Skip to main content

Advertisement

SpringerLink
Log in

Anticonvulsant drug-induced osteomalacia: Alterations in mineral metabolism and response to vitamin D3 administration

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

Summary

Parameters of mineral metabolism were examined in 6 patients with moderately severe anticonvulsant drug-induced osteomalacia. Compared to 15 matched controls, the patients exhibited significantly reduced serum calcium, inorganic phosphate, and 25-hydroxyvitamin D concentration, elevated serum alkaline phosphatase and immunoreactive parathyroid hormone (iPTH) concentration, reduced intestinal47Ca absorption, reduced urinary calcium and increased urinary hydroxyproline excretion, and reduced forearm bone mass. Intestinal absorption of vitamin D3 was normal. Following 4 months of treatment with vitamin D3 (4000 units/day), serum 25-OHD concentration was increased to 3 times mean normal values and all parameters except serum iPTH, urinary calcium excretion, and forearm bone mass were returned to levels not significantly different from normal. Serum iPTH concentration was reduced by 39% (P<0.05); 24-h urinary calcium excretion rose by 98% (P<0.001), and forearm bone mass increased by 5.6% (P<0.05). It is concluded that moderate-dose vitamin D3 supplementation is effective in normalizing parameters of mineral metabolism in this disorder, despite evidence of resistance to the biologic effects of vitamin D.

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. Richens, A., Rowe, D.F.: Disturbance of calcium metabolism by anticonvulsant drugs, Br. Med. J.3:73–76, 1970

    Google Scholar 

  2. Dent, D.E., Richens, A., Rowe, D.F., Stamp, T.C.B.: Osteomalacia with long-term anticonvulsant therapy in epilepsy, Br. Med. J.4:69–72, 1970

    PubMed  CAS  Google Scholar 

  3. Hahn, T.J., Hendin, B.A., Scharp, C.R., Haddad, J.G., Jr.: Effect of chronic anticonvulsant therapy on serum 25-hydroxycalciferol levels in adults, N. Engl. J. Med.287:900–904, 1972

    Article  PubMed  CAS  Google Scholar 

  4. Stamp, T.C.B., Round, J.M., Rowe, D.J.F., Haddad, J.G.: Plasma levels and therapeutic effect of 25-hydroxycholecalciferol levels in epileptic patients taking anticonvulsant drugs, Br. Med. J.4:9–12, 1972

    PubMed  CAS  Google Scholar 

  5. Hahn, T.J., Hendin, B.A., Scharp, C.R., Boisseau, V.C., Haddad, J.G., Jr.: Serum 25-hydroxycalciferol levels and bone mass in children on chronic anticonvulsant therapy, N. Engl. J. Med.292:550–554, 1975

    Article  CAS  Google Scholar 

  6. Tolman, K.G., Jubiz, W., Sannella, J.J., Madsen, J.A.: Osteomalacia associated with anticonvulsant therapy in mentally retarded children, Pediatrics56:45–51, 1975

    PubMed  CAS  Google Scholar 

  7. Bouillon, R., Reynaut, J., Claes, J.G., Lissens, W., DeMoor, P.: The effect of anticonvulsant therapy on serum levels of 25-hydroxy-vitamin D, calcium and parathyroid hormone, J. Clin. Endocrinol. Metab.41:1130–1136, 1975

    PubMed  CAS  Google Scholar 

  8. Christiansen, C., Rodbro, P., Munck, O.: Actions of vitamins D2 and D3 and 25-OHD3 in anticonvulsant osteomalacia, Br. Med. J.2:363–365, 1975

    Article  PubMed  CAS  Google Scholar 

  9. Moskehilde, L., Christensen, M.S., Lund, B., Sorensen, O.H., Melson, F.: The interrelationships between serum 25-hydroxycholecalciferol, serum parathyroid hormone and bone changes in anticonvulsant osteomalacia, Acta Endocrinol. (Kbh.)84:559–565, 1977

    Google Scholar 

  10. Jubiz, W., Haussler, M.R., McCain, T.A., Tolman, K.: Plasma 1,25-dihydroxyvitamin D levels in patients receiving anticonvulsant drugs, J. Clin. Endocrinol. Metab.44:617–621, 1977

    PubMed  CAS  Google Scholar 

  11. Hahn, T.J., Birge, S.J., Scharp, C.R., Avioli, L.V.: Phenobarbital-induced alterations in vitamin D metabolism, J. Clin. Invest.51:741–748, 1972

    PubMed  CAS  Google Scholar 

  12. Glorieux, F.H., Delvin, E.E., Dussault, M.: Evaluation of liver hydroxylation of vitamin D by simultaneous measurement of circulating cholecalciferol and 25-hydroxycholecalciferol, Trans. 22nd Annual Meeting Orthop. Res. Soc.1:123, 1976

