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

SummaryThis 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.IntroductionThe 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.MethodsThis 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.ResultsA 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.ConclusionsALN/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.

Effects of alendronate and alfacalcidol on bone in patients with myasthenia gravis initiating glucocorticoids treatment

“…Few studies had evaluated the effects of vitamin D or calcium supplements on urinary calcium levels. Zhenlin Zhang found 8.4% and 13.9% of patients developed hypercalciuria in postmenopausal osteoporosis patients treated with ALN/D5600 or calcitriol 0.25 μg/d plus calcium 500 mg/d for 12 months, respectively . In patients treated with GCs, the incidence of hypercalciuria was higher than postmenopausal women.…”

Calcifediol (25-hydroxyvitamin D) improvement and calcium-phosphate metabolism of alendronate sodium/vitamin D3 combination in Chinese women with postmenopausal osteoporosis: a post hoc efficacy analysis and safety reappraisal

“…The combination of bisphosphonate and vitamin D analog shows a synergistic effect on skeletal and muscular systems, which is possibly due to the difference in the mode of action between these two regimens [ 13 ]. The previous randomized, controlled study conducted by the investigators also revealed that the ALN/D5600 combination was superior to calcitriol alone in PMO women with respect to BMD gain and bone turnover reduction [ 9 ]. Moreover, a subgroup analysis confirmed the difference in predictive factors for BMD response after 12-month treatment with ALN/D5600 vs. calcitriol [ 10 ].…”

“…The original study was a 6-month, randomized, open-label, active-comparator-controlled, parallel-group study with a 6-month extension to evaluate the efficacy and safety of weekly ALN/D5600 as a combination tablet vs. 0.25 μg of calcitriol daily in the treatment of osteoporosis in postmenopausal women in China (protocol number 264–01, clinicaltrials.gov number NCT01350934). The study protocol, design and inclusion/exclusion criteria were as previously reported [ 9 ]. Briefly, eligible patients were patients who were > 55 years of age and postmenopausal for at least one year, with no prior antiresorptive therapies, patients who had no prior hip fracture, patients who had no pronounced medical history other than osteoporosis, and patients had no uncontrolled primary/secondary hyperparathyroidism (as examined by iPTH at screening) or evidence of metabolic bone disease other than postmenopausal osteoporosis.…”

“…A possible explanation is that loss of bone mass in postmenopausal women results from multiple factors such as ageing, decreased estrogen, obesity and other comorbidities [ 8 ]. However, the previous randomized, controlled study conducted by the investigators demonstrated that a weekly dose of alendronate sodium with vitamin D 3 (ALN/D5600) was superior to 0.25 μg of calcitriol (1,25(OH) 2 D) daily, which is an active derivative of vitamin D 3 , with respect to lumbar spine bone mineral density (BMD) and bone turnover markers (BTMs) [ 9 ]. The further post hoc analysis performed by the investigators revealed that ALN/D5600 was more beneficial for patients with lower baseline serum C-terminal telopeptide (s-CTx) or greater on-treatment s-CTx decrease, in terms of lumbar spine BMD improvement, when compared with calcitriol, which is more beneficial for patients with lower baseline serum vitamin D or prior vertebral fracture [ 10 ].…”

Clinical characteristics associated with bone mineral density improvement after 1-year alendronate/vitamin d3 or calcitriol treatment

“…[ 6 – 8 ] A previous randomized, open label, controlled study demonstrated in Chinese postmenopausal women with osteoporosis that weekly alendronate 70 mg/vitamin D 3 5600 IU (ALN/D5600) resulted in a significantly greater increase in lumbar spine BMD (LS-BMD) and a greater reduction in bone turnover marker (BTM) measurements than daily 0.25 μg calcitriol alone within 1 year, although the benefit regarding the reduction in fracture risk remains to be investigated. [ 9 ]…”