T-score was calculated based upon the database from nationwide survey [13]. A central facility performed quality assurance of the Crizotinib purchase longitudinal adjustment, by calibrating each machine with standardized phantoms. All DXA measurements were analyzed at a central site by a radiologist blinded to treatment group assignment. Serum and postprandial urine samples were collected at baseline, 0.5, 1, and 2 months, and every second month thereafter until 36 months for routine analyses, including Ca concentrations. At baseline, 6, 12, 24, and 36 months, we determined serum bone-specific alkaline phosphatase (BSAP) (Metra-BAP EIA; Quidel, San Diego, CA; reference range 7.9 to 29.0 U/L)

and urinary type I collagen N-telopeptide (NTX) (Osteomark; Inverness Medical

Innovations, Waltham, MA; reference range 9.3 to 54.3 nmol BCE/mol Cr) as bone turnover markers, and 25(OH)D (HPLC-competitive protein binding assay), 1,25(OH)2D (HPLC radioreceptor assay) and intact parathyroid hormone (PTH) (Eclusys PTH, Roche Diagnostics, Penzberg, Germany) as calcium-regulating hormones. Nichols Allegro Lite was used for the measurement of 25(OH)D only at enrollment, because manufacturing of the kit was discontinued thereafter. Regression analysis between the two measurements revealed that there was a linear relationship between the 25(OH)D values from HPLC-competitive binding assay (y) and Nichols Allegro Lite assay (x): y = 1.016x + 4.555. DAPT If increase in serum Ca over 11.0 mg/dL (2.75 mmol/L) developed, or if increase in serum Ca over 10.4 mg/dL (2.6 mmol/L) along with urinary Ca over 0.4 mg/dL GF (0.1 mmol/L GF) developed, treatment was discontinued. If serum Ca in these patients subsequently decreased to below 10.4 mg/dL (2.6 mmol/L) and urinary Ca decreased to below 0.4 mg/dL GF (0.1 mmol/L GF), treatment was resumed with reduced doses 3-mercaptopyruvate sulfurtransferase (0.5 μg eldecalcitol and alfacalcidol). Fifteen patients in eldecalcitol group, and 12 patients in alfacalcidol group discontinued treatment. Among them, all 15 patients in eldecalcitol group and 9 patients in alfacalcidol

group resumed treatment with reduced doses. Compliance with the study treatment was assessed with the use of medication diaries and counts of residual medication supplies. All patients were questioned about adverse events at each visit, and all adverse events were analyzed regardless of the investigators’ assessments of causality. The Medical Dictionary for Regulatory Activities (MedDRA, Version 8) was used to categorize reported adverse events. All randomized patients who took any dose of a study drug were included in the safety analysis, and all randomized patients with drug administration who had a baseline assessment and at least one post-randomization assessment were included in the efficacy analysis (Fig. 1). Analysis of vertebral fracture incidence included patients who underwent radiography at baseline and at least once during the study period.