Skip to main content

Advertisement

SpringerLink
Log in

Indomethacin does not inhibit the anabolic effect of parathyroid hormone on the long bones of rats

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

Summary

Chronic administration of parathyroid hormone, hPTH 1-34, increased bone mass in normocalcemic, young rats [6]. Since PTH can stimulate prostaglandin E2 (PGE2) production in bonein vitro, and since PGE2 can stimulate bone formation, the anabolic effect of PTH could be mediated by PGE2. To test this hypothesis, experiments were done to determine if indomethacin, which blocks endogeneous PG production, would inhibit the anabolic response of bone to PTH. In the first experiment, male Sprague-Dawley rats, 70–100 g, in groups of five, were treated for 12 days with either hPTH 1-34, 8 μg/100g/day; PTH vehicle; indomethacin, 2 mg/kg/day; or a combination of PTH and indomethacin. In the second experiment, groups of 6 rats each were given vehicle or hPTH 1-34, 8 μg/100g/day, in combination with indomethacin, 0, 1, 2, or 4 mg/kg/day. Subcutaneous injections of PTH were given once daily and indomethacin was given orally in divided doses, twice a day. Rats were killed on day 12 in both experiments; their sera were analyzed and the trabecular and cortical bone of distal femurs processed to determine calcium (Ca) and hydroxyproline content and dry weight. PTH and indomethacin had no significant effect on serum Ca, phosphate, alkaline phosphatase, urea nitrogen and creatinine, or systemic and long-bone linear growth. In rats treated with PTH alone or in combination with indomethacin, bone Ca of distal femurs increased by 28–44%; dry weight by 29–41%, and hydroxyproline by 17–45%. Indomethacin alone had no effect on bone growth. Since indomethacin did not block the anabolic effect of hPTH 1-34, we concluded that the anabolic effect of PGHin vivo was unlikely to be mediated by prostaglandins.

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. Parsons JA (1976) Parathyroid physiology and the skeleton. In: Bourne GJ (ed) Biochemistry and physiology of bone, Vol 4. Academic Press, New York, pp 159–225

    Google Scholar 

  2. Dietrich J, Canalis EM, Maina DM, Raisz LG (1976) Hormonal control of bone collagen synthesis in vitro: effects of parathyroid hormone and calcitonin. Endocrinology 98: 943–949.

    PubMed  CAS  Google Scholar 

  3. Johnston CC, Deiss WP (1965) Some effects of hypophysectomy and parathyroid extract on bone matrix biosynthesis. Endocrinology 76: 198–202

    PubMed  Google Scholar 

  4. Kream BE et al (1983) Parathyroid hormone alters collagen synthesis and procollagen mRNA levels in fetal rat calvaria. Proc Natl Acad Sci USA 77: 5654–5658

    Article  Google Scholar 

  5. Raisz LG, Kream BE (1983) Regulation of bone formation. N Engl J Med 309: 29–35, 83–89

    Article  PubMed  CAS  Google Scholar 

  6. Gunness-Hey M, Hock JM (1984) Increased trabecular bone mass in rats treated with parathyroid hormone. Metab Bone Dis Rel Res 5: 177–181

    Article  CAS  Google Scholar 

  7. Howard GA et al (1981) Parathyroid hormone stimulates bone formation and resorption in organ cultures. Evidence for coupling mechanism. Proc Natl Acad Sci USA 78: 3204–3208

    Article  PubMed  CAS  Google Scholar 

  8. Howard GA, Bottemiller BL, Baylink DJ (1980) Evidence for the coupling of bone formation and bone resorption in vitro. Metab Bone Dis Rel Res 2: 131–135

    Article  Google Scholar 

  9. Rodan SB et al (1981) Bone responsive factor produced by osteosarcoma cells with osteoblastic features in PGE2. Biochem Biophys Res Comm 102: 1358–1365

    Article  PubMed  CAS  Google Scholar 

  10. Raisz LG et al (1979) Prostaglandin synthesis by fetal rat bone in vitro: evidence for a role of prostacyclin. Prostaglandins 17: 905–914

    Article  PubMed  CAS  Google Scholar 

  11. Sandberg AL et al (1982) Enhancement of complement-mediated prostaglandin synthesis and bone resorption by arachidonic acid and inhibition by cortisol. Prostaglandins, Leukotrienes Med 8: 419–427

    CAS  Google Scholar 

  12. Raisz LG, Simmons HA (1985) Effect of parathyroid hormone and cortisol on prostaglandin production by neonatal rat calvaria in vitro. Endocrine Res 11: 59–74

    Article  CAS  Google Scholar 

  13. Chung YS, Raisz LG (1984) Stimulation of bone formation by prostaglandin E2. Prostaglandins 27: 97–103

    Google Scholar 

  14. Feyen JHM et al (1984) Stimulation of arachidonic acid metabolism in primary cultures of osteoblast-like cells by hormones and drugs. Prostaglandins 28: 769–781

