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Histomorphometric changes by teriparatide in alendronate-pretreated women with osteoporosis

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Abstract

Summary

The level of increased bone formation after 24 months of treatment with teriparatide (rhPTH (1–34), TPTD) is similar in patients who were either treatment-naïve (TN) or had lower bone turnover initially due to previous alendronate (ALN) therapy.

Introduction

Bone anabolic effects of TPTD in postmenopausal women with osteoporosis may be blunted during the initial phase after switching from ALN to TPTD. To explore the long-term implications, we examined histomorphometric and biochemical markers of bone turnover of patients on TPTD therapy after long-term ALN treatment.

Methods

Paired biopsies were obtained after tetracycline double labeling at baseline and after 24 months of TPTD treatment from 29 ALN-pretreated (64.5 ± 16.4 months) and 16 TN patients. Biochemical markers were measured at baseline, during the treatment, or at study end.

Results

Compared with the baseline, after 24-month TPTD, activation frequency (Ac.F.) and osteoid surface (OS) increased in both groups: 0.11–0.34 cycles per year, 3.96–9.8% in the ALN-pretreated group and 0.19–0.33 cycles per year, 6.2–11.3% (p < 0.05) in the TN group, respectively. Biochemical and histomorphometric markers correlated positively both at baseline and endpoint. Serum amino terminal propeptide of type I procollagen (PINP) correlated with Ac.F. (r = 0.57, p < 0.001 and r = 0.48, p < 0.01) and OS (r = 0.51, p < 0.01 and r = 0.56, p < 0.01) at baseline and endpoint, respectively. Following 3 months of treatment, increases in biochemical markers like PINP predicted the increase in Ac.F. (r = 0.52, p < 0.01) and OS (r = 0.54, p < 0.01) after 24 months.

Conclusions

The increased level of formation is similar in patients who were either TN or had lower bone turnover initially due to previous ALN therapy. Elevated bone formation in postmenopausal women with osteoporosis was sustained over a 24-month period by TPTD. Biochemical markers of bone formation are a good surrogate for the assessment of TPTD effects.

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Acknowledgment

This study (NCT00191893) was sponsored by Eli Lilly and Company. The authors would like to thank Gail Dalsky for critically reviewing the manuscript and Simone Wille for assisting in the preparation of this manuscript.

Conflicts of interest

Dr. Burr is a member of the Scientific Advisory Board for Eli Lilly and Company. He also serves as a consultant to The Alliance for Better Bone Health. He has research support from Eli Lilly and Company, The Alliance for Better Bone Health, and Amgen. Drs. Sipos, Ma, and Pavo are shareholders and full-time employees of Eli Lilly and Company; Petto M.Sc. is a full-time employee of Eli Lilly and Company. All other authors state that they have no conflicts of interests.

Author information

Authors and Affiliations

  1. Institute of Rheumatology, Faculty of Medicine, Charles University, Na Slupi 4, CZ12850, Prague, Czech Republic

    J. J. Stepan

  2. Department of Anatomy and Cell Biology, Indiana University School of Medicine, Indianapolis, IN, USA

    D. B. Burr

  3. Department of Orthopaedic Surgery, Indiana University School of Medicine, Indianapolis, IN, USA

    D. B. Burr

  4. Department of Biology, Indiana University–Purdue University Indianapolis, Indianapolis, IN, USA

    J. Li

  5. Lilly Research Laboratories, Indianapolis, IN, USA

    Y. L. Ma, H. Petto, A. Sipos & I. Pavo

  6. Division of Endocrinology and Nuclear Medicine, Department of Internal Medicine, Medical University of Graz, Graz, Austria

    H. Dobnig & A. Fahrleitner-Pammer

  7. Department of Internal Medicine 3, Faculty of Medicine, Charles University, Prague, Czech Republic

    D. Michalská

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  1. J. J. Stepan
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  2. D. B. Burr
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  10. I. Pavo
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Correspondence to J. J. Stepan.

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Stepan, J.J., Burr, D.B., Li, J. et al. Histomorphometric changes by teriparatide in alendronate-pretreated women with osteoporosis. Osteoporos Int 21, 2027–2036 (2010). https://doi.org/10.1007/s00198-009-1168-7

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  • DOI: https://doi.org/10.1007/s00198-009-1168-7

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