• J N Tsai, A V Uihlein, S M Burnett-Bowie, R M Neer, N P Derrico, H Lee, M L Bouxsein, and B Z Leder.
• Endocrine Unit (J.N.T., A.V.U., S.M.B.-B., R.M.N., N.P.D., M.L.B., B.Z.L.), and Biostatistics Center (H.L.), Massachusetts General Hospital, Boston, Massachusetts 02114; and Department of Orthopedic Surgery (M.L.B.), Beth Israel Deaconess Medical Center, Boston, Massachusetts 02115.
• J. Clin. Endocrinol. Metab. 2016 May 1; 101 (5): 2023-30.

ContextIn postmenopausal osteoporosis, combining denosumab and teriparatide increases hip and spine bone mineral density more than either monotherapy.ObjectiveThe objective of the study was to determine the effects of 2 years of combination therapy on bone microarchitecture and estimated strength.DesignThis was an open-label, randomized controlled trial.Participants And MethodsWe performed high-resolution peripheral quantitative computed tomography at the distal tibia and radius in 94 postmenopausal osteoporotic women randomized to 2 years of teriparatide 20 μg sc daily, denosumab 60 mg sc every 6 months, or both.ResultsTotal volumetric bone mineral density (vBMD) at the radius and tibia, trabecular vBMD at the radius, and cortical vBMD at the tibia all increased more in the combination group than both monotherapy groups (P < .002 for all comparisons with combination). Cortical thickness at the tibia also increased more in the combination group (8.1% ± 4.3%) than both other groups (P < .001). Cortical porosity at both the radius and tibia increased progressively over the 24-month treatment period in the teriparatide group but was stable in both other groups (P < .001 teriparatide vs both other groups). Trabecular vBMD at the tibia increased similarly in all groups, whereas radius trabecular vBMD increased more in the combination group than the other groups (P < .01 for both comparisons). Finite element analysis-estimated strength improved or was maintained by all treatments at both the radius and tibia.ConclusionsTwo years of combined teriparatide and denosumab improves bone microarchitecture and estimated strength more than the individual treatments, particularly in cortical bone. These findings suggest that this regimen may be beneficial in postmenopausal osteoporosis.

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