Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

Effect of prostaglandin D2 on the femoral bone mineral density in ovariectomized rats


We studied the effects of prostaglandin D2 (PGD2) on the femoral bone mineral density (BMD) and other related parameters in ovariectomized (OVx) and shamoperated rats. BMD was measuredin vivo by dual energy X-ray absorptiometry (DXA) for the period of 36 days or 112 days after operation. When 9- or 10-week-old rats were used at the time of operation, the femoral BMD increased during these periods. Ovariectomy resulted in a marked suppression of this steady increase in BMD at both proximal and distal ends of the femur. Subcutaneous administration of a slow-release preparation of PGD2 on days 1 and 21 not only prevented the ovariectomy-induced suppression of BMD, but also augmented the steady increase in BMD of the shamoperated rats. When medication was started on day 70, the depressed rate of increase in BMD was restored to the control level. Serum calcitonin (CT) and parathyroid hormone (PTH) levels were not affected by either ovariectomy or by PGD2 administration. Body weight and bone length were increased, but uterine weight was decreased by ovariectomy. PGD2 administration showed no effects on these parameters. There was a significant increase in the fasting level of urinary hydroxyproline excretion after ovariectomy, and PGD2 administration had no significant effect on this parameter either. These results indicate that the prevention of osteopenia in OVx rats and the increase in BMD in shamoperated and post-OVx rats by PGD2 administration are due to its stimulatory effect on bone formation.

This is a preview of subscription content, log in to check access.


  1. 1.

    Tashjian AH, Tice JE, Sides K (1977) Biological activities of prostaglandin analogues and metabolites on bone in organ culture. Nature 266(14):645–647

  2. 2.

    Raisz LG, Dierich JW, Simmons HA (1977) Effect of prostaglandin endoperoxides and metabolites on bone resorption in vitro. Nature 267(9):532–534

  3. 3.

    Dietrich JW, Goodoson JM, Raisz LG (1975) Stimulation of bone resorption by various prostaglandins in organ culture. Prostaglandins 10(2):231–240

  4. 4.

    Raisz LG, Woodiel FN (1989) Effect of alterations in the cyclopentane ring on bone resorptive activity of prostaglandin. Prostaglandin 37:229–235

  5. 5.

    Ogorochi T, Narumiya S, Mizuno N, Yamasha K, Miyazaki H, Havaishi O (1984) Regional distribution of prostaglandins D2, E2, and F2 and related enzymes in postmortem human brain. J Neurochem 43:71–82

  6. 6.

    Goh Y, Urade Y, Fujimoto N, Hayaishi O (1987) Content and formation of prostaglandins and distribution of prostaglandin-related enzyme activities in the rat ocular system. Biochem Biophys Acta 912:302–311

  7. 7.

    Smith JB, Silver MJ, Ingeruman CM, Kocsis JJ (1974) Prostaglandin D2 inhibits the aggregation of human platelets. Thromb Res 5:291–299

  8. 8.

    Fukishima M, Kato T, Ueda R, Ota K, Narumiya S, Hayaishi O (1982) Prostaglandin D2, a potential antineoplastic agent. Biochem Biophys Res Comm 105(3):956–964

  9. 9.

    Shimizu T, Mizuno N, Amano T, Hayaishi O (1979) Prostaglandin D2, a neuomodulator. Proc Natl Acad Sci USA 7612:6231–6234

  10. 10.

    Yang CY, Gonnerman WA, Menconi M, Taylor L, Polgar PR (1988) Isolation and culture of two cell populations from chick calvaria by density gradient: prostaglandin synthesis by the cell in culture and coculture. Endocrinology 123:2548–2549

  11. 11.

    Koshihara Y, Kawamura M (1989) Prostaglandin D2 stimulates calcification of human osteoblastic cells. Biochem Biophys Res Comm 159:1206–1212

  12. 12.

    Koshhara Y, Amano T, Takamori R (1990) Prostaglandin D2 stimulates calcification by human osteoblastic cells. Advances in prostaglandin, thromboxane, and leukotrien research 21:847–850

  13. 13.

    Tasaki Y, Takamori R, Koshihara Y (1991) Prostaglandin D2 metabolite stimulates collagen synthesis by human osteoblasts during calcification. Prostaglandins 41:303–313

  14. 14.

    Woesnner JF Jr (1961) The determination of hydrozyproline in tissue and protein samples containing small proportions of this imino acid. Arch Biochem Biophys 93:440–447

  15. 15.

    Kalu DN, Liu CC, Hardin RR, Hollis BW (1989) The aged rat model of ovarian hormone deficiency bone loss. Endocrinology 124:7–16

  16. 16.

