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In the recent [i]BoneKEy Reports[/i] review [1], it was noted that combinations of anabolic and antiresorptive agents have potential to improve bone density and bone strength more than either agent as monotherapy. Small clinical trials have been performed evaluating combinations of parathyroid hormone (PTH) – PTH 1-34 (teriparatide) or PTH 1-84 – with a variety of antiresorptives including hormone/estrogen therapy, raloxifene, alendronate, risedronate, ibandronate, zoledronic acid, and denosumab. Most of the studies evaluate dual-energy X-ray absorptiometry outcomes, and a few trials report bone mineral density (BMD) by quantitative computed tomography, followed by finite element modeling to calculate bone strength. None of the studies has been powered to assess differences in fracture incidence between combination therapy and monotherapy. BMD outcomes vary based on the timing of introduction of the anabolic agent (before, during, or after antiresorptive treatment), as well as the specific anabolic and antiresorptive used. Furthermore, effects of combination therapies are site-dependent. The most consistent effect of combining antiresorptive agents with PTH 1-84 or teriparatide is a superior hip BMD outcome compared with teriparatide/PTH 1-84 alone. This is most evident when teriparatide/PTH 1-84 is combined with a bisphosphonate or denosumab. In contrast to findings in the hip, in the majority of studies, there is no benefit to spine BMD with combination therapy vs. monotherapy. The two exceptions to this are when teriparatide is combined with denosumab and when teriparatide is given as monotherapy first for 9 months, followed by the addition of alendronate (with continuation administration of teriparatide). Based on what we now know, in patients previously treated with bisphosphonates who suffer hip fractures or who have very low or declining hip BMD, strong consideration should be given to starting teriparatide and continuing a potent antiresorptive agent (possibly switching to zoledronic acid or denosumab) to improve hip BMD and strength quickly. Furthermore, in treatment-naïve individuals with very severe osteoporosis, such as those with spine and hip fractures, combination therapy with teriparatide and denosumab or teriparatide followed by combination treatment with a potent bisphosphonate or denosumab should be considered to maximize early increases in BMD throughout the skeleton.


  • Andrea Mejia

  • Santiago Palacios
    Palacios Institute of Womens Health, Madrid, Spain


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