Calcified Tissue International

, Volume 86, Issue 6, pp 495–501 | Cite as

Effects of Alendronate and Strontium Ranelate on Cancellous and Cortical Bone Mass in Glucocorticoid-Treated Adult Rats

  • P. Sun
  • D. H. Cai
  • Q. N. Li
  • H. Chen
  • W. M. Deng
  • L. He
  • L. Yang


We studied the effects of alendronate (Aln) and strontium ranelate (SrR) administration on cancellous and cortical bone in glucocorticoid (GC)-treated rats. Thirty-two 3.5-month male Sprague-Dawley rats were randomized into four groups: age-matched normal control (Nrm), methylprednisolone (Met; 5.0 mg/kg/day, sc, for 5 days/week), Met plus Aln orally (1.0 mg/kg/day), and Met plus SrR orally (900 mg/kg/day). The study period was 9 weeks. DXA was used to evaluate the femoral diaphysis and fifth lumbar vertebra (L5). Histomorphometry was performed in the proximal tibial metaphysis and tibial diaphysis. Met significantly decreased body weight and bone mineral density (BMD) compared with Nrm. Aln and SrR significantly increased body weight and BMD compared with Met. SrR resulted in significantly higher BMD than Aln. Met markedly decreased BV/TV, Tb.Th, and Tb.N and increased Tb.Sp compared with Nrm. Aln and SrR showed significantly increased of BV/TV, Tb.Th, and Tb.N and improved bone architecture. Moreover, Met reduced %Ct.Ar, enlarged %Ma.Ar, and decreased bone formation indices in the periosteum as well as increased ES/BS in the endosteum compared with Nrm. Aln significantly decreased endosteal ES/BS compared with Met. SrR significantly increased %Ct.Ar and bone formation indices in the periosteum as well as the endosteum and decreased endosteal ES/BS compared with Met. Furthermore, SrR led to a significantly higher cancellous and endocortical MS/BS and endocortical bone formation compared with Aln. Our findings suggest SrR at a dose of 900 mg/kg has a greater effect than Aln at 1.0 mg/kg, according to BMD and histomorphometric analysis, in preventing GC-induced osteopenia. Therefore, SrR might be applicable as a bone therapeutic agent to treat secondary osteoporosis in the clinic.


Rats Glucocorticoid-induced osteoporosis BMD Histomorphometry Strontium ranelate Alendronate 



This work was supported by the National Natural Science Foundation of China (30971172). The authors are grateful to Ke Fang (doctoral student, Division of Counseling Psychology, Department of Educational and Counseling Psychology, School of Education, State University of New York at Albany) for her excellent English editorial assistance.


