Prevention and management of osteoporosis: consensus statements from the Scientific Advisory Board of the Osteoporosis Society of Canada. 7. Fluoride therapy for osteoporosis (original) (raw)

. 1996 Oct 1;155(7):949–954.

Abstract

OBJECTIVE: To present the latest findings on the use of fluoride in the treatment of osteoporosis. OPTIONS: Plain sodium fluoride (NaF), enteric-coated sodium fluoride (EC-NaF), sodium monofluorophosphate (Na2FPO4), slow-release sodium fluoride (SR-NaF); fluoride with a calcium supplement. OUTCOMES: Fracture and loss of bone mineral density in osteoporosis; increased bone mass, prevention of fractures and improved quality of life associated with treatment. EVIDENCE: Relevant clinical studies and reports were examined, with an emphasis on recent prospective, randomized, controlled trials. Clinical practices in European countries were also considered. VALUES: Reducing fractures, increasing bone mineral density and minimizing side effects of treatment were given a high value. BENEFITS, HARMS AND COSTS: NaF therapy stimulates bone formation and may be effective in preventing osteoporotic fractures. It may be an acceptable alternative treatment to estrogen or bisphosphonate therapy and useful in premenopausal and corticosteroid-induced osteoporosis and in some patients with mild osteogenesis imperfecta. Toxic effects are dependent on formulation and dosage. They include a range of gastrointestinal and musculoskeletal conditions. EC-NaF is associated with less toxicity than plain NaF; its gastrointestinal toxicity is negligible. Na2FPO4 has no gastrointestinal toxicity, but can give rise to skeletal toxicity. SR-NaF appears to have no side effects when given intermittently. Carcinogenicity has not been found in vivo with fluoride therapy, despite in vitro results. RECOMMENDATIONS: New data indicate that fluoride therapy should be re-evaluated as a potentially effective treatment of osteoporosis with minimal side effects. More studies are needed of slow-release fluoride formulations, intermittent treatment schedules and calcium supplementation of fluoride. Studies should be undertaken to see if it is advantageous to initiate treatment with antiresorptive agents before or in combination with fluoride. Conclusive data have not been presented regarding the benefit of any specific type of calcium supplement. Further studies on the basic mechanism of action of fluoride on the skeleton are necessary to evaluate fluoride's potential to stimulate bone formation therapeutically.

