RESEARCH PROGRESS OF EFFECTS OF STRONTIUM RANELATE ON OSTEOARTHRITIS_Chinese Journal of Reparative and Reconstructive Surgery

Authors：

WANGYu ¹ , DAIMuwei ¹ , TIANFaming ² ,  ZHANGLiu ¹

1. Department of Orthopedics, Affiliated Hospital of Hebei United University, Tangshan Hebei, 063000, P. R. China;
2. Medical Research Center, Hebei United University;

Corresponding author：

ZHANGLiu, Email: zhliu130@sohu.com

Keywords：

Osteoarthritis; Strontium ranelate; Bone metabolism; Osteoblasts; Osteoclasts

DOI：

10.7507/1002-1892.20140320

Video：

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Objective To review the research progress focused on the effects of strontium ranelate (SR) on osteoarthritis. Methods The relevant literature about the effects and mechanism of SR intervening osteoarthritis in recent years was extensively reviewed and comprehensively analyzed. Results SR not only could improve the microenvironment of bone metabolism in articular cartilage with osteoarthritis, promote activity of osteoblasts, and inhibit activity of osteoclasts, but also could adjust the expression of key proteases which affect cartilage formation, and therefore it has a potential protective effect on subchondral bone during the progression of osteoarthritis cartilage. Conclusion SR is expected to become a drug of osteoarthritis disease remission, but further studies are needed to clarify the mechanism of SR in osteoarthritis, and finally confirm the best application dosage of SR in osteoarthritis treatment.

Citation： WANGYu, DAIMuwei, TIANFaming, ZHANGLiu. RESEARCH PROGRESS OF EFFECTS OF STRONTIUM RANELATE ON OSTEOARTHRITIS. Chinese Journal of Reparative and Reconstructive Surgery, 2014, 28(12): 1479-1483. doi: 10.7507/1002-1892.20140320 Copy

