Denosumab or Zoledronic Acid in Postmenopausal Women With Osteoporosis Previously Treated With Oral Bisphosphonates

J Clin Endocrinol Metab. 2016 Aug;101(8):3163-70. doi: 10.1210/jc.2016-1801. Epub 2016 Jun 6.


Context: Denosumab and zoledronic acid (ZOL) are parenteral treatments for patients with osteoporosis.

Objective: The objective of the study was to compare the effect of transitioning from oral bisphosphonates to denosumab or ZOL on bone mineral density (BMD) and bone turnover.

Design and setting: This was an international, multicenter, randomized, double-blind trial.

Participants: A total of 643 postmenopausal women with osteoporosis previously treated with oral bisphosphonates participated in the study.

Interventions: Subjects were randomized 1:1 to sc denosumab 60 mg every 6 months plus iv placebo once or ZOL 5 mg iv once plus sc placebo every 6 months for 12 months.

Main outcome measures: Changes in BMD and bone turnover markers were measured.

Results: BMD change from baseline at month 12 was significantly greater with denosumab compared with ZOL at the lumbar spine (primary end point; 3.2% vs 1.1%; P < .0001), total hip (1.9% vs 0.6%; P < .0001), femoral neck (1.2% vs -0.1%; P < .0001), and one-third radius (0.6% vs 0.0%; P < .05). The median decrease from baseline was greater with denosumab than ZOL for serum C-telopeptide of type 1 collagen at all time points after day 10 and for serum procollagen type 1 N-terminal propeptide at month 1 and at all time points after month 3 (all P < .05). Median percentage changes from baseline in serum intact PTH were significantly greater at months 3 and 9 with denosumab compared with ZOL (all P < .05). Adverse events were similar between groups. Three events consistent with the definition of atypical femoral fracture were observed (two denosumab and one ZOL).

Conclusions: In postmenopausal women with osteoporosis previously treated with oral bisphosphonates, denosumab was associated with greater BMD increases at all measured skeletal sites and greater inhibition of bone remodeling compared with ZOL.

Trial registration: NCT01732770.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Administration, Oral
  • Aged
  • Bone Density / drug effects
  • Bone Density Conservation Agents / therapeutic use*
  • Denosumab / therapeutic use*
  • Diphosphonates / administration & dosage*
  • Diphosphonates / therapeutic use
  • Double-Blind Method
  • Drug Substitution
  • Female
  • Humans
  • Imidazoles / therapeutic use*
  • Middle Aged
  • Osteoporosis, Postmenopausal / drug therapy*
  • Zoledronic Acid


  • Bone Density Conservation Agents
  • Diphosphonates
  • Imidazoles
  • Denosumab
  • Zoledronic Acid

Associated data