Skip to main content
SpringerLink
Log in

Bone pathology in experimental osteoporosis: A review

  • Review Articles
  • Published:
Journal of Orthopaedic Science

Abstract

New implants for the internal fixation of porotic bone should first be evaluated in experimental animals before they can be used in humans. If relevant results are to be generated, it is imperative that there is an adequate animal model for these studies. A literature survey of procedures used to develop ostoporosis in experimental animals indicated that none of the models described satisfactorily fulfilled the requirements for an optimal model for the study of porotic bone fracture fixation. The rat model exhibits major pathological differences compared to humans (different pattern of bone remodeling, little or no secondary Haversian remodeling in cortical bone, stable skeletal mass for a life span, small body size, short life span, low blood volume, and high basal metabolic rate). Large animals, such as dogs and primates, require a much longer time to reach a steady-state bone loss and none of them suffer from bone fragility. In the optimal animal model for the study of porotic bone fracture fixation, the histopathological pattern of osteoporosis should be similar to that of humans, and bone loss should be well controlled, appear early, not reverse spontaneously, and be associated with bone fragility.

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. Consensus development conference 1993. Diagnosis, prophylaxis and treatment of osteoporosis. Am J Med 1994;94:646–50.

    Google Scholar 

  2. Albright F, Smith P, Richardson A. Postmenopausal osteoporosis: Its clinical features. J Am Med Assoc 1941;116:2465–474.

    Google Scholar 

  3. Awbrey B, Hangaman J, Lester G. In vivo bone mineral analysis throughout skeletal growth in rats: Differences due to sex or vitamin D deficiency. J Orthop Res 1985;3:456–9.

    Article  PubMed  CAS  Google Scholar 

  4. Barnicot A. The local action of the parathyroid on other tissues in bone in intracerebral gratfts. J Anat 1948;82:233–45.

    Google Scholar 

  5. Barzel U. Acid-induced osteoporosis: An experimental model of human osteoporosis. Calcif Tissue Res 1976;21(Suppl):417–22.

    PubMed  Google Scholar 

  6. Bonucci E, Ballanti P, Martelli A. Ipriflavone inhibits osteoclast differentiation in pararthyroid transplanted parietal bone of rats. Calcif Tissue Int 1992;50:314–7.

    Article  PubMed  CAS  Google Scholar 

  7. Brighton C, Wessenshop C. Treatment of castration-induced osteoporosis by a capacitively coupled electrical stimulation. J Bone Joint Surg Am 1989;71:228–36.

    PubMed  CAS  Google Scholar 

  8. Burkart S, Beresford W. An osteoporosis after the castration of full-grown rats. Anat Rec 1978;190:351–2.

    Google Scholar 

  9. Cameron H, Jakob R, Macnab I, Pilliar R. Use of polymethylmethacrylate to enhance screw fixation in bone. J Bone Joint Surg 1975;57:655–6.

    PubMed  CAS  Google Scholar 

  10. Clark I, Smith M. Effects of hypervitaminosis A and D on skeletal metabolism. J Biol Chem 1965;239:1266–71.

    Google Scholar 

  11. Cummings S, Kelsey J, Nevit M, O'Dowd K. Epidemiology of osteoporosis and osteoporotic fractures. Epidemiol Rev 1985; 7:178–208.

    PubMed  CAS  Google Scholar 

  12. Danielsen C, Mosekilde L, Andreassen T. Long-term effect orchiedectomy on cortical bone from rat femur: Bone mass and mechanical properties. Calcif Tissue Int 1992;50:169–74.

    Article  PubMed  CAS  Google Scholar 

  13. Donaldson C, Hulley S, Vogel J, Hattner R, et al. Effect of prolonged bed rest on bone mineral. Metabolism 1970;19:1071–84.

    Article  PubMed  CAS  Google Scholar 

  14. Ferguson H, Hartles R. The effect of vitamin D on the bones of young rats receiving diets low in calcium and phosphorus. Arch Oral Biol 1963;8:407–18.