1.	Bijlsma JW, Berenbaum F, Lafeber FP. Osteoarthritis:an update with relevance for cl inical practice. Lancet, 2011, 377(9783):2115-2126.
2.	Kwan Tat S, Lajeunesse D, Pelletier JP, et al. Targeting subchondral bone for treating osteoarthritis:what is the evidence? Best Pract Res Clin Rheumatol, 2010, 24(1):51-70.
3.	Li G, Yin J, Gao J, et al. Subchondral bone in osteoarthritis:insight into risk factors and microstructural changes. Arthritis Res Ther, 2013, 15(6):223.
4.	Mastbergen SC, Lafeber FP. Changes in subchondral bone early in the development of osteoarthritis. Arthritis Rheum, 2011, 63(9):2561-2563.
5.	Martel-Pelletier J, Wildi LM, Pelletier JP. Future therapeutics for osteoarthritis. Bone, 2012, 51(2):297-311.
6.	Losina E, Daigle ME, Suter LG, et al. Disease-modifying drugs for knee osteoarthritis:can they be cost-effective? Osteoarthritis Cartilage, 2013, 21(5):655-667.
7.	Jotanovic Z, Mihelic R, Sestan B, et al. Emerging pathways and promising agents with possible disease modifying effect in osteoarthritis treatment. Curr Drug Targets, 2014, 15(6):635-661.
8.	Kaufman JM, Audran M, Bianchi G, et al. Efficacy and safety of strontium ranelate in the treatment of osteoporosis in men. J Clin Endocrinol Metab, 2013, 98(2):592-601.
9.	Reginster JY, Bruyere O, Sawicki A, et al. Long-term treatment of postmenopausal osteoporosis with strontium ranelate:results at 8 years. Bone, 2009, 45(6):1059-1064.
10.	Reginster JY, Seeman E, De Vernejoul MC, et al. Strontium ranelate reduces the risk of nonvertebral fractures in postmenopausal women with osteoporosis:Treatment of Peri pheral Osteoporosis (TROPOS) study. J Clin Endocrinol Metab, 2005, 90(5):2816-2822.
11.	Meunier PJ, Roux C, Seeman E, 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):459-468.
12.	Reginster JY, Kaufman JM, Goemaere S, et al. Maintenance of antifracture efficacy over 10 years with strontium ranelate in postmenopausal osteoporosis. Osteoporos Int, 2012, 23(3):1115-1122.
13.	Alexandersen P, Karsdal MA, Byrjalsen I, et al. Strontium ranelate effect in postmenopausal women with different cl inical levels of osteoarthritis. Climacteric, 2011, 14(2):236-243.
14.	Bingham CO 3rd, Buckland-Wright JC, Garnero P, et al. Risedronate decreases biochemical markers of cartilage degradation but does not decrease symptoms or slow radiographic progression in patients with medial compartment osteoarthritis of the knee:results of the two-year multinational knee osteoarthritis structural arthritis study. Arthritis Rheum, 2006, 54(11):3494-3507.
15.	Bruyere O, Delferriere D, Roux C, et al. Effects of strontium ranelate on spinal osteoarthritis progression. Ann Rheum Dis, 2008, 67(3):335-339.
16.	Kinds MB, Vincken KL, Hoppinga TN, et al. Influence of variation in semiflexed knee positioning during image acquisition on separate quantitative radiographic parameters of osteoarthritis, measured by Knee Images Digital Analysis. Osteoarthritis Cartilage, 2012, 20(9): 997-1003.
17.	Blake GM, Compston JE, Fogelman I. Could strontium ranelate have a synergistic role in the treatment of osteoporosis? J Bone Miner Res, 2009, 24(8):1354-1357.
