Alendronate sodium/vitamin D3 combination tablet versus calcitriol for osteoporosis in Chinese postmenopausal women: a 6-month, randomized, open-label, active-comparator-controlled study with a 6-month extension

Abstract

This study compares efficacy of ALN/D5600 versus that of calcitriol in osteoporotic Chinese postmenopausal women. ALN/D5600 produced greater bone mineral density (BMD) increases, greater bone turnover marker decreases, and less vitamin D insufficiency. This study provided detailed clinical information regarding ALN/D5600 treatment versus calcitriol 0.25 μg/day. The study did not evaluate fracture risk.

Introduction: The aim of this study is to investigate efficacy of alendronate 70 mg/vitamin D3 5600 IU combination tablets (ALN/D5600) versus calcitriol in osteoporotic Chinese postmenopausal women.

Methods: This study is a 6-month, randomized, open-label, active-comparator study with 6-month extension (clinicaltrials.gov number NCT01350934) in postmenopausal women aged >55 years with osteoporosis (low bone mineral density (BMD) with/without prior fragility fracture). Patients were randomized to ALN/D5600 once weekly or calcitriol 0.25 μg daily. The primary efficacy end point of the base study was percent change from baseline in lumbar spine BMD (month 6). Hypercalcemia and hypercalciuria were safety events of special interest.

Results: A total of 219 patients (ALN/D5600 n = 111, calcitriol n = 108) were randomized. Baseline characteristics were similar, 30.3 % baseline 25-hydroxyvitamin D (25(OH)D) ≤15 ng/mL. At months 6 and 12, changes in lumbar spine BMD from baseline were 3.5 versus 1.6 % and 5.2 versus 2.3 % for ALN/D5600 versus calcitriol (between-group differences p < 0.001), respectively. Between-group differences for ALN/D5600 versus calcitriol were significant (p < 0.001) at months 6 and 12 for change from baseline in procollagen type 1 N-terminal propeptide (-59.1 versus -16.8 %, -68.1 versus -17.0 %) and serum C-telopeptides (-79.2 versus -27.2 %, -76.2 versus -24.2 %). Drug-related adverse events (AEs) and discontinuations due to drug-related AEs occurred in 15 (14.0 %) versus 8 (7.4 %) patients and 3 (2.8 %) versus 0 patients in the ALN/D5600 and calcitriol group, respectively. Hypercalciuria 12-month incidence (24-h urine Ca >300 mg) was 8.4 (ALN/D5600) versus 13.9 % (calcitriol) (p > 0.05). One patient (calcitriol) had hypercalcemia.

Conclusions: ALN/D5600 produced greater increases in lumbar spine BMD and greater decreases in bone turnover markers versus calcitriol in osteoporotic Chinese women. It is not known whether the greater increase in BMD results in fewer fractures. ALN/D5600 was generally well tolerated in Chinese patients.

Fig. 1

Patient disposition. ALN/D5600 combination tablet of alendronate 70 mg plus vitamin D₃ 5600 IU once weekly

Fig. 2

Percent change from baseline in BMD at a the lumbar spine, b total hip, c femoral neck, d and trochanter, at months 6 and 12 (FAS). ALN/D5600 combination tablet of alendronate 70 mg plus vitamin D₃ 5600 IU once weekly, BMD bone mineral density, FAS full analysis set, SE standard error

Fig. 3

Percent change from baseline in bone turnover markers: a P1NP and b s-CTx (FAS). ALN/D5600 combination tablet of alendronate 70 mg plus vitamin D₃ 5600 IU once weekly, CI confidence interval, FAS full analysis set, LS least squares, P1NP procollagen of type 1 N-terminal propeptide, s-CTx C-telopeptides of type 1 collagen

Fig. 4

Changes from baseline in serum 25(OH)D concentrations after treatment with ALN/D5600 or calcitriol (FAS). ALN/D5600 combination tablet of alendronate 70 mg plus vitamin D₃ 5600 IU once weekly, FAS full analysis set, SE standard error, 25(OH)D 25-hydroxy vitamin D. *Post hoc analysis: two-sample independent t test without adjustments for covariates