Skip to main content
SpringerLink
Log in

Osteoclast recruitment and modulation by calcium deficiency, fasting, and calcium supplementation in the rat

  • Laboratory Investigations
  • Published:
Calcified Tissue International Aims and scope Submit manuscript

Abstract

In the rat, 1 week of a calcium-deficient diet will recruit large numbers of osteoclasts to long bone endosteal surfaces. Subsequent calcium supplementation causes the osteoclasts to disappear in 1–3 days but as little as 3 hours of calcium supplementation reduces the extent of their ruffled borders. To test the hypothesis that at some point there is an irreversible inhibition of osteoclasts, male, weanling, calcium-deficient, SD rats were given various amounts of calcium-containing diet followed by a 12-hour fast. No changes in seven morphological indices of osteoclast activity were found. The hypothesis that the fast had reversed the effects of the calcium diet was supported by a second experiment indicating that no inhibition threshold had been reached. Another experiment showed differences in the degree of osteoclast inhibition with different amounts of calcium supplementation, again without evidence of a threshold. These experiments raised two questions: (1) Will fasting recruit osteoclasts in calcium-replete rats? and (2) Is osteoclast recruitment facilitated by the presence of postosteoclasts? The results of experiments testing these hypotheses support the conclusion that fasting and calcium deficiency maintain plasma calcium levels by different mechanisms, and post-osteoclasts are not available for reactivation. It is concluded that inhibition of osteoclasts by dietary calcium is a graded phenomenon, and when osteoclasts have lost contact with the bone surface they are unavailable for reactivation; a threshold has been reached.

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. Stauffer M, Baylink D, Wergedal J, Rich C (1972) Bone repletion in calcium-deficient rats fed a high calcium diet. Calcif Tissue Res 9:163–172

    Google Scholar 

  2. Stauffer M, Baylink D, Wergedal J, Rich C (1973) Decreased bone formation, mineralization, and enhanced resorption in calcium-deficient rats. Am J Physiol 225:269–276

    Google Scholar 

  3. De Winter FR, Steendijk R (1975) The effect of a low-calcium diet in lactating rats: observations on the rapid development and repair of osteoporosis. Calcif Tissue Res 17:303–316

    Google Scholar 

  4. Thompson ER, Baylink DJ, Wergedal JE (1975) Increases in number and size of osteoclasts in response to calcium or phosphorus deficiency in the rat. Endocrinology 97:283–289

    Google Scholar 

  5. McMillan PJ, Dewri RA, Joseph EE, Schultz RL, Deftos LJ (1989) Rapid changes of light microscopic indices of osteoclastbone relationships correlated with electron microscopy. Calcif Tissue Int 44:399–405

    Google Scholar 

  6. Liu C-C, Rader JI, Gruber H, Baylink DJ (1982) Acute reduction in osteoclast number during bone repletion. Metab Bone Dis Rel Res 4:201–209

    Google Scholar 

  7. McMillan PJ, Harris JG (1990) Data Voice™: A microcomputerbased general purpose voice-controlled data-collection system. Comput Biol Med 20:415–419

    Google Scholar 

  8. Masoro EJ (1990) Assessment of nutritional components in prolongation of life and health by diet. Proc Soc Exp Biol Med 193:31–34

    Google Scholar 

  9. Staub JF, Tracqui P, Lausson S, Milhaud G, Perault-Staub AM (1989) A physiological view of in vivo calcium dynamics: the regulation of a nonlinear self-organized system. Bone 10:77–86

    Google Scholar 

  10. Holtrop ME, King GJ, Cox KA, Reit B (1979) Time-related changes in the ultrastructure of osteoclasts after injection of parathyroid hormone in young rats. Calcif Tissue Int 27:129–135

    Google Scholar 

  11. Lucht U (1973) Effects of calcitonin on osteoclasts in vivo. An ultrastructural and histochemical study. Zeit Zellforsch Mikro Anat 145:75–87

    Google Scholar 

  12. Selye H (1932) On the stimulation of new bone formation with parathyroid extract and irradiated ergosterol. Endocrinology 16:547–558

    Google Scholar 

  13. Burrows RB (1938) Variations produced in bones of growing rats by parathyroid extracts. Am J Anat 62:237–290

    Google Scholar 

  14. Young VR, Scrimshaw NS (1971) The physiology of starvation. Sci Am 225:14–21

    Google Scholar 

  15. Phillips LS, Young HS (1976) Nutrition and somatomedin. I. Effect of fasting and refeeding on serum somatomedin activity and cartilage growth activity in rats. Endocrinology 99:304

    Google Scholar 

  16. Clemmons DR, Klibanski A, Underwood LE, McArthur JW, Ridgway EC, Beitins IZ, Van Wyk JJ (1981) Reduction of plasma immunoreactive somatomedin C during fasting in humans. J Clin Endocrinol Metab 53:1247

