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Teriparatide in Bisphosphonate-Resistant Osteoporosis: Microarchitectural Changes and Clinical Results After 6 and 18 months

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Abstract

A number of osteoporotic patients under bisphosphonate treatment present persistent fragility fractures and bone loss despite good compliance. The objective of this 18-month prospective study was to investigate the effect of teriparatide [rhPTH(1–34)] in 25 female osteoporotics who were inadequate responders to oral bisphosphonates and to correlate microarchitectural changes in three consecutive iliac crest biopsies measured by micro-computed tomography (μCT) with bone mineral density (BMD) and bone serum markers. Scanned biopsies at baseline (M0), 6 months (M6), and 18 months (M18) demonstrated early significant (P < 0.01) increases in bone volume per tissue volume (+34%) and trabecular number (+14%) at M6 with only moderate changes in most μCT structural parameters between M6 and M18. μCT-measured bone tissue density was significantly decreased at M18, expressing an overall lower degree of tissue mineralization characteristic for new bone formation despite unchanged trabecular thickness due to increased intratrabecular tunneling at M18. μCT results were consistent with serum bone turnover markers, reaching maximal levels of bone alkaline phosphatase and serum β-crosslaps at M6, with subsequent decline until M18. BMD assessed by DXA demonstrated persistent increases at the lumbar spine until M12, whereas no significant change was observed at the hip. Type (alendronate/risedronate) and duration (3.5 ± 4 years) of prior bisphosphonate treatment did not influence outcome on μCT, BMD, or bone marker results. The overall results indicate a positive ceiling effect of teriparatide on bone microarchitecture and bone markers after 6 and 12 months for lumbar spine BMD, with no additional gain until M18 in bisphosphonate nonresponders.

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Acknowledgement

We thank all of the patients who participated in this study. The study was supported by Lilly, Germany. We also greatly appreciate bone biopsy preparations by members of the former Institut of Bone Pathology, University of Hamburg-Eppendorf. B. J. received research funding for this study and travel support for ASBMR meetings from Lilly, Germany. However, the authors were fully responsible for all content and editorial decisions and received no financial support or other form of compensation related to the development of the report. The study sponsor was not involved in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit for publication.

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Authors and Affiliations

  1. Department of Radiology and Biomedical Imaging, Musculoskeletal and Quantitative Imaging Research Group, University of California, San Francisco, San Francisco, CA, USA

    B. Jobke, A. J. Burghardt, T. M. Link & S. Majumdar

  2. Department of Osteology, Immanuel-Hospital and Rheumaklinik Berlin-Buch, Berlin, Germany

    B. Muche & J. Semler

  3. Department of Radiology, Helios Klinikum Berlin-Buch, Schwanebecker Chaussee 50, 13125, Berlin, Germany

    B. Jobke

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  1. B. Jobke
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Correspondence to B. Jobke.

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Jobke and Muche have received travel support from Lilly, Germany. All other authors have stated no conflict of interest.

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Jobke, B., Muche, B., Burghardt, A.J. et al. Teriparatide in Bisphosphonate-Resistant Osteoporosis: Microarchitectural Changes and Clinical Results After 6 and 18 months. Calcif Tissue Int 89, 130–139 (2011). https://doi.org/10.1007/s00223-011-9500-6

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