  1. 1.
    Namkung-Matthai H, Seale JP, Brown K et al (1998) Comparative effects of anti- inflammatory corticosteroids in human bone-derived osteoblast-like cells. Eur Respir J 12:1327–1333CrossRefPubMedGoogle Scholar
  2. 2.
    Sambrook P, Hughes D, Nelson AE et al (2003) Osteocyte viability with glucocorticoid therapy: relation to histomorphometry. Ann Rheum Dis 62:1215–1217CrossRefPubMedGoogle Scholar
  3. 3.
    Takahashi N, Sasaki T, Tsouderos Y et al (2003) S12911-2 inhibits osteoclastic bone resorption in vitro. J Bone Miner Res 18:1082–1087CrossRefPubMedGoogle Scholar
  4. 4.
    Mazziotti G, Angeli A, Bilezikian JP et al (2006) Glucocorticoid-induced osteoporosis: an update. Trends Endocrinol Metab 7:144–149CrossRefGoogle Scholar
  5. 5.
    Dalle Carbonare L, Arlot ME, Chavassieux PM et al (2001) Comparison of trabecular bone microarchitecture and remodeling in glucocorticoid-induced and postmenopausal osteoporosis. J Bone Miner Res 16:97–103CrossRefPubMedGoogle Scholar
  6. 6.
    Dempster DW (1989) Bone histomorphometry in glucocorticoid-induced osteoporosis. J Bone Miner Res 4:137–141CrossRefPubMedGoogle Scholar
  7. 7.
    Chappard D, Legrand E, Basle MF et al (1996) Altered trabecular architecture induced by corticosteroids: a bone histomorphometric study. J Bone Miner Res 11:676–685CrossRefPubMedGoogle Scholar
  8. 8.
    Van Staa TP, Leufkens HG, Abenhaim L et al (2000) Use of oral corticosteroids and risk of fractures. J Bone Miner Res 15:993–1000CrossRefPubMedGoogle Scholar
  9. 9.
    Masaki H, Miki T (2006) The biochemical markers of bone in steroid (glucocorticoid)-induced osteoporosis (GIOP). Clin Calcium 16:51–60Google Scholar
  10. 10.
    De Nijs RN (2008) Glucocorticoid-induced osteoporosis: a review on pathophysiology and treatment options. Minerva Med 99:23–43PubMedGoogle Scholar
  11. 11.
    Mosekilde L, Thomsen JS, Mackey MS et al (2000) Treatment with risedronate or alendronate prevents hind-limb immobilization-induced loss of bone density and strength in adult female rats. Bone 27:639–645CrossRefPubMedGoogle Scholar
  12. 12.
    Saag KG, Emkey R, Schnitzer TJ et al (1998) Alendronate for the prevention and treatment of glucocorticoid-induced osteoporosis. Glucocorticoid-Induced Osteoporosis Intervention Study Group. N Engl J Med 339:292–299CrossRefPubMedGoogle Scholar
  13. 13.
    Orwoll E, Ettinger M, Weiss S et al (2000) Alendronate for the treatment of osteoporosis in men. N Engl J Med 134:604–610CrossRefGoogle Scholar
  14. 14.
    Iwamoto J, Seki A, Takeda T et al (2006) Comparative effects of risedronate and calcitriol on cancellous bone in rats with glucocorticoid-induced osteopenia. J Nutr Sci Vitaminol (Tokyo) 52:212–217Google Scholar
  15. 15.
    Lam S, Zouzias K (2007) Strontium ranelate for the management of osteoporosis. Consult Pharm 23:531–537Google Scholar
  16. 16.
    Cebesoy O, Tutar E, Kose KC et al (2007) Effect of strontium ranelate on fracture healing in rat tibia. Joint Bone Spine 74:590–593CrossRefPubMedGoogle Scholar
  17. 17.
    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 20:1417–1428CrossRefPubMedGoogle Scholar
  18. 18.
    Hott M, Deloffre P, Tsouderos Y et al (2003) S12911-2 reduced bone loss induced by short-term immobilization in rats. Bone 33:115–123CrossRefPubMedGoogle Scholar
  19. 19.
    Hulley PA, Conradie MM, Langeveldt CR et al (2002) Glucocorticoid induced osteoporosis in the rat is prevented by the tyrosine phosphatase inhibitor, sodium orthovanadate. Bone 31:220–229CrossRefPubMedGoogle Scholar
  20. 20.
    Ammann P, Badoud I, Barraud S et al (2007) Treatment improves trabecular and cortical intrinsic bone tissue quality, a determinant of bone strength. J Bone Miner Res 22:1419–1425CrossRefPubMedGoogle Scholar
  21. 21.
    Parfitt AM, Drezner MK, Glorieux FH et al (1987) Bone histomorphometry: standardization of nomenclature, symbols, and units. Report of the ASBMR Histomorphometry Nomenclature Committee. J Bone Miner Res 2:595–610CrossRefPubMedGoogle Scholar