    Yamazaki I, Yamaguchi H (1989) Characteristics of an ovariectomized osteopenic rat model. J Bone Miner Res 4:13–22

  17. 17.

    Kalu DN (1991) The ovariectomized rat model of postmenopausal bone loss. Bone Miner 15:175–192

  18. 18.

    Le Roy EC (1967) The technique and significance of hydroxyproline measurements in man. Adv Clin Chem 10:213–253

  19. 19.

    Gross J, Piez KA (1960) Calcification in biological systems. In: Songgaeo RF (ed) Am Assoc Advancement of Science, Washington DC, p 395

  20. 20.

    Hodginson A, Thomption T (1982) Measurement of the fasting urinary hydroxyproline: creatinine ratio in normal adults and its variation with age and sex. J Clin Pathol 35:807–811

  21. 21.

    Christiansen C, Christiansen SM, Larsen NE, Transbol I (1982) Pathophysiological mechanisms of estrogen effect on bone metabolism. Dose-response relationship in early postmenopausal women. J Clin Endocrinol Metab 55:1124–1130

  22. 22.

    Ke HZ, Li M, Jee WSS (1992) Prostaglandin E2 prevents ovariectomy-induced cancellous bone loss in rats. Bone Miner 19: 45–62

  23. 23.

    Arnett TR, Dempster DW (1987) A comparative study of disaggregated chick and rat osteoclasts in vitro: effects of calcitonin and prostaglandins. Endocrinology 116:602–608

  24. 24.

    Chambers TJ, McSheehy PMJ, Thompson BM, Fuller K (1985) The effect of calcium-regulating hormones and prostaglandins on bone resorption by osteoclasts disaggregated from neonatal rabbit bones. Endocrinology 116:234–239

  25. 25.

    de Vernejoul M-C, Horowitz M, Demignon J, Nef L, Baron R (1988) Bone resorption by isolated chic osteoclasts incluture is stimulated by murine spleen cell supernatant fluids (osteoclast activating factor) and inhibited by calcitonin and prostaglandin E2. J Bone Miner Res 3:69–80

  26. 26.

    Fuller K, Chambers TJ (1989) Effect of arachidnic acid metabolites on bone resorption by isolated rat osteoclasts. J Bone Miner Res 4:209–215

  27. 27.

    Kimmel DB, Wronski TJ (1990) Nondestructive measurement of bone mineral in femurs from ovariectomized rats. Calcif Tissue Int 46:101–110

  28. 28.

    Whiton SW, Dawson LR, Lee WSS (1978) A tetracycline study of cyclic longitudinal bone growth in the female rat. Endocrinology 103:2006–2010

  29. 29.

    Wronski TJ, Lowry PL, Walsh CC, Ignaszewski LA (1985) Skeletal alternations in ovariectomized rats. Calcif Tissue Int 37:324–328

  30. 30.

    Kalu DN, Echon R, Hollis BW (1990) Modulation of ovariectomy-related bone loss by parathyroid hormone in rats. Mech Ageing Dev 56:49–62

  31. 31.

    Tada K, Yamamoto T, Okumura H, Kasai R, Takahashi H (1990) Restoration of axial and appendicular bone volumes by h-PTH(1–34) in parathyroidectomized and osteopenic rats. Bone 11:163–169

  32. 32.

    De Vernejoul M, Pointillart A, Boureau A, Morieux C, Mordowski D, Miravet L, Caulin F (1990) Effect of calcitonin administration on young pig trabecular bone remodeling. Bone 11:29–33

  33. 33.

    Farley JR, Wergedal JE, Hall SL, Herring S, Tarbaux NM (1991) Calcitonin has direct effects of 3[H]-thymidine incorporation and alkaline phosphates activity in human osteoblast-like cells. Calcif Tissue Int 48:297–301

  34. 34.

    Farley JR, Hall SL, Herring S, Tarbaux NM (1992) Two biochemical indices of mouse bone formation are increased, in vivo, in response to calcitonin. Calcif Tissue Int 50:67–73

  35. 35.

    Kikawa T, Narumiya S, Fukusha M, Wakathuka H, Hayaishi O (1984) 9-Deoxy-Δ9Δ12-13, 14-dihydroprostaglandin D2, a metabolite of prostaglandin D2 form in human plasma. Proc Natl Acad Sci USA 81:1317–1321

Download references

Author information

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Takagi, T., Yamamoto, T., Asano, S. et al. Effect of prostaglandin D2 on the femoral bone mineral density in ovariectomized rats. Calcif Tissue Int 52, 442–446 (1993). https://doi.org/10.1007/BF00571334

Download citation

Key words

  • Ovariectomized rat
  • In vivo
  • Bone mineral density
  • Dual energy X-ray absorptiometry
  • Prostaglandin D2