Efficacy and safety of weekly alendronate plus vitamin D₃ 5600 IU versus weekly alendronate alone in Korean osteoporotic women: 16-week randomized trial

Kwang Joon Kim, Yong-Ki Min, Jung-Min Koh, Yoon-Sok Chung, Kyoung Min Kim, Dong-Won Byun, In Joo Kim, Mikyung Kim, Sung-Soo Kim, Kyung Wan Min, Ki Ok Han, Hyoung Moo Park, Chan Soo Shin, Sung Hee Choi, Jong Suk Park, Dong Jin Chung, Ji Oh Mok, Hong Sun Baek, Seong-Hwan Moon, Yong Soo Kim, Sung-Kil Lim, VALUE study group, Kwang Joon Kim, Yong-Ki Min, Jung-Min Koh, Yoon-Sok Chung, Kyoung Min Kim, Dong-Won Byun, In Joo Kim, Mikyung Kim, Sung-Soo Kim, Kyung Wan Min, Ki Ok Han, Hyoung Moo Park, Chan Soo Shin, Sung Hee Choi, Jong Suk Park, Dong Jin Chung, Ji Oh Mok, Hong Sun Baek, Seong-Hwan Moon, Yong Soo Kim, Sung-Kil Lim, VALUE study group

Abstract

Vitamin D (vit-D) is essential for bone health, although many osteoporosis patients have low levels of 25-hydroxy-vit-D [25(OH)D]. This randomized, open-label study compared the effects of once weekly alendronate 70 mg containing 5600 IU vit-D₃ (ALN/D5600) to alendronate 70 mg without additional vit-D (ALN) on the percent of patients with vit-D insufficiency [25(OH)D <15 ng/mL, primary endpoint] and serum parathyroid hormone (PTH, secondary endpoint) levels in postmenopausal, osteoporotic Korean women. Neuromuscular function was also measured. A total of 268 subjects were randomized. Overall, 35% of patients had vit-D insufficiency at baseline. After 16-weeks, there were fewer patients with vit-D insufficiency in the ALN/D5600 group (1.47%) than in the ALN group (41.67%) (p<0.001). Patients receiving ALN/D5600 compared with ALN were at a significantly decreased risk of vit-D insufficiency [odds ratio=0.02, 95% confidence interval (CI) 0.00-0.08]. In the ALN/D5600 group, significant increases in serum 25(OH)D were observed at weeks 8 (9.60 ng/mL) and 16 (11.41 ng/mL), where as a significant decrease was recorded in the ALN group at week 16 (-1.61 ng/mL). By multiple regression analysis, major determinants of increases in serum 25(OH)D were ALN/D5600 administration, seasonal variation, and baseline 25(OH)D. The least squares mean percent change from baseline in serum PTH in the ALN/D5600 group (8.17%) was lower than that in the ALN group (29.98%) (p=0.0091). There was no significant difference between treatment groups in neuromuscular function. Overall safety was similar between groups. In conclusion, the administration of 5600 IU vit-D in the ALN/D5600 group improved vit-D status and reduced the magnitude of PTH increase without significant side-effects after 16 weeks in Korean osteoporotic patients.

Keywords: Alendronate; osteoporosis; parathyroid hormone; vitamin-D; vitamin-D insufficiency.

Conflict of interest statement

The authors have no financial conflicts of interest.

Figures

Fig. 1
Fig. 1
Summary of patient disposition.
Fig. 2
Fig. 2
Mean change of 25-hydroxyvitamin D according to baseline 25-hydroxyvitamin D status. (A) Mean change of 25-hydroxyvitamin D in patients receiving alendronate containing 5600 IU of vitamin D3. (B) Mean change of 25-hydroxyvitamin D in patients receiving alendronate. ALN, alendronate.
Fig. 3
Fig. 3
Percent change from baseline in serum PTH at 16 weeks. *p<0.01 between treatments. PTH, parathyroid hormone; ALN, alendronate.
Fig. 4
Fig. 4
Neuromuscular Function Tests at 16 Weeks. *Fisher's exact test, **Chi-square test. ALN, alendronate.

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