, Ye C, Brown EM (2007) The calcium-sensing receptor (CaR) is involved in strontium ranelate-induced osteoblast proliferation. Biochem Pharmacol 74:438–447
Hurtel AS, Mentaverri R, Caudrillier A et al (2008) The calcium-sensing receptor is involved in strontium ranelate-induced osteoclast apoptosis: new insights into the associated signalling pathways. J Biol Chem 2(284):575–584
Brennan TC, Rybchyn MS, Green W et al (2009) Osteoblasts play key roles in the mechanisms of action of strontium ranelate. Br J Pharmacol 157:1291–1300
Marie PJ, Amman P, Boivin G, Rey C (2001) Mechanisms of action and therapeutic potential of strontium ranelate in bone. Calcif Tissue Int 69:121–129
Marie PJ (2007) Strontium ranelate: new insights into its dual mode of action. Bone 40:S5–S8
Marie PJ, Hott M, Modrowski D et al (1993) An uncoupling agent containing strontium ranelate prevents bone loss by depressing bone resorption and maintaining bone formation in estrogen-deficient rats. J Bone Miner Res 8:607–615
Buehler J, Chappuis P, Saffar JL, Tsouderos Y, Vignery A (2001) Strontium ranelate ranelate inhibits bone resorption while maintaining bone formation in alveolar bone in monkeys (Macaca fascicularis). Bone 29:176–179
Ammann P, Shen V, Robin B et al (2004) Strontium ranelate improves bone resistance by increasing bone mass and improving architecture in intact female rats. J Bone Miner Res 19:2012–2020
Ammann P, Badoud I, Barraud S et al (2007) Strontium ranelate treatment improves trabecular and cortical intrinsic bone tissue quality, a determinant of bone strength. J Bone Miner Res 22:1419–1425
Bain SD, Jerome C, Shen V et al (2009) Strontium ranelate improves bone strength in ovariectomized rat by positively influencing bone resistance determinants. Osteoporos Int 20:1417–1428
Meunier PJ, Roux C, Seeman E, Ortolani S, Badurski JE, Spector TD et al (2004) (2004) The effects of strontium ranelate 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 et al (2005) Strontium ranelate ranelate reduces the risk of nonvertebral fracture in postmenopausal women with osteoporosis: TROPOS study. J Clinl Endocrinol Metab 90:2816–2822
Recker RR, Marin F, Ish-Shalom S et al (2009) Comparative effects of teriparatide and strontium ranelate ranelate on bone biopsies and biochemical markers of bone turnover in postmenopausal women with osteoporosis. J Bone Miner Res 24:1358–1368
Arlot ME, Jiang Y, Genant HK et al (2008) Histomorphometric and microCT analysis of bone biopsies from postmenopausal osteoporotic women treated with strontium ranelate ranelate. J Bone Miner Res 23:215–222
Blake GM, Compston JE, Fogelman I (2009) Could strontium ranelate ranelate have a synergistic role in the treatment of osteoporosis? J Bone Miner Res 24:1354–1357
Meunier PJ, Slosman DO, Delmas PD et al (2002) Strontium ranelate ranelate: dose-dependent effects in established postmenopausal vertebral osteoporosis—a 2-year randomized placebo controlled trial. J Clin Endocrinol Metab 87:2060–2066
Meunier PJ, Roux C, Ortolani S et al (2009) Effects of long-term strontium ranelate ranelate treatment on vertebral fracture risk in postmenopausal women with osteoporosis. Osteoporos Int 20:1663–1673
McCloskey EV, Johansson H, Oden A, Vasireddy S, Kayan K, Pande K, Jalava T, Kanis JA (2009) Anti-fracture efficacy in women selected by 10-year fracture probability – results of a double blind, placebo controlled randomised study. Osteoporos Int 20:811–818
Kanis JA, Johansson H, Oden A, McCloskey EV (2009) Bazedoxifene reduces vertebral and clinical fractures in postmenopausal women at high risk assessed with FRAX®. Bone 44:1049–1054
Committee for Medicinal Products for Human Use (CHMP) (2006) Guideline on the evaluation of medicinal products in the treatment of primary osteoporosis. Ref CPMP/EWP/552/95Rev.2. London, CHMP. Nov 2006