    Article  PubMed  CAS  Google Scholar 

  15. Ferguson H, Hartles R. The effect of diets deficient in calcium or phosphorus in the presence and absence of supplement of vitamin D on the incisor teeth and bone of adult rats. Arch Oral Biol 1966;11:1345–64.

    Article  PubMed  CAS  Google Scholar 

  16. Foldes I, Gyarmati J, Rapcsak M, et al. Effect of plastercast immobilization on the bone. Acta Physiol Hung 1986;67:413–8.

    PubMed  CAS  Google Scholar 

  17. Follis R. Effect of cortisone on growing bone of the rat. Soc Exper Biol and Med Proc 1951;76:722–4.

    CAS  Google Scholar 

  18. Geiser M, Trueta J. Muscle action, bone rarefaction and bone formation. J Bone Joint Surg Br 1958;40:282–311.

    PubMed  Google Scholar 

  19. Goulding A, Gold E. A new way to induce estrogen deficiency in the rat: Comparison of the effect of surgical ovariectomy and administration of the LHRH agonist buserelin on bone resorption and composition. J Endocrinol 1989;121:193–8.

    Google Scholar 

  20. Guenet J, Stanescu R, Maroteaux P, Stanescu V. Fragilitas ossium: A new autosomal recessive mutation in the mouse. J Hereid 1981;72:440–1.

    CAS  Google Scholar 

  21. Hahnel H, Lindenhayn K, Muhlbach R, Schmidt U. Heparin-induced osteopathy in animal experiments a model for osteoporosis? Influence of heparin on the concentrations of hydroxyapatite, citrate, and hydroxyproline in the bones of rats of various ages. Bone 1973;27:71–5.

    CAS  Google Scholar 

  22. Harrison M, Fraser R. Bone structure and metabolism in calcium-deficient rats. J Endocrinol 1960;21:197–204.

    Article  PubMed  CAS  Google Scholar 

  23. Hertel R, Aebi M, Ganz R. Osteosynthese bei hochgradiger osteoporose. Unfallchirurg 1990;10:112–6.

    Google Scholar 

  24. Holbrook T, Grazier K, Kelsey J, Stauffer R. The frequency of occurence, impact and cost of selected musuloskeletal condtions in the United States. Proc Am Acad Orthop Surg 1984:221.

  25. Hori M, Uzawa T, Morita L, et al. Effect of human parathyroid hormone (PTH(1–34)), on experimental osteopenia of rats induced by ovariectomy. Bone Miner Res 1988;3:193–9.

    CAS  Google Scholar 

  26. Jaworski Z, Uhthoff H. Reversibility of nontraumatic disuse osteoporosis during its active phase. Bone 1986;7:431–9.

    Article  PubMed  CAS  Google Scholar 

  27. Jayo M, Weaver D, Adams M, Ranklin S. Effects on bone of surgical menopause and estrogen therapy with or without progesterone replacement in cynomolgus monkey. Am J Obstet Gynecol 1990;163:614–8.

    PubMed  CAS  Google Scholar 

  28. Jee W, Li X, Ke H. The skeletal adaptation to mechanical usage in the rat. Cells Mater 1991;Suppl 1:131–42.

    Google Scholar 

  29. Jee W, Mori S, Li X, Chan S. Protagladin E2 enhances cortical bone mass and activates intracortical bone remodeling in intact and ovariectomized female rats. Bone 1990;11:253–66.

    Article  PubMed  CAS  Google Scholar 

  30. Jelmoni G, Benazo F, Naccari, Calrlazi C. Stimulazione della crescita ossea con campi elettromagnetici. Feder Med 1989; 42:175–80.

    Google Scholar 

  31. Jowsey J, Gordon G. Bone turnover and osteoporosis. The biochemistry and physiology of bone, 1971. New York: Academic, 3:201–38.