18.	Reginster JY, Badurski J, Bellamy N, et al. Efficacy and safety of strontium ranelate in the treatment of knee osteoarthritis:results of a double-blind, randomised placebo-controlled trial. Ann Rheum Dis, 2013, 72(2):179-186.
19.	Altman R, Asch E, Bloch D, et al. Development of criteria for the classification and reporting of osteoarthritis. Classification of osteoarthritis of the knee. Diagnostic and Therapeutic Criteria Committee of the American Rheumatism Association. Arthritis Rheum, 1986, 29(8): 1039-1049.
20.	Capuccini C, Torricell i P, Sima F, et al. Strontium-substituted hydroxyapatite coatings synthesized by pulsed-laser deposition:in vitro osteoblast and osteoclast response. Acta Biomater, 2008, 4(6):1885-1893.
21.	Gregory MH, Capito N, Kuroki K, et al. A review of translational animal models for knee osteoarthritis. Arthritis, 2012, 2012:764621.
22.	Yu DG, Ding HF, Mao YQ, et al. Strontium ranelate reduces cartilage degeneration and subchondral bone remodeling in rat osteoarthritis model. Acta Pharmacol Sin, 2013, 34(3):393-402.
23.	Appleton CT, Usmani SE, Bernier SM, et al. Transforming growth factor alpha suppression of articular chondrocyte phenotype and Sox9 expression in a rat model of osteoarthritis. Arthritis Rheum, 2007, 56(11):3693-3705.
24.	Pelletier JP, Kapoor M, Fahmi H, et al. Strontium ranelate reduces the progression of experimental dog osteoarthritis by inhibiting the expression of key proteases in cartilage and of IL-1beta in the synovium. Ann Rheum Dis, 2013, 72(2):250-257.
25.	Marie PJ, Felsenberg D, Brandi ML. How strontium ranelate, via opposite effects on bone resorption and formation, prevents osteoporosis. Osteoporos Int, 2011, 22(6):1659-1667.
26.	Takaoka S, Yamaguchi T, Yano S, et al. The Calcium-sensing Receptor (CaR) is involved in strontium ranelate-induced osteoblast differentiation and mineralization. Horm Metab Res, 2010, 42(9):627-631.
27.	Brennan TC, Rybchyn MS, Green W, et al. Osteoblasts play key roles in the mechanisms of action of strontium ranelate. Br J Pharmacol, 2009, 157(7):1291-1300.
28.	Tat SK, Pelletier JP, Mineau F, et al. Strontium ranelate inhibits key factors affecting bone remodel ing in human osteoarthritic subchondral bone osteoblasts. Bone, 2011, 49(3):559-567.
29.	Henrotin Y, Labasse A, Zheng SX, et al. Strontium ranelate increases cartilage matrix formation. J Bone Miner Res, 2001, 16(2):299-308.
30.	Bonnevier J, Maimqvist U, Sonntag D, et al. Sustained norpinephrine contraction in the rat portal vein is lost when is Ca²⁺ replaced with Sr²⁺. Am J Physiol Cell Physiol, 2002, 282(4):C845-C852.
31.	Pors Nielsen S. The biological role of strontium. Bone, 2004, 35(3): 583-588.
32.	Cooper C, Fox KM, Borer JS. Ischaemic cardiac events and use of strontium ranelate in postmenopausal osteoporosis:a nested casecontrol study in the CPRD. Osteoporos Int, 2014, 25(2):737-745.
33.	Jonville-Bera AP, Autret-Leca E. Adverse drug reactions of strontium ranelate(Protelos(^®) in France. Presse Med, 2011, 40(10): e453-462.
34.	Cooper C, Reginster JY, Chapurlat R, et al. Efficacy and safety of oral strontium ranelate for the treatment of knee osteoarthritis:rationale and design of randomised, double-blind, placebo-controlled trial. Curr Med Res Opin, 2012, 28(2):231-239.

