The Effects of Combined Denosumab and Teriparatide Administration on Bone Mineral Density in Postmenopausal Women: The DATA (Denosumab and Teriparatide Administration) Study

Introduction:  Osteoporosis medications can increase bone mineral density (BMD) modestly, and they can reduce—but not eliminate—fractures.  A combination of the most commonly prescribed class of antiresorptive agents (bisphosphonates) and an anabolic agent (teriparatide [TPTD]) does not increase BMD more than individual therapies.  However, animal models have suggested that combining the recently-approved antiresorptive denosumab (DMAB) with TPTD might increase BMD more than either drug alone.

Methods:  The study involved 92 postmenopausal women (ages 51-91 years) who were at high risk of fracture.  It was a 12-month, open-label, randomized clinical trial that compared the effects of TPTD (20 mcg SC daily; n = 31), DMAB (60 mg SQ Q6 mo; n = 33), or a combination of the 2 medications (n = 30) on hip, spine, and 1/3 radius DXA BMD.  Exclusion criteria were:  use of oral bisphosphonates in the past 6 months or any prior use of strontium or IV bisphosphonates.

The participants were stratified by prior bisphosphonate use and age, and using mixed model ANCOVA, between-group changes in BMD were compared.

Results:  At baseline, there were no significant between-group differences.  At 12 months, though, total hip BMD (mean ± SD) increased more in the combination group (4.9% ± 2.9%) than in the TPTD group (0.7% ± 2.7%, p < 0.0001) or in the DMAB group (2.5% ± 2.6%, p = 0.0001).

Similar results were seen in the femoral neck:  the combination group showed a greater increase (4.7% ± 4.3%) in BMD than in the TPTD (0.8% ± 4.1%, p < 0.001) or in the DMAB (2.1% ± 3.8%, p = 0.013) groups.

Spine BMD also increased more in the combination group (9.1% ± 3.9%) than in TPTD (6.2% ± 4.6%, p = 0.0005) or in DMAB (5.5% ± 3.3%, p < 0.0001) groups.

However, at the 1/3 radius, BMD increased similarly in the DMAB (1.7% ± 3.2%) and combination groups (2.5% ± 2.8%).  There was a decrease in 1/3 radius BMD in the TPTD group (-1.8% ± 3.6%, p < 0.001), and this decrease was significantly different from the increases seen in the other 2 groups.

At the total hip, DMAB alone increased BMD more than TPTD alone (p = 0.003); in the spine and at the femoral neck, DMAB and TPTD showed similar BMD gains (spine, p = 0.7; femoral neck p = 0.09).

Conclusions:  The combination of TPTD and DMAB increased BMD at the hip and spine more than either drug alone.  The combination also led to greater BMD increases at the femoral neck, total hip, and spine than any currently available treatments, so this combined therapy may be an important treatment option for patients with a high risk of fracture.

Commentary by Pauline M. Camacho MD, FACE

It is well-known that teriparatide, a drug which induces bone formation, and denosumab, an agent which reduces bone resorption, are highly efficacious in reducing fracture risk in osteoporotic patients. This study looked at the effect of combining these drugs. The study results showed a more pronounced increase in spine and hip BMD in the combination group compared to the teriparatide and denosumab alone groups.

This is a relatively small study with bone density as the primary endpoint. A study that clearly shows superior fracture risk reduction with combination therapy is needed before this practice can be recommended to clinicians. It would also be important to look at the cost implications of combination therapy and whether the reduction in the number of fractures is significant enough to justify the increased cost.