Sodium fluoride therapy of postmenopausal osteoporosis

More than 30 yr of research has clearly established sodium fluoride as the most potent agent currently available for increasing spinal bone mass. The increase is dose-dependent and linear with time for at least 6 yr, probably as long as 10 yr. This is in keeping with observed pharmacological actions of fluoride to enhance recruitment of osteoblasts and matrix deposition without any consistent effect on bone resorption. Unfortunately this has not translated into therapeutic efficacy in terms of preventing the VFR in patients who are already fractured at the initiation of therapy. Whether fluoride will be effective in preventing the first fracture is currently being investigated. If successful in this regard it will not only be extremely useful as prophylaxis against osteoporotic vertebral fractures, but will also provide substantial insight into the pathogenesis of these fractures and the management of patients seen after the first or subsequent fracture. We predict that fluoride will turn out to be extremely useful for prophylaxis. Whether or not lower doses or intermittent fluoride therapy will prove to be effective in patients who have already sustained fractures, is also being actively investigated in controlled clinical trials. Given the difficulty in demonstrating therapeutic efficacy over the past 30 yr, with favorable outcomes only reported from uncontrolled studies, we are not as optimistic about these investigations. Side-effects of NaF are becoming more clearly understood and easier to manage. The gastrointestinal symptoms are short-lived and dependent on the dose and formulation. These symptoms infrequently prohibit the use of the drug. The painful lower extremity syndrome appears to us to represent a 'positive' response to NaF, reflecting abundant formation of new bone that is poorly mineralized. If detected on the basis of symptoms, therapy should be interrupted for 6-8 weeks, then restarted at a lower dose. This syndrome, while clearly related to NaF, appears to be idiosyncratic and not dose or formulation dependent. The data relating NaF to hip fractures cannot be completely ignored because of the major community health problem posed by hip fractures. However, the data are largely anecdotal. Putting all this together, we feel that there may be an important role for NaF in osteoporosis treatment but, for now, its use should be restricted to properly conducted controlled clinical trials.