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Erschienen in: Osteoporosis International 4/2010

01.04.2010 | Original Article

In osteoporotic women treated with strontium ranelate, strontium is located in bone formed during treatment with a maintained degree of mineralization

verfasst von: G. Boivin, D. Farlay, M. T. Khebbab, X. Jaurand, P. D. Delmas, P. J. Meunier

Erschienen in: Osteoporosis International | Ausgabe 4/2010

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Abstract

Summary

In postmenopausal osteoporotic women and up to 3 years of treatment with strontium ranelate, strontium was present only in recently deposited bone tissue resulting from formation activity during the period of treatment. Strontium was shown to be dose-dependently deposited into this newly formed bone with preservation of the mineralization.

Introduction

Interactions between strontium (Sr) and bone mineral and its effects on mineralization were investigated in women treated with strontium ranelate.

Methods

Bone biopsies from osteoporotic women were obtained over 5-year strontium ranelate treatment from phases II and III studies. Bone samples obtained over 3-year treatment were investigated by X-ray microanalysis for bone Sr uptake and focal distribution, and by quantitative microradiography for degree of mineralization. On some samples, Sr distribution (X-ray cartography) was analyzed on whole sample surfaces and the percentage of bone surface containing Sr was calculated. Bone Sr content was chemically measured on whole samples.

Results

In treated women, Sr was exclusively present in bone formed during treatment; Sr deposition depended on the dose with higher focal content in new bone structural units than in old ones constantly devoid of Sr, even after 3-year treatment. A plateau in global bone Sr content was reached after 3 years of treatment. Cartography illustrated the extent of surfaces containing Sr, and formation activity during strontium ranelate treatment was higher in cancellous than in cortical bone. Mineralization was maintained during treatment.

