Effect of short-term treatment with alendronate on ulnar bone adaptation to cyclic fatigue loading in rats.
Targeted remodeling of fatigue-injured bone involves activation of osteoclastic resorption followed by local bone formation by osteoblasts. We studied the effect of parenteral alendronate (ALN) on bone adaptation to cyclic fatigue. The ulnae of 140 rats were cyclically loaded unilaterally until 40% loss of stiffness developed. We used eight treatment groups: (1) baseline control; (2) vehicle (sterile saline) and (3) alendronate before fatigue, no adaptation (Pre-VEH, Pre-ALN, respectively); (4) vehicle and (5) alendronate during adaptation to fatigue (Post-VEH, Post-ALN, respectively); (6) vehicle before fatigue and during adaptation (Pre-VEH/Post-VEH); (7) alendronate before fatigue and vehicle during adaptation (Pre-ALN/Post-VEH); (8) alendronate before fatigue and during adaptation (Pre-ALN/Post-ALN). Bones from half the rats/group were tested mechanically; remaining bones were examined histologically. The following variables were quantified: volumetric bone mineral density (vBMD); ultimate force (F(u)); stiffness (S); work-to-failure (U); cortical area (Ct.Ar); new woven bone tissue area (Ne.Wo.B.T.Ar); resorption space density (Rs.N/T.Ar). Microcracking was only seen in fatigue-loaded ulnae. A significant effect of alendronate on vBMD was not found. Preemptive treatment with alendronate did not protect the ulna from structural degradation during fatigue. After fatigue, recovery of mechanical properties by adaptation occurred; here a significant alendronate effect was not found. An alendronate-specific effect on adaptive Ne.Wo.B.T.Ar was not found. In the fatigue-loaded ulna, Rs.N/T.Ar was increased in vehicle-treated adapted groups, but not alendronate-treated adapted groups, when compared with baseline control. These data suggest that short-term alendronate treatment does not protect bone from fatigue in this model. Inhibition of remodeling may reduce microcrack repair over time.
Barrett
Jennifer G
JG
Comparative Orthopaedic Research Laboratory, School of Veterinary Medicine, University of Wisconsin--Madison, 2015 Linden Drive, Madison, Wisconsin 53706, USA.
Sample
Susannah J
SJ
McCarthy
Jenna
J
Kalscheur
Vicki L
VL
Muir
Peter
P
Prokuski
Laura
L
D000222:Adaptation, Physiological / Q000187:drug effects*; D019386:Alendronate / Q000494:pharmacology*; D000818:Animals; D015519:Bone Density / Q000187:drug effects; D016723:Bone Remodeling / Q000187:drug effects / Q000502:physiology; D015775:Fractures, Stress / Q000209:etiology* / Q000517:prevention & control; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D014457:Ulna / Q000502:physiology*; D014458:Ulna Fractures / Q000209:etiology
D019386:Alendronate