949

Selected References

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

  1. Aaron J. E., de Vernejoul M. C., Kanis J. A. The effect of sodium fluoride on trabecular architecture. Bone. 1991;12(5):307–310. doi: 10.1016/8756-3282(91)90015-b. [DOI] [PubMed] [Google Scholar]
  2. Ahn H. W., Fulton B., Moxon D., Jeffery E. H. Interactive effects of fluoride and aluminum uptake and accumulation in bones of rabbits administered both agents in their drinking water. J Toxicol Environ Health. 1995 Mar;44(3):337–350. doi: 10.1080/15287399509531963. [DOI] [PubMed] [Google Scholar]
  3. Antich P. P., Pak C. Y., Gonzales J., Anderson J., Sakhaee K., Rubin C. Measurement of intrinsic bone quality in vivo by reflection ultrasound: correction of impaired quality with slow-release sodium fluoride and calcium citrate. J Bone Miner Res. 1993 Mar;8(3):301–311. doi: 10.1002/jbmr.5650080307. [DOI] [PubMed] [Google Scholar]
  4. Boivin G., Duriez J., Chapuy M. C., Flautre B., Hardouin P., Meunier P. J. Relationship between bone fluoride content and histological evidence of calcification defects in osteoporotic women treated long term with sodium fluoride. Osteoporos Int. 1993 Jul;3(4):204–208. doi: 10.1007/BF01623677. [DOI] [PubMed] [Google Scholar]
  5. Bucher J. R., Hejtmancik M. R., Toft J. D., 2nd, Persing R. L., Eustis S. L., Haseman J. K. Results and conclusions of the National Toxicology Program's rodent carcinogenicity studies with sodium fluoride. Int J Cancer. 1991 Jul 9;48(5):733–737. doi: 10.1002/ijc.2910480517. [DOI] [PubMed] [Google Scholar]
  6. Budden F. H., Bayley T. A., Harrison J. E., Josse R. G., Murray T. M., Sturtridge W. C., Kandel R., Vieth R., Strauss A. L., Goodwin S. The effect of fluoride on bone histology in postmenopausal osteoporosis depends on adequate fluoride absorption and retention. J Bone Miner Res. 1988 Apr;3(2):127–132. doi: 10.1002/jbmr.5650030202. [DOI] [PubMed] [Google Scholar]
  7. Burkhart J. M., Jowsey J. Effect of variations in calcium intake on the skeleton of fluoride-fed kittens. J Lab Clin Med. 1968 Dec;72(6):943–950. [PubMed] [Google Scholar]
  8. Caverzasio J., Imai T., Ammann P., Burgener D., Bonjour J. P. Aluminum potentiates the effect of fluoride on tyrosine phosphorylation and osteoblast replication in vitro and bone mass in vivo. J Bone Miner Res. 1996 Jan;11(1):46–55. doi: 10.1002/jbmr.5650110108. [DOI] [PubMed] [Google Scholar]
  9. Crespi C. L., Seixas G. M., Turner T., Penman B. W. Sodium fluoride is a less efficient human cell mutagen at low concentrations. Environ Mol Mutagen. 1990;15(2):71–77. doi: 10.1002/em.2850150203. [DOI] [PubMed] [Google Scholar]
  10. Dambacher M. A., Ittner J., Ruegsegger P. Long-term fluoride therapy of postmenopausal osteoporosis. Bone. 1986;7(3):199–205. doi: 10.1016/8756-3282(86)90018-9. [DOI] [PubMed] [Google Scholar]
  11. Gruber H. E., Baylink D. J. The effects of fluoride on bone. Clin Orthop Relat Res. 1991 Jun;(267):264–277. [PubMed] [Google Scholar]
  12. Gutteridge D. H., Price R. I., Kent G. N., Prince R. L., Michell P. A. Spontaneous hip fractures in fluoride-treated patients: potential causative factors. J Bone Miner Res. 1990 Mar;5 (Suppl 1):S205–S215. doi: 10.1002/jbmr.5650051332. [DOI] [PubMed] [Google Scholar]
  13. Hall B. K. Sodium fluoride as an initiator of osteogenesis from embryonic mesenchyme in vitro. Bone. 1987;8(2):111–116. doi: 10.1016/8756-3282(87)90079-2. [DOI] [PubMed] [Google Scholar]
  14. Heaney R. P., Baylink D. J., Johnston C. C., Jr, Melton L. J., 3rd, Meunier P. J., Murray T. M., Nagant de Deuxchaisnes C. Fluoride therapy for the vertebral crush fracture syndrome. A status report. Ann Intern Med. 1989 Oct 15;111(8):678–680. doi: 10.7326/0003-4819-111-8-678. [DOI] [PubMed] [Google Scholar]
  15. Hedlund L. R., Gallagher J. C. Increased incidence of hip fracture in osteoporotic women treated with sodium fluoride. J Bone Miner Res. 1989 Apr;4(2):223–225. doi: 10.1002/jbmr.5650040214. [DOI] [PubMed] [Google Scholar]
  16. Hodsman A. B., Drost D. J. The response of vertebral bone mineral density during the treatment of osteoporosis with sodium fluoride. J Clin Endocrinol Metab. 1989 Nov;69(5):932–938. doi: 10.1210/jcem-69-5-932. [DOI] [PubMed] [Google Scholar]
  17. Jowsey J., Riggs B. L., Kelly P. J., Hoffman D. L. Effect of combined therapy with sodium fluoride, vitamin D, and calcium in osteoporosis. J Lab Clin Med. 1971 Dec;78(6):994–995. [PubMed] [Google Scholar]
