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. 1997 Jun;56(6):357–363. doi: 10.1136/ard.56.6.357

Is addition of sodium fluoride to cyclical etidronate beneficial in the treatment of corticosteroid induced osteoporosis?

W Lems 1, J Jacobs 1, J Bijlsma 1, G J M van Veen 1, H Houben 1, H Haanen 1, M Gerrits 1, H J M van Rijn 1
PMCID: PMC1752400  PMID: 9227164

Abstract

OBJECTIVE—To investigate whether administration of sodium fluoride (NaF) in addition to cyclical etidronate has a positive effect on bone mineral density (BMD) in patients with established osteoporosis during continued treatment with corticosteroids.
PATIENTS AND METHODS—47 patients who were receiving treatment with corticosteroids were included in a two year randomised, double blind, placebo controlled trial. Established osteoporosis was defined as a history of a peripheral fracture or a vertebral deformity, or both, on a radiograph. All patients were treated with cyclical etidronate, calcium, and either NaF (25 twice daily) or placebo. Vitamin D was supplemented in the case of a low serum 25 (OH) vitamin D concentration. BMD of the lumbar spine and hips was measured at baseline and at 6, 12, 18, and 24 months.
RESULTS—After two years of treatment, the BMD of the lumbar spine in the etidronate/NaF group had increased by +9.3% (95% confidence intervals (CI): +2.3% to +16.2%, p<0.01), while the BMD in the etidronate/placebo group was unchanged: +0.3% (95% CI: −2.2% to +2.8%). The difference in the change in BMD between groups was +8.9% (95% CI: +1.9% to +16.0%, p<0.01). For the hips, no significant changes in BMD were observed in the etidronate/NaF group after two years: −2.5% (95% CI: −6.8% to +1.8%); in the etidronate/placebo group BMD had significantly decreased: −4.0% (95% CI: −6.6% to −1.4%; p<0.01). The difference between the groups was not significant: +1.5% (95% CI: −3.4% to +6.4%). No significant differences in number of vertebral deformities and peripheral fractures were observed between the two groups.
CONCLUSION—The effect of combination treatment with NaF and etidronate on the BMD of the lumbar spine in corticosteroid treated patients with established osteoporosis is superior to that of etidronate alone.



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Figure 1  .

Figure 1  

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Effect of NaF/etidronate compared with that of placebo/etidronate on bone mineral density of the lumbar spine in corticosteroid treated patients with established osteoporosis. * p< 0.05, difference in changes between groups; ** p< 0.01, difference in changes between groups.

Figure 2  .

