Teriparatide and denosumab, alone or combined, in women with postmenopausal osteoporosis: the DATA study randomised trial

Abstract

Background: Osteoporosis medications increase bone-mineral density (BMD) and lower but do not eliminate fracture risk. The combining of anabolic agents with bisphosphonates has not improved efficacy. We compared combined teriparatide and denosumab with both agents alone.

Methods: From September, 2009, to January, 2011, we enrolled postmenopausal women with osteoporosis into this randomised, controlled trial. Patients were assigned in a 1:1:1 ratio to receive 20 μg teriparatide daily, 60 mg denosumab every 6 months, or both. BMD was measured at 0, 3, 6, and 12 months. Women who completed at least one study visit after baseline were assessed in a modified intention-to-treat analysis. This trial is registered with ClinicalTrials.gov, number NCT00926380.

Findings: 94 (94%) of 100 eligible women completed at least one study visit after baseline. At 12 months, posterior-anterior lumbar spine BMD increased more in the combination group (9·1%, [SD 3·9]) than in the teriparatide (6·2% [4·6], p=0·0139) or denosumab (5·5% [3·3], p=0·0005) groups. Femoral-neck BMD also increased more in the combination group (4·2% [3·0]) than in the teriparatide (0·8% [4·1], p=0·0007) and denosumab (2·1% [3·8], p=0·0238) groups, as did total-hip BMD (combination, 4·9% [2·9]; teriparatide, 0·7% [2·7], p<0·0001; denosumab 2·5% [2·6], p=0·0011).

Interpretation: Combined teriparatide and denosumab increased BMD more than either agent alone and more than has been reported with approved therapies. Combination treatment might, therefore, be useful to treat patients at high risk of fracture.

Funding: Amgen, Eli Lilly, National Center for Research Resources.

figure 1

subject disposition.

Figure 2

Mean percent change (SEM) in BMD from baseline to 24 months in the lumbar spine (A), one-third distal radius (B), femoral neck (C), and total hip (D) in the teriparatide (TPTD), denosumab (DMAB), and combination (Combo) groups. *, P < .05 compared with other groups.

Figure 3

Mean percent change (SEM) in BMD (grams per square centimeter) from months 0 to 12 (gray) and months 12 to 24 (yellow) in the teriparatide (TPTD), denosumab (DMAB), and combination (Combo) groups. *, P < .05 vs other groups for the overall 0 to 24 month change. Changes between 12 and 24 months did not differ significantly among groups.

Figure 4

Markers. Mean percent change (SEM) in bone turnover markers from baseline to 24 months in the teriparatide (TPTD, A–C) and denosumab (DMAB) and combination (Combo) groups (D–F). ^a, P < .0001 vs denosumab and combination at all time points. ^b, P < .005 vs denosumab at all time points. Data for the teriparatide group and other groups are graphed separately for figure clarity. Error bars that are not seen are contained within the symbols.