Skip to main content
SpringerLink
Log in

Effects of risedronate on femoral bone mineral density and bone strength in sciatic neurectomized young rats

  • ORIGINAL ARTICLE
  • Published:
Journal of Bone and Mineral Metabolism Aims and scope Submit manuscript

Abstract

Immobilization induces a rapid loss of bone density and bone strength in rats. The purpose of the present study was to examine the effects of risedronate (Ris) on the femoral bone density and bone strength of sciatic neurectomized young rats. Forty male Sprague–Dawley rats, 6 weeks of age, were randomized by the stratified weight method into the following four treatment groups of 10 rats each: sham-operation, bilateral sciatic neurectomy (NX), NX + low-dose Ris (0.25 mg/kg/day, orally), and NX + high-dose Ris (0.5 mg/kg/day, orally). After 8 weeks of feeding, the volumetric bone mineral density (vBMD) and stress strain index (SSI) of the femoral distal metaphysis and middiaphysis of the rats were measured by peripheral quantitative computed tomography. The mechanical properties of the femoral distal metaphysis and middiaphysis were measured by the compression and three-point bending tests, respectively. The femoral length was also measured. As compared with the findings in the sham-operated controls, NX resulted in a loss of femoral length, cancellous vBMD, SSI, maximum load, stiffness, and breaking energy of the femoral distal metaphysis; there was also loss of cortical thickness, SSI, maximum load, and stiffness of the femoral middiaphysis, with no significant effects on the cortical vBMD or breaking energy of the femoral middiaphysis. High-dose Ris increased the vBMD to values higher than those in the sham-operated controls, and prevented the loss of SSI, maximum load, and stiffness of the femoral distal metaphysis, while low-dose Ris prevented the loss of cancellous vBMD of the femoral distal metaphysis. Neither high- nor low-dose Ris affected any of the cortical bone parameters of the femoral middiaphysis, except for cortical thickness, or the femoral length. These findings suggest that Ris may prevent immobilization-induced loss of cancellous bone density and bone strength in a dose-dependent manner without interfering with bone growth, but has no apparent effects on the cortical bone in sciatic neurectomized young rats. The results of the present preclinical study should be taken into consideration prior to the commencement of Ris treatment for disabled children.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. T Sugiyama T Taguchi S Kawai (2004) ArticleTitleSpontaneous fractures and quality of life in cerebral palsy Lancet 364 IssueID9428 28 Occurrence Handle10.1016/S0140-6736(04)16585-9 Occurrence Handle15234852

    Article  PubMed  Google Scholar 

  2. F Rauch H Plotkin L Zeitlin FH Glorieux (2003) ArticleTitleBone mass, size, and density in children and adolescents with osteogenesis imperfecta: effect of intravenous pamidronate therapy J Bone Miner Res 18 610–614 Occurrence Handle12674321

    PubMed  Google Scholar 

  3. F Rauch H Plotkin R Travers L Zeitlin FH Glorieux (2003) ArticleTitleOsteogenesis imperfecta types I, III, and IV: effect of pamidronate therapy on bone and mineral metabolism J Clin Endocrinol Metab 88 986–992 Occurrence Handle10.1210/jc.2002-021371 Occurrence Handle12629073

    Article  PubMed  Google Scholar 

  4. F Rauch R Travers H Plotkin FH Glorieux (2002) ArticleTitleThe effects of intravenous pamidronate on the bone tissue of children and adolescents with osteogenesis imperfecta J Clin Invest 110 1293–1299 Occurrence Handle10.1172/JCI200215952 Occurrence Handle12417568

    Article  PubMed  Google Scholar 

  5. FH Glorieux (2000) ArticleTitleBisphosphonate therapy for severe osteogenesis imperfecta J Pediatr Endocrinol Metab 13 IssueIDSuppl 2 989–992 Occurrence Handle11086652

    PubMed  Google Scholar 

  6. H Plotkin F Rauch NJ Bishop K Montpetit J Ruck-Gibis R Travers FH Glorieux (2000) ArticleTitlePamidronate treatment of severe osteogenesis imperfecta in children under 3 years of age J Clin Endocrinol Metab 85 1846–1850 Occurrence Handle10.1210/jc.85.5.1846 Occurrence Handle10843163

    Article  PubMed  Google Scholar 

  7. FH Glorieux NJ Bishop H Plotkin G Chabot G Lanoue R Travers (1998) ArticleTitleCyclic administration of pamidronate in children with severe osteogenesis imperfecta N Engl J Med 339 947–952 Occurrence Handle10.1056/NEJM199810013391402 Occurrence Handle9753709

