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

https://doi.org/10.1016/j.jocd.2016.01.004Get rights and content

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.

Introduction

Dual-energy X-ray absorptiometry (DXA)-derived bone mineral density (BMD) is a surrogate marker commonly monitored to assess an individual patient's response to osteoporosis therapy. Decisions regarding continuing therapy or switching to an alternative drug are often made on the basis of changes in BMD over time (1). Two of our most potent osteoporosis medications, the osteoanabolic agent, teriparatide, and the antiresorptive agent, denosumab, increase spine and hip BMD significantly and reduce the risk of vertebral and nonvertebral fractures 2, 3 Moreover, with both of these agents, the magnitude of the BMD improvements has been shown to predict the observed reduction in fracture incidence, though to varying degrees 4, 5. In the DATA study, we recently reported that 2 yr of combined denosumab and teriparatide increases BMD at the hip and spine more than either drug alone and more than can be achieved with any currently available agent 6, 7. To assess the variability of the response to combination therapy, we now compare the individual response rates in women treated with denosumab, teriparatide, or both medications at the total hip (TH), femoral neck (FN), lumbar spine (LS), and distal 1/3 radius.

Section snippets

Subjects and Methods

The details of the DATA study design and subjects have been described previously 6, 7. Ninety-four postmenopausal women aged 45 or older were recruited through targeted mailings, advertisements, and physician referrals. Subjects were required to be at least 36 mo since last menses (or since hysterectomy if follicle-stimulating hormone (FSH) level >40 U/L) and at high fracture risk, defined as a BMD T-score ≤−2.5 at the spine, hip, or FN; a T-score ≤−2.0 with at least 1 BMD-independent risk

Results

The baseline characteristics of the 82 subjects completing all visits are shown in Table 1, as are the 2-yr mean percent changes in BMD achieved in each treatment group. As reported previously, after 24 mo, LS BMD increased more in women receiving both drugs (12.9 ± 5.0%) than both the teriparatide (9.5 ± 5.9%, p = 0.01) and denosumab (8.3 ± 3.4%, p = 0.008) groups. FN BMD also increased more in the combination group (6.8 ± 3.6%) than both the teriparatide (2.8 ± 3.9%, p = 0.003) and denosumab

Discussion

In the present study, we have demonstrated that a greater proportion of postmenopausal osteoporotic women treated with 24 mo of combined denosumab and teriparatide experience meaningful improvement in hip and spine BMD than those treated with either teriparatide or denosumab alone. Moreover, not only are the response rates for combined denosumab and teriparatide higher than those reported for the individual agents in the present study, but also when compared to prior studies of other

Acknowledgments

We wish to thank Dr. John Potts for his consistent advice and support, the staff at the MGH Bone Density Center, and our dedicated study volunteers.

Funding sources: This study was supported by Eli Lilly Inc. and Amgen Inc. (Grant Number 1 UL1 RR025758-04). Neither Eli Lilly nor Amgen had any role in the study design or data analysis, or data interpretation.

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    Conflict of interest: BZL has served as a consultant for Eli Lilly, Amgen and Merck. RMN JNT SMB AVU and PMW report no conflict of interest.

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