Osteoporosis International

, Volume 6, Issue 3, pp 219–227 | Cite as

Bone density and shape as determinants of bone strength in IGF-I and/or pamidronate-treated ovariectomized rats

  • P. Ammann
  • R. Rizzoli
  • J. -M. Meyer
  • J. -P. Bonjour
Original Article


Areal bone mineral density (BMD) is a major determinant of bone strength and thereby of fracture risk. Other factors including trabecular microarchitecture and bone dimensions also contribute to bone strength. To investigate the relative importance for bone strength of BMD and bone dimensions, the relations between strength and the latter variables were evaluated under different experimental conditions in ovariectomized rats. Bone strength was assessed in compression and bending with measurement of BMD by dual-energy X-ray absorptiometry. Interventions were designed to increase trabecular BMD in rats with estrogen deficiency-induced bone loss (OVX) by treatment with pamidronate, an inhibitor of bone resorption, or to modify bone dimensions, particularly diameter, by administration of the growth factor IGF-I. In OVX rats, pamidronate treatment increased BMD with a commensurate increase in bone strength at the level of lumbar vertebrae and femoral neck (r=0.789,p<0.0001 andr=0.535,p<0.001, respectively). IGF-I increased the external diameter of midshaft tibia and femoral neck, which also correlated with bone strength (r=0.678,p<0.0001 andr=0.507,p<0.0002, respectively). Thus, both bone dimensions and BMD contributed to the determination of bone strength. In conclusion, adult rats with estrogen deficiency-induced bone loss represent a useful experimental model for investigating bone strength and its determinants such as BMD and external bone dimensions.


