Skip to main content

Advertisement

Log in

Single and combined effect of high-frequency loading and bisphosphonate treatment on the bone micro-architecture of ovariectomized rats

  • Original Article
  • Published:
Osteoporosis International Aims and scope Submit manuscript

Abstract

Summary

Mechanical loading at high frequency affects bone. Whether this also applies to osteoporotic bone, combined or not with bisphosphonate therapy, was investigated in this animal study through imaging. An anabolic effect of high-frequency loading on osteoporotic bone, however non-synergistic with bisphosphonates, was found, thereby revealing its potential for treatment of osteoporosis.

Introduction

In an effort to elucidate the effect of high-frequency (HF) loading on bone and to optimize its potential for treatment osteoporosis, this study aimed to investigate the effect of HF loading via whole body vibration (WBV), alone or in association with bisphosphonate treatment (alendronate—ALN), on the micro-architecture of ovariectomy (OVX)-induced compromised bone.

Methods

Eighty-four female Wistar rats were ovariectomized (OVX) or sham-operated (shOVX). OVX animals were treated either with ALN (3 days/week at a dose of 2 mg/kg) or with saline solution. Each group (shOVX, OVX, ALN) was further divided into subgroups relative to the loading status (sham-WBV versus WBV) and the duration of experimental period (4 days versus 14 days). (Sham)WBV loading was applied for 10 min/day using 10 consecutive steps of HF loading (130, 135, 140, 145, 150, 130, 135, 140, 145, 150 Hz). Tibial bone structural responses to WBV and/or ALN treatment were analyzed using ex vivo micro-computed tomography.

Results

The animal’s hormonal status displayed a major impact on the trabecular and cortical bone structural parameters. Furthermore, mechanical treatment with HF WBV increased the cortical thickness and reduced the medullar area in OVX rats. However, OVX trabecular bone was not affected by HF stimuli. Finally, ALN prevented OVX-associated bone loss, but the association of ALN with WBV did not lead to a synergistic bone response in OVX bone.

Conclusions

HF WBV mechanical stimulation displayed an anabolic effect on osteoporotic cortical bone, confirming its therapeutic properties for enhancing compromised bone. Additionally, its association with bisphosphonates’ administration did not produce any additive effect on the bone micro-architecture in the present study.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Rachner TD, Khosla S, Hofbauer LC (2011) Osteoporosis: now and the future. Lancet 377:1276–1287. doi:10.1016/S0140-6736(10)62349-5

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  2. Melton LJ III, Chrischilles EA, Cooper C et al (2005) How many women have osteoporosis? J Bone Miner Res 7:1005–1010

    Article  Google Scholar 

  3. Burge R, Dawson-Hughes B, Solomon DH et al (2007) Incidence and economic burden of osteoporosis-related fractures in the United States, 2005-2025. J Bone Miner Res Off J Am Soc Bone Miner Res 22:465–475

    Article  Google Scholar 

  4. Inada M, Miyaura C (2010) Cytokines in bone diseases. Cytokine and postmenopausal osteoporosis. Clin Calcium 20:1467–1472

    CAS  PubMed  Google Scholar 

  5. Pacifici R (1996) Estrogen, cytokines, and pathogenesis of postmenopausal osteoporosis. J Bone Miner Res Off J Am Soc Bone Miner Res 11:1043–1051

    Article  CAS  Google Scholar 

  6. Sambrook P, Cooper C (2006) Osteoporosis. Lancet 367:2010–2018

    Article  CAS  PubMed  Google Scholar 

  7. Siris ES, Selby PL, Saag KG et al (2009) Impact of osteoporosis treatment adherence on fracture rates in North America and Europe. Am J Med 122:S3–S13

    Article  PubMed  Google Scholar 

  8. E O, Luu Y, B A, et al. (2010) Mechanical signals as anabolic agents in bone. Nature 6:50–59

  9. Judex S, Rubin CT (2010) Is bone formation induced by high-frequency mechanical signals modulated by muscle activity? J Musculoskelet neuronal Interact 10:3–11

    CAS  PubMed Central  PubMed  Google Scholar 

  10. Judex S, Lei X, Han D, Rubin C (2007) Low-magnitude mechanical signals that stimulate bone formation in the ovariectomized rat are dependent on the applied frequency but not on the strain magnitude. J Biomech 40:1333–1339

    Article  PubMed  Google Scholar 

  11. Oxlund B, Ørtoft G, Andreassen T, Oxlund H (2003) Low-intensity, high-frequency vibration appears to prevent the decrease in strength of the femur and tibia associated with ovariectomy of adult rats. Bone 32:69–77. doi:10.1016/S8756-3282(02)00916-X

    Article  CAS  PubMed  Google Scholar 

  12. Chen B, Li Y, Yang X, Xie D (2013) Comparable effects of alendronate and strontium ranelate on femur in ovariectomized rats. Calcif Tissue Int 93:481–486

