AbstractWe 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,p5 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 elemen