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Postmenopausal women treated with combination parathyroid hormone (1–84) and ibandronate demonstrate different microstructural changes at the radius vs. tibia: the PTH and Ibandronate Combination Study (PICS)

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Abstract

Summary

In postmenopausal women receiving combination parathyroid hormone (PTH) (1–84) therapy and ibandronate, we evaluated bone microarchitecture and biomechanics using high-resolution peripheral quantitative computed tomography (HR-pQCT). Cortical and trabecular changes were different at the nonweight-bearing radius vs. the weight-bearing tibia, with more favorable overall changes at the tibia.

Introduction

PTH therapy and bisphosphonates decrease fracture risk in postmenopausal osteoporosis, but their effects on bone microstructure and strength have not been fully characterized, particularly during combination therapy. PTH increases trabecular bone mineral density (BMD) substantially but may decrease cortical BMD, possibly by stimulating intracortical remodeling. We evaluated bone microarchitecture and biomechanics with HR-pQCT at the radius (a nonweight-bearing site) and tibia (weight bearing) in women receiving combination PTH(1–84) and ibandronate.

Methods

Postmenopausal women with low bone mass (n = 43) were treated with 6 months of PTH(1–84) (100 μg/day), either as one 6- or two 3-month courses, in combination with ibandronate (150 mg/month) over 2 years. HR-pQCT was performed before and after therapy.

Results

Because changes in HR-pQCT parameters did not differ between treatment arms, groups were pooled into one cohort for analysis. Trabecular BMD increased at both radius and tibia (p < 0.01 for each). Cortical thickness and BMD decreased at the radius (p < 0.01), consistent with changes in dual-energy X-ray absorptiometry, while these parameters did not change at the tibia (p ≤ 0.02 for difference between radius and tibia). In contrast, cortical porosity increased at the tibia (p < 0.01) but not radius. Stiffness and failure load decreased at the radius (p < 0.0001) but did not change at the tibia.

Conclusions

Cortical and trabecular changes in response to the PTH/ibandronate treatment combinations utilized in this study were different at the nonweight-bearing radius vs. the weight-bearing tibia, with more favorable overall changes at the tibia. Our findings support the possibility that weight bearing may optimize the effects of osteoporosis therapy.

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Acknowledgments

The PICS trial was supported by an investigator-initiated grant (to DMB) from Genentech, Inc., a member of the Roche group. The sponsor was involved in study design but not in the collection, analysis, or interpretation of data, nor in the writing of the article. Study drugs were supplied by NPS Pharmaceuticals (PTH[1–84]), Genentech (ibandronate), and Bayer (calcium citrate + D3). Reagents for bone turnover marker assays were provided by Roche Diagnostics. The authors have full control of all data. Additional support was provided by the Department of Veterans Affairs through an Advanced Fellowship in Women’s Health (to ALS), a Career Development Award under contract 5 IK2 CX000549-02 (to ALS), and the Research Enhancement Award Program (to DMS); by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) under contracts R01-AR055588 (to DMS) and R01-AR060700 (to AJB); and by NIAMS, the National Institute on Aging, and the National Institute of Biomedical Imaging and Bioengineering under contract R01-AG017762 (to SM). The authors thank Jean Hietpas, Lucy Wu, and Laurel Denton for their roles in study direction and data coordination; Rayshawnda Davis, Natasha Rathbun, Andrea Hacker, and Makani da Silva for study coordination and DXA scan acquisition; Melissa Guan, Thelma Munoz, and S. Paran Yap for their roles in HR-pQCT coordination, image acquisition, and analysis; and Richard Eastell, MD, and Fatma Gossiel for analysis of bone turnover markers.

Conflicts of interest

ALS, AJB, and SM state that they have nothing to disclose. DES has received research support from Amgen and Novartis. LP has consulted for NPS and Nycomed. DMS has consulted for Lilly. DMB has received research support from Amgen, Merck, Novartis, and Roche and has consulted for Nycomed.

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Authors and Affiliations

  1. Endocrine Research Unit, San Francisco Veterans Affairs Medical Center, 4150 Clement Street, 111N, San Francisco, CA, 94121, USA

    A. L. Schafer & D. M. Shoback

  2. Department of Medicine, University of California, San Francisco, USA

    A. L. Schafer & D. M. Shoback

  3. Department of Radiology and Biomedical Imaging, University of California, San Francisco, USA

    A. J. Burghardt & S. Majumdar

  4. Department of Medicine, Johns Hopkins University, Baltimore, USA

    D. E. Sellmeyer

  5. Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco USA

    L. Palermo & D. M. Black

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  1. A. L. Schafer
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  2. A. J. Burghardt
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  3. D. E. Sellmeyer
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  4. L. Palermo
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  5. D. M. Shoback
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  6. S. Majumdar
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Correspondence to A. L. Schafer.

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Schafer, A.L., Burghardt, A.J., Sellmeyer, D.E. et al. Postmenopausal women treated with combination parathyroid hormone (1–84) and ibandronate demonstrate different microstructural changes at the radius vs. tibia: the PTH and Ibandronate Combination Study (PICS). Osteoporos Int 24, 2591–2601 (2013). https://doi.org/10.1007/s00198-013-2349-y

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