4 mg/dL (2.6 mmol/L) or urinary Ca excretion of over 0.4 mg/dL glomerular filtrate (GF) (0.1 mmol/L GF); had serum creatinine above 1.3 mg/dL (115 μmol/L); or had clinically significant hepatic or cardiac disorders. The protocol was approved by the internal human studies review board at each center, and informed consent was obtained Selleckchem PD332991 from each patient. Patients who satisfied all eligibility criteria were randomly assigned in a 1:1 ratio to receive eldecalcitol or alfacalcidol. Treatment was assigned by use of dynamic allocation, via a central
enrollment center. The randomization sequence was created by the person responsible for investigational product randomization. Randomization was stratified by study site with minimization for 25(OH)D level (< 50 nmol/L, ≥ 50 nmol/L) at provisional enrollment. Both patients and investigators were masked to treatment assignment throughout the study follow-up. The primary end point was incident vertebral fractures. Secondary end points included any non-vertebral fractures, changes in bone mineral density of the total hip and lumbar spine,
and changes in bone turnover markers. All investigators who performed end point evaluations were unaware of the study-group assignments of Aprepitant patients. Lateral radiographs of the thoracic and lumbar spine were taken at baseline and at 6, 12, 24, and 36 months IWR-1 mouse or at termination. Three expert investigators independently evaluated vertebrae from T4 to L4. Prevalent fractures were assessed semiquantitatively as grades 0 to 3 [15]. Incident vertebral fractures were diagnosed quantitatively if the anterior, posterior, or middle vertebral height had decreased by at least 15% and by ≥ 4 mm in a vertebra that was assessed at baseline as grade 0, 1, or 2 [16]. If the investigators’
assessments disagreed, the final assessment was made after conference by all the investigators. Seven subgroups due to age, serum 25(OH)D, the presence or absence, the number, and the semi-quantitative grade of prevalent vertebral fractures, lumbar spine BMD, and total hip BMD were predefined to test for interaction. All non-vertebral fractures were identified symptomatically as clinical fractures. Suspected non-vertebral fractures without excessive trauma assessed centrally were confirmed radiographically. Subgroup analyses were predefined at major six non-vertebral sites (clavicle, humerus, wrist, pelvis, hip and leg) and major three non-vertebral sites (humerus, wrist and hip).