The resistance of cortical bone tissue to failure under cyclic loading is reduced with alendronate.
Bisphosphonates are the most prescribed preventative treatment for osteoporosis. However, their long-term use has recently been associated with atypical fractures of cortical bone in patients who present with low-energy induced breaks of unclear pathophysiology. The effects of bisphosphonates on the mechanical properties of cortical bone have been exclusively studied under simple, monotonic, quasi-static loading. This study examined the cyclic fatigue properties of bisphosphonate-treated cortical bone at a level in which tissue damage initiates and is accumulated prior to frank fracture in low-energy situations. Physiologically relevant, dynamic, 4-point bending applied to beams (1.5 mm × 0.5 mm × 10 mm) machined from dog rib (n=12/group) demonstrated mechanical failure and micro-architectural features that were dependent on drug dose (3 groups: 0, 0.2, 1.0mg/kg/day; alendronate [ALN] for 3 years) with cortical bone tissue elastic modulus (initial cycles of loading) reduced by 21% (p<0.001) and fatigue life (number of cycles to failure) reduced in a stress-life approach by greater than 3-fold with ALN1.0 (p<0.05). While not affecting the number of osteons, ALN treatment reduced other features associated with bone remodeling, such as the size of osteons (-14%; ALN1.0: 10.5±1.8, VEH: 12.2±1.6, ×10(3) μm2; p<0.01) and the density of osteocyte lacunae (-20%; ALN1.0: 11.4±3.3, VEH: 14.3±3.6, ×10(2) #/mm2; p<0.05). Furthermore, the osteocyte lacunar density was directly proportional to initial elastic modulus when the groups were pooled (R=0.54, p<0.01). These findings suggest that the structural components normally contributing to healthy cortical bone tissue are altered by high-dose ALN treatment and contribute to reduced mechanical properties under cyclic loading conditions.
Department of Orthopaedics, New Jersey Medical School, Rutgers University, 205 S. Orange Avenue, Newark, NJ 07103, USA. Electronic address: devendrabajaj@gmail.com.
Devendra
D
Bajaj
Department of Orthopaedics, New Jersey Medical School, Rutgers University, 205 S. Orange Avenue, Newark, NJ 07103, USA; Department of Biomedical Engineering, New Jersey Institute of Technology, 323 Martin Luther King, Jr. Boulevard, Newark, NJ 07102, USA. Electronic address: geissljr@rutgers.edu.
Joseph R
JR
Geissler
Department of Anatomy and Cell Biology, Indiana University School of Medicine, 635 Barnhill Drive, Indianapolis, IN 46202, USA. Electronic address: matallen@iupui.edu.
Matthew R
MR
Allen
Department of Anatomy and Cell Biology, Indiana University School of Medicine, 635 Barnhill Drive, Indianapolis, IN 46202, USA. Electronic address: dburr@iupui.edu.
David B
DB
Burr
Department of Orthopaedics, New Jersey Medical School, Rutgers University, 205 S. Orange Avenue, Newark, NJ 07103, USA; Department of Biomedical Engineering, New Jersey Institute of Technology, 323 Martin Luther King, Jr. Boulevard, Newark, NJ 07102, USA. Electronic address: chris.fritton@rutgers.edu.
J C
JC
Fritton
D019386:Alendronate / Q000494:pharmacology*; D000818:Animals; D001696:Biomechanical Phenomena; D015519:Bone Density; D050071:Bone Density Conservation Agents / Q000494:pharmacology*; D001842:Bone and Bones / Q000187:drug effects* / Q000502:physiology; D004285:Dogs; D005260:Female; D013314:Stress, Mechanical
D050071:Bone Density Conservation Agents; D019386:Alendronate
Antiresorptives; Atypical fracture; Bone remodeling; Osteocytes; Osteoporosis