During FIRST, the calcium and vitamin D status of all women was assessed, and they were given daily supplements of up to 1,000 mg of elemental calcium and up to 800 IU of vitamin D for a period of 2 weeks to 6 months. Supplementation doses and duration were adjusted for each patient according to their baseline calcium and 25-OH vitamin D status. After the run-in period, eligible women were proposed for enrolment in either the SOTI or TROPOS studies,
and supplementation was continued at the same doses throughout the randomised treatment periods of both these studies. The SOTI study included women ≥50 years of age with low lumbar BMD (<0.840 g/cm2 measured with Hologic instruments, T-score ≤−2.4) and at least one prevalent BIBW2992 datasheet vertebral fracture confirmed by spinal radiography. The TROPOS study included women with femoral
neck BMD <0.600 g/cm2 and aged ≥74 years or 70–74 years with one additional risk factor (history of osteoporotic fracture after menopause, residence in a retirement home, frequent falls or maternal history of osteoporotic fracture of the hip, spine or wrist). Study design and efficacy measurements Patients were randomised to receive strontium ranelate 2 g/day or placebo for 5 years (TROPOS) AZD5363 nmr or 4 years followed by a 1-year treatment-switch period (SOTI). In both studies, main efficacy analyses were performed at 3 years, and the vertebral fracture data over 3 years were used for the present analysis. Baseline refers to the commencement of the SOTI and TROPOS studies, Ponatinib clinical trial not the time of inclusion in FIRST. Vertebral fractures were determined from radiographs taken at baseline and annually thereafter and were analysed in the same way in both studies. Radiographs were analysed by the semi-quantitative method of Genant et al. [22, 23], using a four-point grading scale: grade 0—normal; grade 1—mild deformity (20–25% decrease in at least one vertebral height); grade 2—moderate deformity (25–40% decrease); and grade 3—severe deformity (>40% decrease). A new vertebral fracture was defined as a change
from a non-fractured vertebra (grade 0) to a vertebra rated grade 1 or higher. All radiographs were analysed at a central facility (CEMO, France) blinded to treatment assignment but not to temporal sequence. Lumbar L2–4 and femoral neck BMD were measured at baseline, and lumbar BMD was measured every 6 months post-baseline by dual-energy X-ray absorptiometry using Hologic devices. All scans were analysed centrally, and a programme of cross-calibration across centres was performed throughout both studies . Blood samples were collected at baseline, 3 months, 6 months, and then every 6 months. Serum samples were stored at −80°C and analysed centrally after a maximum 6 months period of storage (University of Liège, Belgium).