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Dose-effect and evidence of escape of inhibition after indomethacin treatment in a synchronized model of bone resorption

  • Bone and Cartilage
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Abstract

We previously showed that cyclooxygenase inhibition by indomethacin (7.5 mg/kg/d) prevented resorption in a model of synchronized remodeling. In the present paper, we (i) tested the effectiveness of three doses of indomethacin (2, 4, 7.5 mg/kg/d) in this model, and (ii) verified whether indomethacin action was sustained in time. For that purpose, on day 6 after induction, untreated controls were compared with a group treated for six days with indomethacin (7.5 mg/kg/d), and an interrupted treatment group (4 days indomethacin + 2 days free). Indomethacin inhibited resorption and total number of osteoclasts in a dose-dependent manner. In the second experiment in the discontinued group, the resorption and total number of osteoclasts were similar to sham-treated animals. Indomethacin was still effective in the continuous treatment group; however, resorption was distinctly higher than in the rats treated for four days. These data indicate that despite cyclooxygenase inhibition, another metabolic pathway started resorption. The stoppage of prostanoid inhibition permitted the rapid and complete restoration of resorption.

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References

  1. D. C. Klein and L. G. Raisz,Prostaglandins: Stimulation of bone resorption in tissue culture. Endocrinology80, 1436–1440 (1970).

    Google Scholar 

  2. S. H. Schelling, H. J. Wolfe and A. H. Tashjian,Role of the osteoclast in prostaglandin E2-stimulated bone resorption. A correlative morphometric and biochemical analysis. Lab. Invest.42, 290–295 (1980).

    Google Scholar 

  3. J. R. Nefussi and R. Baron,PGE2 stimulates both resorption and formation of bone in vitro: Differential responses of the periosteum and the endosteum in fetal rat long bone cultures. Anat. Rec.211, 9–16 (1985).

    Google Scholar 

  4. J. L. Saffar and P. Leroux,Role of prostaglandins in bone resorption in a synchronized remodeling sequence in the rat. Bone9, 141–145 (1988).

    Google Scholar 

  5. P. Tran Van, A. Vignery and R. Baron,Cellular kinetics of the bone remodeling sequence in the rat. Anat. Rec.202, 445–451 (1982).

    Google Scholar 

  6. M. Klapisz-Wolikow and J. L. Saffar,Etude d'une séquence de remaniement expérimental induite sur le périoste mandibulaire du rat. J. Biol. Buccale14, 263–271 (1986).

    Google Scholar 

  7. P. J. McMillan, R. A. Dewri, E. E. Joseph, R. L. Schultz and L. J. Deftos,Rapid changes of light microscopic indices of osteoclast-bone relationships correlated with electron microscopy. Calcif. Tissue Int.44, 399–405 (1989).

    Google Scholar 

  8. C. S. B. Galasko, R. Rawlins and A. Bennett,Timing of indomethacin in the control of prostaglandins, osteoclasts and bone destruction produced by VX2 carcimoma in rabbits. Br. J. Cancer40, 360–364 (1979).

    Google Scholar 

  9. J. J. Lasfargues and J. L. Saffar,Effect of indomethacin on bone destruction during experimental periodontal disease in the hamster. J. Period. Res.18, 110–117 (1983).

    Google Scholar 

  10. K. Yamasaki, F. Miura and T. Suda,Prostaglandin as a mediator of bone resorption induced by experimental tooth movement in rats. J. Dent. Res.59, 1635–1642 (1980).

    Google Scholar 

  11. J. J. Lasfargues and J. L. Saffar,Effects of prostaglandin inhibition on the bone activities associated with the spontaneous drift of molar teeth in the rat. Anat. Rec.234, 310–316 (1992).

    Google Scholar 

  12. U. Lerner,Indomethacin inhibits bone resorption in vitro without affecting bone collagen synthesis. Agents and Actions12, 466–470 (1982).

    Google Scholar 

  13. P. Carter-Bartlett, J. M. Dersot and J. L. Saffar,Periodontal and femoral bone status in periodontitis-affected hamsters receiving a high dose indomethacin treatment. J. Biol. Buccale17, 93–101 (1989).

    Google Scholar 

  14. A. Schoutens, M. Verhas, N. Dourov, P. Bergmann, F. Caulin, A. Verschaeren, M. Mone and A. Heilporn,Bone loss and bone blood flow in paraplegic rats treated with calcitonin, diphosphonate, and indomethacin. Calcif. Tissue Int.42, 136–143 (1988).

    Google Scholar 

  15. I. R. Garrett and G. R. Mundy,Relationship between interleukin-1 and prostaglandins in resorbing neonatal calvaria. J. bone Mineral Res.4, 789–794 (1989).

    Google Scholar 

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Authors and Affiliations

  1. Laboratoire de Biologie et Biomatériaux du Milieu Buccal et Osseux, Groupe Physiopathologic Osseuse, Faculté de Chirurgie Dentaire, Université Paris-V, 1 rue Maurice Arnoux, 92120, Montrouge, France

    P. Leroux & J. L. Saffar

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  1. P. Leroux
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  2. J. L. Saffar
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Leroux, P., Saffar, J.L. Dose-effect and evidence of escape of inhibition after indomethacin treatment in a synchronized model of bone resorption. Agents and Actions 38, 290–294 (1993). https://doi.org/10.1007/BF01976223

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  • DOI: https://doi.org/10.1007/BF01976223

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