Strontium ranelate has no bone anabolic (dual) effects in treatment of osteoporosis
Authors:
J. Štěpán
Authors‘ workplace:
Revmatologický ústav a 1. lékařská fakulta UK, Praha
Published in:
Čes. Revmatol., 22, 2014, No. 1, p. 18-24.
Category:
Comments
Overview
The results of studies for approval for the treatment of osteoporosis in postmenopausal women and in men have demonstrated a significant increase in BMD at the lumbar spine and proximal femur and reduction in the relative risk of vertebral and non-vertebral fractures. Strontium deposited in bone attenuates X-rays more strongly than calcium, and causes an artifactual increase in BMD. Neither biochemical markers of bone remodeling, nor histomorphometry of unpaired and paired bone biopsies in women postmenopausal osteoporosis treated with SrR have provided sufficient evidence for the bone anabolic (or dual) effect of SrR. Experimental as well as clinical results have confirmed that strontium, like calcium, slightly reduce osteoclastic bone resorption. These effects of strontium are explained by the effects on calcium-sensing receptor of osteoclasts and osteocytes, and parathyroid glands. Further studies are need to test the hypothesis that the reduced fracture risk is due to changes in distribution of strontium in newly formed bone packets. Strontium ranelate is, hence, a medicine with evidenced effects on the risk of fractures, yet the mechanism of these effects still has not been clearly explained and requires further studies. The knowledge of the mechanism of action of strontium ranelate (SrR) is important not only for the explanation of the effects of SrR upon the skeleton, but also for the safety treatment for other tissues.
Key words:
Osteoporosis, bone mineral density, dual effect, strontium ranelate
Sources
1. Souhrn údajů o přípravku Protelos. http://www.sukl.cz/modules/medication/detail.php?code=0028269&tab=texts].
2. Meunier PJ, Roux C, Seeman E, Ortolani S, Badurski JE, Spector TD, et al. The effects of strontium ranelate on the risk of vertebral fracture in women with postmenopausal osteoporosis. N Engl J Med 2004; 350(5): 459–68.
3. Reginster JY, Seeman E, De Vernejoul MC, 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(5): 2816–22.
4. Seeman E, Vellas B, Benhamou C, Aquino JP, Semler J, Kaufman JM, 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(7): 1113–20.
5. Reginster JY, Bruyere O, Sawicki A, Roces-Varela A, Fardellone P, Roberts A, et al. Long-term treatment of postmenopausal osteoporosis with strontium ranelate: results at 8 years. Bone 2009; 45(6): 1059–64.
6. Reginster JY, Kaufman JM, Goemaere S, Devogelaer JP, Benhamou CL, Felsenberg D, et al. Maintenance of antifracture efficacy over 10 years with strontium ranelate in postmenopausal osteoporosis. Osteoporos Int 2012; 23(3): 1115–22.
7. Bonnelye E, Chabadel A, Saltel F, Jurdic P. Dual effect of strontium ranelate: Stimulation of osteoblast differentiation and inhibition of osteoclast formation and resorption in vitro. Bone 2008; 42(1): 129–38.
8. Burlet N, Reginster JY. Strontium ranelate: The first dual acting treatment for postmenopausal osteoporosis. Clin Orthop Relat Res 2006; 443: 55–60.
9. Hurtel-Lemaire AS, Mentaverri R, Caudrillier A, Cournarie F, Wattel A, Kamel S, et al. The calcium-sensing receptor is involved in strontium ranelate-induced osteoclast apoptosis. New insights into the associated signaling pathways. J Biol Chem 2009; 284(1): 575-84.
10. Caudrillier A, Hurtel-Lemaire AS, Wattel A, Cournarie F, Godin C, Petit L, et al. Strontium ranelate decreases receptor activator of nuclear factor-KappaB ligand-induced osteoclastic differentiation in vitro: involvement of the calcium-sensing receptor. Mol Pharmacol 2010; 78(4): 569–76.
11. Bakker AD, Zandieh-Doulabi B, Klein-Nulend J. Strontium Ranelate affects signaling from mechanically-stimulated osteocytes towards osteoclasts and osteoblasts. Bone 2013; 53(1): 112–9.
