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Effects of sequential osteoporosis treatments on trabecular bone in adult rats with low bone mass

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Abstract

Summary

We used an osteopenic adult ovariectomized (OVX) rat model to evaluate various sequential treatments for osteoporosis, using FDA-approved agents with complementary tissue-level mechanisms of action. Sequential treatment for 3 months each with alendronate (Aln), followed by PTH, followed by resumption of Aln, created the highest trabecular bone mass, best microarchitecture, and highest bone strength.

Introduction

Individual agents used to treat human osteoporosis reduce fracture risk by ∼50–60 %. As agents that act with complementary mechanisms are available, sequential therapies that mix antiresorptive and anabolic agents could improve fracture risk reduction, when compared with monotherapies.

Methods

We evaluated bone mass, bone microarchitecture, and bone strength in adult OVX, osteopenic rats, during different sequences of vehicle (Veh), parathyroid hormone (PTH), Aln, or raloxifene (Ral) in three 90- day treatment periods, over 9 months. Differences among groups were evaluated. The interrelationships of bone mass and microarchitecture endpoints and their relationship to bone strength were studied.

Results

Estrogen deficiency caused bone loss. OVX rats treated with Aln monotherapy had significantly better bone mass, microarchitecture, and bone strength than untreated OVX rats. Rats treated with an Aln drug holiday had bone mass and microarchitecture similar to the Aln monotherapy group but with significantly lower bone strength. PTH-treated rats had markedly higher bone endpoints, but all were lost after PTH withdrawal without follow-up treatment. Rats treated with PTH followed by Aln had better bone endpoints than those treated with Aln monotherapy, PTH monotherapy, or an Aln holiday. Rats treated initially with Aln or Ral, then switched to PTH, also had better bone endpoints, than monotherapy treatment. Rats treated with Aln, then PTH, and returned to Aln had the highest values for all endpoints.

Conclusion

Our data indicate that antiresorptive therapy can be coupled with an anabolic agent, to produce and maintain better bone mass, microarchitecture, and strength than can be achieved with any monotherapy.

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Acknowledgments

This work was funded by National Institutes of Health (NIH) grants R01 AR043052, 1K12HD05195801 and 5K24AR048841-09. Statistical support was made possible by grant no. UL1 RR024146 from the National Center for Research Resources (NCRR), a component of the NIH and NIH Roadmap for Medical Research. The involvement of ROR was supported by NIH (NIH/NIDCR) under grant no. 5R01 DE015633 to the Lawrence Berkeley National Laboratory (LBNL).

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Authors and Affiliations

  1. Center for Musculoskeletal Health and Department of Medicine, University of California Davis Medical Center, 4625 2nd Avenue, Suite 1002, Sacramento, CA, 95817, USA

    S. K. Amugongo, W. Yao, J. Jia, Y.-A. E. Lay, W. Dai, L. Jiang, D. Walsh & N. E. Lane

  2. Division of Biostatistics, Department of Public Health Sciences, University of California, Davis, CA, USA

    C.-S. Li

  3. Lawrence Berkeley National Laboratory, and Department of Materials Science and Engineering, University of California, Berkeley, CA, USA

    N. K. N. Dave, D. Olivera, B. Panganiban & R. O. Ritchie

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  1. S. K. Amugongo
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  2. W. Yao
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  3. J. Jia
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  4. Y.-A. E. Lay
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  13. N. E. Lane
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Correspondence to N. E. Lane.

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Amugongo, S.K., Yao, W., Jia, J. et al. Effects of sequential osteoporosis treatments on trabecular bone in adult rats with low bone mass. Osteoporos Int 25, 1735–1750 (2014). https://doi.org/10.1007/s00198-014-2678-5

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  • DOI: https://doi.org/10.1007/s00198-014-2678-5

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