    Article  PubMed  CAS  Google Scholar 

  15. MacDonald BR et al (1984) Effect of bovine parathyroid hormone and 1,25-hydroxyvitamin D3 on the production of prostaglandins by cells derived from human bone. FEBS Letters 169: 49–52

    Article  PubMed  CAS  Google Scholar 

  16. Ringell RE et al (1982) Prostaglandin-induced periostitis: a complication of long-term PGE1 infusion in an infant with congenital heart disease. Radiology 142: 657–658

    Google Scholar 

  17. Ueda K (1980) Cortical hyperostosis following long-term administration of prostaglandin E1 in infants with cyanotic congenital heart disease. J Pediatr, 97: 834–836

    Article  PubMed  CAS  Google Scholar 

  18. Abe K, Shimada Y, Takezawa J, Oka N, Yoshiya I (1982) Long-term administration of prostaglandin E1: report of two cases with tetralogy of Fallot and esophageal atresia. Crit Care Med 10: 155–158

    Article  PubMed  CAS  Google Scholar 

  19. Lund JE, Brown WP, Tegerman L (1982) The toxicology of PGE1 and PGE2. In: Wu KK, Rossi EC (eds) Prostaglandins in clinical medicine: cardiovascular and thrombotic disorders. Year Book Medical Publishers, pp 93–109

  20. Ueno K et al (1985) The effect of prostaglandin E2 in rapidly growing rats: depressed longitudinal and radial growth and increased metaphyseal hard tissue mass. Bone 6: 79–86

    Article  PubMed  CAS  Google Scholar 

  21. Schmid RN, Reilly CN (1957) New complexion for the titration of calcium in the presence of magnesium. Anal Chem 29: 264–268

    Article  CAS  Google Scholar 

  22. Snedecor GW, Cochran WC (1967) Statistical methods. Iowa State University Press, Ames, IA

    Google Scholar 

  23. Tam CS, Wilson DR, Harrison JE (1980) Effect of parathyroid extract on bone apposition and the interaction between parathyroid hormone and vitamin D. Min Electroyte Metab 3: 74–80

    CAS  Google Scholar 

  24. Tam CS, Heersche J, Murray T, Parsons, JA (1982) Parathyroid hormone stimulates the bone apposition rate independently of its resorptive action: differential effects of intermitted and continuous administration. Endocrinology 110: 506–512

    Article  PubMed  CAS  Google Scholar 

  25. Winter CA (1965) Anti-inflammatory testing methods: comparative evaluation of indomethacin and other agents. International Congress Series. Vol. 82, pp 190–202

    Google Scholar 

  26. Ro J, Sudmann E, Marton PF (1976) Effect of indomethacin on fracture healing in rats. Acta Orthoped Scand 47: 588–599

    Google Scholar 

  27. Sudmann E, Dregelid E, Bessesen A, Morland J (1979) Inhibition of fracture healing by indomethacin in rats. Eur J Clin Invest 9: 333–339

    Article  PubMed  CAS  Google Scholar 

  28. Elves MW, Bayley I, Roylance PJ (1982) The effect of indomethacin upon experimental fractures in the rat. Acta Orthop Scand 53: 35–41

    PubMed  CAS  Google Scholar 

  29. Tornkvist H, Bauer FCH, Nilsson OS (1985) Influence of indomethacin on experimental bone metabolism in rats. Clin Orthop Rel Res 193: 264–270

    Google Scholar 

  30. Sudmann E, Band G (1979) Indomethacin-induced inhibition of haversian remodeling in rabbits. Acta Orthop Scand 50: 621–627

    Article  PubMed  CAS  Google Scholar 

  31. Sudmann E (1975) Effect of Indomethacin on bone remodeling in rabbit ear chambers. Acta Orthop Scand 160 (Suppl): 91–115

    CAS  Google Scholar 

  32. Sudmann E (1982) Lack of effect of indomethacin on ordered growth of femur in rats. Acta Orthop Scand 53: 43–49

    PubMed  CAS  Google Scholar 

  33. Alva G, Orme M, Bertilsson L, Ekstrad R, Palmer L (1976) Pharmacokinetics of indomethacin. Clin Pharmacol Ther 18: 364–373

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Semmelweis Medical University, Budapest, Hungary

    I. Gera

  2. the VA Medical Center, Research Building No. 5, 06111, Newington, Connecticut

    J. M. Hock & J. Fonseca

  3. School of Medicine, University of Connecticut Health Center, Farmington, Connecticut

    M. Gunness-Hey & L. G. Raisz

Authors
  1. I. Gera
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. J. M. Hock
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. M. Gunness-Hey
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. J. Fonseca
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. L. G. Raisz
    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

Gera, I., Hock, J.M., Gunness-Hey, M. et al. Indomethacin does not inhibit the anabolic effect of parathyroid hormone on the long bones of rats. Calcif Tissue Int 40, 206–211 (1987). https://doi.org/10.1007/BF02556623

Download citation

  • Received:

  • Revised:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02556623

Key words

Search

Navigation