Effect of alendronate on fracture healing and bone remodeling in dogs.
To examine the effect of alendronate (4-amino-1-hydroxybutylidene bisphosphonate) on fracture repair, the drug was given to mature beagle dogs orogastrically at 2 mg/kg/day for 9 weeks preceding fracture. 16 weeks after fracture, or both before and after fracture (25 weeks). A transverse mid-diaphyseal fracture of the right radius was surgically induced and was stabilized by external coaptation splinting. Fracture healing and bone remodeling were evaluated by radiography, gross and histological examination, and bone histomorphometry. The mechanical properties of the fracture callus were determined by a four-point bending test. Radiographs and gross and microscopic examination demonstrated normal bone healing at the fracture site in all dogs. In dogs that received alendronate during the fracture healing period, at 16 weeks the calluses were approximately 2-3 times larger than those in dogs that received a placebo during the healing period. This is consistent with slower callus bone remodeling, an expected pharmacological effect of the compound. Bone histomorphometry demonstrated that treatment with alendronate did not inhibit bone formation or mineralization. Mechanical testing showed that the ultimate load at failure and the flexural rigidity of both the fractured and contralateral intact bone were unaffected by treatment with alendronate. Therefore, in this study, treatment with alendronate before or during fracture healing, or both, resulted in no adverse effects on the union, strength, or mineralization of bone in mature beagle dogs.
Peter
C P
CP
Merck Research Laboratories, West Point, PA 19486, USA.
Cook
W O
WO
Nunamaker
D M
DM
Provost
M T
MT
Seedor
J G
JG
Rodan
G A
GA
D019386:Alendronate; D000818:Animals; D001696:Biomechanical Phenomena; D015519:Bone Density; D016723:Bone Remodeling / Q000187:drug effects*; D004164:Diphosphonates / Q000494:pharmacology*; D004285:Dogs; D005260:Female; D017102:Fracture Healing / Q000187:drug effects*; D008297:Male; D011859:Radiography; D011885:Radius Fractures / Q000000981:diagnostic imaging / Q000503:physiopathology*
D004164:Diphosphonates; D019386:Alendronate