SIDE EFFECTS OF SODIUM FLUORIDE THERAPY

The experts in sodium fluoride treatment of otosclerosis suggest a skeletal survey of the patient, which should be made at the beginning of treatment and repeated every two years, for there is the remote possibility of skeletal fluorosis being produced.  Shambauch has observed radiological evidence of early fluorosis, of the spine in 0,25% of his cases and this condition is reversible when therapy was continued.

          Disturbance, as a result of the production of  hydrofluoric acid in the stomach, is the most common side effect and this is largely prevented by enteric coated tablets of sodium fluoride.  Patients with peptic ulcer may rarely complain of a flare-up of their symptom and the treatment must    stopped.

In some patients with chronic arthritis there may be an increase of the joint symptoms but with cessation of treatment a return to the previous state occurs within a few weeks.  Permanent harm to the patient has never resulted from sodium fluoride therapy and a desirable side effect, in the older age group, is a reduction in the incidence of osteoporosis and the occurrence of fractures.

RESULTS OF TREATMENT WITH SODIUM FLUORIDE

Shambauch and Cause ⁽⁵⁾ reported the results of treatment with sodium fluoride of more than 4000 patients, from the practices of each of the auth  over a ten year period The result is surgically confirmed stapedial fixation due to otosclerosis and in a pure cochlear otosclerosis, were fairly uniform and showed that in about 80% of cases the sensorineural component of the hearing loss was stabilized.  There were a few patients who showed a slight but significant recovery of sensorineural hearing.  The remainder continued to show slow progression of the sensorineural deafness and there was a smaller control group of cases, who did not receive the treatment, where the progression of the sensorineural hearing loss occurred in a much higher percentage than in the treated cases.

Shambauch and Causse believe that about 25% of patients without therapy will show spontaneous stabilization of the sensorineural hearing loss and the remaining 75% wills how progression of the sensorineural hearing loss if they do not receive medical treatment.

The authors noticed that there were a few patients who responded favorably to sodium fluoride, with stabilization of the demineralized focus, but a few years after discontinuing the fluoride there was reappearance of a demineralized focus and an increase of the sensorineural hearing loss, indicating reactivation of the lesion.  In order to prevent this phenomenon they prescribe a maintenance dose of 20 mg daily for the rest of the patient's life once the focus has become nature and inactive.

Causse and Chevance ⁽¹⁾ demonstrated that in addition to the known effects of sodium fluoride on the calcification of the focus there may also be an antienzymatic effect, which neutralizes the cytotoxic enzyme, or enzymes, which may produce sensorineural hearing loss.

Sensorineural hearing loss is common in otosclerosis.  It develops insidiously over the years whether the patient has had a stapedectomy operation or not; and it fro    the result of a successful stapedectomy and compels the patient to use a hearing aid.  It is possible that an unknown number of persons may have a slowly progressive hearing loss which is not the result of presplyacusis but is caused by undetected cochlear otosclerosis and this be stabilized an any early stage if fluoride therapy is used.  The reluctance of some doctors to prescribe moderate doses of sodium fluoride for otosclerosis is presumably due partly to unknown toxic effects of prolonged medication with fluoride and partly to the known cases of severe crippling skeletal fluorosis seen in certain parts of the world where the drinking water has a very high fluoride content and manual laborers in the hot sun consume large quantities of water.

According to W.H.O. 1970 there has not been a single case reported of permanent harm to a patient from moderate dosage of sodium fluoride therapy.

Unfortunately there is still widespread prejudice and almost  an emotional dislike of fluoride therapy by many members of the medical profession, which is not justified and   due to ignorance about the facts of this form of treatment. 

TREATMENT OF OTOSCLEROSIS WITH DIPHOSPHONATES

Several investigators suggest diphosphonates for the treatment of Otosclerosis as inhibitor agents of bone resorption (e.g. etidronate).  The efficacy of etidronate, was assessed as a treatment for the inner ear symptoms, of otosclerosis in a retrospective study, with primary complain of dizziness, hearing loss, tinnitus or Menier's syndrome ⁽¹⁰⁾. The diagnosis of otosclerosis was based no small-pixel computed tomography of the temporal bones.  Of the 896 patients on an etidronte protocol, 545 were followed for more than sic months and were analyzed.  The symptomatic response to editronate, as well as audiologic and computerized rotary chair results were used in the assessment.  Patients who were previously on Sodium Fluoride were separately analyzed.  In this preliminary study etidronate appeared to be ant effective treatment for the new neurootologic symptoms of otosclerosis.  Prospective blinded efficacy studies of the bisphosphonates in the treatment of otosclerosis should be unclear taken.