12. Maresova KB, Franek T, Vondracek T, Stepan JJ. A comparison of the acute effects of calcium and strontium ranelate on the serum marker of bone resorption. Clin Chem Lab Med 2012; 50(2): 333–5.
13. Marie PJ. The calcium-sensing receptor in bone cells: a potential therapeutic target in osteoporosis. Bone 2010; 46(3): 571–6.
14. Carnevale V, Del Fiacco R, Romagnoli E, Fontana A, Cipriani C, Pepe J, et al. Effects of strontium ranelate administration on calcium metabolism in female patients with postmenopausal osteoporosis and primary hyperparathyroidism. Calcif Tissue Int 2013; 92(1): 15–22.
15. Chavassieux P, Meunier PJ, Roux JP, Portero-Muzy N, Pierre M, Chapurlat R. Bone histomorphometry of transiliac paired bone biopsies after 6 or 12 months of treatment with oral strontium ranelate in 387 osteoporotic women. Randomized comparison to alendronate. J Bone Miner Res 2014; 29(3): 618-28.
16. Kaufman JM, Audran M, Bianchi G, Braga V, Diaz-Curiel M, Francis RM, et al. Efficacy and safety of strontium ranelate in the treatment of osteoporosis in men. J Clin Endocrinol Metab 2013; 98(2): 592–601.
17. Atkins GJ, Welldon KJ, Halbout P, Findlay DM. Strontium ranelate treatment of human primary osteoblasts promotes an osteocyte-like phenotype while eliciting an osteoprotegerin response. Osteoporos Int 2009; 20(4): 653–64.
18. Brennan TC, Rybchyn MS, Green W, Atwa S, Conigrave AD, Mason RS. Osteoblasts play key roles in the mechanisms of action of strontium ranelate. Br J Pharmacol 2009; 157(7): 1291–300.
19. Ammann P, Shen V, Robin B, Mauras Y, Bonjour JP, Rizzoli R. Strontium ranelate improves bone resistance by increasing bone mass and improving architecture in intact female rats. J Bone Miner Res 2004; 19(12): 2012–20.
20. Marie PJ, Hott M, Modrowski D, De Pollak C, Guillemain J, Deloffre P, et al. An uncoupling agent containing strontium prevents bone loss by depressing bone resorption and maintaining bone formation in estrogen-deficient rats. J Bone Miner Res 1993; 8(5): 607–15.
21. Fuchs RK, Allen MR, Condon KW, Reinwald S, Miller LM, McClenathan D, et al. Strontium ranelate does not stimulate bone formation in ovariectomized rats. Osteoporos Int 2008; 19(9): 1331-41.
22. Fuchs RK, Allen MR, Condon KW, Reinwald S, Miller LM, McClenathan D, et al. Calculating clinically relevant drug doses to use in animal studies. Osteoporos Int. 2008;19(12):1815-7.
23. Bruel A, Vegger JB, Raffalt AC, Andersen JE, Thomsen JS. PTH (1–34), but not strontium ranelate counteract loss of trabecular thickness and bone strength in disuse osteopenic rats. Bone 2013; 53(1): 51–8.
24. Arlot ME, Jiang Y, Genant HK, Zhao J, Burt-Pichat B, Roux JP, et al. Histomorphometric and microCT analysis of bone biopsies from postmenopausal osteoporotic women treated with strontium ranelate. J Bone Miner Res. 2008;23(2):215–22.
25. Dempster DW, Compston JE, Drezner MK, Glorieux FH, Kanis JA, Malluche H, et al. Standardized nomenclature, symbols, and units for bone histomorphometry: a 2012 update of the report of the ASBMR Histomorphometry Nomenclature Committee. J Bone Miner Res 2013; 28(1): 2–17.
26. Ma YL, Marin F, Stepan J, Ish-Shalom S, Moricke R, Hawkins F, et al. Comparative effects of teriparatide and strontium ranelate in the periosteum of iliac crest biopsies in postmenopausal women with osteoporosis. Bone 2011; 48(5): 972–8.
27. Anastasilakis AD, Goulis DG, Polyzos SA, Gerou S, Ballaouri I, Efstathiadou Z, et al. No difference between strontium ranelate (SR) and calcium/vitamin D on bone turnover markers in women with established osteoporosis previously treated with teriparatide: a randomized controlled trial. Clin Endocrinol (Oxf) 2009; 70(4): 522–6.