    Google Scholar 

  17. Merimee TJ, Zapf J, Froesch ER (1982) Insulin-like growth factors in the fed and fasted states. J Clin Endocrinol Metab 55:999

    Google Scholar 

  18. Isley WL, Underwood LE, Clemmons DR, (1983) Dietary components that regulate serum somatomedin-C concentrations in humans. J Clin Invest 71:175–182

    Google Scholar 

  19. Goldstein S, Harp JB, Phillips LS (1991) Nutrition and somatomedin XXII: molecular regulation of insulin-like growth factor-I during fasting and refeeding in rats. J Mol Endocrinol 6:33–43

    Google Scholar 

  20. Maes M, Underwood LE, Ketelslegers J-M (1983) Plasma somatomedin-C in fasted and refed rats: close relationship with changes in liver somatogenic but not lactogenic binding sites. J Endocrinol 97:243–252

    Google Scholar 

  21. Caufriez A, Goldstein J, Lebrun P, Herchuelz A, Furlanetto R, Copinschi G (1984) Relations between immunoreactive somatomedin C, insulin and T3 patterns during fasting in obese subjects. Clin Endocrinol 20:65–70

    Google Scholar 

  22. Emler CA, Schalch DS (1987) Nutritionally induced changes in hepatic insulin-like growth factor I (IGF-I) gene expression in rats. Endocrinology 120:832–834

    Google Scholar 

  23. Lowe WL, Adamo M, Werner H, Roberts CT, LeRoth D (1989) Regulation by fasting of rat insulin-like growth factor I and its receptor. J Clin Invest 84:619–626

    Google Scholar 

  24. McCusker RH, Cohick WS, Busby WH, Clemmons DR (1991) Evaluation of the developmental and nutritional changes in porcine insulin-like growth factor-binding protein-1 and-2 serum levels by immunoassay. Endocrinology 129:2631–2638

    Google Scholar 

  25. Brixen K, Nielsen HK, Mosekilde L, Flyvbjerg A (1990) A short course of recombinant human growth hormone treatment stimulates osteoblasts and activates bone remodeling in normal human volunteers. J Bone Miner Res 5:609

    Google Scholar 

  26. Schlemmer A, Johansen JS, Pedersen SA, Jorgensen JOL, Hassager C, Christiansen C (1991) The effect of growth hormone (GH) therapy on urinary pyridinoline cross-links in GH-deficient adults. Clin Endocrinol 35:471–476

    Google Scholar 

  27. Hock JM, Fonesca J (1990) Anabolic effect of human synthetic parathyroid hormone-(1–34) depends on growth hormone. Endocrinology 127:1804–1810

    Google Scholar 

  28. Canalis E (1980) Effect of insulin-like growth factor I on DNA and protein synthesis in cultured rat calvaria. J Clin Invest 66: 709–719

    Google Scholar 

  29. Hock JM, Centrella M, Canalis E (1988) Insulin-like growth factor I has independent effects on bone matrix formation and cell replication. Endocrinology 122:254–260

    Google Scholar 

  30. Canalis E, Centrella M, Burch W, McCarthy TL (1989) Insulin-like growth factor I mediates selective anabolic effects of parathyroid hormone in bone cultures. J Clin Invest 83:60–65

    Google Scholar 

  31. Spencer EM, Liu CC, Si ECC, Howard GA (1991) In vivo actions of insulin-like growth factor-I (IGF-I) on bone formation and resorption in rats. Bone 12:21–26

    Google Scholar 

  32. Linkhart TA, Mohan S (1989) Parathyroid hormone stimulates release of insulin-like growth factor-I (IGF-I) and IGF-II from neonatal mouse calvaria in organ culture. Endocrinology 125: 1484–1491

    Google Scholar 

  33. Slootweg MC, Most WW, Van Beek E, Schot LPC, Papapoulos SE, Lvwik CWGM (1992) Osteoclast formation together with interleukin-6 production in mouse long bones is increased by insulin-like growth factor-I. J Endocrinol 132:433–438

    Google Scholar 

Download references

Author information

Author notes

  1. K. R. Wright

    Present address: University of Texas Health Science Center, San Antonio, TX

Authors and Affiliations

  1. Department of Anatomy, School of Medicine, Loma Linda University, 92350, Loma Linda, California, USA

    K. R. Wright & P. J. McMillan

Authors
  1. K. R. Wright
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. P. J. McMillan
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wright, K.R., McMillan, P.J. Osteoclast recruitment and modulation by calcium deficiency, fasting, and calcium supplementation in the rat. Calcif Tissue Int 54, 62–68 (1994). https://doi.org/10.1007/BF00316292

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00316292

Key words

Search

Navigation