    Google Scholar 

  32. Jowsey J, Raisz L. Experimental osteoporosis and parathyroid activity. Endocrinology 1968;82:384–96.

    PubMed  CAS  Google Scholar 

  33. Kalu D, Liu C, Hardin R, Hollis B. The aged rat model of ovarian hormone deficiency bone loss. Endocrinology 1989;124:7–16.

    PubMed  CAS  Google Scholar 

  34. Kanis JA, Melton LJ, Christiansen C, et al. The diagnosis of osteoporosis. J Bone Miner Res 1994;9:1137–41.

    PubMed  CAS  Google Scholar 

  35. Kimmel D, Jee W. A quantitative histologic study of bone turnover in young adult beagles. Anat Rec 1982;203:31–45.

    Article  PubMed  CAS  Google Scholar 

  36. Konieczna D. Model of experimental osteoporosis caused by the application of heat using paraffin packing. Chir Narzadow Ruchu Ortop Pol 1971;36:609–16.

    PubMed  CAS  Google Scholar 

  37. Krolner B, Toft B. Vertebral bone loss: An unheeded side effect of therapeutic bed rest. Clin Science 1983;64:537–40.

    CAS  Google Scholar 

  38. Laros G. The role of osteoporosis in intertrochanteric fractures. Orthop Clin North Am 1980;11:525–37.

    PubMed  CAS  Google Scholar 

  39. Larsson S. The effect of combined oophorectomy and prednisolone administration on the skeletal tissue and calcium retention in 1-year-old rat. Calcif Tiss Res 1968;Suppl:84–84b.

    Google Scholar 

  40. Lee S. Experimental microsurgery. Tokyo, Igaku-Shoin 1987.

    Google Scholar 

  41. Lewis D, Liggit H, Effmann E, et al. Osteoporosis induced in mice by overproduction of interleukin 4. Proc Natl Acad Sci USA 1993;90:11618–22.

    Article  PubMed  CAS  Google Scholar 

  42. Li X, Jee W, Patterson-Buckendahl P. Transient effects of subcutaneously administered prostaglandin E2 on cancellous and cortical bone in young adult dogs. Bone 1990;11:363–4.

    Article  Google Scholar 

  43. Lindgren J, DeLuca H. Role of parathyroid hormone and 1,25 dihydroxyvitamin D3 in the development of osteopenia in the oophorectomized rat. Calcif Tissue Int 1982;34:510–4.

    Article  PubMed  CAS  Google Scholar 

  44. Lindgren J, Merchnat C, DeLuca H. Effect of 1,25-dihydroxyvitamin D3 on osteopenia induced by prednisolone in adult rats. Calcif Tissue Int 1982;34:253–7.

    Article  PubMed  CAS  Google Scholar 

  45. Lindgren J. Studies of the calcium accretion rate of bone during immobilisation in intact and parathyroidectomized adults rats. Calcif Tissue Res 1976;22:41–7.

    Article  PubMed  CAS  Google Scholar 

  46. Lindgren U, Mattson S. The reversibility of disuse osteoporosis. Calcif Tissue Res 1977;23:179–84.

    Article  PubMed  CAS  Google Scholar 

  47. Liu C, Kalu D. Human parathyroid hormone (1–34) prevents bone loss and augments bone formation in sexually mature ovariectomized rats. J Bone Miner Res 1990;5:973–82.

    PubMed  CAS  Google Scholar 

  48. Malluche H, Faugere M, Friedler R, Fanti P. 1,25-Dihydroxyvitamin D3 corrects bone loss but suppresses bone remodelling in ovariohysterectomized beagle dogs. Endocrinology 1988;122:1998–2005.

    Article  PubMed  CAS  Google Scholar 

  49. Martin R, Butcher R, Sherwood L, et al. Effects of ovariectomy in beagle dogs. Bone 1987;8:23–31.

    Article  PubMed  CAS  Google Scholar 

  50. Mattson S. The reversibility of disuse osteoporosis. Experimental studies in the adult rat. Acta Orthop Scand Suppl 1972;144:1–135.