28. Recker RR, Marin F, Ish-Shalom S, Moricke R, Hawkins F, Kapetanos G, et al. Comparative effects of teriparatide and strontium ranelate on bone biopsies and biochemical markers of bone turnover in postmenopausal women with osteoporosis. J Bone Miner Res 2009; 24(8): 1358–68.
29. Seeman E, Delmas PD, Hanley DA, Sellmeyer D, Cheung AM, Shane E, et al. Microarchitectural deterioration of cortical and trabecular bone: differing effects of denosumab and alendronate. J Bone Miner Res 2010; 25(8): 1886–94.
30. Millan JL. The role of phosphatases in the initiation of skeletal mineralization. Calcif Tissue Int 2013; 93(4): 299–306.
31. Vasikaran S, Eastell R, Bruyere O, Foldes AJ, Garnero P, Griesmacher A, et al. Markers of bone turnover for the prediction of fracture risk and monitoring of osteoporosis treatment: a need for international reference standards. Osteoporos Int 2011; 22(2): 391–420.
32. Frost ML, Moore AE, Siddique M, Blake GM, Laurent D, Borah B, et al. (18)F-fluoride PET as a noninvasive imaging biomarker for determining treatment efficacy of bone active agents at the hip: a prospective, randomized, controlled clinical study. J Bone Miner Res 2013; 28(6): 1337–47.
33. Prentice RL, Pettinger MB, Jackson RD, Wactawski-Wende J, Lacroix AZ, Anderson GL, et al. Health risks and benefits from calcium and vitamin D supplementation: Women's Health Initiative clinical trial and cohort study. Osteoporos Int 2013; 24(2): 567–80.
34. Bruyere O, Roux C, Detilleux J, Slosman DO, Spector TD, 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(8): 3076–81.
35. Blake GM, Fogelman I. Long-term effect of strontium ranelate treatment on BMD. J Bone Miner Res 2005; 20(11): 1901–4.
36. Oliveira JP, Querido W, Caldas RJ, Campos AP, Abracado LG, Farina M. Strontium is incorporated in different levels into bones and teeth of rats treated with strontium ranelate. Calcif Tissue Int. 2012;91(3):186–95.
37. Barenholdt O, Kolthoff N, Nielsen SP. Effect of long-term treatment with strontium ranelate on bone strontium content. Bone 2009; 45(2): 200–6.
38. Roschger P, Manjubala I, Zoeger N, Meirer F, Simon R, Li C, et al. Bone material quality in transiliac bone biopsies of postmenopausal osteoporotic women after 3 years of strontium ranelate treatment. J Bone Miner Res 2010; 25(4): 891–900.
39. Rizzoli R, Laroche M, Krieg MA, Frieling I, Thomas T, Delmas P, et al. Strontium ranelate and alendronate have differing effects on distal tibia bone microstructure in women with osteoporosis. Rheumatol Int 2010; 30(10): 1341–8.
40. Rizzoli R, Chapurlat RD, Laroche JM, Krieg MA, Thomas T, Frieling I, et al. Effects of strontium ranelate and alendronate on bone microstructure in women with osteoporosis. Results of a 2-year study. Osteoporos Int 2012; 23(1): 305-15.
41. Ammann P, Badoud I, Barraud S, Dayer R, Rizzoli R. Strontium ranelate treatment improves trabecular and cortical intrinsic bone tissue quality, a determinant of bone strength. J Bone Miner Res. 2007; 22(9): 1419–25.
42. Cacoub P, Descamps V, Meyer O, Speirs C, Belissa-Mathiot P, Musette P. Drug rash with eosinophilia and systemic symptoms (DRESS) in patients receiving strontium ranelate. Osteoporos Int 2013; 24(5): 1751-7.
43. Jonville-Bera AP, Autret-Leca E. [Adverse drug reactions of strontium ranelate(Protelos((R)) in France]. Presse Med 2011; 40(10): e453–62.
44. Lee YY, Yang CH, Chen CH, Hwang JS. Alopecia associated with strontium ranelate use in a 62-year-old woman. Osteoporos Int 2013; 24(3): 1127–9.
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