title: Effects of alendronate plus alfacalcidol in osteoporosis patients with a high risk of fracture: the Japanese Osteoporosis Intervention Trial (JOINT) - 02.
abstract: OBJECTIVE
  The authors conducted a randomized controlled trial to clarify the efficacy and safety of alendronate plus alfacalcidol versus alendronate alone in a clinical setting.
  
  
  METHODS
  Eligible patients were postmenopausal women with severe osteoporosis who were aged 70 years or older and had several risk factors for incident fractures. The primary endpoint was prevention of incident fractures, and the anti-fracture efficacy was evaluated in relation to the baseline serum 25(OH)D level.
  
  
  RESULTS
  A total of 2164 patients were randomized to alendronate plus alfacalcidol (combination therapy) or alendronate alone (monotherapy). Although the overall difference in the incidence of vertebral fracture between the two groups was not significant, the combination therapy group had a significantly reduced risk of vertebral fractures after the first 6 months (HR, 0.53). In subgroup analyses, the combination therapy group was superior in the strata of number of prevalent vertebral fractures of ≥2 (HR, 0.51) and grade 3 of prevalent vertebral fractures (HR, 0.55). The rate of non-vertebral weight-bearing bone fractures was significantly lower in the combination therapy group than in the monotherapy group during the follow-up period (HR, 0.31). A lower baseline 25(OH)D level was associated with a higher incidence of non-vertebral weight-bearing bone fractures (HR, 3.42) despite alendronate use. Although one patient given the combination therapy had mild hypercalcemia, serious hypercalcemia and unknown adverse events were not encountered. Because of the limitations presented in this study, these results may not apply to female patients with longer than 2 years of treatments, and to male osteoporosis patients.
  
  
  CONCLUSIONS
  The combination therapy was no more effective for overall vertebral fracture prevention. However, subgroup analysis has shown that it was more effective for fracture prevention in patients with severe vertebral deformity, multiple prevalent vertebral fractures, and for non-vertebral weight-bearing bone fracture prevention.
authors.affiliation: Health Science University, Yamanashi, Japan.
authors.forename: Hajime
authors.initials: H
authors.lastname: Orimo
authors.forename: Toshitaka
authors.initials: T
authors.lastname: Nakamura
authors.forename: Masao
authors.initials: M
authors.lastname: Fukunaga
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Ohta
authors.forename: Takayuki
authors.initials: T
authors.lastname: Hosoi
authors.forename: Yukari
authors.initials: Y
authors.lastname: Uemura
authors.forename: Tatsuhiko
authors.initials: T
authors.lastname: Kuroda
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Miyakawa
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Ohashi
authors.forename: Masataka
authors.initials: M
authors.lastname: Shiraki
mesh_terms: D019386:Alendronate / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D050071:Bone Density Conservation Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D050723:Fractures, Bone / Q000517:prevention & control*; D006887:Hydroxycholecalciferols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D007564:Japan; D010024:Osteoporosis / Q000517:prevention & control*
chemical_list: D050071:Bone Density Conservation Agents; D006887:Hydroxycholecalciferols; C008088:alfacalcidol; D019386:Alendronate