  18. Kleerekoper M., Peterson E. L., Nelson D. A., Phillips E., Schork M. A., Tilley B. C., Parfitt A. M. A randomized trial of sodium fluoride as a treatment for postmenopausal osteoporosis. Osteoporos Int. 1991 Jun;1(3):155–161. doi: 10.1007/BF01625446. [DOI] [PubMed] [Google Scholar]
  19. Lau K. H., Farley J. R., Freeman T. K., Baylink D. J. A proposed mechanism of the mitogenic action of fluoride on bone cells: inhibition of the activity of an osteoblastic acid phosphatase. Metabolism. 1989 Sep;38(9):858–868. doi: 10.1016/0026-0495(89)90232-1. [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. Mamelle N., Meunier P. J., Netter P. Fluoride and vertebral fractures. Lancet. 1990 Jul 28;336(8709):243–243. doi: 10.1016/0140-6736(90)91764-2. [DOI] [PubMed] [Google Scholar]
  22. Nagant de Deuxchaisnes C., Devogelaer J. P., Depresseux G., Malghem J., Maldague B. Treatment of the vertebral crush fracture syndrome with enteric-coated sodium fluoride tablets and calcium supplements. J Bone Miner Res. 1990 Mar;5 (Suppl 1):S5–26. doi: 10.1002/jbmr.5650051303. [DOI] [PubMed] [Google Scholar]
  23. Nagant de Deuxchaisnes C., Devogelaer J. P., Stein F. Fluoride treatment for osteoporosis. Lancet. 1990 Jul 7;336(8706):48–49. doi: 10.1016/0140-6736(90)91556-p. [DOI] [PubMed] [Google Scholar]
  24. Pak C. Y., Adams-Huet B., Sakhaee K., Bell N. H., Licata A., Johnston C., Rubin B., Bonnick S., Piziak V., Graham H. Comparison of nonrandomized trials with slow-release sodium fluoride with a randomized placebo-controlled trial in postmenopausal osteoporosis. J Bone Miner Res. 1996 Feb;11(2):160–168. doi: 10.1002/jbmr.5650110204. [DOI] [PubMed] [Google Scholar]
  25. 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]
  26. Power G. R., Gay J. D. Sodium fluoride in the treatment of osteoporosis. Clin Invest Med. 1986;9(1):41–43. [PubMed] [Google Scholar]
  27. 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]
  28. Reeve J., Davies U. M., Hesp R., McNally E., Katz D. Treatment of osteoporosis with human parathyroid peptide and observations on effect of sodium fluoride. BMJ. 1990 Aug 11;301(6747):314–318. doi: 10.1136/bmj.301.6747.314. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Resch H., Libanati C., Farley S., Bettica P., Schulz E., Baylink D. J. Evidence that fluoride therapy increases trabecular bone density in a peripheral skeletal site. J Clin Endocrinol Metab. 1993 Jun;76(6):1622–1624. doi: 10.1210/jcem.76.6.8501171. [DOI] [PubMed] [Google Scholar]
  30. Riggs B. L., Baylink D. J., Kleerekoper M., Lane J. M., Melton L. J., 3rd, Meunier P. J. Incidence of hip fractures in osteoporotic women treated with sodium fluoride. J Bone Miner Res. 1987 Apr;2(2):123–126. doi: 10.1002/jbmr.5650020207. [DOI] [PubMed] [Google Scholar]
  31. Riggs B. L., Hodgson S. F., Hoffman D. L., Kelly P. J., Johnson K. A., Taves D. Treatment of primary osteoporosis with fluoride and calcium. Clinical tolerance and fracture occurrence. JAMA. 1980 Feb 1;243(5):446–449. [PubMed] [Google Scholar]
  32. 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]
  33. 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]
  34. Storm T., Thamsborg G., Steiniche T., Genant H. K., Sørensen O. H. Effect of intermittent cyclical etidronate therapy on bone mass and fracture rate in women with postmenopausal osteoporosis. N Engl J Med. 1990 May 3;322(18):1265–1271. doi: 10.1056/NEJM199005033221803. [DOI] [PubMed] [Google Scholar]
  35. Søgaard C. H., Mosekilde L., Richards A., Mosekilde L. Marked decrease in trabecular bone quality after five years of sodium fluoride therapy--assessed by biomechanical testing of iliac crest bone biopsies in osteoporotic patients. Bone. 1994 Jul-Aug;15(4):393–399. doi: 10.1016/8756-3282(94)90815-x. [DOI] [PubMed] [Google Scholar]
  36. Turner C. H., Akhter M. P., Heaney R. P. The effects of fluoridated water on bone strength. J Orthop Res. 1992 Jul;10(4):581–587. doi: 10.1002/jor.1100100413. [DOI] [PubMed] [Google Scholar]
  37. Turner R. T., Francis R., Brown D., Garand J., Hannon K. S., Bell N. H. The effects of fluoride on bone and implant histomorphometry in growing rats. J Bone Miner Res. 1989 Aug;4(4):477–484. doi: 10.1002/jbmr.5650040405. [DOI] [PubMed] [Google Scholar]
  38. Zerwekh J. E., Hagler H. K., Sakhaee K., Gottschalk F., Peterson R. D., Pak C. Y. Effect of slow-release sodium fluoride on cancellous bone histology and connectivity in osteoporosis. Bone. 1994 Nov-Dec;15(6):691–699. doi: 10.1016/8756-3282(94)90319-0. [DOI] [PubMed] [Google Scholar]