Skip to main content
SpringerLink
Log in

Effect of omeprazole, an inhibitor of H+, K+-ATPase, on bone resorption in humans

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

Summary

Omeprazole is an inhibitor of gastric H+, K+-ATPase. Although the major proton transport of osteoclast is mediated by a vacuolar-type H+-ATPase which is different from the gastric H+, K+-ATPase,in vitro studies have demonstrated that omeprazole inhibits bone resorption. In this study, the effect of omeprazole on bone resorption was evaluated in patients who had a history of gastric ulcer and were treated with maintenance doses of H2 blocker without any gastric complaints at the study time. H2 blocker administration was changed to omeprazole treatment in the study group and to no treatment in the control group. Urinary excretion of hydroxyproline and calcium decreased after omeprazole treatment in the study group. Serum intact PTH, alkaline phosphatase, osteocalcin, and tartrate-resistant acid phosphatase (TRAP) increased in this group. In the control group, there were not any changes in these parameters. The discrepancy between serum TRAP and urinary excretion of hydroxyproline and calcium in the study group was thought to be due to the suppression of bone resorption by omeprazole, which probably interfered the acidification at resorption lacunae and resulted in the inactivation of TRAP and other lysosomal enzymes. The results of our study suggest the possibility that the specific inhibitors of the osteoclastic proton pump (such as bafilomycins) will more effectively suppress bone resorption and be useful for the treatment of metabolic bone diseases with increased bone resorption.

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

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

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. Baron R (1989) Molecular mechanisms of bone resorption by the osteoclast. Anat Rec 224:317–329

    Google Scholar 

  2. Blair HC, Teitelbaum SL, Ghiselli R, Gluck S (1989) Osteoclastic bone resorption by a polarized vacuolar proton pump. Science 245:855–857

    Google Scholar 

  3. Arnett TR, Dempster DW (1990) Protons and osteoclasts. J Bone Miner Res 5:1099–1103

    Google Scholar 

  4. Lindberg P, Nordberg P, Alminger T, Brändsröm A, Wallmark B (1986) The mechanism of action of the gastric acid secretion inhibitor omeprazole. J Med Chem 29:1327–1329

    Google Scholar 

  5. Morii M, Takata H, Takeguchi N (1990) Binding site of omeprazole in hog gastric H+,K+-ATPase. Biochem Biophys Res Commun 167:754–760

    Google Scholar 

  6. Bekker PJ, Gay CV (1990) Biochemical characterization of an electrogenic vacuolar proton pump in purified chicken osteoclast plasma membrane vesicles. J Bone Miner Res 5:569–579

    Google Scholar 

  7. Väänänen HK, Kahrhukorpi EK, Sundquist K, Wallmark B, Roininen I, Hentunen T, Tuukkanen J, Loakkakorpi P (1990) Evidence for the presence of a proton pump of the vacuolar H+-ATPase type in the ruffled borders of osteoclasts. J Cell Biol 111:1305–1311

    Google Scholar 

  8. Tuukkanen J, Väänänen HK (1986) Omeprazole, a specific inhibitor of H+-K+-ATPase, inhibits bone resorption in vitro. Calcif Tissue Int 38:123–125

    Google Scholar 

  9. Andersen RE, Woodbury DM, Jee WS (1986) Humoral and ionic regulation of osteoclast acidity. Calcif Tissue Int 39:252–258

    Google Scholar 

  10. Eftradiadis T, Moss DW (1985) Tartrate-resistant acid phosphatase of human lung: apparent identity with osteoclastic acid phosphatase. Enzyme 33:34–40

    Google Scholar 

  11. Clark SA, Ambrose WW, Anderson TR, Terrell RS, Toverud SV (1989) Ultrastructural localization of tartrate-resistant, purple acid phosphatase in rat osteoclasts by histochemistry and immunocytochemistry. J Bone Miner Res 4:399–405

    Google Scholar 

  12. Miller SC (1985) The rapid appearance of acid phosphatase activity at the developing ruffled border of parathyroid hormone activated medullary bone osteoclasts. Calcif Tissue Int 37:526–529

    Google Scholar 

  13. Chambers TJ, Fuller K, Darby JA (1987) Hormonal regulation of acid phosphatase released by osteoclasts disaggregated from neonatal rat bone. J Cell Physiol 132:90–96