    Google Scholar 

  13. Hahn, T.J., Scharp, C.R., Halstead, L.R., Haddad, J.G., Karl, D.M., Avioli, L.V.: Parathyroid hormone status and renal responsiveness in familial hypophosphatemic rickets, J. Clin. Endocrinol. Metab.41:926–937, 1975

    PubMed  CAS  Google Scholar 

  14. Medical Laboratory Technology and Clinical Pathology, 2nd Ed., p. 169. W.B. Saunders, Co., Philadelphia, 1969

  15. Haddad, J.G., Chyu, K.F.: Competitive protein-binding assay for 25-hydroxycholecalciferol, J. Clin. Endocrinol. Metab.33:992–995, 1971

    PubMed  CAS  Google Scholar 

  16. Slatopolsky, E.S., Caglar, S., Pennell, J.P.: On the pathogenesis of hyperparathyroidism in chronic experimental renal insufficiency in the dog, J. Clin. Invest.50:492–499, 1971

    PubMed  CAS  Google Scholar 

  17. Prockop, D.J., Udenfriend, S.: A specific method for the analysis of hydroxyproline in tissues and urine, Anal. Biochem.1:228–237, 1960

    Article  PubMed  CAS  Google Scholar 

  18. Wills, M.R., Zisman, E., Wortsman, J., Evans, R.G., Pak, C.Y.C., Bartter, F.C.: The measurement of intestinal calcium absorption by external radioisotope counting: application to study of nephrolithiasis, Clin. Sci.39:95–106, 1970

    PubMed  CAS  Google Scholar 

  19. Hahn, T.J., Boisseau, V.C., Avioli, L.V.: Effect of chronic corticosteroid administration on diaphyseal and metaphyseal bone mass, J. Clin. Endocrinol. Metab.39:274–282, 1974

    Article  PubMed  CAS  Google Scholar 

  20. Avioli, L.V., Birge, S.J., Lee, S.W., Slatopolsky, E.: The metabolic fate of vitamin D3-3H in chronic renal failure, J. Clin. Invest.47:2239–2252, 1968

    PubMed  CAS  Google Scholar 

  21. Hahn, T.J.: Bone complications of anticonvulsants. Drugs12:201–211, 1976

    PubMed  CAS  Google Scholar 

  22. Koch, H.V., Kraft, D., von Herrath, D., Schaeffer, K.: Influence of diphenylhydantoin and phenobarbital on intestinal calcium transport in the rat, Epilepsia13:829–841, 1972

    PubMed  CAS  Google Scholar 

  23. Harrison, H.C., Harrison, H.E.: Inhibition of vitamin D-stimulated active transport of calcium by rat intestine by diphenylhydantoin-phenobarbital treatment, Proc. Soc. Exp. Biol. Med.153:220–224, 1976

    PubMed  CAS  Google Scholar 

  24. Hahn, T.J., Scharp, C.R., Richardson, C.A., Halstead, L.R., Kahn, A.J., Teitelbaum, S.L.: Interaction of diphenylhydantoin (phenytoin) and phenobarbital with hormonal mediation of fetal rat bone resorption in vitro, J. Clin. Invest.62:406–414, 1978

    Article  PubMed  CAS  Google Scholar 

  25. Tanaka, Y., DeLuca, H.F.: The control of 25-hydroxyvitamin D metabolism by inorganic phosphorus, Arch. Biochim. Biophys.154:566–574, 1973

    Article  CAS  Google Scholar 

  26. DeLuca, H.F.: Recent advances in our understanding of the vitamin D endocrine system, J. Lab. Clin. Med.87:7–26, 1976

    CAS  Google Scholar 

  27. Hahn, T.J., Halstead, L.R.: Initial alterations in vitamin D metabolism and biologic activity produced by phenobarbital administration in the rat. Submitted for publication

  28. Silver, J., Davies, T.J., Kupersmitt, E., Orme, M., Petrie, A., Vojda, F.: Prevalence and treatment of vitamin D deficiency in children on anticonvulsant drugs, Arch. Dis. Child.49:344–350, 1974

    Article  PubMed  CAS  Google Scholar 

  29. Wilson, C.R.: The use of in vivo bone mineral determination to predict the strength of bone. Norland-Cameron Bone Mineral Analyzer Applications. Note No. 3, Norland-Cameron Instruments, Fort Atchinson, Wisc., 1972

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Bone and Mineral Metabolism, Jewish Hospital of St. Louis and Washington University School of Medicine, 216 South Kingshighway, 63110, St. Louis, Missouri, USA

    Theodore J. Hahn & Linda R. Halstead

Authors
  1. Theodore J. Hahn
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Linda R. Halstead
    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

Hahn, T.J., Halstead, L.R. Anticonvulsant drug-induced osteomalacia: Alterations in mineral metabolism and response to vitamin D3 administration. Calcif Tissue Int 27, 13–18 (1979). https://doi.org/10.1007/BF02441155

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02441155

Key words

Search

Navigation