Recent Advances in Understanding Bisphosphonate Effects on Bone Mechanical Properties
Purpose of the Review
Bisphosphonates have well-established effects on suppressing bone resorption and slowing bone loss, yet the effects on bone mechanical properties are less clear. We review recent data from pre-clinical and clinical experiments that assessed mechanical properties of bisphosphonate-treated specimens.
Pre-clinical work has utilized new techniques to show reduced fatigue life and transfer of stress from the mineral to collagen. Several notable studies have examined mechanical properties of tissue from patients treated with bisphosphonates with mixed results. Pre-clinical data suggest effects on mechanics may be independent of remodeling suppression.
The direct effect of bisphosphonates on bone mechanics remains unclear but recent work has set a solid foundation for the coming years.
KeywordsAtypical fracture Zoledronate Remodeling suppression Anti-remodeling Biomechanics
This work was supported by a United States (U.S.) Department of Veterans Affairs Merit Award (BX003025) and a NIH grant AR62002 to MRA.
Compliance with Ethical Standards
Conflict of Interest
Matthew Allen declares no conflict of interest.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
Papers of particular interest, published recently, have been highlighted as: •• Of major importance
- 4.•• Ettinger B, Burr DB, Ritchie RO. Proposed pathogenesis for atypical femoral fractures: lessons from materials research. Bone. 2013;55(2):495–500. A high-level review of atypical femoral fractures with proposed mechanisms written by thought-leaders in the field. Google Scholar
- 7.Allen MR. Preclinical models for skeletal research: how commonly used species mimic (or don’t) aspects of human bone. Toxicol Pathol. 2017;4:019262331773392–4.Google Scholar
- 10.•• Kostenuik P. On the evolution and contemporary roles of bone remodeling. In: Marcus R, Feldman D, Dempster DW, Luckey M, Cauley JA, editors. Osteoporosis. 4th ed. Amsterdam: Academic Press; 2013. pp. 873–914. A review of pre-clinical studies focused on bisphosphonates (actually on anti-osteoporosis agents in general) and mechanical properties. CrossRefGoogle Scholar
- 18.Ma S, Goh EL, Jin A, Bhattacharya R, Boughton OR, Patel B, et al. Long-term effects of bisphosphonate therapy: perforations, microcracks and mechanical properties. Sci Rep Nat Publ Group. 2017:1–10.Google Scholar
- 19.•• Zimmermann EA, Schaible E, Gludovatz B, Schmidt FN, Riedel C, Krause M, et al. Intrinsic mechanical behavior of femoral cortical bone in young, osteoporotic and bisphosphonate- treated individuals in low- and high energy fracture conditions. Sci Rep Nat PublGroup. 2016:1–12. https://www.ncbi.nlm.nih.gov/pubmed/26879146. Detailed mechanical assessment of clinical tissue from bisphosphonate (and control) treated individuals.
- 21.•• Lloyd AA, Gludovatz B, Riedel C, Luengo EA, Saiyed R, Marty E, et al. Atypical fracture with long-term bisphosphonate therapy is associated with altered cortical composition and reduced fracture resistance. Proc Natl Acad Sci U S A. 2017;49:201704460–6. Detailed mechanical assessment of clinical tissue from bisphosphonate (and control)-treated individuals. A sub-set of these samples were from patients who experienced atypical femoral fractures—the only data that currently exists from such patients. Google Scholar
- 22.Ward J, Wood C, Rouch K, Pienkowski D, Malluche HH. Stiffness and strength of bone in osteoporotic patients treated with varying durations of oral bisphosphonates. Osteoporos Int. 2016;27(9):2681–2688.Google Scholar