    Google Scholar 

  51. Melton LJ, Chrischilles EA, Cooper C, et al. How many women have osteoporosis. J Bone Miner Res 1992;7:1005–10.

    Article  PubMed  Google Scholar 

  52. Melton LJ, Riggs BL. Editors. Osteoporosis: Etiology, diagnosis and management. New York: Raven, 1988;155–79.

    Google Scholar 

  53. Minaire P, Meunier P, Edouard C, et al Quantitative histological data on disuse osteoporosis: Comparison with biological data. Calcif Tissue Res 1974;17:57–73.

    PubMed  CAS  Google Scholar 

  54. Moselkilde L, Kragstrup J, Richards A. Compressive strength, ash weight, and volume of vetebral trabecular bone in experimental fluorosis in pigs. Calcif Tissue Int 1987;40:318–22.

    Google Scholar 

  55. Naessen T, Persson I, Adami H, et al. Hormone replacement therapy and the risk for first hip fracture. Ann Intern Med 1990;103:95–110.

    Google Scholar 

  56. Nakamura T, Nagai Y, Yamato H, et al. Regulation of bone turnover and prevention of bone atrophy in ovariectomized beagle dogs by the administration of 24R,25(OH)2D3. Calcif Tissue Int 1992;50:221–7.

    Article  PubMed  CAS  Google Scholar 

  57. Nelson ME, Fischer EC, Dilmanian FA, et al. A 1-year walking program and increased dietary calcium in postmenopausal women: Effects on bone. Am J Clin Nutr 1991;53:1304–06.

    PubMed  CAS  Google Scholar 

  58. Nilsson B. Post-traumatic osteopenia: A quantitative study of the bone mineral mass in the femur following fracture of the tibia in man using americium 241 as a photon source. Acta Orthop Scand 1966;37:1–55.

    Article  PubMed  Google Scholar 

  59. Park A. Ovariectomized sheep. A model for osteoporosis? Calcif Tissue Res 1986;21:71–3.

    Google Scholar 

  60. Rasmussen P. Calcium deficiency, pregnancy, and lactation in rats. Calcif Tiss Res 1977;23:87–94.

    Article  CAS  Google Scholar 

  61. Rodgers JB, Monier Faugere MC, Malluche H. Animal models for the study of bone loss after cessation of ovarian function. Bone 1993;14:369–77.

    Article  PubMed  CAS  Google Scholar 

  62. Rosenquist JB, Spengler DM. The reversibility of disuse osteoporosis: Fluoride treatment and bone strength. Clin Orthop Rel Res 1977;126:305.

    Google Scholar 

  63. Ruth E. Bone studies II. An experimental study of the Haversian-type vascular channels. Am J Anat 1953;93:429–55.

    Article  PubMed  CAS  Google Scholar 

  64. Saville P. Change in the skeletal mass and fragility with castration in the rat; a model of osteoporosis. J Am Geriatr Soc 1969;17:155–66.

    PubMed  CAS  Google Scholar 

  65. Schnitzler C, Ripamonti U, Mesquita J. Bone histomorphometry in baboons in captivity. Bone 1993;14:383–7.

    Article  PubMed  CAS  Google Scholar 

  66. Sevastic J, Lindgen J. Osteoporosis. Experimental and clinical studies. Clin Orthop 1984;191:35–42.

    Google Scholar 

  67. Shen V, Dempster D, Birchman R, et al. Lack of changes in histomorphometric bone mass and biomechanical parameters in ovariectomized dogs. Bone 1992;13:311–6.

