Abstract
Summary
It has been suggested that some patients undergoing prolonged treatment for osteoporosis with anti-resorptive agents may benefit from discontinuing treatment. Here we use a computer simulation of bone cell activity to estimate changes in bone mineral density (BMD) and tissue age when treatment is discontinued.
Introduction
Although anti-resorptive agents are effective at reducing fracture risk, questions remain regarding how long patients should continue treatment and how long treatment should be discontinued. Suspending treatment as part of a drug holiday may reduce the risk of adverse effects, but may also lead to reduced BMD.
Methods
We use a computer simulation of the bone remodeling process to estimate how BMD and mean tissue age are changed after treatment is suspended. Mean tissue age is studied because increased tissue age has been associated with impaired bone quality and has been linked to the risk of adverse effects.
Results
Our simulations suggest that BMD gains from anti-resorptive therapy can be lost over time, especially with anti-resorptive agents that have little residual effects. With regard to mean tissue age, the simulations suggest that increases in tissue age from anti-resorptive treatment are long lasting; increases in mean tissue age caused by treatment may remain for as long as 15 years after treatment is suspended. After stopping treatment, reductions in BMD are expected to occur long before mean tissue age returns to normal.
Conclusions
Our simulations suggest that, when using a long-lasting anti-resorptive agent, 1- to 5-year drug holidays may have little effect on BMD in most patients but that drug holiday intervals that maintain BMD are unlikely to reverse alterations in tissue age caused by treatment. Our analysis echoes recent reviews suggesting patient selection and monitoring when anti-resorptive treatment is discontinued.
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Acknowledgments
This publication was made possible by Grant Number AR057362 from NIAMS/NIH. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIAMS or NIH.
Conflicts of interest
Dr. Hernandez has received research support from AMGEN and the Musculoskeletal Transplant Foundation. Dr. Lane serves on scientific boards for Bone Therapeutics, CollPlant, Graftys, and Zimmer, and is on the Speaker’s Bureau for Eli Lilly. Ms. Lopez has no potential conflicts of interest.
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Hernandez, C.J., Lopez, H.K. & Lane, J.M. Theoretical consideration of the effect of drug holidays on BMD and tissue age. Osteoporos Int 25, 1577–1584 (2014). https://doi.org/10.1007/s00198-014-2653-1
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DOI: https://doi.org/10.1007/s00198-014-2653-1