    Article  PubMed  Google Scholar 

  8. T Sugiyama Y Saito I Kaichi M Sugi H Tanaka S Kawai (2000) ArticleTitleMenatetrenone plus alfacalcidol treatment for bone problems in eight children with skeletal unloading J Bone Miner Metab 18 41–44 Occurrence Handle10.1007/s007740050009 Occurrence Handle10633277

    Article  PubMed  Google Scholar 

  9. T Sugiyama H Tanaka S Kawai (1999) ArticleTitleClinical vignette. Vitamin K plus vitamin D treatment of bone problems in a child with skeletal unloading J Bone Miner Res 14 1466–1467 Occurrence Handle10457281

    PubMed  Google Scholar 

  10. J Iwamoto T Takeda S Ichimura Y Sato JK Yeh (2003) ArticleTitleComparative effects of orchidectomy and sciatic neurectomy on cortical and cancellous bone in young growing rats J Bone Miner Metab 21 211–216 Occurrence Handle12811625

    PubMed  Google Scholar 

  11. J Iwamoto JK Yeh T Takeda (2003) ArticleTitleEffect of vitamin K2 on cortical and cancellous bones in orchidectomized and/or sciatic neurectomized rats J Bone Miner Res 18 776–783 Occurrence Handle12674339

    PubMed  Google Scholar 

  12. I Moriyama J Iwamoto T Takeda Y Toyama (2002) ArticleTitleComparative effects of intermittent administration of human parathyroid hormone (1–34) on cancellous and cortical bone loss in tail-suspended and sciatic neurectomized young rats J Orthop Sci 7 379–385 Occurrence Handle10.1007/s007760200063 Occurrence Handle12077665

    Article  PubMed  Google Scholar 

  13. QQ Zeng WS Jee AE Bigornia JG King SuffixJr SM D'Souza XJ Li YF Ma WJ Wechter (1996) ArticleTitleTime responses of cancellous and cortical bones to sciatic neurectomy in growing female rats Bone 19 13–21 Occurrence Handle10.1016/8756-3282(96)00112-3 Occurrence Handle8830982

    Article  PubMed  Google Scholar 

  14. M Weinreb GA Rodan DD Thompson (1989) ArticleTitleOsteopenia in the immobilized rat hind limb is associated with increased bone resorption and decreased bone formation Bone 10 187–194 Occurrence Handle10.1016/8756-3282(89)90052-5 Occurrence Handle2803854

    Article  PubMed  Google Scholar 

  15. JK Yeh CC Liu JF Aloia (1993) ArticleTitleEffects of exercise and immobilization on bone formation and resorption in young rats Am J Physiol 264 E182–E189 Occurrence Handle8447384

    PubMed  Google Scholar 

  16. J Iwamoto T Takeda T Katsumata T Tanaka S Ichimura Y Toyama (2002) ArticleTitleEffect of etidronate on bone in orchidectomized and sciatic neurectomized adult rats Bone 30 360–367 Occurrence Handle10.1016/S8756-3282(01)00687-1 Occurrence Handle11856643

    Article  PubMed  Google Scholar 

  17. H Murakami T Nakamura H Tsurukami M Abe A Barbier K Suzuki (1994) ArticleTitleEffects of tiludronate on bone mass, structure, and turnover at the epiphyseal, primary, and secondary spongiosa in the proximal tibia of growing rats after sciatic neurectomy J Bone Miner Res 9 1355–1364 Occurrence Handle7529459

    PubMed  Google Scholar 

  18. K Notoya K Yoshida R Tsukuda S Taketomi M Tsuda (1996) ArticleTitleIncrease in femoral bone mass by ipriflavone alone and in combination with 1 alpha-hydroxyvitamin D3 in growing rats with skeletal unloading Calcif Tissue Int 58 88–94 Occurrence Handle10.1007/s002239900016 Occurrence Handle8998683

    Article  PubMed  Google Scholar 

  19. R Tarvainen I Arnala H Olkkonen R Lappalainen T Nevalainen E Alhava (1994) ArticleTitleClodronate prevents immobilization osteopenia in rats Acta Orthop Scand 65 643–646 Occurrence Handle7839852

    PubMed  Google Scholar 

  20. J Tuukkanen P Jalovaara K Vaananen (1991) ArticleTitleCalcitonin treatment of immobilization osteoporosis in rats Acta Physiol Scand 141 119–124 Occurrence Handle2053438

    PubMed  Google Scholar 

  21. DD Thompson JG Seedor M Weinreb S Rosini GA Rodan (1990) ArticleTitleAminohydroxybutane bisphosphonate inhibits bone loss due to immobilization in rats J Bone Miner Res 5 279–286 Occurrence Handle2333787