    Article  PubMed  CAS  Google Scholar 

  68. Sissons H, Hadifield G. The influence of cortisone on the structure and growth of bone. J Anat 1955;89:69–78.

    PubMed  CAS  Google Scholar 

  69. Steinberg ME, Trueta J. Effects of activity on bone growth and development in the rat. Clin Orthop 1981;156:52–61.

    PubMed  Google Scholar 

  70. Storey E. The influence of adrenal cortisone hormones on bone formation and resorption. Clin Orthop 1963;30:197–217.

    PubMed  CAS  Google Scholar 

  71. Thompson RC. Heparin osteoporosis. An experimental model using rats. J Bone Joint Surg 1973;55:606–12.

    PubMed  CAS  Google Scholar 

  72. Tsuboyama T, Takahashi K, Yamuro T, et al. Cross-mating study on bone mass in the spontaneously osteoporotic mouse (SAM-P/6). Bone Miner 1993;23:57–64.

    Article  PubMed  CAS  Google Scholar 

  73. Turner T, Vandersteenhoven J, Bell N. The effects of ovariectomy and 17β-estradiol on cortical bone histomorphometry in growing rats. J Bone Miner Res 1984;2:155–62.

    Google Scholar 

  74. Uhthff H, Sekaly G, Jaworski Z. Effect of long-term nontraumatic immobilization on metaphyseal spongiasa in young adult and old beagle dogs. Clin Orthop 1985;192:278–84.

    Google Scholar 

  75. Vanderschueren D, Van Herck E, Schot P, et al. The aged male rat as a model for human osteoporosis: Evaluation by nondestructive measurements and biomechanical testing. Calcif Tissue Int 1993;53:342–7.

    Article  PubMed  CAS  Google Scholar 

  76. Wessler S. Introduction: What is a model? In: Animal models of thrombosis and hemorrhagic disease. Workshop organized by the Institute of Animal Laboratory Resource (ILAR), Committee for animal models for thrombosis and hemorrhagic disease 1975;March 12–13, National Academy of Sciences, Washington DC. DHEW Pub No (NIH) 76-82. Washington DC: US Department of Health, Education and Welfare, 1976;xi-xvi.

    Google Scholar 

  77. Wink C, Felts W. Effects of castration on the bone structure of male rats: A model of osteoporosis. Calcif Tissue Int 1980;32:77–82.

    Article  PubMed  CAS  Google Scholar 

  78. Wronski TJ, Morey E. Inhibition of cortical and trabecular bone formation in the long bones of immobilized monkey. Clin Orthop 1983;181:269–76.

    PubMed  Google Scholar 

  79. Wronski TJ, Cintron M, Dann L. Temporal relationship between bone loss and increased bone turnover in ovarietomized rats. Calcif Tissue Int 1988;43:179–83.

    PubMed  CAS  Google Scholar 

  80. Wronski TJ, Dann LM, Scott KS, Cintron M. Long-term effects of ovariectomy and aging on the rat skeleton. Calcif Tissue Int 1989;45:360–6.

    PubMed  CAS  Google Scholar 

  81. Ziegler R, Bellwinkel S, Gozariu L. Effects of serum on calcitonin-dependent bone resorption in vitro. Endocrinol Exp 1973;7:129–32.

    PubMed  Google Scholar 

  82. Zuber K, Koch P, Lustenberger A, Ganz R. Femurfraktur nach hufttotalprothese. Unfallchirurgie 1990;93:467–722.

    CAS  Google Scholar 

Download references

Author information

Author notes

  1. Pierre Mainil-Varlet

    Present address: Department of Orthopaedic Surgery, Hõpital Cantonal de Fribourg, 1708, Friborug, Switzerland

Authors and Affiliations

  1. AO/ASIF Research Institute, Clavadelerstrasse, CH-7270, Davos, Switzerland

    Pierre Mainil-Varlet

Authors
  1. Pierre Mainil-Varlet
    View author publications

    You can also search for this author in PubMed Google Scholar

About this article

Cite this article

Mainil-Varlet, P. Bone pathology in experimental osteoporosis: A review. J Orthop Sci 2, 185–190 (1997). https://doi.org/10.1007/BF02492976

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02492976

Key words

Search

Navigation