Trabecular bone microcrack accumulation in patients treated with bisphosphonates for durations up to 16 years

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This study quantified the length, number, and density of microcracks in bone from patients treated with bisphosphonates as a function of duration. Anterior iliac crest bone samples from 51 osteoporotic Caucasian females continuously treated with oral bisphosphonates for 1–16 years were obtained by bone biopsy. Samples were histologically processed and analyzed for bone area, microcrack number, and microcrack length. The analyses used statistical modeling and considered patient age, bone mineral density, bone volume/total volume, trabecular thickness, and bone turnover as potential covariates. Microcrack density (number of microcracks/total examined bone area) was linearly related (p = 0.018) to bisphosphonate treatment duration. None of the analyzed covariates contributed significantly to the observed relationship between microcrack density and bisphosphonate treatment duration. Observed increases in microcrack density with increasing bisphosphonate treatment duration is important because increasing levels of microcracks may not only affect bone remodeling but also reduce elastic modulus and are suspected to adversely affect other mechanical properties that may influence fracture risk. The present findings add to our prior results showing changes in bone material properties and modulus with bisphosphonate treatment duration and thereby provide a more comprehensive assessment of the relationship between bisphosphonate treatment duration and bone quality. Statement of Clinical Significance: The present findings provide information guiding clinical use of oral bisphosphonates for post-menopausal osteoporosis therapy.

Original languageEnglish
Pages (from-to)1033-1039
Number of pages7
JournalJournal of Orthopaedic Research
Issue number5
StatePublished - May 2023

Bibliographical note

Funding Information:
Sole sources of funding for this study were the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health (R01 AR061578) and the Kentucky Nephrology Research Trust. Stephanie L. Pagano, MS and Pinar Emecen Huja, DDS, MS provided valuable technical assistance. Opinions expressed herein are those of the authors and do not necessarily represent the official views of the National Institutes of Health.

Publisher Copyright:
© 2022 Orthopaedic Research Society. Published by Wiley Periodicals LLC.


  • bisphosphonates
  • bone biopsy
  • bone quality
  • microcracks
  • osteoporosis therapy

ASJC Scopus subject areas

  • Orthopedics and Sports Medicine


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