Response to Therapy With Teriparatide, Denosumab, or Both in Postmenopausal Women in the DATA (Denosumab and Teriparatide Administration) Study Randomized Controlled Trial.

ABSTRACT

Both antiresorptive and anabolic osteoporosis medications increase bone mineral density (BMD), but no single agent can restore normal bone strength in most osteoporotic patients. Moreover, the magnitude and consistency of the patient response to each individual agent vary depending on the anatomic site. In the DATA study, we reported that in postmenopausal osteoporotic women, 2 years of combined denosumab and teriparatide increase mean BMD at the hip and spine more than either drug alone. In the current analysis, we wished to determine if the individual rates of BMD response were also greater among women treated with both drugs. In DATA, 94 postmenopausal osteoporotic women (ages 51-91) were randomized to receive teriparatide (20 mcg subcutaneously daily), denosumab (60 mg subcutaneously every 6 mo), or both medications for 24 mo. The BMD of the total hip (TH), femoral neck (FN), and lumbar spine (LS) were assessed by dual-energy X-ray absorptiometry. The 82 subjects who completed all 2-yr treatments were analyzed. Responders were defined as experiencing BMD increases of >3%. An "excellent response" was defined as an increase of >6%. Over 24 mo, TH BMD increased by >3% in 36%, 53%, and 92% of women in the teriparatide, denosumab, and combination groups, respectively, and by >6% in 11%, 17%, and 50% in the teriparatide, denosumab, and combination groups, respectively (p < 0.01 for all comparisons vs combination). FN response rates were similar to TH. In the LS, BMD increased by >3% in 85%, 93%, and 100% of women in the teriparatide, denosumab, and combination groups, respectively (p = nonsignificant for all comparisons) and by >6% in 63%, 78%, and 100% of women in the teriparatide, denosumab, and combination groups, respectively (combination vs teriparatide, p = 0.001; combination vs denosumab, p = 0.016). In summary, more women treated with 24 mo of combined denosumab and teriparatide achieved a significant response at the TH and FN than those treated with either drug alone. All women treated with both agents together experienced an excellent response at the LS. These results support the continued investigation of combined denosumab and teriparatide therapy in postmenopausal osteoporotic women utilizing clinical endpoints such as fracture reduction.