Patients and Methods

In our randomized prospective study we included 145 postmenopausal women with established osteoporosis. The patients were recruited from our outpatients who fulfilled the criteria of being postmenopausal women not older than 75 years with primary generalized osteoporosis (BMD at L2-4: T-score < -2.5) presenting at least one osteoporotic vertebral fracture. Patients with a disorder or a medication that might significantly influence bone metabolism were excluded from the study. The patients were randomly assigned to three groups: Group A received 1000 mg Ca/day intermittently 114 mg, MFP, equal to 15 mg, fluoride, in a schedule of 3 months on followed by I month off, corresponding to an average daily fluoride dose of 11.2 mg over the whole year. Group B received 1000 mg Ca/day and continuously 152 mg MFP, corresponding to 20 mg, fluoride per day. Group C was treated only with 1000 mg- Ca/day. At enrolment and every 6 months thereafter BMD was measured by a technician masked to the therapy with dual-energy X-ray absorptiometry (DXA) at L2-4 and at three sites in the femur (femoral neck, Ward's triangle and trochanter). BMD at the distal radius (radius 1/10) and shaft of the radius (radius 1/3) of the nondominant arm was measured with single photon absorptiometry (SPA). Lunar densitometers (Madison, WI) were used for all BMD studies. All BMD finding at enrollment were expressed as T-scores and the variation observed during treatment expressed as percent-ages of the baseline value. Vertebral fractures were identified on lateral radiographs of the thoracic and lumbar spine at the start of the study and every 12 months thereafter. New fractures were diagnosed by an independent radiologist (masked to the therapy) if the measured anterior, median or posterior height of a vertebra was reduced by >20% with respect to baseline findings. At enrollment and every 6 months a physical examination of the patient, laboratory tests, and an evaluation of parameters such as blood pressure, heart rate and weight were performed. Patients were questioned as to their habits with regard to sports, smoking drinking and eating. Non vertebral fractures and coexisting disorders were documented. Compliance and subjective complaints such as back pain (at rest, with movement and after load), mobility and use of analgesics were recorded using a four-point scale to rate each parameter. The sum of the individual scores was calculated to obtain a combined pain-mobility score (CPMS). See Table 1 The initial characteristics of the patients are shown in The following analyses were by intention to treat, including all 134 patients achieving at least the first control visit after month 6. All available data on efficacy and tolerability were subjected to statistical analysis. Differences between changes in the BMD and fracture rates were evaluated with ANOVA and the Mann- Whitney U-test (two-sided). Descriptive statistical analysis was used for all other data.