Conclusion

The quality of bone mineral was preserved after treatment with strontium ranelate, supporting the safety of this agent at the bone tissue level.
Literatur
1.
Zurück zum Zitat Meunier PJ, Slosman DO, Delmas PD, Sebert JL, Brandi ML, Albanese C, Lorenc R, Pors Nielsen S, De Vernejoul MC, Roces A, Reginster JY (2002) Strontium ranelate: dose-dependent effects in established postmenopausal vertebral osteoporosis—a 2-year randomized placebo controlled trial. J Clin Endocrinol Metab 87:2060–2066CrossRefPubMed Meunier PJ, Slosman DO, Delmas PD, Sebert JL, Brandi ML, Albanese C, Lorenc R, Pors Nielsen S, De Vernejoul MC, Roces A, Reginster JY (2002) Strontium ranelate: dose-dependent effects in established postmenopausal vertebral osteoporosis—a 2-year randomized placebo controlled trial. J Clin Endocrinol Metab 87:2060–2066CrossRefPubMed
2.
Zurück zum Zitat Meunier PJ, Roux C, Seemar E, Ortolani S, Badurski JE, Spector TM, 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 350:459–468CrossRefPubMed Meunier PJ, Roux C, Seemar E, Ortolani S, Badurski JE, Spector TM, 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 350:459–468CrossRefPubMed
3.
Zurück zum Zitat Reginster JY, Seeman E, De Vernejoul C, 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 nonvertebral fractures in postmenopausal women with osteoporosis: treatment of peripheral osteoporosis (TROPOS) study. J Clin Endocrinol Metab 90:2816–2822CrossRefPubMed Reginster JY, Seeman E, De Vernejoul C, 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 nonvertebral fractures in postmenopausal women with osteoporosis: treatment of peripheral osteoporosis (TROPOS) study. J Clin Endocrinol Metab 90:2816–2822CrossRefPubMed
4.
Zurück zum Zitat Barbara A, Delannoy P, Denis BG, Marie PJ (2004) Normal matrix mineralization induced by strontium ranelate in MC3T3–E1 osteogenic cells. Metabolism 53:532–537CrossRefPubMed Barbara A, Delannoy P, Denis BG, Marie PJ (2004) Normal matrix mineralization induced by strontium ranelate in MC3T3–E1 osteogenic cells. Metabolism 53:532–537CrossRefPubMed
5.
Zurück zum Zitat Baron R, Tsouderos Y (2002) In vitro effects of S12911–2 on osteoclast function and bone marrow macrophage differentiation. Eur J Pharmacol 450:11–17CrossRefPubMed Baron R, Tsouderos Y (2002) In vitro effects of S12911–2 on osteoclast function and bone marrow macrophage differentiation. Eur J Pharmacol 450:11–17CrossRefPubMed
6.
Zurück zum Zitat Bonnelye E, Chabadel A, Saltel F, Jurdic P (2008) Dual effect of strontium ranelate: stimulation of osteoblast differentiation and inhibition of osteoclast formation and resorption in vitro. Bone 42:129–138CrossRefPubMed Bonnelye E, Chabadel A, Saltel F, Jurdic P (2008) Dual effect of strontium ranelate: stimulation of osteoblast differentiation and inhibition of osteoclast formation and resorption in vitro. Bone 42:129–138CrossRefPubMed
7.
Zurück zum Zitat 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 18:517–523CrossRefPubMed 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 18:517–523CrossRefPubMed
8.
Zurück zum Zitat Marie PJ, Hott M, Modrowski D, De PC, 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 8:607–615CrossRefPubMed Marie PJ, Hott M, Modrowski D, De PC, 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 8:607–615CrossRefPubMed
9.
Zurück zum Zitat Takahashi N, Sasaki T, Tsouderos Y, Suda T (2003) S12911–2 inhibits osteoclastic bone resorption in vitro. J Bone Miner Res 18:1082–1087CrossRefPubMed Takahashi N, Sasaki T, Tsouderos Y, Suda T (2003) S12911–2 inhibits osteoclastic bone resorption in vitro. J Bone Miner Res 18:1082–1087CrossRefPubMed
10.
Zurück zum Zitat Zhu LL, Zaidi S, Peng Y, Zhou H, Moonga BS, Blesius A, Dupin-Roger I, Zaidi M, Sun L (2007) Induction of a program gene expression during osteoblast differentiation with strontium ranelate. Biochem Biophys Res Commun 355:307–311CrossRefPubMed Zhu LL, Zaidi S, Peng Y, Zhou H, Moonga BS, Blesius A, Dupin-Roger I, Zaidi M, Sun L (2007) Induction of a program gene expression during osteoblast differentiation with strontium ranelate. Biochem Biophys Res Commun 355:307–311CrossRefPubMed
