Journal of Bone and Mineral Metabolism

, Volume 12, Supplement 1, pp S61–S67 | Cite as

Some characteristics of three ageing rat models for osteopenia with emphasis on effects of PTH

  • Harry M. Theuns
  • Erik Offerman
  • Bep Blauw
  • Ploni van den Hoven
  • Herman Bekker
  • Paul J. M. Roholl


Ageing rats are more appropriate for studies on age-related osteopenia than growing or young adult rats, because of the better similarity with ageing man. Both have a negative bone balance, a low bone turnover, decreasing intestinal calcium absorption and decreasing levels of systemic hormones influencing the calcium and bone metabolism. According to the purpose of the study, different models can be used, as for example ageing and recently or long ago ovariectomized rats showing respectively high or low bone turnover with concomitant negative bone balance (model for postmenopausal osteopenia), aged rats showing low bone turnover (model for senile osteopenia), ageing rats with shortage or deficiency of vitamin D at normocalcaemia (model for age related osteopenia with concomitant vitamin D deficiency) or at hypocalcaemia (model for age related osteopenia with concomitant vitamin D deficiency at renal insufficiency). In intact ageing female rats, monitoring of the cyclic pattern is important, as irregularly occurring estrous cycles during an experimental study can influence the results considerably. Moreover, account should be taken of the age related diseases which can influence the number of ageing rats to be used (unpredictability of spontaneous deaths) and the strain of rats (age related diseases) to be used. Because of the naturally occurring decrease in osteoprogenetor calls and the retarded maturation of preosteoblasts into osteoblasts, the aged rat model for senile osteopenia seems especially suited for studies on drugs influencing these osteoblast precursors. Intermittent PTH treatment appears to be effective in all rat models for osteopenia. For the inconsistency of the results in the aged rat model for senile osteopenia, some explanations are suggested.

Key words

ageing rat models for osteopenia histomorphometry postmenopausal osteopenia senile osteopenia vitamin D deficiency 