  22. 22.
    Ogoshi T, Hagino H, Fukata S et al (2008) Influence of glucocorticoid on bone in 3-, 6-, and 12-month-old rats as determined by bone mass and histomorphometry. Mod Rheumatol 18:55–61CrossRefGoogle Scholar
  23. 23.
    King CS, Weir EC, Gundberg CW et al (1996) Effects of continuous glucocorticoid infusion on bone metabolism in the rat. Calcif Tissue Int 59:184–191CrossRefPubMedGoogle Scholar
  24. 24.
    Iwamoto J, Seki A, Takeda T et al (2008) Effects of combined administration of alfacalcidol and risedronate on cancellous and cortical bone mass of the tibia in glucocorticoid-treated young rats. Chin J Physiol 51:121–128PubMedGoogle Scholar
  25. 25.
    Iwamoto J, Matsumoto H, Tadeda T et al (2009) Comparison of the effect of vitamin K2 and risedronate on trabecular bone in glucocorticoid-treated rats: a bone histomorphometry study. Yonsei Med J 50:189–194CrossRefPubMedGoogle Scholar
  26. 26.
    Shane E, Addesso V, Namerow PB et al (2004) Alendronate versus calcitriol for the prevention of bone loss after cardiac transplantation. N Engl J Med 350:767–776CrossRefPubMedGoogle Scholar
  27. 27.
    Roschger P, Rinnerthaler S, Yates JA et al (2001) Alendronate increases degree and uniformity of mineralisation in cancellous bone and decreases the porosity in cortical bone of osteoporotic women. Bone 29:185–191CrossRefPubMedGoogle Scholar
  28. 28.
    Fratzl P, Roschger P, Fratzl-Zelman N et al (2007) Evidence that treatment with risedronate in women with post menopausal osteoporosis affects bone mineralisation and bone volume. Calcif Tissue Int 81:73–80CrossRefPubMedGoogle Scholar
  29. 29.
    Iwamoto J, Matsumoto H, Takeda T et al (2008) Effects of vitamin K2 and risedronate on bone formation and resorption, osteocyte lacunar system, and porosity in the cortical bone of glucocorticoid-treated rats. Calcif Tissue Int 83:121–128CrossRefPubMedGoogle Scholar
  30. 30.
    Bonnelye E, Chabadel A, Saltel F et al (2008) Dual effect of strontium ranelate: stimulation of osteoblast differentiation and inhibition of osteoclast formation and resorption in vitro. Bone 42:129–138CrossRefPubMedGoogle Scholar
  31. 31.
    Arlot ME, Jiang Y, Genant HK et al (2008) Histomorphometric and microCT analysis of bone biopsies from postmenopausal osteoporotic women treated with strontium ranelate. J Bone Miner Res 23:215–222CrossRefPubMedGoogle Scholar
  32. 32.
    Marie PJ (2006) Strontium ranelate: a physiological approach for optimizing bone formation and resorption. Bone 38(Suppl 1):10–14CrossRefGoogle Scholar
  33. 33.
    Marie PJ, Hott M, Modrowski D et al (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 8:607–615CrossRefPubMedGoogle Scholar
  34. 34.
    Marie PJ, Hott M (1986) Short-term effects of fluoride and strontium on bone formation and resorption in the mouse. Metabolism 35:547–551CrossRefPubMedGoogle Scholar
  35. 35.
    Boivin G, Deloffre P, Perrat B et al (1996) Strontium distribution and interactions with bone mineral in monkey iliac bone after strontium salt (S 12911) administration. J Bone Miner Res 11:1302–1311CrossRefPubMedGoogle Scholar
  36. 36.
    Grynpas M, Marie PJ (1990) Effects of low doses of strontium on bone quality and quantity in rats. Bone 11:313–319CrossRefPubMedGoogle Scholar

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© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  1. 1.Department of EndocrinologyZhujiang Hospital, Southern Medical UniversityGuangzhouChina
  2. 2.The Center for New Drug Function Research, School of Life Science and BiopharmacologyGuangdong Pharmaceutical UniversityGuangzhouChina
  3. 3.Department of Overseas ChineseGuangzhou General Hospital of Guangzhou Military Area Command of Chinese PLAGuangzhouChina

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