Skip to main content
SpringerLink
Log in

Does Exercise Modify the Effects of Zoledronic Acid on Bone Mass, Microarchitecture, Biomechanics, and Turnover in Ovariectomized Rats?

  • Published:
Calcified Tissue International Aims and scope Submit manuscript

Abstract

Regular activity has effects on bone size, shape, and density, resulting in an increase in mechanical strength. The mechanism of action that underlies this improvement in bone strength is mainly linked to an increase in bone formation. Zoledronic acid (Z), in contrast, may prevent bone strength changes in ovariectomized (OVX) rodents by its potent antiresorptive effects. Based on these assumptions we hypothesized that combined effects of exercise (E) and Z may produce higher benefits on bone changes resulting from estrogen deficiency than either intervention alone. At 6 months of age, 60 female Wistar rats were OVX or sham operated (SH) and divided into five groups: SH, OVX, OVX-E, OVX-Z, and OVX-ZE. OVX rats were treated with a single IV injection of Z (20 μg/kg) or vehicle and submitted or not to treadmill exercise (15 m/min, 60 min/day, 5 days/week) for 12 weeks. Whole-body BMD and bone turnover markers were analyzed longitudinally. At sacrifice, femurs were removed. BMD by DXA, three-point bending test, and μCT were performed to study biomechanical and trabecular structure parameters, respectively. After 12 weeks, bone volume fraction decreased in OVX rats, whereas bone turnover rate, trabecular spacing, and structure model index increased compared with those in the SH group (P < 0.05). Zoledronic acid prevented the ovariectomy-induced trabecular bone loss and its subsequent trabecular microarchitectural deterioration. Treadmill exercise running was shown to preserve the bone strength and to induce bone turnover changes in favor of bone formation. However, the combined effects of zoledronic acid and running exercise applied simultaneously did not produce any synergetic or additive effects.

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

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Johnell O, Kanis JA (2006) An estimate of the worldwide prevalence and disability associated with osteoporotic fractures. Osteoporos Int 17:1726–1733

    Article  PubMed  CAS  Google Scholar 

  2. Boonen S (2007) Bisphosphonate efficacy and clinical trials for postmenopausal osteoporosis: similarities and differences. Bone 40:S26–S31

    Article  CAS  Google Scholar 

  3. Black DM, Delmas PD, Eastell R, Reid IR, Boonen S, Cayley JA, Cosman F, Lakatos P, Chung Leung P, Man Z, Mautalen C, Mesenbrick P, Hu H, Caminis J, Tong K, Rosario-Jansen T, Krasnow J, Hue TF, Sellmeyer D, Fink Eriksen E, Cummings SR (2007) Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis. N Engl J Med 356:1809–1822

    Article  PubMed  CAS  Google Scholar 

  4. Hugues DE, Wright KR, Ui HL, Sasaki A, Yoneda T, Roodman GD, Mundy GR, Boyce BF (1995) Bisphosphonates promote apoptosis in murine osteoclasts in vitro and in vivo. J Bone Miner Res 10:1478–1487

    Google Scholar 

  5. Walsh MC, Hunter GR, Livingstone MB (2006) Sarcopenia in premenopausal and postmenopausal women with osteopenia, osteoporosis and normal bone mineral density. Osteoporos Int 17(1):61–67

    Article  PubMed  Google Scholar 

  6. Wallace BA, Cummings RG (2000) Systematic review of randomized trials pf the effect pf exercise on bone mass in pre-and postmenopausal women. Calcif Tissue Int 67:10–18

    Article  PubMed  CAS  Google Scholar 

  7. Bonaiuti D et al (2003) Exercise for preventing and treating osteoporosis in postmenopausal women. Cochrane Database Syst Rev 3:CD000333 Review

  8. National Osteoporosis Foundation (2008) Clinician’s guide to prevention and treatment of osteoporosis. NOF, Washington, DC

    Google Scholar 

  9. National Osteoporosis Foundation (2004) Bone health and osteoporosis: a report of the surgeon general. NOF, Washington, DC

