Comparison of concurrent treatment with vitamin K 2 and risedronate compared with treatment with risedronate alone in patients with osteoporosis: Japanese Osteoporosis Intervention Trial-03

J Bone Miner Metab. 2017 Jul;35(4):385-395. doi: 10.1007/s00774-016-0768-5. Epub 2016 Aug 2.

Abstract

The aim of this study was to investigate the efficacy of concurrent treatment with vitamin K2 and risedronate compared with treatment with risedronate alone in patients with osteoporosis and to explore subsets of patients for which concurrent treatment is particularly efficacious. Women with osteoporosis aged 65 years or older were recruited from 123 institutes in Japan and allocated to take either vitamin K2 (45 mg/day) and risedronate (2.5 mg/day or 17.5 mg/week) or risedronate (2.5 mg/day or 17.5 mg/week) alone. The primary end point was the incidence of any fracture (vertebral and nonvertebral). The secondary end points were bone mineral density, height, undercarboxylated osteocalcin concentration, quality of life, and safety. Over a 2-year follow-up, vertebral or nonvertebral fractures occurred in 117 or 22 sites respectively among 931 patients in the risedronate and vitamin K2 group and in 104 or 26 sites respectively among 943 patients in the risedronate alone group. The rates of any incident fracture were similar between the two groups (incidence rate ratio 1.074, 95 % confidence interval 0.811-1.422, p = 0.62), implying that the primary end point was not met. There were no differences in the degree of increase in bone mineral density between the two groups. Undercarboxylated osteocalcin concentration decreased from 5.81 ± 3.93 ng/mL to 2.59 ± 1.52 ng/mL at 6 months in the risedronate and vitamin K2 group, whereas the change in the risedronate alone group was minimal (from 5.96 ± 4.36 ng/mL to 4.05 ± 3.40 ng/mL at 6 months) (p < 0.01). The treatment discontinuation rate was higher in the risedronate and vitamin K2 group than in the risedronate alone group (10.0 % vs 6.7 %). No unknown adverse drug reactions were reported. In conclusion, concurrent treatment with vitamin K2 and risedronate was not efficacious compared with monotherapy with risedronate in terms of fracture prevention.

Keywords: Osteoporosis; Risedronate; Undercarboxylated osteocalcin; Vitamin K2.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Bone Density Conservation Agents / adverse effects
  • Bone Density Conservation Agents / therapeutic use
  • Drug Therapy, Combination
  • Endpoint Determination
  • Female
  • Humans
  • Incidence
  • Japan
  • Medication Adherence
  • Middle Aged
  • Osteoporosis / drug therapy*
  • Osteoporotic Fractures / drug therapy
  • Osteoporotic Fractures / epidemiology
  • Quality of Life
  • Risedronic Acid / adverse effects
  • Risedronic Acid / therapeutic use*
  • Vitamin K 2 / adverse effects
  • Vitamin K 2 / therapeutic use*

Substances

  • Bone Density Conservation Agents
  • Vitamin K 2
  • Risedronic Acid