Bone mechanical properties IGF-I Osteoporosis Pamidronate Rats 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Peck WA. Burckhardt P. Christiansen C, Fleisch HA, Genant HK, Gennari C, Martin TJ, Martini L, Morita R, Ogata E, Rapado A, Shulman IF, Stern PH, Young RTT. Consensus development conference: diagnosis, prophylaxis, and treatment of osteoporosis [rapid publication]. Am J Med 1993;94:646–50.Google Scholar
  2. 2.
    Brinckmann P, Biggemann M, Hilweg D. Prediction of the compressive strength of human lumbar vertebrae. Spine 1989;14:606–10.Google Scholar
  3. 3.
    Dalen N, Hellström LG, Jacobson B. Bone mineral content and mechanical strength of the femoral neck. Acta Orthop Scand 1976;47:503–8.Google Scholar
  4. 4.
    Granhed H, Johnson R, Hansson T. Mineral content and strength of lumbar vertebrae: a cadaver study. Acta Orthop Scand 1989;60:105–9.Google Scholar
  5. 5.
    Lang SM, Moyle DD, Berg CEW, Detorie N, Gilpin AT, Pappas NJ, Reynolds JC, Tkacik M, Waldron RL II. Correlation of mechanical properties of vertebral trabecular bone with equivalent mineral density as measured by computed tomography. J Bone Joint Surg [Am] 1988;70:1531–8.Google Scholar
  6. 6.
    Mosekilde L, Danielsen CC, Knudsen UB. The effect of aging and ovariectomy on the vertebral bone mass and biomechanical properties of mature rats. Bone 1993;14:1–6.Google Scholar
  7. 7.
    Thompson DD, Seedor JG, Quartuccio H, Solomon H, Fioravanti C, Davidson J, Klein H, Jackson R, Clair J, Frankenfield D, Brown F, Simmons HA, Rodan GA. The bisphosphonate alendronate, prevents bone loss in ovariectomized baboons. J Bone Miner Res 1992;7:951–60.Google Scholar
  8. 8.
    Toolan BC, Shea M, Myers ER, Borchers RE, Seedor JG, Quartuccio H, Rodan G, Hayes WC. Effects of 4-amino-1-hydroxybutylidene bisphosphonate on bone biomechanics in rats. J Bone Miner Res 1992;7:1399–406.Google Scholar
  9. 9.
    Cummings SR, Black DM, Nevitt MC, Browner W, Cauley J, Ensrud K, Genant HK, Palermo L, Scott J, Vogt TM. Bone density at various sites for prediction of hip fractures. Lancet 1993;341:72–5.Google Scholar
  10. 10.
    Gärdsell P, Johnell O, Nilsson BE. The predictive value of bone loss for fragility fractures in women: a longitudinal study over 15 years. Calcif Tissue Int 1991;49:90–4.Google Scholar
  11. 11.
    Melton LJ III, Atkinson EJ, O'Fallon WM, Wahner HW, Riggs BL. Long-term fracture prediction by bone mineral assessed at different skeletal sites. J Bone Miner Res 1993;8:1227–233.Google Scholar
  12. 12.
    Ross PD, Genant HK, Davis JW, Miller PD, Wasnich RD. Predicting vertebral fracture incidence from prevalent fractures and bone density among non-black, osteoporotic women. Osteoporosis Int 1993;3:120–6.Google Scholar
  13. 13.
    Dempster DW, Li XF, Birchman R, Xu R, Shen V, Lindsay R. On the mechanism of cancellous bone loss in the ovariectomized rat. In: Cohn DV, Gennari C, Tashjian AH, editors. Calcium regulating hormones and bone metabolism. Amsterdam: Elsevier, 1992:460–4.Google Scholar
  14. 14.
    Miller SC, Wronski TJ. Long-term osteopenic changes in cancellous bone structure in ovariectomized rats. Anat Rec 1992;236:433–41.Google Scholar
  15. 15.
    Parfitt AM. Trabecular bone architecture in the pathogenesis and prevention of fracture. Am J Med 1987;82:68–72.Google Scholar
  16. 16.
    Shen V, Dempster DW, Birchman R, Xu R, Lindsay R. Loss of cancellous bone mass and connectivity in ovariectomized rats can be restored by combined treatment with parathyroid hormone and estradiol. J Clin Invest 1993;91:2479–87.Google Scholar
  17. 17.
    Bonad J, Jepsen KJ, Mansoura MK, Jaenisch R, Kuhn JL, Goldstein SA. A murine skeletal adaptation that significantly increases cortical bone mechanical properties. J Clin Invest 1993;92:1697–705.Google Scholar
  18. 18.
    Turner CH. Toward a cure for osteoporosis: reversal of excessive bone fragility. Osteoporosis Int 1991;2:12–9.Google Scholar
  19. 19.
    Ammann P, Rizzoli R, Caverzasio J, Shigematsu T, Slosman D, Bonjour JP. Effects of the bisphosphate tiludronate on bone resorption, calcium balance and bone mineral density. J Bone Miner Res 1993;8:1491–8.Google Scholar
  20. 20.
