A systematic review of combination treatment strategies for osteoporosis.

The evidence and scientific guidance regarding the efficacy of combination treatment strategies for osteoporosis is currently limited. We performed a systematic review of primary studies that evaluated the effect of combination bone-active medication therapy on BMD and/or fracture outcomes. Eleven studies that assessed 7 different combinations of medications were included. Evidence for superior efficacy of combination treatment compared with monotherapy was strong for only 3 medication combinations: teriparatide and denosumab, teriparatide and zoledronic acid, and alendronate and raloxifene. Three small studies that evaluated combination teriparatide and denosumab found evidence of statistically significant benefit for increasing BMD at the lumbar spine and/or hip more than either medication alone. One large study that evaluated combination teriparatide and zoledronic acid found that after 1 yr of treatment BMD at the lumbar spine increased significantly more in the combination treatment group than the zoledronic acid alone group, and BMD at the hip increased significantly more in the combination treatment group than the teriparatide alone group. This study also found significantly reduced risk of clinical fractures with combination therapy compared with zoledronic acid alone, but not when compared with teriparatide alone. Two studies that evaluated combination alendronate and raloxifene found evidence of significant benefit on BMD outcomes. We found insufficient evidence for superior efficacy of other bone-active medication combinations compared with monotherapy on either BMD outcomes or the very limited data on fracture outcomes. In conclusion, there is evidence supporting the use of combination treatment with teriparatide and denosumab, teriparatide and zoledronic acid, and alendronate and raloxifene for osteoporosis for increasing BMD more than monotherapy, although several of the studies showing benefit of these combinations are small, and data are lacking on fracture outcomes. These combinations can be considered for treatment of patients with osteoporosis; however, further larger studies would be useful to evaluate fracture outcomes as well as other combinations for potential efficacy.