The effect of osteoporosis treatments on fatigue properties of cortical bone tissue

Garry R. Brock, Julia T. Chen, Anthony R. Ingraffea, Jennifer MacLeay, G. Elizabeth Pluhar, Adele L. Boskey, Marjolein C.H. van der Meulen

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20 Scopus citations


Bisphosphonates are commonly prescribed for treatment of osteoporosis. Long-term use of bisphosphonates has been correlated to atypical femoral fractures (AFFs). AFFs arise from fatigue damage to bone tissue that cannot be repaired due to pharmacologic treatments. Despite fatigue being the primary damage mechanism of AFFs, the effects of osteoporosis treatments on fatigue properties of cortical bone are unknown. To examine if fatigue-life differences occur in bone tissue after different pharmacologic treatments for osteoporosis, we tested bone tissue from the femurs of sheep given a metabolic acidosis diet to induce osteoporosis, followed by treatment with a selective estrogen reception modulator (raloxifene), a bisphosphonate (alendronate or zoledronate), or parathyroid hormone (teriparatide, PTH). Beams of cortical bone tissue were created and tested in four-point bending fatigue to failure. Tissue treated with alendronate had reduced fatigue life and less modulus loss at failure compared with other treatments, while tissue treated with PTH had a prolonged fatigue life. No loss of fatigue life occurred with zoledronate treatment despite its greater binding affinity and potency compared with alendronate. Tissue mineralization measured by microCT did not explain the differences seen in fatigue behavior. Increased fatigue life with PTH suggests that current treatment methods for AFF could have beneficial effects for restoring fatigue life. These results indicate that fatigue life differs with each type of osteoporosis treatment.

Original languageEnglish (US)
Pages (from-to)8-13
Number of pages6
JournalBone Reports
StatePublished - Jun 1 2015

Bibliographical note

Funding Information:
Funding provided by NIH AR053571 , NIH AR041325 , NIH EB004321 , and the NSF GRFP . We thank Laura Nielsen for her help preparing the PTH samples.

Funding Information:
Disclosures:Garry R. Brock: no disclosures.Julia T. Chen: no disclosures.Anthony R. Ingraffea: no disclosures.Jennifer MacLeay: current address 3631 SW Stonybrook Drive, Topeka, KS.G. Elizabeth Pluhar: no disclosures.Adele Boskey: grant paid to institution: NIH AR041325 . Marjolein C.H. van der Meulen: grant paid to institution: NIH AR053571 , NIH EB004321 ; and board membership: Relievant Medsystems, Scientific Advisory Board.

Publisher Copyright:
© 2014 Elsevier Inc.


  • Biomechanics
  • Bisphosphonate
  • Fatigue testing
  • Metabolic acidosis
  • Osteoporosis
  • Raloxifene


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