11.
Zurück zum Zitat 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 19:2012–2020CrossRefPubMed 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 19:2012–2020CrossRefPubMed
12.
Zurück zum Zitat Ammann P, Badoud I, Barraud 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 22:1419–1425CrossRefPubMed Ammann P, Badoud I, Barraud 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 22:1419–1425CrossRefPubMed
13.
Zurück zum Zitat Bain SD, Jerome C, Shen V, Dupin-Roger I, Ammann P (2008) Strontium ranelate improves bone strength in ovariectomized rat by positively influencing bone resistance determinants. Osteoporos Int doi:10.1007/s00198-008-0815-8. Bain SD, Jerome C, Shen V, Dupin-Roger I, Ammann P (2008) Strontium ranelate improves bone strength in ovariectomized rat by positively influencing bone resistance determinants. Osteoporos Int doi:10.​1007/​s00198-008-0815-8.
14.
Zurück zum Zitat Marie PJ (2003) Optimizing bone metabolism in osteoporosis: insight into the pharmacologic profile of strontium ranelate. Osteoporos Int 14:S9–S12PubMed Marie PJ (2003) Optimizing bone metabolism in osteoporosis: insight into the pharmacologic profile of strontium ranelate. Osteoporos Int 14:S9–S12PubMed
15.
Zurück zum Zitat Boivin G, Deloffre P, Perrat 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 11:1302–1311CrossRefPubMed Boivin G, Deloffre P, Perrat 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 11:1302–1311CrossRefPubMed
16.
Zurück zum Zitat Cazalbou S, Combes C, Rey C (2002) S12911 treatment maintains bone mineral crystal characteristics. J Bone Miner Res 17:S376–S377 Cazalbou S, Combes C, Rey C (2002) S12911 treatment maintains bone mineral crystal characteristics. J Bone Miner Res 17:S376–S377
17.
Zurück zum Zitat 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 degrees of mineralisation of bone. J Bone Miner Res 20:1569–1578CrossRefPubMed 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 degrees of mineralisation of bone. J Bone Miner Res 20:1569–1578CrossRefPubMed
18.
Zurück zum Zitat LeGeros RZ, Lin S, LeGeros JP, Cazalbou S, Combes C, Dupin Roger I, Rey C (2004) Strontium ranelate treatment preserves bone crystal characteristics and bone mineral reactivity. Osteoporos Int 15:S116–S117 LeGeros RZ, Lin S, LeGeros JP, Cazalbou S, Combes C, Dupin Roger I, Rey C (2004) Strontium ranelate treatment preserves bone crystal characteristics and bone mineral reactivity. Osteoporos Int 15:S116–S117
19.
Zurück zum Zitat Boivin G, Meunier PJ (2002) Changes in bone remodeling rate influence the degree of mineralization of bone. Connect Tissue Res 43:535–537PubMed Boivin G, Meunier PJ (2002) Changes in bone remodeling rate influence the degree of mineralization of bone. Connect Tissue Res 43:535–537PubMed
20.
Zurück zum Zitat Boivin G, Meunier PJ (2002) Effects of bisphosphonates on matrix mineralization. J Musculoskelet Neuronal Interact 2:538–543PubMed Boivin G, Meunier PJ (2002) Effects of bisphosphonates on matrix mineralization. J Musculoskelet Neuronal Interact 2:538–543PubMed
21.
Zurück zum Zitat Boivin G, Meunier PJ (2002) The degree of mineralization of bone tissue measured by computerized quantitative contact microradiography. Calcif Tissue Int 70:503–511CrossRefPubMed Boivin G, Meunier PJ (2002) The degree of mineralization of bone tissue measured by computerized quantitative contact microradiography. Calcif Tissue Int 70:503–511CrossRefPubMed
22.
Zurück zum Zitat Boivin G, Meunier PJ (2003) The mineralization of bone tissue: a forgotten dimension in osteoporosis research. Osteoporos Int 14:S19–S24CrossRefPubMed Boivin G, Meunier PJ (2003) The mineralization of bone tissue: a forgotten dimension in osteoporosis research. Osteoporos Int 14:S19–S24CrossRefPubMed
23.
Zurück zum Zitat Boivin G, Meunier PJ (2003) Methodological considerations in measurement of bone mineral content. Osteoporos Int 14 (Suppl 5):S22–S27CrossRefPubMed Boivin G, Meunier PJ (2003) Methodological considerations in measurement of bone mineral content. Osteoporos Int 14 (Suppl 5):S22–S27CrossRefPubMed
24.
