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

Abstract

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: ClinicalTrials.gov NCT01732770.

Figure 1.

Subject disposition. DMAb, denosumab; Q6M, every 6 months; Q12M, every 12 months.

Figure 2.

Mean percentage change from baseline in areal BMD at month 12. Data represent least squares means and 95% CIs based on an analysis of covariance model adjusting for treatment, serum CTX stratification variable (<300 pg/mL vs 300–500 pg/mL), baseline BMD, DXA machine type, and baseline value-by–machine type interaction. a, P < .0001 for noninferiority; b, P < .0001 for superiority; c, P = .018 for superiority.

Figure 3.

Serum CTX and P1NP concentrations. Values represent median and interquartile (Q1, Q3) range. Lower limit of quantification is 40 pg/mL for CTX and 5 ng/mL for P1NP. Dashed horizontal lines indicate premenopausal reference ranges for CTX (200–900 pg/mL) and P1NP (17.4–61.6 ng/mL) (28). DMAb, denosumab.

Figure 4.

Median (Q1, Q3) percentage change in albumin-adjusted calcium and iPTH concentrations from baseline to month 12. Values represent median and interquartile (Q1, Q3) range. a, P < .05 compared with ZOL. DMAb, denosumab.