Top

Osteoporosis International

Published in:

01-08-2009 | Original Article

Strontium ranelate improves bone strength in ovariectomized rat by positively influencing bone resistance determinants

Authors: S. D. Bain, C. Jerome, V. Shen, I. Dupin-Roger, P. Ammann

Published in: Osteoporosis International | Issue 8/2009

Abstract

Summary

Treatment of adult ovariectomized (OVX) rats with strontium ranelate prevented vertebral biomechanics degradation as a result of the prevention of bone loss and micro-architecture deterioration associated to an effect on intrinsic bone material quality. Strontium ranelate influenced the determinants of bone strength by prevention of ovariectomy-induced changes which contribute to explain strontium ranelate antifracture efficacy.

Introduction

Strontium ranelate effects on the determinants of bone strength in OVX rats were evaluated.

Methods

Adult female Sprague–Dawley rats were OVX, then treated daily for 52 weeks with 125, 250, or 625 mg strontium ranelate/kg. Bone strength, mass, micro-architecture, turnover, and intrinsic quality were assessed.

Results

Strontium ranelate prevented ovariectomy-induced deterioration in mechanical properties with energy necessary for fracture completely maintained vs. SHAM at 625 mg/kg/day, which corresponds to the clinical dose. This was related to a dose-dependent effect on bone volume, higher trabeculae number, and lower trabecular separation in strontium ranelate vs. OVX. Load and energy required to induce lamella deformation were higher with strontium ranelate than in OVX and in SHAM, indicating that the bone formed with strontium ranelate is able to withstand greater damage before fracture. Bone formation was maintained high or even increased in strontium ranelate as shown by mineralizing surfaces and alkaline phosphatase while strontium ranelate led to reductions in deoxypyridinoline.

Conclusion

Strontium ranelate administered at 625 mg/kg/day for 52 weeks prevented OVX-induced biomechanical properties deterioration by influencing the determinants of bone strength: it prevented bone loss and micro-architecture degradation in association with an effect on intrinsic bone quality. These beneficial effects on bone contribute to explain strontium ranelate antifracture efficacy.

Delmas PD (2002) Treatment of postmenopausal osteoporosis. Lancet 359:2018–2026PubMedCrossRef

Riggs BL, Parfitt AM (2005) Drugs used to treat osteoporosis: the critical need for a uniform nomenclature based on their action on bone remodeling. J Bone Miner Res 20:177–184PubMedCrossRef

Reginster J-Y, Deroisy R, Jupsin I (2003) Strontium ranelate: a new paradigm in the treatment of osteoporosis. Drugs Today 39:89–101PubMedCrossRef

Meunier PJ, Roux C, Seeman E, Ortolani S, Badurski JE, Spector TD, Cannata J, Balogh A, Lemmel EM, Pors-Nielsen S, Rizzoli R, Genant HK, Reginster JY (2004) The effects of strontium ranelate on the risk of vertebral fracture in women with postmenopausal osteoporosis. N Engl J Med 350:459–468PubMedCrossRef

Reginster JY, Seeman E, de Vernejoul MC, Adami S, Compston J, Phenekos C, Devogelaer JP, Diaz-Curiel M, Sawicki A, Goemaere S, Sorensen OH, Felsenberg D, Meunier PJ (2005) Strontium ranelate reduces the risk of non vertebral fractures in postmenopausal women with osteoporosis: TROPOS study. J Clin Endocrinol Metab 90:2816–2822PubMedCrossRef

Delannoy P, Bazot D, Marie P (2002) Long-term treatment with strontium ranelate increases vertebral bone mass without deleterious effect in mice. Metabolism 51:906–911PubMedCrossRef

Ammann P, Shen V, Robin B, Mauras Y, Bonjour JP, Rizzoli R (2004) Strontium ranelate improves bone resistance by increasing bone mass and improving architecture in intact female rats. J Bone Miner Res 19:2012–2020PubMedCrossRef

Buehler J, Chappuis P, Saffar JL, Tsouderos Y, Vignery A (2001) Strontium ranelate inhibits bone resorption while maintaining bone formation in alveolar bone in monkeys (Macaca fascicularis). Bone 29:176–179PubMedCrossRef

Marie PJ, Hott M, Modrowski D, De Pollak C, Guillemain J, Deloffre P, Tsouderos Y (1993) An uncoupling agent containing strontium prevents bone loss by depressing bone resorption and maintaining bone formation in estrogen-deficient rats. J Bone Miner Res 8:607–615PubMed

10.

