Bone alkaline phosphatase (bALP) was assayed by immunoradiometric assay (Tandem®-R

Ostase®, Beckman Coulter, formerly Hybritech, San Diego, CA, USA), and serum C-telopeptide GSK2118436 in vivo cross-link of type I collagen (sCTX) was assayed using an enzyme-linked immunosorbent assay (serum CrossLaps®ELISA—Nordic Bioscience Diagnostic, formerly Osteometer BioTech, Herlev, Denmark). Parathyroid hormone was assessed with an immunoradiometric assay (N-tact®PTH SP IRMA, Diasorin, USA). QoL was assessed using self-administered questionnaires: the Short-Form 36 (SF-36®), a widely used generic 36-item instrument [23], and QUALIOST®, a disease-specific 23-item instrument designed to complement the SF-36® in postmenopausal patients with vertebral osteoporosis [24]. Both questionnaires were completed

every 6 months throughout the trial. In the SF-36®, items are grouped into eight dimensions, ACP-196 cell line which were further combined into summary scores for mental and physical 4SC-202 chemical structure components. In each case, scores range from 0 to 100, with higher scores indicating better QoL. QUALIOST® contains two dimensions, physical (10 items) and emotional (13 items). Scores again range from 0 to 100, higher scores indicate greater impairment of QoL. One QUALIOST® item (physical dimension item 6) relates specifically to back pain. The QUALIOST® cross-cultural validity and responsiveness have been validated using earlier (3-year) data from the present (SOTI) trial [25]. Statistical analysis Randomized assignment of treatment was stratified by country and performed using permutation blocks with a fixed size of four. All these pre-planned efficacy analyses were performed in accordance with the intention-to-treat Cyclic nucleotide phosphodiesterase (ITT) principle. For the M0–M48 period, ITT population for fracture incidence analysis was defined as all randomized patients who took at least one sachet of study drug and with (at least two) X-ray assessments between M0 and M48. For the M48–M60 period, ITT population was

defined as all patients who performed the M48 visit, took at least one sachet of study drug between M0 and M48 and after M48, with validated L2–L4DXA measurements at M0 and M48, and post M48. The ITT population for QoL analysis comprised patients from the ITT population who had at least one assessable SF-36® (i.e., <50% missing data) and one assessable QUALIOST® completed at baseline, plus at least one assessable SF36® and one assessable QUALIOST® completed post baseline (>12 months, until 4 years of treatment). For the 4-year analysis, the incidence over time of patients with at least one new osteoporotic vertebral fracture and new clinical vertebral fracture were analyzed by Kaplan–Meier method.