Figure 2  

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Effect of NaF/etidronate compared with that of placebo/etidronate on bone mineral density of the hips in corticosteroid treated patients with established osteoporosis. Difference in changes between groups not statistically significant.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Adachi J. D., Bensen W. G., Hodsman A. B. Corticosteroid-induced osteoporosis. Semin Arthritis Rheum. 1993 Jun;22(6):375–384. doi: 10.1016/s0049-0172(05)80029-0. [DOI] [PubMed] [Google Scholar]
  2. Adachi J., Cranney A., Goldsmith C. H., Bensen W. G., Bianchi F., Cividino A., Craig G. L., Kaminska E., Sebaldt R. J., Papaioannou A. Intermittent cyclic therapy with etidronate in the prevention of corticosteroid induced bone loss. J Rheumatol. 1994 Oct;21(10):1922–1926. [PubMed] [Google Scholar]
  3. Adinoff A. D., Hollister J. R. Steroid-induced fractures and bone loss in patients with asthma. N Engl J Med. 1983 Aug 4;309(5):265–268. doi: 10.1056/NEJM198308043090502. [DOI] [PubMed] [Google Scholar]
  4. Bayley T. A., Muller C., Harrison J., Basualdo J., Sturtridge W., Josse R., Murray T. M., Pritzker K. P., Vieth R., Goodwin S. The long-term treatment of steroid osteoporosis with fluoride. J Bone Miner Res. 1990 Mar;5 (Suppl 1):S157–S161. doi: 10.1002/jbmr.5650051342. [DOI] [PubMed] [Google Scholar]
  5. Cooper C., Kanis J. A., Compston J. How to assess drug efficacy in osteoporosis. Lancet. 1995 Mar 25;345(8952):743–744. doi: 10.1016/s0140-6736(95)90635-5. [DOI] [PubMed] [Google Scholar]
  6. Delmas P. D. Biochemical markers of bone turnover. J Bone Miner Res. 1993 Dec;8 (Suppl 2):S549–S555. doi: 10.1002/jbmr.5650081323. [DOI] [PubMed] [Google Scholar]
  7. Dempster D. W., Lindsay R. Pathogenesis of osteoporosis. Lancet. 1993 Mar 27;341(8848):797–801. doi: 10.1016/0140-6736(93)90570-7. [DOI] [PubMed] [Google Scholar]
  8. Dykman T. R., Gluck O. S., Murphy W. A., Hahn T. J., Hahn B. H. Evaluation of factors associated with glucocorticoid-induced osteopenia in patients with rheumatic diseases. Arthritis Rheum. 1985 Apr;28(4):361–368. doi: 10.1002/art.1780280402. [DOI] [PubMed] [Google Scholar]
  9. Garnero P., Grimaux M., Demiaux B., Preaudat C., Seguin P., Delmas P. D. Measurement of serum osteocalcin with a human-specific two-site immunoradiometric assay. J Bone Miner Res. 1992 Dec;7(12):1389–1398. doi: 10.1002/jbmr.5650071206. [DOI] [PubMed] [Google Scholar]
  10. Gerrits M. I., Thijssen J. H., van Rijn H. J. Determination of pyridinoline and deoxypyridinoline in urine, with special attention to retaining their stability. Clin Chem. 1995 Apr;41(4):571–574. [PubMed] [Google Scholar]
  11. Gough A. K., Lilley J., Eyre S., Holder R. L., Emery P. Generalised bone loss in patients with early rheumatoid arthritis. Lancet. 1994 Jul 2;344(8914):23–27. doi: 10.1016/s0140-6736(94)91049-9. [DOI] [PubMed] [Google Scholar]
  12. Greenwald M., Brandli D., Spector S., Silverman S., Golde G. Corticosteroid-induced osteoporosis: effects of a treatment with slow-release sodium fluoride. Osteoporos Int. 1992 Nov;2(6):303–304. doi: 10.1007/BF01623187. [DOI] [PubMed] [Google Scholar]
  13. Kleerekoper M. Fluoride: the verdict is in, but the controversy lingers. J Bone Miner Res. 1996 May;11(5):565–567. doi: 10.1002/jbmr.5650110503. [DOI] [PubMed] [Google Scholar]
  14. Laan R. F., van Riel P. L., van de Putte L. B., van Erning L. J., van't Hof M. A., Lemmens J. A. Low-dose prednisone induces rapid reversible axial bone loss in patients with rheumatoid arthritis. A randomized, controlled study. Ann Intern Med. 1993 Nov 15;119(10):963–968. doi: 10.7326/0003-4819-119-10-199311150-00001. [DOI] [PubMed] [Google Scholar]
  15. Lau K. H., Farley J. R., Baylink D. J. Phosphotyrosyl protein phosphatases. Biochem J. 1989 Jan 1;257(1):23–36. doi: 10.1042/bj2570023. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Lems W. F., Gerrits M. I., Jacobs J. W., van Vugt R. M., van Rijn H. J., Bijlsma J. W. Changes in (markers of) bone metabolism during high dose corticosteroid pulse treatment in patients with rheumatoid arthritis. Ann Rheum Dis. 1996 May;55(5):288–293. doi: 10.1136/ard.55.5.288. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Lems W. F., Jahangier Z. N., Jacobs J. W., Bijlsma J. W. Vertebral fractures in patients with rheumatoid arthritis treated with corticosteroids. Clin Exp Rheumatol. 1995 May-Jun;13(3):293–297. [PubMed] [Google Scholar]
