Bone Mineral Density Response With Denosumab in Combination With Standard or High-Dose Teriparatide: The DATA-HD RCT

Abstract

Context: In the Denosumab and High-Dose Teriparatide Administration (DATA-HD) study, we reported that 15 months of combined high-dose (HD) teriparatide and denosumab increased mean areal bone mineral density (aBMD) at the hip and spine more than combined denosumab and standard-dose (SD) teriparatide.

Objective: In the current analysis, we compare the individual rates of aBMD response between the treatment groups.

Design: Single-site, open-label, randomized controlled trial in which postmenopausal women received either teriparatide 20-μg daily (SD) or 40-μg daily (HD) given months 0 through 9, overlapped with denosumab 60 mg, given months 3 through 15 (15 months' total duration). The proportion of participants in the SD and HD groups experiencing total hip, femoral neck, and lumbar spine aBMD gains of >3%, >6%, and >9% were compared.

Participants: Postmenopausal women with osteoporosis completing all study visits (n = 60).

Main outcome measure(s): aBMD (dual x-ray absorptiometry).

Results: At the end of the 15-month treatment period, a higher proportion of women in the HD group had aBMD increases >3% (83% vs. 58%, P = .037) and >6% (45% vs. 19%, P = .034) at the total hip, and >3% at the femoral neck (86% vs. 63%, P = .044). At the lumbar spine, >3% response rates were similar, whereas the >6% and >9% response rates were greater in the HD group (100% vs. 79%, P = .012 and 93% vs. 59%, P = .003, respectively).

Conclusion: Compared with the SD regimen, more women treated with the HD regimen achieved clinically meaningful and rapid gains in hip and spine aBMD. These results suggest that this approach may provide unique benefits in the treatment of postmenopausal osteoporosis.

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Figures

Figure 1.

Flow diagram of treatment schedule over the15-month study period.

Figure 2.

Cumulative relative frequency distribution plots of percent change in bone mineral density from baseline to 9 and 15 months. aBMD, bone mineral density; HD, high-dose teriparatide (40 μg) plus denosumab; SD, standard-dose teriparatide (20 μg) plus denosumab. aIncludes 60 participants who had areal bone mineral density (aBMD) determinations at all study visits (baseline, month 9, and month 15, 79% of the DATA-HD population at enrollment). Data missing for 1 participant in the SD group for femoral neck aBMD at 9 and 15 months and 2 participants in the SD group and 2 participants in the HD group for lumbar spine aBMD at 9 and 15 months.

Figure 3.

Proportion of participants achieving bone mineral density increases of >3%, >6%, and >9% at the total hip, femoral neck, and lumbar spine from baseline to 9 and 15 months.a BL, baseline; HD, high-dose teriparatide (40-μg) plus denosumab; M, month; SD, standard-dose teriparatide (20 μg) plus denosumab. *P < .05. **P < .01. aIncludes 60 participants who had areal bone mineral density (aBMD) determinations at all study visits (baseline, month 9, and month 15, 79% of the Denosumab and High-Dose Teriparatide Administration population at enrollment). Data missing for 1 participant in the SD group for femoral neck aBMD at 9 and 15 months; and 2 participants in the SD group and 2 participants in the HD group for lumbar spine aBMD at 9 and 15 months.

Figure 4.

Proportion of participants achieving bone mineral density increases of >3% at all 3 sites from baseline to 9 and 15 months.b BL, baseline; FN, femoral neck; HD, high-dose teriparatide (40 μg) plus denosumab; LS, lumbar spine; M, month; SD, standard-dose teriparatide (20 μg) plus denosumab; TH, total hip. *P < .05. **P < .01. b Includes 55 participants who had areal bone mineral density determinations at all study visits (baseline, month 9, and month 15) and at all sites (total hip, femoral neck, and lumbar spine).