AbstractIn this study, the relationship between fluoride pharmacokinetics and the response in spinal bone density to fluoride treatment was studied in 14 patients with primary osteoporosis treated with fluoride for at least 1 year. Serum concentrations and urinary excretion of fluoride were determined after ingestion of 10 mg fluoride as monofluorophosphate. The pharmacokinetic parameters were calculated according to a linear one‐compartment open model. The fasting serum fluoride level was 8.8 ± 0.98 μmol/liter. The peak serum fluoride level was 20.5 ± 1.4 μmol/liter and was reached within 2 h after ingestion of fluoride. When the patients were divided into good and poor responders, based on whether they did or did not exhibit a change in spinal bone density of 13 mg/cc per year or more, we found that good responders had decreased renal fluoride clearance (−62 ± 13%,p<.02), increased maximum change in serum fluoride (+38 ± 18%,p<.01), increased extrarenal clearance (+62 ± 57%,p<.05) and increased change in serum alkaline phosphatase (ALP) (+241 ± 169%,p<0.02) compared with poor responders. Our data suggest that one factor accounting for a good response is a relatively high serum level of fluoride. However, although the maximum change in serum fluoride was greater in good responders compared with poor responders, variations in fluoride levels could not explain all of the variation in spinal bone density. Therefore, we propose that in addition to differences in serum fluoride, other factors are also responsible for the go