Kanis JA on behalf of the World Health Organization Scientific Group (2008a) Assessment of osteoporosis at the primary health-care level. Technical Report. WHO Collaborating Centre, University of Sheffield, UK. Accessible at http://www.shef.ac.uk/FRAX
Kanis JA, Johnell O, Oden A, Johansson H, McCloskey E (2008) FRAX™ and the assessment of fracture probability in men and women from the UK. Osteoporos Int 19:385–397
World Health Organization (2007) Assessment of osteoporosis at the primary health care level. Summary Report of a WHO Scientific Group. WHO, Geneva. (www.who.int/chp/topics/rheumatic/en/index.html). Full report available at http://www.shef.ac.uk/FRAX
Looker AC, Wahner HW, Dunn WL, Calvo MS, Harris TB, Heyse SP (1998) Updated data on proximal femur bone mineral levels of US adults. Osteoporos Int 8:468–486
Genant HK, Jergas M, Palermo L et al (1996) Comparison of semiquantitative visual and quantitative morphometric assessment of prevalent and incident vertebral fractures in osteoporosis. J Bone Miner Res 11:984–996
Genant HK, Wu CY, van Kuijk C, Nevitt MC (1993) Vertebral fracture assessment using a semiquantitative technique. J Bone Miner Res 8:1137–1148
Dawson-Hughes B, Looker AC, Tosteson AN, Johansson H, Kanis JA, Melton LJ 3rd (2010) The potential impact of new National Osteoporosis Foundation guidance on treatment patterns. Osteoporos Int 21:41–52
Kanis JA, Oden A, Johnell O, Jonsson B, de Laet C, Dawson A (2001) The burden of osteoporotic fractures: a method for setting intervention thresholds. Osteoporos Int 12:417–427
Breslow NE, Day NE (1987) Statistical methods in cancer research. IARC Scientific Publications, Lyon, No 32 Vol. II:pp 131–135
Collette J, Bruyère O, Kaufman JM, Lorenc R, Felsenberg D, Spector TD, Diaz-Curiel M, Boonen S, Reginster J-Y (2010) Vertebral antifracture efficacy of strontium ranelate according to pretreatment bone turnover. Osteoporos Int 21:233–241
Johnell O, Kanis JA (2006) An estimate of the worldwide prevalence and disability associated with osteoporotic fractures. Osteoporos Int 17:1726–1733
Roux C, Reginster JY, Fechtenbaum J, Kolta S, Sawicki A, Tulassay Z et al (2006) Vertebral fracture risk reduction with strontium ranelate ranelate in women with postmenopausal osteoporosis is independent of baseline risk factors. J Bone Miner Res 21:536–542
Kanis JA, Johansson H, Oden A, McCloskey EV (2010) A meta-analysis of the efficacy of raloxifene on all clinical and vertebral fractures and its dependency on FRAX®. Bone 47:729–735
McCloskey EV, Beneton M, Charlesworth D, Kayan K, de Takats D, Dey A et al (2007) Clodronate reduces the incidence of fractures in community dwelling elderly women unselected for osteoporosis: results of a double-blind, placebo-controlled randomized study. J Bone Miner Res 22:135–141
Kanis JA, Oden A, Johnell O, Johansson H, De Laet C, Brown J et al (2007) The use of clinical risk factors enhances the performance of BMD in the prediction of hip and osteoporotic fractures in men and women. Osteoporos Int 18:1033–1046
Acknowledgements
This work was an independent study funded by a grant from Servier. We thank Dr Patricia Chatelain for her help with the preparation and transfer of the data.
Conflicts of interest
None.
Author information
Authors and Affiliations
Corresponding author
Additional information
An erratum to this article can be found at http://dx.doi.org/10.1007/s00198-011-1683-1
Rights and permissions
About this article
Cite this article
Kanis, J.A., Johansson, H., Oden, A. et al. A meta-analysis of the effect of strontium ranelate on the risk of vertebral and non-vertebral fracture in postmenopausal osteoporosis and the interaction with FRAX® . Osteoporos Int 22, 2347–2355 (2011). https://doi.org/10.1007/s00198-010-1474-0
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00198-010-1474-0