1. Bijlsma JW, Berenbaum F, Lafeber FP. Osteoarthritis:an update with relevance for cl inical practice. Lancet, 2011, 377(9783):2115-2126.
2. Kwan Tat S, Lajeunesse D, Pelletier JP, et al. Targeting subchondral bone for treating osteoarthritis:what is the evidence? Best Pract Res Clin Rheumatol, 2010, 24(1):51-70.
3. Li G, Yin J, Gao J, et al. Subchondral bone in osteoarthritis:insight into risk factors and microstructural changes. Arthritis Res Ther, 2013, 15(6):223.
4. Mastbergen SC, Lafeber FP. Changes in subchondral bone early in the development of osteoarthritis. Arthritis Rheum, 2011, 63(9):2561-2563.
5. Martel-Pelletier J, Wildi LM, Pelletier JP. Future therapeutics for osteoarthritis. Bone, 2012, 51(2):297-311.
6. Losina E, Daigle ME, Suter LG, et al. Disease-modifying drugs for knee osteoarthritis:can they be cost-effective? Osteoarthritis Cartilage, 2013, 21(5):655-667.
7. Jotanovic Z, Mihelic R, Sestan B, et al. Emerging pathways and promising agents with possible disease modifying effect in osteoarthritis treatment. Curr Drug Targets, 2014, 15(6):635-661.
8. Kaufman JM, Audran M, Bianchi G, et al. Efficacy and safety of strontium ranelate in the treatment of osteoporosis in men. J Clin Endocrinol Metab, 2013, 98(2):592-601.
9. Reginster JY, Bruyere O, Sawicki A, et al. Long-term treatment of postmenopausal osteoporosis with strontium ranelate:results at 8 years. Bone, 2009, 45(6):1059-1064.
10. Reginster JY, Seeman E, De Vernejoul MC, et al. Strontium ranelate reduces the risk of nonvertebral fractures in postmenopausal women with osteoporosis:Treatment of Peri pheral Osteoporosis (TROPOS) study. J Clin Endocrinol Metab, 2005, 90(5):2816-2822.
11. Meunier PJ, Roux C, Seeman E, 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):459-468.
12. Reginster JY, Kaufman JM, Goemaere S, et al. Maintenance of antifracture efficacy over 10 years with strontium ranelate in postmenopausal osteoporosis. Osteoporos Int, 2012, 23(3):1115-1122.
13. Alexandersen P, Karsdal MA, Byrjalsen I, et al. Strontium ranelate effect in postmenopausal women with different cl inical levels of osteoarthritis. Climacteric, 2011, 14(2):236-243.
14. Bingham CO 3rd, Buckland-Wright JC, Garnero P, et al. Risedronate decreases biochemical markers of cartilage degradation but does not decrease symptoms or slow radiographic progression in patients with medial compartment osteoarthritis of the knee:results of the two-year multinational knee osteoarthritis structural arthritis study. Arthritis Rheum, 2006, 54(11):3494-3507.
15. Bruyere O, Delferriere D, Roux C, et al. Effects of strontium ranelate on spinal osteoarthritis progression. Ann Rheum Dis, 2008, 67(3):335-339.
16. Kinds MB, Vincken KL, Hoppinga TN, et al. Influence of variation in semiflexed knee positioning during image acquisition on separate quantitative radiographic parameters of osteoarthritis, measured by Knee Images Digital Analysis. Osteoarthritis Cartilage, 2012, 20(9): 997-1003.
17. Blake GM, Compston JE, Fogelman I. Could strontium ranelate have a synergistic role in the treatment of osteoporosis? J Bone Miner Res, 2009, 24(8):1354-1357.
18. Reginster JY, Badurski J, Bellamy N, et al. Efficacy and safety of strontium ranelate in the treatment of knee osteoarthritis:results of a double-blind, randomised placebo-controlled trial. Ann Rheum Dis, 2013, 72(2):179-186.
19. Altman R, Asch E, Bloch D, et al. Development of criteria for the classification and reporting of osteoarthritis. Classification of osteoarthritis of the knee. Diagnostic and Therapeutic Criteria Committee of the American Rheumatism Association. Arthritis Rheum, 1986, 29(8): 1039-1049.
20. Capuccini C, Torricell i P, Sima F, et al. Strontium-substituted hydroxyapatite coatings synthesized by pulsed-laser deposition:in vitro osteoblast and osteoclast response. Acta Biomater, 2008, 4(6):1885-1893.
21. Gregory MH, Capito N, Kuroki K, et al. A review of translational animal models for knee osteoarthritis. Arthritis, 2012, 2012:764621.
22. Yu DG, Ding HF, Mao YQ, et al. Strontium ranelate reduces cartilage degeneration and subchondral bone remodeling in rat osteoarthritis model. Acta Pharmacol Sin, 2013, 34(3):393-402.
23. Appleton CT, Usmani SE, Bernier SM, et al. Transforming growth factor alpha suppression of articular chondrocyte phenotype and Sox9 expression in a rat model of osteoarthritis. Arthritis Rheum, 2007, 56(11):3693-3705.
24. Pelletier JP, Kapoor M, Fahmi H, et al. Strontium ranelate reduces the progression of experimental dog osteoarthritis by inhibiting the expression of key proteases in cartilage and of IL-1beta in the synovium. Ann Rheum Dis, 2013, 72(2):250-257.
25. Marie PJ, Felsenberg D, Brandi ML. How strontium ranelate, via opposite effects on bone resorption and formation, prevents osteoporosis. Osteoporos Int, 2011, 22(6):1659-1667.
26. Takaoka S, Yamaguchi T, Yano S, et al. The Calcium-sensing Receptor (CaR) is involved in strontium ranelate-induced osteoblast differentiation and mineralization. Horm Metab Res, 2010, 42(9):627-631.
27. Brennan TC, Rybchyn MS, Green W, et al. Osteoblasts play key roles in the mechanisms of action of strontium ranelate. Br J Pharmacol, 2009, 157(7):1291-1300.
28. Tat SK, Pelletier JP, Mineau F, et al. Strontium ranelate inhibits key factors affecting bone remodel ing in human osteoarthritic subchondral bone osteoblasts. Bone, 2011, 49(3):559-567.
29. Henrotin Y, Labasse A, Zheng SX, et al. Strontium ranelate increases cartilage matrix formation. J Bone Miner Res, 2001, 16(2):299-308.
30. Bonnevier J, Maimqvist U, Sonntag D, et al. Sustained norpinephrine contraction in the rat portal vein is lost when is Ca²⁺ replaced with Sr²⁺. Am J Physiol Cell Physiol, 2002, 282(4):C845-C852.
31. Pors Nielsen S. The biological role of strontium. Bone, 2004, 35(3): 583-588.
32. Cooper C, Fox KM, Borer JS. Ischaemic cardiac events and use of strontium ranelate in postmenopausal osteoporosis:a nested casecontrol study in the CPRD. Osteoporos Int, 2014, 25(2):737-745.
33. Jonville-Bera AP, Autret-Leca E. Adverse drug reactions of strontium ranelate(Protelos(^®) in France. Presse Med, 2011, 40(10): e453-462.
34. Cooper C, Reginster JY, Chapurlat R, et al. Efficacy and safety of oral strontium ranelate for the treatment of knee osteoarthritis:rationale and design of randomised, double-blind, placebo-controlled trial. Curr Med Res Opin, 2012, 28(2):231-239.

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