  18. Lindsay R. Fluoride and bone--quantity versus quality. N Engl J Med. 1990 Mar 22;322(12):845–846. doi: 10.1056/NEJM199003223221210. [DOI] [PubMed] [Google Scholar]
  19. Lukert B. P., Raisz L. G. Glucocorticoid-induced osteoporosis: pathogenesis and management. Ann Intern Med. 1990 Mar 1;112(5):352–364. doi: 10.7326/0003-4819-112-5-352. [DOI] [PubMed] [Google Scholar]
  20. Mamelle N., Meunier P. J., Dusan R., Guillaume M., Martin J. L., Gaucher A., Prost A., Zeigler G., Netter P. Risk-benefit ratio of sodium fluoride treatment in primary vertebral osteoporosis. Lancet. 1988 Aug 13;2(8607):361–365. doi: 10.1016/s0140-6736(88)92834-6. [DOI] [PubMed] [Google Scholar]
  21. Meunier P. J., Dempster D. W., Edouard C., Chapuy M. C., Arlot M., Charhon S. Bone histomorphometry in corticosteroid-induced osteoporosis and Cushing's syndrome. Adv Exp Med Biol. 1984;171:191–200. [PubMed] [Google Scholar]
  22. Mulder H., Struys A. Intermittent cyclical etidronate in the prevention of corticosteroid-induced bone loss. Br J Rheumatol. 1994 Apr;33(4):348–350. doi: 10.1093/rheumatology/33.4.348. [DOI] [PubMed] [Google Scholar]
  23. Pak C. Y., Sakhaee K., Adams-Huet B., Piziak V., Peterson R. D., Poindexter J. R. Treatment of postmenopausal osteoporosis with slow-release sodium fluoride. Final report of a randomized controlled trial. Ann Intern Med. 1995 Sep 15;123(6):401–408. doi: 10.7326/0003-4819-123-6-199509150-00001. [DOI] [PubMed] [Google Scholar]
  24. Pak C. Y., Zerwekh J. E., Antich P. P., Bell N. H., Singer F. R. Slow-release sodium fluoride in osteoporosis. J Bone Miner Res. 1996 May;11(5):561–564. doi: 10.1002/jbmr.5650110502. [DOI] [PubMed] [Google Scholar]
  25. RICH C., ENSINCK J., IVANOVICH P. THE EFFECTS OF SODIUM FLORIDE ON CALCIUM METABOLISM OF SUBJECTS WITH METABOLIC BONE DISEASES. J Clin Invest. 1964 Apr;43:545–555. doi: 10.1172/JCI104940. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Reid I. R., Heap S. W. Determinants of vertebral mineral density in patients receiving long-term glucocorticoid therapy. Arch Intern Med. 1990 Dec;150(12):2545–2548. [PubMed] [Google Scholar]
  27. Riggs B. L., Hodgson S. F., O'Fallon W. M., Chao E. Y., Wahner H. W., Muhs J. M., Cedel S. L., Melton L. J., 3rd Effect of fluoride treatment on the fracture rate in postmenopausal women with osteoporosis. N Engl J Med. 1990 Mar 22;322(12):802–809. doi: 10.1056/NEJM199003223221203. [DOI] [PubMed] [Google Scholar]
  28. Riggs B. L., O'Fallon W. M., Lane A., Hodgson S. F., Wahner H. W., Muhs J., Chao E., Melton L. J., 3rd Clinical trial of fluoride therapy in postmenopausal osteoporotic women: extended observations and additional analysis. J Bone Miner Res. 1994 Feb;9(2):265–275. doi: 10.1002/jbmr.5650090216. [DOI] [PubMed] [Google Scholar]
  29. Riggs B. L., Seeman E., Hodgson S. F., Taves D. R., O'Fallon W. M. Effect of the fluoride/calcium regimen on vertebral fracture occurrence in postmenopausal osteoporosis. Comparison with conventional therapy. N Engl J Med. 1982 Feb 25;306(8):446–450. doi: 10.1056/NEJM198202253060802. [DOI] [PubMed] [Google Scholar]
  30. Rizzoli R., Chevalley T., Slosman D. O., Bonjour J. P. Sodium monofluorophosphate increases vertebral bone mineral density in patients with corticosteroid-induced osteoporosis. Osteoporos Int. 1995 Jan;5(1):39–46. doi: 10.1007/BF01623657. [DOI] [PubMed] [Google Scholar]
  31. Ross P. D., Davis J. W., Epstein R. S., Wasnich R. D. Pre-existing fractures and bone mass predict vertebral fracture incidence in women. Ann Intern Med. 1991 Jun 1;114(11):919–923. doi: 10.7326/0003-4819-114-11-919. [DOI] [PubMed] [Google Scholar]
  32. Sambrook P., Birmingham J., Kelly P., Kempler S., Nguyen T., Pocock N., Eisman J. Prevention of corticosteroid osteoporosis. A comparison of calcium, calcitriol, and calcitonin. N Engl J Med. 1993 Jun 17;328(24):1747–1752. doi: 10.1056/NEJM199306173282404. [DOI] [PubMed] [Google Scholar]
  33. Struys A., Snelder A. A., Mulder H. Cyclical etidronate reverses bone loss of the spine and proximal femur in patients with established corticosteroid-induced osteoporosis. Am J Med. 1995 Sep;99(3):235–242. doi: 10.1016/s0002-9343(99)80154-5. [DOI] [PubMed] [Google Scholar]

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