Efficacy of combined teriparatide & denosumab vs. single-drug treatment for osteoporosis

Study Type: Therapy
OE Level of Evidence: 2
Journal Level of Evidence: N/A
94 postmenopausal women with osteoporosis were randomized to receive either teriparatide, denosumab, or a combination of the two treatments. The purpose of this study was to determine the effectiveness of combined therapy with regards to bone microarchitecture and estimated strength. Findings indicated that Please login to view the rest of this report. Please login to view the rest of this report.
Funding: Industry funded
Sponsor: National Institutes of Health/National Center for Research Resources Equipment, National Institutes of Health/National Institute of Arthritis and Musculoskeletal and Skin Diseases, Eli Lilly, and Amgen
Conflicts: Other
Why was this study needed now?
In the treatment of postmenopausal women with osteoporosis, monotherapies such as teriparatide or denosumab are often used but can be unsuccessful or inadequate for patients in more advanced stages of the disease. A combination treatment of teriparatide and denosumab has been suggested as an alternative management method. The previously conducted Denosumab and Teriparatide Administration (DATA) study reported beneficial outcomes in the combined therapy for bone mineral density (BMD) at the femoral neck, total hip, and lumbar spine, compared to either drug alone. High-resolution quantitative computed tomography (HR-pQCT) was performed to analyze the microarchitectural effects associated with the BMD increase to determine if the combination treatment had improved cortical bone density, cortical microarchitecture, and estimated bone strength at the distal radius and tibia. However, long-term outcomes of combined therapy have yet to be studied, thus warranting the present 2-year follow-up assessment.
What was the principal research question?
In the treatment of postmenopausal women with osteoporosis, does the combination of teriparatide and denosumab yield significantly greater improvements in microarchitecture and estimated strength as compared to either teriparatide or denosumab treatments alone when assessed after 2 years?
Population: 94 postmenopausal women at least 45 years of age were included. Before randomization, patients were sorted by age (older vs. younger than 65 years of age) and previous bisphosphonate use. Eligible patients had a high risk of fracture, classified by a T-score of -2.5 or lower at the spine or hip, or a T-score of -2.0 or lower along with at least one of the following BMD-independent risk factors: fracture or parental hip fracture after 50 years of age, previous hyperthyroidism, inability to stand from a chair with arms raised, or currently a smoker.
Intervention: Combination therapy group: Patients received both teriparatide 20 ug sc daily and denosumab 60mg sc every 6 months for 2 years. (n=30, 24 completed 2-year follow-up)
Comparison: Teriparatide group: Patients received teriparatide 20ug sc daily for 2 years. (n=30, 28 completed 2-year follow-up) Denosumab group: Patients received denosumab 60mg sc every 6 months for 2 years. (n=33, 31 completed 2-year follow-up)
Outcomes: Outcomes included volumetric density and microarchitecture of the distal radius and distal tibia, measured using HR-pQCT (XtremeCT; Scanco Medical AG). Volumetric density outcomes consisted of the total, trabecular, and cortical volumetric bone density (vBMD; mg hydroxyapatite per cubic cm). Microarchitecture parameters included cortical thickness (mm), trabecular thickness (mm), trabecular numbers (mm^-1), and trabecular separation (mm). Cortical tissue mineral density (TMD; mg hydroxyapatite per cubic cm) and cortical porosity (%) were also assessed in further analysis. The microfinite element analysis (uFEA) was used to estimate stiffness (measured in kilonewtons [kN] per mm) and failure to load (kN).
Methods: RCT; open-label
Time: Volumetric density and microarchitecture were assessed at 3, 6, 12, 18, and 24 months. Cortical TMD and porosity were assessed at 12 and 24 months. The microfinite element analysis was assessed at 24 months.
What were the important findings?
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How will this affect the care of my patients?
The authors responsible for this critical appraisal and ACE Report indicate no potential conflicts of interest relating to the content in the original publication.