Grynpas MD, Hamilton E, Cheung R, Tsouderos Y, Deloffre P, Hott M, Marie PJ (1996) Strontium increases vertebral bone volume in rats at a low dose that does not induce detectable mineralization defect. Bone 18:253–259PubMedCrossRef

11.

Hott M, Deloffre P, Tsouderos Y, Marie PJ (2003) S12911-2 reduces bone loss induced by short-term immobilization in rats. Bone 33:115–123PubMedCrossRef

12.

Baron R, Tsouderos Y (2002) In vitro effects of S12911 on osteoclastic function and bone marrow macrophages differentiation. Eur J Pharmacol 450:11–17PubMedCrossRef

13.

Takahashi N, Sasaki T, Tsouderos Y, Suda T (2003) Strontium ranelate inhibits osteoclastic bone resorption in vitro. J Bone Miner Res 18:1082–1087PubMedCrossRef

14.

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 18:517–523PubMedCrossRef

15.

Turner CH, Burr DB (1993) Basic biochemical measurements of bone: a tutorial. Bone 14:595–608PubMedCrossRef

16.

Wronski TJ, Lowry PL, Walsh CC, Ignaszewski LA (1985) Skeletal alterations in ovariectomized rats. Calcif Tissue Int 37:324–328PubMedCrossRef

17.

Wronski TJ, Dann LM, Scott KS, Crooke LR (1989) Endocrine and pharmacological suppressors of bone turnover protect against osteopenia in ovariectomized rats. Endocrinology 125:810–816PubMedCrossRef

18.

Kalu DK (1991) The ovariectomized rat model of postmenopausal bone loss. Bone Miner 15:175–192PubMedCrossRef

19.

Bain SD, Impeduglia T, Rubin CT (1990) Cement line staining in undecalcified thin sections of cortical bone. Stain Technol 65:1–5PubMed

20.

Parfitt AM, Drezner MK, Glorieux FH, Kanis JA, Malluche H, Meunier PJ, Ott SM, Recker RR (1987) Bone histomorphometry: standardization of nomenclature, symbols, and units. J Bone Miner Res 2:595–610PubMed

21.

Hengsberger S, Ammann P, Legros B, Rizzoli R, Zysset P (2005) Intrinsic bone tissue properties in adult rat vertebrae: modulation by dietary protein. Bone 36:134–141PubMedCrossRef

22.

Oliver WC, Pharr GM (1992) An improved technique for determining hardness and elastic modulus using load and displacement sensing indentation experiments. J Mater Res 7:1564–1583CrossRef

23.

Steel RGD, Torrie JH (1980) Principles and procedures of statistics: a biometrical approach, 2nd edn. McGraw-Hill, New York, NY

24.

Parfitt AM, Oliver I, Villanueva AR (1979) Bone histology in metabolic bone disease: the diagnostic value of bone biopsy. Orthop Clin North Am 10:329–345PubMed

25.

Wronski TJ, Walsh CC, Ignaszewski LA (1986) Histologic evidence for osteopenia and increased bone turnover in ovariectomized rats. Bone 7:119–123PubMedCrossRef

26.

Wronski TJ, Cintron M, Dann LM (1988) Temporal relationship between bone loss and increased bone turnover in ovariectomized rats. Calcif Tissue Int 43:179–183PubMedCrossRef

27.

Wronski TJ, Dann LM, Scott KS, Cintron M (1989) Long-term effects of ovariectomy and aging on the rat skeleton. Calcif Tissue Int 45:360–366PubMedCrossRef

28.

Yamazaki I, Yamaguchi H (1989) Characteristics of an ovariectomized osteopenic rat model. J Bone Miner Res 4:13–22PubMed

29.

Wronski TJ, Dann LM, Horner SL (1989) Time course of vertebral osteopenia in ovariectomized rats. Bone 10:295–301PubMedCrossRef

30.

