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In vivo assessment of skeletal biomechanical properties reveals beneficial effects of combination anti‐remodeling drug treatment
Author(s) -
Organ Jason M.,
Gallant Maxime A.,
Aref Mohammad,
Wallace Joseph M.,
Burr David B.,
Newman Christopher L.,
Brown Drew M.,
Allen Matthew R.
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.lb32
Subject(s) - osteoporosis , raloxifene , in vivo , medicine , bone remodeling , ex vivo , tibia , pharmacology , materials science , surgery , biology , microbiology and biotechnology , cancer , estrogen receptor , breast cancer
Pharmaceutical agents used to treat osteoporosis significantly reduce fracture risk via different mechanisms. Bisphosphonates, such as alendronate (ALN), increase bone volume and density, whereas raloxifene (RAL) improves material properties by increasing skeletal hydration. This study was designed to assess whether combination treatment improves mechanical properties more than either monotherapy. Skeletally mature female dogs (n=24) were treated with vehicle, ALN, RAL, or ALN+RAL at clinical doses used for treating post‐menopausal osteoporosis. After 6 months of daily treatment, all animals underwent in vivo biomechanical assessment using reference point indentation (RPI) on the anterior tibia cortex. The main outcome variable of RPI is indentation distance increase (IDI), a measure of cyclic indentation resistance of the bone, which is inversely related to bone toughness. IDI was significantly lower in animals treated with RAL monotherapy (−15%) and ALN+RAL (−24%) compared to vehicle‐treated animals, whereas ALN alone had no significant effect. Data suggest that RAL, and its combination with ALN, makes bone more resistant to damage initiation and propagation. Results also indicate that RPI can detect treatment‐induced alterations in skeletal mechanical properties in vivo – something previously restricted to ex vivo assessment. Funded by NIH ( AR062002 ) and Active Life Scientific.