    PubMed  Google Scholar 

  22. RG Erben L Mosekilde JS Thomsen K Weber K Stahr A Leyshon SY Smith R Phipps (2002) ArticleTitlePrevention of bone loss in ovariectomized rats by combined treatment with risedronate and 1-alpha,25-dihydroxyvitamin D3 J Bone Miner Res 17 1498–1511 Occurrence Handle12162504

    PubMed  Google Scholar 

  23. L Mosekilde JS Thomsen MS Mackey RJ Phipps (2000) ArticleTitleTreatment with risedronate or alendronate prevents hind-limb immobilization-induced loss of bone density and strength in adult female rats Bone 27 639–645 Occurrence Handle10.1016/S8756-3282(00)00375-6 Occurrence Handle11062350

    Article  PubMed  Google Scholar 

  24. JL Ferretti RF Capozza JR Zanchetta (1996) ArticleTitleMechanical validation of a tomographic (pQCT) index for noninvasive estimation of rat femur bending strength Bone 18 97–102 Occurrence Handle10.1016/8756-3282(95)00438-6 Occurrence Handle8833202

    Article  PubMed  Google Scholar 

  25. PM Lind L Lind S Larsson J Orberg (2001) ArticleTitleTortional testing and peripheral quantitative computed tomography in rat humerus Bone 29 265–270 Occurrence Handle10.1016/S8756-3282(01)00576-2 Occurrence Handle11557371

    Article  PubMed  Google Scholar 

  26. HM Frost WS Jee (1992) ArticleTitleOn the rat model of human osteopenias and osteoporoses Bone Miner 18 227–236 Occurrence Handle10.1016/0169-6009(92)90809-R Occurrence Handle1392696

    Article  PubMed  Google Scholar 

  27. HM Frost (1987) ArticleTitleBone “mass” and the “mechanostat”: a proposal Anat Rec 219 1–9 Occurrence Handle10.1002/ar.1092190104 Occurrence Handle3688455

    Article  PubMed  Google Scholar 

  28. HM Frost (1988) ArticleTitleStructural adaptations to mechanical usage: a “three-way” rule for lamellar bone modeling Comp Vet Orthop Trauma 1 7–17

    Google Scholar 

  29. MJ Rogers JC Frith SP Luckman FR Coxon HL Benford J Monkkonen S Auriola KM Chilton RGG Russell (1999) ArticleTitleMolecular mechanism of action of bisphosphonate Bone 24 IssueID5 Suppl 73S–79S Occurrence Handle10.1016/S8756-3282(99)00070-8 Occurrence Handle10321934

    Article  PubMed  Google Scholar 

  30. D Chappard M Petitjean C Alexandre L Vico P Minaire G Riffat (1991) ArticleTitleCortical osteoclasts are less sensitive to etidronate than trabecular osteoclasts J Bone Miner Res 6 673–680 Occurrence Handle1950672

    PubMed  Google Scholar 

  31. H Otomo A Sakai S Ikeda S Tanaka M Ito RJ Phipps T Nakamura (2004) ArticleTitleRegulation of mineral-to-matrix ratio of lumbar trabecular bone in ovariectomized rats treated with risedronate in combination with or without vitamin K2 J Bone Miner Metab 22 404–414 Occurrence Handle10.1007/s00774-004-0502-6 Occurrence Handle15316861

    Article  PubMed  Google Scholar 

  32. Y Kodama K Nakayama H Fuse S Fukumoto H Kawahara H Takahashi T Kurokawa C Sekiguchi T Nakamura T Matsumoto (1997) ArticleTitleInhibition of bone resorption by pamidronate cannot restore normal gain in cortical bone mass and strength in tail-suspended rapidly growing rats J Bone Miner Res 12 1058–1067 Occurrence Handle9200005

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Sports Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan

    Jun Iwamoto & Tsuyoshi Takeda

  2. Hamri Co., Tokyo, Japan

    Azusa Seki

  3. Department of Neurology, Mitate Hospital, Fukuoka, Japan

    Yoshihiro Sato

  4. Department of Orthopaedic Surgery, Fujita Health University, Aichi, Japan

    Harumoto Yamada

Authors
  1. Jun Iwamoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Azusa Seki
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Tsuyoshi Takeda
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yoshihiro Sato
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Harumoto Yamada
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jun Iwamoto.

About this article

Cite this article

Iwamoto, J., Seki, A., Takeda, T. et al. Effects of risedronate on femoral bone mineral density and bone strength in sciatic neurectomized young rats. J Bone Miner Metab 23, 456–462 (2005). https://doi.org/10.1007/s00774-005-0628-1

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00774-005-0628-1

Key words

Search

Navigation