    Article  CAS  PubMed  Google Scholar 

  13. Chen B, Li Y, Xie D, Yang X (2012) Low-magnitude high-frequency loading via whole body vibration enhances bone-implant osseointegration in ovariectomized rats. J Orthop Res 30:733–739. doi:10.1002/jor.22004

    Article  PubMed  Google Scholar 

  14. Ogawa T, Possemiers T, Zhang X et al (2011) Influence of whole-body vibration time on peri-implant bone healing: a histomorphometrical animal study. J Clin Periodontol 38:180–185. doi:10.1111/j.1600-051X.2010.01637.x

    Article  PubMed  Google Scholar 

  15. Ogawa T, Zhang X, Naert I et al (2011) The effect of whole-body vibration on peri-implant bone healing in rats. Clin Oral Implants Res 22:302–307. doi:10.1111/j.1600-0501.2010.02020.x

    Article  PubMed  Google Scholar 

  16. Tezval M, Biblis M, Sehmisch S et al (2011) Improvement of femoral bone quality after low-magnitude, high-frequency mechanical stimulation in the ovariectomized rat as an osteopenia model. Calcif Tissue Int 88:33–40

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  17. Brouwers JEM, Van Rietbergen B, Ito K, Huiskes R (2010) Effects of vibration treatment on tibial bone of ovariectomized rats analyzed by in vivo micro-CT. J Orthop Res 28:62–69

    PubMed  Google Scholar 

  18. Sehmisch S, Galal R, Kolios L, et al. (2009) Effects of low-magnitude, high-frequency mechanical stimulation in the rat osteopenia model. Osteoporos Int a J Establ as result Coop between Eur Found Osteoporos Natl Osteoporos Found USA 20:1999–2008

  19. Rubinacci A, Marenzana M, Cavani F et al (2008) Ovariectomy sensitizes rat cortical bone to whole-body vibration. Calcif Tissue Int 82:316–326

    Article  CAS  PubMed  Google Scholar 

  20. Bouxsein ML, Boyd SK, Christiansen BA et al (2010) Guidelines for assessment of bone microstructure in rodents using micro-computed tomography. J Bone Miner Res Off J Am Soc Bone Miner Res 25:1468–1486

    Article  Google Scholar 

  21. Adams JE (2013) Advances in bone imaging for osteoporosis. Nat Rev Endocrinol 9:28–42. doi:10.1038/nrendo.2012.217

    Article  CAS  PubMed  Google Scholar 

  22. Khosla S, Oursler MJ, Monroe DG (2012) Estrogen and the skeleton. Trends Endocrinol Metab TEM 23:576–581. doi:10.1016/j.tem.2012.03.008

    Article  CAS  Google Scholar 

  23. Ishihara A, Sasaki T, Debari K et al (1999) Effects of ovariectomy on bone morphology in maxillae of mature rats. J Electron Microsc (Tokyo) 48:465–469

    Article  CAS  Google Scholar 

  24. Shi H-F, Cheung W-H, Qin L et al (2010) Low-magnitude high-frequency vibration treatment augments fracture healing in ovariectomy-induced osteoporotic bone. Bone 46:1299–1305. doi:10.1016/j.bone.2009.11.028

    Article  PubMed  Google Scholar 

  25. Van Der Jagt OP, Van Der Linden JC, Waarsing JH et al (2012) Low-magnitude whole body vibration does not affect bone mass but does affect weight in ovariectomized rats. J Bone Miner Metab 30:40–46. doi:10.1007/s00774-011-0293-5

    Article  PubMed  Google Scholar 

  26. Burghardt AJ, Kazakia GJ, Sode M et al (2010) A longitudinal HR-pQCT study of alendronate treatment in postmenopausal women with low bone density: relations among density, cortical and trabecular microarchitecture, biomechanics, and bone turnover. J Bone Miner Res Off J Am Soc Bone Miner Res 25:2558–2571. doi:10.1002/jbmr.157

    Article  Google Scholar 

  27. Eastell R, Walsh JS, Watts NB, Siris E (2011) Bisphosphonates for postmenopausal osteoporosis. Bone 49:82–88. doi:10.1016/j.bone.2011.02.011

    Article  CAS  PubMed  Google Scholar 

  28. Rogers MJ, Crockett JC, Coxon FP, Mönkkönen J (2011) Biochemical and molecular mechanisms of action of bisphosphonates. Bone 49:34–41

    Article  CAS  PubMed  Google Scholar 

  29. Roschger P, Rinnerthaler S, Yates J et al (2001) Alendronate increases degree and uniformity of mineralization in cancellous bone and decreases the porosity in cortical bone of osteoporotic women. Bone 29:185–191

    Article  CAS  PubMed  Google Scholar 

  30. Feher A, Koivunemi A, Koivunemi M et al (2010) Bisphosphonates do not inhibit periosteal bone formation in estrogen deficient animals and allow enhanced bone modeling in response to mechanical loading. Bone 46:203–207