Zurück zum Zitat Boivin G, Bala Y, Doublier A, Farlay D, Ste-Marie LG, Meunier PJ, Delmas PD (2008) The role of mineralization and organic matrix in the microhardness of bone tissue from controls and osteoporotic patients. Bone 43:532–538CrossRefPubMed Boivin G, Bala Y, Doublier A, Farlay D, Ste-Marie LG, Meunier PJ, Delmas PD (2008) The role of mineralization and organic matrix in the microhardness of bone tissue from controls and osteoporotic patients. Bone 43:532–538CrossRefPubMed
25.
Zurück zum Zitat Meunier PJ, Boivin G (1997) Bone mineral density reflects bone mass but also the degree of mineralization of bone: therapeutic implications. Bone 21:373–377CrossRefPubMed Meunier PJ, Boivin G (1997) Bone mineral density reflects bone mass but also the degree of mineralization of bone: therapeutic implications. Bone 21:373–377CrossRefPubMed
26.
Zurück zum Zitat Arlot M, Meunier PJ, Boivin G, Haddock L, Tamayo J, Correa-Rotter R, Jasqui S, Donley DW, Dalsky GP, Martin JS, Eriksen EF (2005) Differential effects of teriparatide and alendronate on bone remodeling in postmenopausal women assessed by histomorphometric parameters. J Bone Miner Res 20:1244–1253CrossRefPubMed Arlot M, Meunier PJ, Boivin G, Haddock L, Tamayo J, Correa-Rotter R, Jasqui S, Donley DW, Dalsky GP, Martin JS, Eriksen EF (2005) Differential effects of teriparatide and alendronate on bone remodeling in postmenopausal women assessed by histomorphometric parameters. J Bone Miner Res 20:1244–1253CrossRefPubMed
27.
Zurück zum Zitat Misof BM, Roschger P, Cosman F, Kurland ES, Tesch W, Messmer P, Dempster DW, Nieves J, Shane E, Fratzl P, Klaushofer K, Bilezikian J, Lindsay R (2003) Effects of intermittent parathyroid hormone administration on bone mineralization density in iliac crest biopsies from patients with osteoporosis: a paired study before and after treatment. J Clin Endocrinol Metab 88:1150–1156CrossRefPubMed Misof BM, Roschger P, Cosman F, Kurland ES, Tesch W, Messmer P, Dempster DW, Nieves J, Shane E, Fratzl P, Klaushofer K, Bilezikian J, Lindsay R (2003) Effects of intermittent parathyroid hormone administration on bone mineralization density in iliac crest biopsies from patients with osteoporosis: a paired study before and after treatment. J Clin Endocrinol Metab 88:1150–1156CrossRefPubMed
28.
Zurück zum Zitat Boivin G, Lips P, Ott SM, Harper KD, Sarkar S, Pinette KV, Meunier PJ (2003) Contribution of raloxifene and calcium and vitamin D3 supplementation to the increase of the degree of mineralization of bone in postmenopausal women. J Clin Endocrinol Metab 88:4199–4205CrossRefPubMed Boivin G, Lips P, Ott SM, Harper KD, Sarkar S, Pinette KV, Meunier PJ (2003) Contribution of raloxifene and calcium and vitamin D3 supplementation to the increase of the degree of mineralization of bone in postmenopausal women. J Clin Endocrinol Metab 88:4199–4205CrossRefPubMed
29.
Zurück zum Zitat Boivin G, Vedi S, Purdie DW, Compston JE, Meunier PJ (2005) Influence of estrogen therapy at conventional and high doses on the degree of mineralization of iliac bone tissue: a quantitative microradiographic analysis in postmenopausal women. Bone 36:562–567CrossRefPubMed Boivin G, Vedi S, Purdie DW, Compston JE, Meunier PJ (2005) Influence of estrogen therapy at conventional and high doses on the degree of mineralization of iliac bone tissue: a quantitative microradiographic analysis in postmenopausal women. Bone 36:562–567CrossRefPubMed
30.
Zurück zum Zitat Boivin GY, Chavassieux PM, Santora AC, Yates J, Meunier PJ (2000) Alendronate increases bone strength by increasing the mean degree of mineralization of bone tissue in osteoporotic women. Bone 27:687–694CrossRefPubMed Boivin GY, Chavassieux PM, Santora AC, Yates J, Meunier PJ (2000) Alendronate increases bone strength by increasing the mean degree of mineralization of bone tissue in osteoporotic women. Bone 27:687–694CrossRefPubMed
31.
Zurück zum Zitat Arlot ME, Jiang Y, Genant HK, Zhao J, Burt-Pichat B, Roux JP, Delmas PD, Meunier PJ (2008) Histomorphometric and microCT analysis of bone biopsies from postmenopausal osteoporotic women treated with strontium ranelate. J Bone Miner Res 23:215–222CrossRefPubMed Arlot ME, Jiang Y, Genant HK, Zhao J, Burt-Pichat B, Roux JP, Delmas PD, Meunier PJ (2008) Histomorphometric and microCT analysis of bone biopsies from postmenopausal osteoporotic women treated with strontium ranelate. J Bone Miner Res 23:215–222CrossRefPubMed