  1. 1.
    Mammalian models for research on aging. Introduction Nat. Academic Press. Washington DC pp. 1–6, 1981Google Scholar
  2. 2.
    Snell KC: Renal disease of the rat. In: Pathology of laboratory rats and mice, E. Cotchin and F.J.C. Roe (eds.). Blackwell Scientific Publications, Oxford, pp. 105–147. 1967Google Scholar
  3. 3.
    Boorman GA, Hollander CF: Spontaneous lesions in the female WAG ¥ Rij (Wistar) rat. J Gerontol 28: 152–159, 1973PubMedGoogle Scholar
  4. 4.
    Burek JD. Pathology of aging rats. CRC Press, Inc., West Palm Beach, Florida, 1978Google Scholar
  5. 5.
    Solleveld HA, Boorman GA: Spontaneous renal lesions in five rat strains. Toxicol Pathol 14: 168–174, 1986PubMedGoogle Scholar
  6. 6.
    Fox J: Regulation of parathyroid hormone secretion by plasma calcium in aging rats. Am. J. Physiol 260: E220-E225, 1991PubMedGoogle Scholar
  7. 7.
    Armbrecht HJ, Wongsurawat N: Changes in the production and action of 1,25-dihydroxyvitamin D and parathyroid hormone with age. In: Armbrecht, Coe, Wongsurawat. Endocrine function and aging. Chapter 7. New York: Springer Verlag pp. 79–87, 1990Google Scholar
  8. 8.
    Fox J, Mathew MB: Heterogenous response to PTH in aging rats: evidence for skeletal PTH resistance. Am J Physiol 260: E933-E937, 1991PubMedGoogle Scholar
  9. 9.
    Hock JM, Wood RJ: Bone response to parathyroid hormone in aged rats. Cells and Materials S1: 53–58, 1991Google Scholar
  10. 10.
    Kleinbaum DG, Kupper LL, Muller KE: Basic statistics: a review. In: Applied regression analysis and other multivariable methods. Boston: PWS-Kent: pp. 16–35, 1988Google Scholar
  11. 11.
    Kimmel DB, Jee WSS: A quantitative histologic analysis of the growing long bone metaphysis. Calcif Tissue Int 32: 113–122, 1980PubMedGoogle Scholar
  12. 12.
    Kalu DN: The ovariectomized rat model of post-Google Scholar
  13. 13.
    Kimmel DB: Quantitative histologic changes in the proximal tibial growth cartilage of aged female rats. Cells and Materials S1: 11–18, 1991Google Scholar
  14. 14.
    Theuns HM, Zurcher C, Knook DL: Aging rats as a model for osteoporosis: trabecular bone mass, dry bone weight and the age period at which the rat should be used. In: van Bezooijen CFA, Ravid R, Verhofstad AAJ, (eds.) From gene to man. Gerontologic research in the Netherlands. Rijswijk: Stichting Gerontologie en Geriatrie: pp. 369–373, 1990Google Scholar
  15. 15.
    Theuns HM, Knook DL: The aging rat as a model for senile osteoporosis (abstract). J Bone Miner Res 4: S1: 1094A, 1989Google Scholar
  16. 16.
    Kalu DN, Hardin RH, Cockerham R et al.: Aging and dietary modulation of rat skeleton and parathyroid hormone. Endocrinology 115: 1239–1247, 1984PubMedGoogle Scholar
  17. 17.
    Wronski TJ, Dann LM, Scott KS et al.: Long-term effects of ovariectomy and aging on the rat skeleton. Calcif Tissue Int 45: 360–366, 1989PubMedGoogle Scholar
  18. 18.
    Li XJ, Jee WSS, Ke HZ et al.: Age-related changes of cancellous and cortical bone histomorphometry in female sprague-dawley rats. Cells and Materials S1: 25–35, 1991Google Scholar
  19. 19.
    Meites J, Huang HH, Simpkins JW: Recent studies on neuroendocrine control of reproductive senescence in rats. Aging: 213–235, 1978Google Scholar
  20. 20.
    Lu KH, Hopper BR, Vargo TM, Yen SSC: Chronological changes in sex steroid, gonadotropin and prolactin secretion in aging female rats displaying different reproductive states. Biol Reprod 21: 193–203, 1979CrossRefPubMedGoogle Scholar
  21. 21.
    Theuns HM, Knook DL: Effects of IGF-I and PTH on bone and cyclic activity of aged rats. (abstract) Calcif Tissue Int 12: S1: 53A, 1993Google Scholar
  22. 22.
    Wakley GK, Turner RT: Sex steroids and the regulation of bone volume in the rat. Cells and Materials S1: 85–91, 1991Google Scholar
  23. 23.
    Edén S: Age- and sex-related differences in episodic growth hormone secretion in the rat. Endocrinology 105: 555–560, 1979PubMedGoogle Scholar
  24. 24.
    Jansson J-O, Ekberg S, Isakson P et al.: Influence of gonadal steroids on age- and sex-related secretory patterns of growth hormone in the rat. Endocrinology 114: 1287–1294, 1984PubMedGoogle Scholar
  25. 25.
    Jansson J-O, Edén S, Isaksson O: Sexual dimorphism in the control of growth hormone secretion. Endocrine Rev 6: 128–150, 1985Google Scholar
  26. 26.
    Jansson J-O, Carlsson LH, Seeman H: Estradiolbut not testosteron-stimulates the secretion of growth hormone in rats with the pituitary gland autotransplaned to the kidney capsule. Acta Endocrinol 103: 212, 1983Google Scholar
  27. 27.
    Jansson J-O, Mode A, Gustafsson J-A: Influence of neonatal androgen secretion on plasma growth hormone levels, body growth and hepatic steroid metabolism in adult male rats. (abstract) Endocrinology 114: 868, 1984Google Scholar