    Article  CAS  PubMed  Google Scholar 

  31. Lee K, Jessop H, Suswillo R, et al. (2003) Endocrinology: bone adaptation requires oestrogen receptor-alpha. Nature 24;389

  32. Lee KCL, Lanyon LE (2004) Mechanical loading influences bone mass through estrogen receptor [alpha]. Exerc Sport Sci Rev 32:64–68

    Article  PubMed  Google Scholar 

  33. Lim SK, Won YJ, Lee HC et al (1999) A PCR analysis of ERalpha and ERbeta mRNA abundance in rats and the effect of ovariectomy. J Bone Miner Res Off J Am Soc Bone Miner Res 14:1189–1196

    Article  CAS  Google Scholar 

  34. Hoyland J (1999) Effect of ovarian steroid deficiency on oestrogen receptor alpha expression in bone. J Pathol 188:294–303

    Article  CAS  PubMed  Google Scholar 

  35. Seeman E (2007) The periosteum—a surface for all seasons. Osteoporos Int 18:123–128

    Article  CAS  PubMed  Google Scholar 

  36. Saxon L, Turner C (2005) Estrogen receptor beta: the antimechanostat? Bone 36:185–192

    Article  CAS  PubMed  Google Scholar 

  37. Saxon LK, Robling AG, Castillo AB et al (2007) The skeletal responsiveness to mechanical loading is enhanced in mice with a null mutation in estrogen receptor. Am J Physiol Endocrinol Metab 293:E484–E491. doi:10.1152/ajpendo.00189.2007

    Article  CAS  PubMed  Google Scholar 

  38. Saxon LK, Turner CH (2006) Low-dose estrogen treatment suppresses periosteal bone formation in response to mechanical loading. Bone 39:1261–1267

    Article  CAS  PubMed  Google Scholar 

  39. Iwamoto J, Takeda T, Sato Y, Uzawa M (2005) Effect of whole-body vibration exercise on lumbar bone mineral density, bone turnover, and chronic back pain in post-menopausal osteoporotic women treated with alendronate. Aging Clin Exp Res 17:157–163

    Article  CAS  PubMed  Google Scholar 

  40. Iwamoto J, Sato Y, Takeda T, Matsumoto H (2012) Whole body vibration exercise improves body balance and walking velocity in postmenopausal osteoporotic women treated with alendronate: Galileo and Alendronate Intervention Trail (GAIT). J Musculoskelet Neuronal Interact 12:136–143

    CAS  PubMed  Google Scholar 

  41. Lespessailles E, Jaffré C, Beaupied H et al (2009) Does exercise modify the effects of zoledronic acid on bone mass, microarchitecture, biomechanics, and turnover in ovariectomized rats? Calcif Tissue Int 85:146–157

    Article  CAS  PubMed  Google Scholar 

  42. Fuchs R, Shea M, Durski S et al (2007) Individual and combined effects of exercise and alendronate on bone mass and strength in ovariectomized rats. Bone 41:290–296

    Article  CAS  PubMed  Google Scholar 

  43. Waarsing JH, Day JS, Van Der Linden JC et al (2004) Detecting and tracking local changes in the tibiae of individual rats: a novel method to analyse longitudinal in vivo micro-CT data. Bone 34:163–169

    Article  CAS  PubMed  Google Scholar 

  44. Boyd SK, Davison P, M??ller R, Gasser JA (2006) Monitoring individual morphological changes over time in ovariectomized rats by in vivo micro-computed tomography. Bone 39:854–862

  45. Pei L, Tontonoz P (2004) Fat’s loss is bone’s gain. J Clin Invest 113:805–806

    Article  CAS  PubMed Central  PubMed  Google Scholar 

Download references

Acknowledgments

The author would like to acknowledge Dr. A. Ivanova for the help with the statistical analysis. This work was supported by the Fund for Scientific Research Flanders (FWO Flanders—postdoctoral researcher K. Vandamme) and by the Brazilian Science Without Borders Program (246131/2012-8 process, Phd student G.V. Camargos; 245450/2012-2 process, Postdoctoral researcher F. Faot).

Conflicts of interest

The authors Kouki Hatori, Germana De Villa Camargos, Marissa Chatterjee, Fernanda Faot, Keiichi Sasaki, Joke Duyck, and Katleen Vandamme declare that there are no conflicts of interest related to the manuscript.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to K. Vandamme.

Electronic supplementary material

Below is the link to the electronic supplementary material.

ESM 1

(DOCX 4726 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Hatori, K., Camargos, G.V., Chatterjee, M. et al. Single and combined effect of high-frequency loading and bisphosphonate treatment on the bone micro-architecture of ovariectomized rats. Osteoporos Int 26, 303–313 (2015). https://doi.org/10.1007/s00198-014-2857-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00198-014-2857-4

Keywords

Navigation