32.
Zurück zum Zitat Boivin G, Meunier PJ (1993) Histomorphometric methods applied to bone. In: Grupe G, Garland AN (eds) Histology of ancient human bone. Springer, Berlin, pp 137–156 Boivin G, Meunier PJ (1993) Histomorphometric methods applied to bone. In: Grupe G, Garland AN (eds) Histology of ancient human bone. Springer, Berlin, pp 137–156
33.
Zurück zum Zitat Basle MF, Mauras Y, Audran M, Clochon P, Rebel A, Allain P (1990) Concentration of bone elements in osteoporosis. J Bone Miner Res 5:41–47CrossRefPubMed Basle MF, Mauras Y, Audran M, Clochon P, Rebel A, Allain P (1990) Concentration of bone elements in osteoporosis. J Bone Miner Res 5:41–47CrossRefPubMed
35.
Zurück zum Zitat Staub JF, Foos E, Courtin B, Jochemsen R, Perault Staub AM (2003) A nonlinear compartmental model of Sr metabolism. II. Its physiological relevance for Ca metabolism. Am J Physiol Regul Integr Comp Physiol 284:R835–R852PubMed Staub JF, Foos E, Courtin B, Jochemsen R, Perault Staub AM (2003) A nonlinear compartmental model of Sr metabolism. II. Its physiological relevance for Ca metabolism. Am J Physiol Regul Integr Comp Physiol 284:R835–R852PubMed
36.
Zurück zum Zitat Staub JF, Foos E, Courtin B, Jochemsen R, Perault Staub AM (2003) A nonlinear compartmental model of Sr metabolism. I. Non-steady-state kinetics and model building. Am J Physiol Regul Integr Comp Physiol 284:R819–R834PubMed Staub JF, Foos E, Courtin B, Jochemsen R, Perault Staub AM (2003) A nonlinear compartmental model of Sr metabolism. I. Non-steady-state kinetics and model building. Am J Physiol Regul Integr Comp Physiol 284:R819–R834PubMed
37.
Zurück zum Zitat Dahl SG, Allain P, Marie PJ, Mauras Y, Boivin G, Ammann P, Tsouderos Y, Delmas PD, Christiansen C (2001) Incorporation and distribution of strontium in bone. Bone 28:446–453CrossRefPubMed Dahl SG, Allain P, Marie PJ, Mauras Y, Boivin G, Ammann P, Tsouderos Y, Delmas PD, Christiansen C (2001) Incorporation and distribution of strontium in bone. Bone 28:446–453CrossRefPubMed
38.
Zurück zum Zitat Marie PJ, Ammann P, Boivin G, Rey C (2001) Mechanisms of action and therapeutic potential of strontium in bone. Calcif Tissue Int 69:121–129CrossRefPubMed Marie PJ, Ammann P, Boivin G, Rey C (2001) Mechanisms of action and therapeutic potential of strontium in bone. Calcif Tissue Int 69:121–129CrossRefPubMed
39.
Zurück zum Zitat LeGeros RZ, Lin S, Mijares D, LeGeros JP (2003) Strontium ranelate treatment preserves bone crystal characteristics and dissolution properties of bone apatite. J Bone Miner Res 18 (Suppl 2):276 LeGeros RZ, Lin S, Mijares D, LeGeros JP (2003) Strontium ranelate treatment preserves bone crystal characteristics and dissolution properties of bone apatite. J Bone Miner Res 18 (Suppl 2):276
40.
Zurück zum Zitat Parfitt AM (2002) Misconceptions (2): turnover is always higher in cancellous than in cortical bone. Bone 30:807–809CrossRefPubMed Parfitt AM (2002) Misconceptions (2): turnover is always higher in cancellous than in cortical bone. Bone 30:807–809CrossRefPubMed
41.
Zurück zum Zitat Boivin G, Meunier PJ (2004) Inter-individual heterogeneity index of mineralization is an important determinant of the quality of bone. J Bone Miner Res 19 (suppl 1):S114 Boivin G, Meunier PJ (2004) Inter-individual heterogeneity index of mineralization is an important determinant of the quality of bone. J Bone Miner Res 19 (suppl 1):S114
Metadaten
Titel
In osteoporotic women treated with strontium ranelate, strontium is located in bone formed during treatment with a maintained degree of mineralization
verfasst von
G. Boivin
D. Farlay
M. T. Khebbab
X. Jaurand
P. D. Delmas
P. J. Meunier
Publikationsdatum
01.04.2010
Verlag
Springer-Verlag
Erschienen in
Osteoporosis International / Ausgabe 4/2010
Print ISSN: 0937-941X
Elektronische ISSN: 1433-2965
DOI
https://doi.org/10.1007/s00198-009-1005-z

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