Denosumab versus zoledronic acid in patients previously treated with zoledronic acid

Denosumab and zoledronic acid are potent antiresorptives. In this study in patients pre-treated with zoledronic acid, denosumab achieved similar increases with zoledronic acid in lumbar spine BMD despite the more prominent reduction of bone turnover markers. Denosumab reversibly reduced endogenous RANKL.

We aimed to compare yearly changes in lumbar spine (LS) bone mineral density (BMD), bone turnover markers, free soluble receptor activator of nuclear factor kappaB ligand (sRANKL) and sclerostin levels between denosumab and zoledronic acid.

Postmenopausal women with low bone mass previously treated with zoledronic acid for 1 year were assigned to denosumab injection (n = 32) or zoledronic acid infusion (n = 26). Procollagen type 1 N-terminal propeptide (P1NP), C-terminal cross-linking telopeptide of type 1 collagen (CTx), sRANKL, and sclerostin levels were measured in serum samples obtained at baseline and 3, 6, and 12 months after denosumab injection or zoledronic acid infusion. LS BMD was measured at baseline and 12 months.

The mean LS increase was 4.5 and 4.4% with denosumab and zoledronic acid, respectively (p = 0.560). Denosumab caused a larger decrease in CTx at 3 months (p < 0.001) and P1NP at 3 (p < 0.001), 6 (p = 0.021), and 12 months (p = 0.042). Denosumab significantly decreased sRANKL by 87.4% at 3 months (p < 0.001). Sclerostin levels were not changed with either intervention (p = 0.162 and p = 0.214, respectively).

In patients previously treated with zoledronic acid, denosumab reduces bone turnover more than zoledronic acid, but the increases in LS BMD are comparable. Furthermore, denosumab administration results in reversible inhibition of the metabolically significant endogenous free soluble RANKL levels. Serum sclerostin is not affected by either agent.