Recent experience from different groups suggests that low
fluoride doses resulting in moderate increases in bone mineral density (BMD) may be advantageous in terms of fracture-reducing potency. In a randomized prospective 3-year study we examined the therapeutic efficacy of different dosages of
monofluorophosphate (MFP) plus
calcium in comparison with
calcium alone in 134 women with established
postmenopausal osteoporosis (mean age 64.0 years, average vertebral fractures per patient 3.6). Group A received 1000 mg
calcium/day and a low-dose intermittent MFP regimen (3 months on, 1 month off) corresponding to an average daily
fluoride ion dose of 11.2 mg. Group B received 1000 mg
calcium/day plus continuous MFP corresponding to 20 mg
fluoride ions per day. Group C was treated with 1000 mg
calcium alone throughout the study period. Bone density was measured with dual-energy X-ray absorptiometry at L2-4 and three proximal femur areas and with single photon absorptiometry at two radius sites. New vertebral fractures were identified from annual lateral radiographs of the spine. A significant reduction in subjective complaints as measured by a combined
pain-mobility score (
CPMS) was found in both
fluoride groups in comparison with the
calcium monotherapy group. Group A showed increases in BMD at all six measuring sites, reaching +12.6% at the spine after 3 years. In group B we found significant increases at the spine, Ward's triangle and distal radius, but slight decreases at the femoral neck and radius shaft. For the spine the average change amounted to +19.5% after 3 years. In group C losses of BMD were observed at all six sites, with an average loss of 1.6% for the spine at the end of the study. The incidence of new vertebral fractures per 100 patient-years was 8.6, 17.0 and 31.6 in groups A, B and C, respectively. In conclusion, both
calcium-MFP regimens resulted in significantly lower vertebral fracture rates than
calcium monotherapy. However, the low intermittent MFP regimen, leading to a mean annual increase in spinal BMD of only 4.2%, showed a clear trend to greater effectiveness in reducing vertebral fracture than the higher
fluoride dosage that was followed by an average spinal BMD increase of 6.5% per year. Furthermore the rate of
fluoride-specific side effects (lower-extremity
pain syndrome) was 50% lower in patients receiving the lower
fluoride dosage.