    Google Scholar 

  10. Huiskes R, Ruimerman R, van Lenthe GH, Janssen JD (2000) Effects of mechanical forces on maintenance and adaptation of form in trabecular bone. Nature 405(8):704–706

    Article  PubMed  CAS  Google Scholar 

  11. Lespessailles E, Prouteau S (2006) Is there a synergy between physical exercise and drug therapies for osteoporosis? Clin Exp Rheumatol 24:191–195

    PubMed  CAS  Google Scholar 

  12. Delmas PD, Vergnaud P, Arlot ME, Pastoureau P, Meunier PJ, Nilssen MJL (1995) The anabolic effect of human PTH (1–34) on bone formation is blunted when bone resorption is inhibited by the bisphosphonate tiludronate—Is activated resorption a prerequisite for the in vivo effect of PTH on formation in a remodelling system? Bone 16:603–610

    Article  PubMed  CAS  Google Scholar 

  13. Gasser JA, Kneissel M, Thomsen JS, Mosekilde L (2000) PTH and interactions with bisphosphonates. J Musculoskel Neuron Interact 1:53–56

    CAS  Google Scholar 

  14. Fuchs RK, Shea M, Durski SL, Winters-Stone KM, Widrick J, Snow CM (2007) Individual and combined effects of exercise and alendronate on bone mass and strength in ovariectomized rats. Bone 41:290–296

    Article  PubMed  CAS  Google Scholar 

  15. Tamaki H, Akamine T, Kurata H, Sakou T (1998) Effects of exercise training and etidronate treatment on bone mineral density and trabecular bone in ovariectomized rats. Bone 23:147–153

    Article  PubMed  CAS  Google Scholar 

  16. Wronski TJ, Schenck PA, Cintron M, Walsh CC (1987) Effect of body weight on osteopenia in ovariectomized rats. Calcif Tissue 40:155–159

    Article  CAS  Google Scholar 

  17. Gasser JA, Green JR (2002) Long-term protective effect of a single IV injection of zoledronic acid on cancellous bone structure and cortical bone in ovariectomized rats. Bone 30(Suppl 3):41S

    Google Scholar 

  18. Eastell R, Robins SP, Colwell T, Assiri AM, Riggs BL, Russell RG (1993) Evaluation of bone turnover in type I osteoporosis using biochemical markers specific for both bone formation and bone resorption. Osteoporos Int 3:255–260

    Article  PubMed  CAS  Google Scholar 

  19. Pastoureau P, Chomel A, Bonnet J (1995) Specific evaluation of localized bone mass and bone loss in the rat using dual-energy X-ray absorptiometry subrregional analysis. Osteoporos Int 5:143–149

    Article  PubMed  CAS  Google Scholar 

  20. Muller R, Van Campenhout H, Van Damme B, Van der Perre G, Dequeker J, Hildebrand T, Ruegsegger P (1998) Morphometric analysis of human bone biopsies: a quantitative structural comparison of histological sections and micro-computed tomography. Bone 23:59–66

    Article  PubMed  CAS  Google Scholar 

  21. Lorensen WE, Cline HE (1987) Marching cubes: a high resolution 3D surface construction algorithm ACM SIGGRAPH 21:1249–1252

  22. Hildebrand T, Ruegsegger P (1997) A new method for the model independent assessment of thickness in three dimensional images. J Microsc 185:67–75

    Article  Google Scholar 

  23. 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 2:595–610

    Article  PubMed  CAS  Google Scholar 

  24. Hildebrand T, Ruegsegger P (1997) Quantification of bone microarchitecture with the structure model index. Comput Meth Biomech Biomed Eng 1:15–23

    Article  Google Scholar 

  25. Hahn M, Vogel M, Pompesius-Kempa M, Delling G (1992) Trabecular bone pattern factor:a new parameter for simple quantification of bone microarchitecture. Bone 13:327–330

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  27. Neter J, Wasserman W, Ahitmore GA (1982) Applied statistics. Allyn and Bacon, Boston, pp 544–572

