Two years of Denosumab and teriparatide administration in postmenopausal women with osteoporosis (The DATA Extension Study): a randomized controlled trial

Abstract

Context: Current osteoporosis medications increase bone mineral density (BMD) modestly and reduce, but do not eliminate, fracture risk. Attempts to improve efficacy by administering anabolic agents and bisphosphonates concomitantly have been unsuccessful. Conversely, 12 months of concomitant denosumab and teriparatide therapy increases BMD more than either drug alone.

Objective: The purpose of this study was to determine whether 24 months of combined denosumab and teriparatide will increase hip and spine BMD more than either individual agent.

Design: Preplanned continuation of the Denosumab and Teriparatide Administration (DATA) randomized controlled trial in which postmenopausal osteoporotic women received teriparatide (20 μg daily), denosumab (60 mg every 6 months), or both medications for 24 months.

Participants: Participants were 94 postmenopausal women with osteoporosis.

Outcome measures: Lumbar spine, femoral neck, total hip, and distal radius BMD and serum markers of bone turnover were measured.

Results: At 24 months, lumbar spine BMD increased more in the combination group (12.9 ± 5.0%) than in either the teriparatide (9.5 ± 5.9%, P = .01) or denosumab (8.3 ± 3.4%, P = .008) groups. Femoral neck BMD also increased more in the combination group (6.8 ± 3.6%) than in either the teriparatide (2.8 ± 3.9%, P = .003) or denosumab (4.1 ± 3.8%, P = .008) groups. Similarly, total hip BMD increased more in the combination group (6.3 ± 2.6%) than in the teriparatide (2.0 ± 3.0%) or denosumab (3.2 ± 2.5%) groups (P < .001 for both). Although spine and hip BMD continued to increase in the second year in all groups, these year 2 increases did not differ among groups. Serum C-telopeptide and N-terminal propeptide of type 1 procollagen were equally suppressed in the denosumab and combination groups, whereas osteocalcin decreased more in the denosumab group than in the combination group, a difference that persisted, but lessened, in the second year of therapy.

Conclusions: Two years of concomitant teriparatide and denosumab therapy increases BMD more than therapy with either medication alone and more than has been reported with any current therapy. The combination of these agents may prove to be an important treatment option in patients at high risk of fracture.

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.