Journal of Bone and Mineral Research

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Abstract
We report on 61 women with postmenopausal osteoporosis who were treated with either plain sodium fluoride (NaF) capsules or enteric‐coated NaF tablets for 4 years, in whom possible therapeutic and toxic effects were monitored. In these patients there was a mean increase in axial bone mineral mass, assessed by neutron activation analysis, of 26.2% ± 2.4% (SEM) during the 4 years. This corresponds to a decrease in the bone deficit (compared with reference values) of 48.6%. The response was linear over 4 years. The main predictors of the osteogenic response were bone fluoride (r = 0.52, p < 0.01), serum fluoride (r = 0.50, p < 0.01), and age (0.39, p < 0.01). Patients over 65 years of age achieved higher bone fluoride (F) levels and a significantly greater increase in bone mineral than younger patients (32.8 vs. 17.9%, p < 0.01), associated with an age‐related decline in renal function; serum fluoride was significantly and negatively correlated to creatinine clearance (r = −0.52, p < 0.01). Although the effect of NaF on fracture rate could not be assessed in this uncontrolled study, the major factors associated with the occurrence of new vertebral fractures were the number of vertebral fractures and the bone mineral mass at the beginning of therapy. There was no correlation between vertebral fracture rate and serum or bone fluoride or other parameters of the osteogenic response, but patients who did not experience new vertebral fractures achieved a normal bone mineral content sooner than those who had new fractures during therapy. Only 18% of patients did not respond with an increase in bone mineral. These patients had significantly lower serum fluoride levels, and were significantly younger, with better renal function. The data suggest that younger patients may need a somewhat higher dose of fluoride to achieve the same effect. Side effects were tolerable for most patients. Gastrointestinal (GI) side effects were significantly reduced by the use of an enteric‐coated preparation; very mild, transient GI side effects occurred in 11.1% of patients so treated. Transient lower extremity pain occurred in 9 patients (14.7%), and an additional 4 patients had transient symptoms from lower extremity stress fractures. Another 7 patients had femoral neck fractures during treatment. NaF causes a sustained, long‐term increase in bone mineral with acceptable side effects in most patients. The dose of fluoride should be optimized individually for each patient on the basis of serum fluoride > 5 μmol/liter), histological effects of fluoride (or bone fluoride), and toxicity. The mean dose of enteric‐coated tablets required to achieve a histologic fluoride effect (hyperosteoidosis) in 88% of patients so treated was 42.6 mg/day (19.3 mg elemental fluoride).
Funding Information
  • Canadian Geriatrics Research Society
  • Queen Elizabeth Hospital Research Institute
  • St. Joseph's Health Centre Research Foundation.