Boyce RW, Wronski TJ, Ebert DC, Stevens ML, Paddock CL, Youngs TA, Gundersen HJG (1995) Direct stereological estimation of the three-dimensional connectivity in rat vertebrae: effect of estrogen, etidronate and risedronate following ovariectomy. Bone 16:209–213PubMedCrossRef

31.

Turner RT, Vandersteenhoven JJ, Bell NH (1987) The effects of ovariectomy and 17 beta-estradiol on cortical bone histomorphometry in growing rats. J Bone Miner Res 2:115–122PubMed

32.

Bagi CM, Mecham M, Weiss J, Miller SC (1993) Comparative morphometric changes in rat cortical bone following ovariectomy and/or immobilization. Bone 14:877–883PubMedCrossRef

33.

Comar CL, Wasserman RH (1966) Strontium. Mineral Metabolism 2:523–571

34.

Perault-Staub AM (1990) Extracellular calcium homeostasis. Elsevier, Amsterdam

35.

Fuchs RK, Allen MR, Condon KW, Reinwald S, Miller LM, McClenathan D, Keck B, Phipps RJ, Burr DB (2008) Strontium ranelate does not stimulate bone formation in ovariectomized rats. Osteoporosis Int 19(9):1331–141CrossRef

36.

Zhang Y, Lai W-P, Wu C-F, Favus MJ, Leung PC, Wong MS (2007) Ovariectomy worsens secondary hyperparathyroidism in mature rats during low-ca diet. Am J Physiol Endocrinol Metab 292:E723–E731PubMedCrossRef

37.

Creedon A, Cashman KD (2001) The effect of calcium intake on bone composition and bone resorption in young growing rat. Br J Nutr 86:453–459PubMedCrossRef

38.

Marie PJ, Ammann P, Boivin G, Rey C (2001) Mechanisms of action and therapeutic potential of strontium in bone. Calcif Tissue Int 69:121–129PubMedCrossRef

39.

Ammann P, Badoud I, Barrauld S, Dayer R, Rizzoli R (2007) Strontium ranelate treatment improves trabecular and cortical intrinsic bone tissue quality, a determinant of bone strength. J Bone Miner Res 22:1419–1425PubMedCrossRef

40.

Boivin G, Deloffre P, Berat B, Panczer G, Boudeulle M, Mauras Y, Allain P, Tsouderos Y, Meunier PJ (1996) Strontium distribution and interactions with bone mineral in monkey iliac bone after strontium salt (S12911) administration. J Bone Miner Res 11:1302–1311PubMedCrossRef

41.

Farlay D, Boivin G, Panczer G, Lalande A, Meunier PJ (2005) Long-term strontium ranelate administration in monkeys preserves characteristics of bone mineral crystals and degree of mineralisation od bone. J Bone Miner Res 20:1569–1578PubMedCrossRef

42.

Cazalbou S, Combes C, Rey C (2002) S12911 treatment maintains bone mineral crystal characteristics. J Bone Miner Res 17(Suppl 1):S376–S377

Title: Strontium ranelate improves bone strength in ovariectomized rat by positively influencing bone resistance determinants
Authors: S. D. Bain
C. Jerome
V. Shen
I. Dupin-Roger
P. Ammann
Publication date: 01-08-2009
Publisher: Springer-Verlag
Published in: Osteoporosis International / Issue 8/2009
Print ISSN: 0937-941X
Electronic ISSN: 1433-2965
DOI: https://doi.org/10.1007/s00198-008-0815-8

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Strontium ranelate improves bone strength in ovariectomized rat by positively influencing bone resistance determinants

Abstract

Summary

Introduction

Methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Summary

Introduction

Methods

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 8/2009

Bone microdamage: a clinical perspective

Which water for alendronate administration?

Cortical and trabecular architecture are altered in postmenopausal women with fractures

Determination of rat vertebral bone compressive fatigue properties in untreated intact rats and zoledronic-acid-treated, ovariectomized rats

Comment on Przybelski et al.: rapid correction of low vitamin D status in nursing home residents

Effect of daily oral minodronate on vertebral fractures in Japanese postmenopausal women with established osteoporosis: a randomized placebo-controlled double-blind study