    Google Scholar 

  14. Bergman I, Loxley R (1970) The determination of hydroxyproline in urine hydrolysates. Clin Chim Acta 27:347–353

    Google Scholar 

  15. Nussbaum S, Zahradnik R, Lavigne J, Brennan G, Nozawa-Ung K, Kim L, Keutman H, Wnag CA, Potts JT Jr, Segre G (1987) Development of a high sensitive two site immunoradiometric assay for parathyroid hormone and its clinically utility in evaluation of patients with hypercalcemia. Clin Chem 33:1364–1367

    Google Scholar 

  16. Eilon G, Raisz LG (1978) Comparison of the effects of stimulators and inhibitors of resorption on the release of lysosomal enzymes and radioactive calcium from fetal bone in organ culture. Endocrinology 103:1969–1975

    Google Scholar 

  17. Quarles LD, Lobaugh B, Murphy G (1992) Intact parathyroid hormone overestimates the presence and severity of parathyroid-mediated osseous abnormalities in uremia. J Clin Endocrinol Metab 75:145–150

    Google Scholar 

  18. Williams GA, Longley RS, Bowser EN, Hargis GK, Kukreja SC, Vora NM, Johnson PA, Jackson BL, Kawahara WJ, Henderson WJ (1981) Parathyroid hormone secretion in normal man and in primary hyperparathyroidism: role of histamine H2 receptors. J Clin Endocrinol Metab 52:122–127

    Google Scholar 

  19. Brown EM, Garder DG, Windeck RA, Hurwitz S, Brannan MF, Aurbach GD (1979) β-adrenergically-stimulated adenosine 3′,5′-monophosphate accumulation in and parathyroid hormone release from dispersed human parathyroid cells. J Clin Endocrinol Metab 48:618–626

    Google Scholar 

  20. Heath H III (1980) Biogenic amines and the secretion of parathyroid hormone and calcitonin. Endocrinol Rev 1:319–338

    Google Scholar 

  21. Baron R, Neff L, Louvard D, Courtoy PJ (1985) Cell-mediated extracellular acidification and bone resorption: evidence for a low pH in resorbing lacunae and localization of a 100-kD lysosomal membrane protein at the osteoclast ruffled border. J Cell Biol 101:2210–2222

    Google Scholar 

  22. Gluck S (1992) The osteoclast as a unicellular proton-transporting epithelium. Am J Med Sci 303:134–139

    Google Scholar 

  23. Mattsson JP, Väänänen K, Wallmark B, Lorentzon P (1991) Omeprazole and bafilomycin, two proton pump inhibitors: differentiation of their effects on gastric, kidney and bone H+-translocating ATPases. Biochim Biophys Acta 1065:261–268

    Google Scholar 

  24. Lindberg P, Bränström A, Wallmark B, Mattsson H, Rikner L, Hoffman KJ (1990) Omeprazole: the first proton inhibitor. Med Res Rev 10:1–54

    Google Scholar 

  25. Silver IA, Murrills RJ, Etherington DJ (1988) Microelectrode studies on the acid microenvironment beneath adherent macrophages and osteoclasts. Exp Cell Res 175:266–276

    Google Scholar 

  26. Borg KO, Olbe L (1985) Omeprazole—a survey of preclinical data. Scand J Gastroent 20:1–120

    Google Scholar 

  27. Bowman EJ, Sibers A, Altendorf K (1988) Bafilomycins: a class of inhibitors of membrane ATPases from microorganisms, animal cells, and plant cells. Proc Natl Acad Sci USA 85:7972–7976

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. The Second Department of Internal Medicine, Tohoku University School of Medicine, 1-1, Seiryo-cho, Aoba-ku, Sendai, Japan

    Kazutoshi Mizunashi & Keishi Abe

  2. Department of Internal Medicine, Sendai City Hospital, 3-1, Shimizukoji, Wakabayashi-ku, Sendai, Japan

    Yohtaro Furukawa

  3. Department of Internal Medicine, Iwate Prefecture Takata Hospital, 34, Nakaseki, Kesencho, Rikuzentakata, Japan

    Kaichiro Katano

Authors
  1. Kazutoshi Mizunashi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yohtaro Furukawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kaichiro Katano
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Keishi Abe
    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

Mizunashi, K., Furukawa, Y., Katano, K. et al. Effect of omeprazole, an inhibitor of H+, K+-ATPase, on bone resorption in humans. Calcif Tissue Int 53, 21–25 (1993). https://doi.org/10.1007/BF01352010

Download citation

  • Received:

  • Revised:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01352010

Key words

Search

Navigation