  28. 28.
    Turner RT, Hannon KS, Demers LM et al.: Differential effects of gonadal function on bone histomorphometry in male and female rats. J Bone Miner Res 4: 557–563, 1989PubMedGoogle Scholar
  29. 29.
    Turner RT, Wakley GK, Hannon KS: Differential effects of androgens on cortical bone histomorphometry in gonadectomized male and female rats. J Orth Res 8: 612–617, 1990Google Scholar
  30. 30.
    Theuns HM, Spencer EM: Parathyroid hormone and insuline-like growth factor-I effects in two aging rat models for osteoporosis. (abstract) J Bone Miner Res 7: S1, 758A, 1992Google Scholar
  31. 31.
    Hock JM, Gera I, Fonseca J et al.: Human parathyroid hormone (1-34) increase bone mass in ovariectomized and orchidectomized rats. Endocrinology 122: 2899–2904, 1988PubMedGoogle Scholar
  32. 32.
    Liu CC, Kalu DN, Salerno E et al.: Preexisting bone loss associated with ovariectomy in rats is reversed by parathyroid hormone. J Bone Miner Res 6: 1071–1080, 1991PubMedGoogle Scholar
  33. 33.
    Ibbotson KJ, Orcutt CM, D'Souza SM et al.: Contrasting effects of parathyroid hormone and insulin-like growth factor I in an aged ovariectomized rat model of postmenopausal osteoporosis. J Bone Miner Res 7: 425–432, 1992PubMedGoogle Scholar
  34. 34.
    Kimmel DB, Bozzato RP, Kronis KA et al.: The effect of recombinant human (1-84) or synthetic human (1-34) parathyroid hormone on the skeleton of adult osteopenic ovariectomized rats. Endocrinology 132: 1577–1584, 1993CrossRefPubMedGoogle Scholar
  35. 35.
    Wronski TJ, Yen CF, Qi H et al.: Parathyroid hormone is more effective than estrogen or bisphosphonates for restoration of lost bone mass in ovariectomized rats. Endocrinology 132: 823–831, 1993CrossRefPubMedGoogle Scholar
  36. 36.
    DeVogelaer JP, DeDeuxchaisnes CN, Donnez J et al.: LHRH analogues and bone loss. Lancet i: 1498, 1987Google Scholar
  37. 37.
    Goulding A, Gold E: A new way to indnce oestrogen-deficiency osteopenia in the rat: comparison of the effects of surgical ovariectomy and adminissration of the LHRH agonist buserelin on bone resorption and composition. J Endocrinol 121: 293–298, 1988Google Scholar
  38. 38.
    Goulding A, Fisher L: 17β-Estradiol protects rats from osteopenia associated with administration of the luteinising hormone releasing hormone (LHRH) agonist, buserelin. Bone Miner 13: 47–53, 1991CrossRefPubMedGoogle Scholar
  39. 39.
    Roholl PJM, Blauw E, Zurcher C et al.: Evidence for a diminished maturation of preosteoblasts into osteoblasts during aging in rats: an ultrastructural analysis. J Bone Miner Res 9: 355–366, 1994PubMedGoogle Scholar
  40. 40.
    Theuns HM, van der Vijgh WJF, Hackeng WHL, et al.: Parathyroid hormone (PTH1-34) and vitamin D metabolites throughout life twoinbred rat strains. In: Norman AW, Bouillon R, Thomasset M (eds.) Vitamin D Gene regulation, Structure-function analysis and clinical application. New York: Walter de Gruyter, pp. 769–770, 1991Google Scholar
  41. 41.
    Lips P, Netelenbos JC, Jongen MJM et al.: Histomorphometric profile and vitamin D status in patients with femoral neck fracture. Metab Bone Dis Rel Res. 4: 85–93, 1982CrossRefGoogle Scholar
  42. 42.
    Lester E, Skinner RK, Mills MR: Seasonal variation in serum 25-hydroxyvitamin D in the elderly in Britain. Lancet 1: 979–980, 1977PubMedGoogle Scholar
  43. 43.
    Lester GE, van der Wiel CJ, Gray TK et al: Vitamin D deficiency in rats with normal serum calcium concentrations. Proc Natl Acad Sci 79: 4791–4794, 1982PubMedGoogle Scholar
  44. 44.
    Kollenkirchen U, Fox J, Walters MR: Normocalcaemia without hyperparathyroidism in vitamin D-deficient rats. J Bone Miner Res 6: 273–278, 1991PubMedGoogle Scholar
  45. 45.
    Sips AJAM, van der Vijgh WJF, Leeuwenkamp OR et al.: Age-related pharmacokinetics of intestinal calcium absorption. In: Norman AW, Bouillon R, Thomasset M (eds.) Vitamin D Gene regulation, Structure-function analysis and clinical application. New York: Walter de Gruyter, pp. 771–772, 1991Google Scholar
  46. 46.
    Theuns HM, Offerman EH, van den Hoven AE et al.: The effect of PTH in aging vitamin D deficient female rats. (abstract) Third Int. Conf. New Actions of PTH 1994Google Scholar

Copyright information

© Japanese Society of Bone Metabolism Research 1994

Authors and Affiliations

  • Harry M. Theuns
    • 1
  • Erik Offerman
    • 1
  • Bep Blauw
    • 1
  • Ploni van den Hoven
    • 1
  • Herman Bekker
    • 1
  • Paul J. M. Roholl
    • 2
  1. 1.TNO-PG, Department for Vascular and Connective Tissue ResearchLeidenThe Netherlands
  2. 2.National Institute of Public Health and Environmental Protection (RIVM), Laboratory of PathologyThe Netherlands

Personalised recommendations