    Fromm GA, Vega E, Plantalech L, Galich AM, Mautalen CA. Differential action of pamidronate on trabecular and cortical bone in women with involutional osteoporosis. Osteoporosis Int 1991;1:129–33.Google Scholar
  21. 21.
    Ammann P, Rizzoli R, Müller K, Slosman D, Bonjour JP. IGF-I and pamidronate increase bone mineral density in ovariectomized adult rats. Am J Phys 1993;265:E770-E776.Google Scholar
  22. 22.
    Tobias JH, Chow JWM, Chambers TJ. Opposite effects of insulin-like growth factor-1 on the formation of trabecular and cortical bone in adult female rats. Endocrinology 1992;131:2387–92.Google Scholar
  23. 23.
    Spencer EM, Liu CC, Si ECC, Howard GA. In vivo actions of insulin-like growth factor-1 (IGF-I) on bone formation and resorption in rats. Bone 1991;12:21–6.Google Scholar
  24. 24.
    Ammann P, Rizzoli R, Slosman D, Bonjour JP. Sequential and precise in vivo measurement of bone mineral density in rats using dual-energy X-ray absorptiometry. J Bone Miner Res 1992;7:311–6.Google Scholar
  25. 25.
    Engesaeter LB, Ekeland A, Langeland N. Methods for testing the mechanical properties of the rat femur. Acta Orthop Scand 1978;49:512–8.Google Scholar
  26. 26.
    Søgaard CH, Wronski TJ McOsker JE, Mosekilde L. The positive effect of parathyroid hormone on femoral neck bone strength in ovariectomized rats is more pronounced than that of estrogen or bisophosphonates. Endocrinology 1994;134:650–7.Google Scholar
  27. 27.
    Riggs BL, O'Fallon WM, Lane A, Hodgson SF, Wahner HW, Muhs J, Chao E, Melton LJ III. Clinical trial of fluoride therapy in postmenopausal osteoporotic women: extended observations and additional analysis. J Bone Miner Res 1994;9:265–75.Google Scholar
  28. 28.
    Faulkner KG, Cummings SR, Black D, Palermo L, Glüer CC, Genant HK. Simple measurement of femoral geometry predicts hip fracture: the study of osteoporotic fractures. J Bone Miner Res 1993;8:1211–7.Google Scholar
  29. 29.
    Turner CH, Burr DB. Basic biochemical measurements of bone: a tutorial. Bone 1993;14:595–608.Google Scholar
  30. 30.
    Kenedi RM. Textbook of biomedical engineering. Glasgow: Blackie, 1980:39–73.Google Scholar
  31. 31.
    Ejersted C, Andreassen TT, Nilsson MHL, Oxlund H. Human parathyroid hormone (1–34) increases bone formation and strength of cortical bone in aged rats. Eur J Endocrinol 1994;130:201–7.Google Scholar
  32. 32.
    Jørgensen PH, Bak B, Andreassen TT. Mechanical properties and biochemical composition of rat cortical femur and tibia after long-term treatment with biosynthetic human growth hormone. Bone 1991;12:353–9.Google Scholar
  33. 33.
    Kalu DN, Arjmandi BH, Liu CC, Salih MA, Birnbaum RS. Effects of ovariectomy and estrogen on the serum levels of insulin-like growth factor-I and insulin-like growth factor binding protein-3. Bone Miner 1993;25:135–48.Google Scholar
  34. 34.
    Wronski TJ, Yen CF. Anabolic effects of parathyroid hormone on cortical bone in ovariectomized rats. Bone 1994;15:51–8.Google Scholar
  35. 35.
    Aerssens J, Van Audekercke R, Geusens P, Schot IPC, Abdel-Hamid Osman A, Dequeker J. Mechanical properties, bone mineral content and bone composition (collagen, osteocalcin, IGF-I) of the rat femur: influence of ovariectomy and nandrolone decanoate (anabolic steroid) treatment. Calcif Tissue Int 1993;53:269–77.Google Scholar
  36. 36.
    Lin BY, Jee WSS, Ma YF, Ke HZ, Kimmel DB, Li XJ. Effects of prostaglandin E2 and risedronate administration on cancellous bone in older female rats. Bone 1994;15:489–96.Google Scholar
  37. 37.
    Mosekilde L, Danielsen C, Gasser J. The effect on vertebral bone mass and strength of long term treatment with antiresorptive agents (estrogen and calcitonin), human parathyroid hormone (1–38), and combination therapy, assessed in aged ovariectomized rats. Endocrinology 1994;134:2126–34.Google Scholar

Copyright information

© European Foundation for Osteoporosis 1996

Authors and Affiliations

  • P. Ammann
    • 1
  • R. Rizzoli
    • 1
  • J. -M. Meyer
    • 2
  • J. -P. Bonjour
    • 1
  1. 1.Division of Clinical Pathophysiology, WHO Collaborating Center for Osteoporosis and Bone DiseaseUniversity HospitalGenevaSwitzerland
  2. 2.School of DentistryUniversity HospitalGenevaSwitzerland
  3. 3.Division of Clinical Pathophysiology, Department of Internal MedicineUniversity HospitalGeneva 14Switzerland

Personalised recommendations