A  2-year prospective double-blind study was performed by Kennedy DW, et al (1993) (17) to evaluate the role of etidronate disodium for the treatment of progressive hearing loss in patients with otosclerosis. A pulsed dosage regimen was used during the 2-year period and the patients were followed up with otologic and audiometric examinations. Although statistically significant differences were not achieved between the study and control groups, the study did reveal a trend toward stabilization or improvement in air conduction thresholds in some frequencies (1000 and 4000 Hz) and in bone conduction thresholds at other frequencies (500, 1000, and 2000 Hz). The incidence of adverse side effects was similar in the treatment and control groups. Although no definite conclusions can be drawn from this pilot study, the findings provide encouragement for performing a larger and longer-term study                           

LITERATURE 

1)       Causse J. and Chevance L.G. Bases biologique d' un traitement fluore de l' otospongiose Ann. Otol. Chir. Cervicofac. 1973, 90, 139.

2)       Petrovic A. and Shambaugh G.E. Jr. Promotion of bone calcification by sodium fluoride.  Arch. Otolaryngol. 1966b, 83, 12.

3)       Causse J.R. et al. Etiology of otospongiotic sensorineural losses.  American journal of Otology, 1998, 10 (2): p, 99-107.

4)       Shambauch G.E. Jr.  Sensorineural deafness due to cochlear otospongiosis: pathogenesis, clinical diagnosis and therapy Otolaryng. Clin. N. Amer. 1978: 2, 135.

5)       Shambauch G.E. Jr. and causse J. Ten years' experience with fluoride in otosclerotic (otospongiotic) patients.  Ann. Otol. 1974 : 83 : 635.

6)       Colleti V, Fiorino FG Effect of sodium fluoride on early stages of otosclerosis.  Am J. Otol. 1991 : 12 (3) : 195-8.

7)       Linthicum F.H., Jr Histopathology of otosclerosis, Otolaryngologic clinics of North America, 1993 26(3) : p 335-52.

8)       Shambauch G.E. Glasscock M.E. Surgery of the ear p. 474, N.B. Sounders Co. Philodelphia, 1980.

9)       Wiet, R.J. W. Raslan, and G.E. Shambaugh Jr, Otosclerosis 1981 to 1985.  Our four-year review and current perspective.  American journal of Otology, 1986.7(3): p. 221-8.

10)    Brookler KH, Tanyeri H. Etidronate for the neurotologic symptoms of otosclerosis: preliminary study.  Ear.  Nose Throat J. 1997 Jun; 76(6): 371-6, 379-81.

11)    Vartiainen E, Vartiainen J. : Effect of drinking water fluoridation on the prevalence of otosclerosis.  Journal of Laryngology and Otology 111(1) : 20-2 1997

12)    Jan Hodsman A., Adach J, Olszynski W : prevention and management of osteoporosis : consensus statement from the Scientific Advisory Board of the Osteoporosis Society of Canada 6 Use of bisphosphonates in the treatment of osteoporosis.  Canadian Medical Association Journal 1996 ; 155 (suppl) : 945-948. 

13)    Vartiainen E. Vartiainen J., The influence of fluoridation of drinking water or the long-term hearing results of stapedectomy.  Clinical Otolaryngology and Applied Sciences 22(1) : 34-6, 1997 Feb.

14)    W.H.O. (1970). Fluorides and Human Health. Geneva: World Health Organisation.

15)    Derks W, De Groot JA, Raymakers JA, Veldman JE.  Fluoride therapy for cochlear otosclerosis? an audiometric and computerized tomography evaluation. Acta Otolaryngol. 2001 Jan;121(2):174-7.

16)    Grayeli AB, Escoubet B, Bichara M, Julien N, Silve C, Friedlander G, Sterkers O, 

     Ferrary E. Increased activity of the diastrophic dysplasia sulfate transporter in  

     otosclerosis and its inhibition by sodium fluoride. Otol Neurotol. 2003

     Nov;24(6):854-62.

17)    Kennedy DW, Hoffer ME, Holliday M.The effects of etidronate disodium on

     progressive hearing loss from otosclerosis. Otolaryngol Head Neck Surg. 1993

     Sep;109(3 Pt 1):461-7.