    Google Scholar 

  28. Yao W, Cheng Z, Koester KJ, Ager JW, Balooch M, Pham A, Chefo S, Busse C, Ritchie R, Lane NE (2007) The degree of bone mineralization is maintained with single intravenous bisphosphonates in aged estrogen-deficient rats and is a strong predictor of bone strength. Bone 41:804–812

    Article  PubMed  CAS  Google Scholar 

  29. Lee JI, Kim HW, Rhee WI, Park JH, Lim SH, Im S, Ko YJ (2006) The beneficial effect of intravenous zoledronic acid therapy following an acute stroke in rats. Bone 39:377–382

    Article  PubMed  CAS  Google Scholar 

  30. Browers JEM, Lambers FM, Gasser JA, van Rietbergen B, Huiskes R (2008) Bone degeneration and recovery after early and late bisphosphonate treatment of ovariectomized Wistar rats assessed by in vivo micro-computed tomography. Calcif Tissue Int 82:202–211

    Article  CAS  Google Scholar 

  31. Gasser JA, Ingold P, Venturiere A, Shen V, Green JR (2008) Long-term protective effects of zoledronic acid on cancellous and cortical bone in ovariectomized rat. J Bone Miner Res 23:544–551

    Article  PubMed  CAS  Google Scholar 

  32. Bonnet N, Laroche N, Beaupied H, Vico L, Dolleans E, Benhamou CL, Courteix D (2007) Doping dose of salbutamol and exercise training: impact on the skeleton of ovariectomized rats. J Appl Physiol 103:524–533

    Article  PubMed  CAS  Google Scholar 

  33. Honda A, Umemura Y, Nagasawa S (2001) Effect of high-impact and low-repetition training on bones in ovariectomized rats. J Bone Miner Res 16:1688–1693

    Article  PubMed  CAS  Google Scholar 

  34. Adami S, Gatti D, Braga V, Bianchini V, Rossini M (1999) Site-specific effects of strength training on bone structure and geometry of ultradistal radius in post-menopausal women. J Bone Miner Res 14:120–124

    Article  PubMed  CAS  Google Scholar 

  35. Jarvinen TLN, Kannus P, Sievanen H, Jolma P, Heinonen A, Jarvinen M (1998) Randomized controlled study of effects of sudden impact loading on rat femur. J Bone Miner Res 13:1475–1482

    Article  PubMed  CAS  Google Scholar 

  36. Iwamoto J, Takeda T, Sato Y (2005) Effect of treadmill exercise on bone mass in female rats. Exp Anim 54:1–6

    Article  PubMed  CAS  Google Scholar 

  37. Fukuda S, Lida H, Hyakutake S, Yan X (2002) Preventive effects of running exerse on bones in heavy ion particle irradiated rats. J Radiat Res 43(Suppl):S233–S238

    Article  PubMed  Google Scholar 

  38. Bonnet N, Beaupied H, Vico L, Dolléans E, Laroche L, Courteix D, Benhamou CL (2007) Combined effects of exercise and propranolol on bone tissue in ovarectomized rats. J Bone Miner Res 22(4):578–588

    Article  PubMed  CAS  Google Scholar 

  39. Bourrin S, Palle S, Genty C, Alexandre C (1995) Physical exercise during remobilization restores a normal bone trabecular network after tail suspension-induced osteopenia in young rats. J Bone Miner Res 10:820–828

    PubMed  CAS  Google Scholar 

  40. Hagihara Y, Fukuda S, Goto S, Lida H, Yamazaki M, Moriya H (2005) How many days per week should rats undergo running exercise to increase BMD? J Bone Miner Metab 23:289–294

    Article  PubMed  Google Scholar 

  41. Li CY, Jee SS, Chen JL, Mo A, Setterberg RB, Su M, Tian XY, Ling F, Yao W (2003) Estrogen and “exercise” have a synergistic effect in preventing bone loss in the lumbar vertebra and femoral neck of the ovariectomized rat. Calcif Tissue Int 72:42–49

