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Anabolic and Antiresorptive Therapy for Osteoporosis: Combination and Sequential Approaches

  • Therapeutics and Medical Management (E Shane and RA Adler, Section Editors)
  • Published:
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Abstract

In the recent Bone Key Reports review, 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 PTH1-34 (TPTD) or PTH1-84 (PTH) 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 volumetric 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 or TPTD is a superior hip BMD outcome compared with TPTD/PTH alone. This is most evident when TPTD/PTH 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 2 exceptions to this are when TPTD is combined with denosumab and when TPTD is given as monotherapy first for 9 months, followed by the addition of alendronate (with continuation administration of TPTD). 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 TPTD 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 TPTD and denosumab or TPTD followed by combination treatment with a potent bisphosphonate or denosumab should be considered to maximize early increases in BMD throughout the skeleton (Cosman BoneKEy Rep 3, 2014)[1].

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

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Conflict of Interest

F. Cosman has received research support from NIH; personal fees from Lilly, Novartis, Amgen, Merck, Zosano, GSK, Pfizer, Enteris, Radius, Asahi-Kasei; and nonfinancial support from Lilly.

Human and Animal Rights and Informed Consent

All studies by the author involving animal and/or human subjects were performed after approval by the appropriate institutional review boards. When required, written informed consent was obtained from all participants.

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Authors and Affiliations

  1. Columbia College of Physicians and Surgeons, Columbia University, New York, NY, 10025, USA

    Felicia Cosman

  2. Helen Hayes Hospital, Clinical Research Center, Route 9 W, West Haverstraw, New York, NY, 10993, USA

    Felicia Cosman

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  1. Felicia Cosman
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Correspondence to Felicia Cosman.

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Author’s Note

This review is an update to a recent review published in BoneKEy Reports I entitled “Combination therapy for osteoporosis: a reappraisal” (doi: 10.1038/bonekey.2014.13. I have added more information based on reports published since it’s acceptance in December 2013.

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Cosman, F. Anabolic and Antiresorptive Therapy for Osteoporosis: Combination and Sequential Approaches. Curr Osteoporos Rep 12, 385–395 (2014). https://doi.org/10.1007/s11914-014-0237-9

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  • DOI: https://doi.org/10.1007/s11914-014-0237-9

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