Denosumab effects on bone density and turnover in postmenopausal women with low bone mass with or without previous treatment.

Abstract

Prior osteoporosis therapies may affect the skeletal response to denosumab. We compared the effect of denosumab (60 mg every 6 months for 12 months) on bone mineral density and bone metabolism parameters in postmenopausal women with low bone mass who were either treatment-naïve (n = 30), or previously treated either with zoledronic acid (n = 30), or teriparatide (n = 22). We assessed lumbar spine bone mineral density (BMD) and measured serum concentrations of the bone turnover markers pro-collagen type 1 N-terminal propeptide (PINP) and C-terminal-cross-linking telopeptide of type 1 collagen (CTX), as well as sclerostin, dickkopf-1 (Dkk-1), and myostatin. Lumbar spine BMD increased equivalently in all three groups after 12 months of denosumab compared to baseline (p < 0.001). Serum PINP and CTX decreased significantly with denosumab in pre-treated women reaching the same nadir levels as in treatment-naïve patients (p < 0.001). Women pre-treated with teriparatide displayed lower baseline myostatin concentrations as compared to the other two groups (p < 0.001). Changes in lumbar spine BMD in teriparatide pre-treated women correlated with changes in bone turnover markers and myostatin. Denosumab induced similar increases in lumbar spine BMD in treatment-naïve and pre-treated patients and suppressed serum PINP and CTX to the same levels regardless of prior treatments. In teriparatide pre-treated patients the magnitude of change in bone turnover markers is associated with BMD response.