    Article  PubMed  CAS  Google Scholar 

  42. Iwamoto J, Yeh JK, Aloia JF (1999) Differential effect of treadmill exercise on three cancellous bone sites in the young growing rat. Bone 24:163–169

    Article  PubMed  CAS  Google Scholar 

  43. Joo YI, Sone T, Fukuna ga M, Lim SG, Onodera S (2003) Effects of endurance exercise on three-dimensional trabecular bone microarchitecture in young growing rats. Bone 33:485–493

    Article  PubMed  Google Scholar 

  44. Newhall KM, Rodnick KJ, van der Meulen MC, Carter DR, Marcus RT (1991) Effects of voluntary exercise on bone mineral content in rats. J Bone Miner Res 6:289–296

    Article  PubMed  CAS  Google Scholar 

  45. Yeh JK, Aloia JF, Chen MM, Tierney JM, Sprintz S (1993) Influence of exercise on cancellous bone of the aged female rat. J Bone Miner Res 8:117–1125

    Google Scholar 

  46. Iwamoto J, Shimamura C, Yakeda T, Abe H, Ichimura S, Sato Y, Toyama Y (2004) Effects of treadmill exercise on bone mass, bone metabolism, and calciotropic hormones in young rats. J Bone Miner Metab 22:26–31

    Article  PubMed  CAS  Google Scholar 

  47. Black BL, Gree’nspan FL, Ensrud KE, Palermo L, Mc Gowan JA, Lang TF, Garnero P, Bouxsein ML, Bilezikian JP, Rosen CJ, PATH Study Investigators (2003) The effect of parathyroid hormones and alendronate alone or in combination in post-menopausal osteoporosis. N Engl J Med 349:1207–1215

    Article  PubMed  CAS  Google Scholar 

  48. Rhee Y, Won YY, Baek MY, Lim SK (2004) Maitenance of increased bone mass after recombinant human parathyroid hormone(1–84) with sequential zoledronate treatment in ovariectomized rats. J Bone Miner Res 19:931–937

    Article  PubMed  CAS  Google Scholar 

  49. Chilibeck PD, Davison KS, Whiting SJ, Suzuki Y, Janzen CL, Peloso P (2002) Efffect of strength training combined with bisphosphonate (etidronate) therapy on bone mineral, lean tissue, and fat mass in postmenopausal women. Can J Physiol Pharmacol 80:941–950

    Article  PubMed  CAS  Google Scholar 

  50. Uusi-Rasi K, Kannus P, Cheng S, Sievänen H, Pasanen M, Heinonen A, Nenoren A, Halleen J, Fuerst T, Genant H, Vuori I (2003) Effect of alendronate and exercise on bone and physical performance of postmenopausal women:a randomized controlled trial. Bone 33:132–143

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgment

This work was supported by a grant from Novartis France.

Author information

Authors and Affiliations

  1. INSERM U658, Laboratoire de Caractérisation du Tissu Osseux par Imagerie: Techniques et Applications, CHR d’Orleans, Orleans, France

    E. Lespessailles, C. Jaffré, H. Beaupied, P. Nanyan, E. Dolléans & C. L. Benhamou

  2. UFR STAPS, Université d’Orléans, 45067, Orleans Cedex 2, France

    C. Jaffré

  3. Laboratoire de Biologie des APS, UFR STAPS, Université Blaise Pascal, BP 104, 63172, Aubière Cedex, France

    D. Courteix

Authors
  1. E. Lespessailles
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. C. Jaffré
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. H. Beaupied
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. P. Nanyan
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. E. Dolléans
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. C. L. Benhamou
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. D. Courteix
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to E. Lespessailles.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lespessailles, E., Jaffré, C., Beaupied, H. et al. Does Exercise Modify the Effects of Zoledronic Acid on Bone Mass, Microarchitecture, Biomechanics, and Turnover in Ovariectomized Rats?. Calcif Tissue Int 85, 146–157 (2009). https://doi.org/10.1007/s00223-009-9269-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00223-009-9269-z

Keywords

Search

Navigation