An animal trial to study damage and repair in ovariectomized rabbits

Microdamage accumulates in bone matrix and is repaired through bone remodeling. Conditions such as osteoporosis and treatment with antiresorptive bisphosphonates can influence this remodeling process. In order to study microdamage accrual and repair in the context of osteoporosis and osteon structures, we set out to modify the rabbit forelimb fatigue model. New Zealand White rabbits (N = 43, 10 months old) received either ovariectomy (OVX) or sham surgeries and were used for forelimb fatigue loading. OVX increased fluorochrome labeling of intracortical and periosteal bone of the ulna, without changes in bone mass. Monotonic and cyclic loading of the forelimb did not reveal any statistical differences between stiffness, ultimate force, or displacement to failure between sham and OVX rabbits. Two levels of fatigue loading, chosen to represent "low" and "moderate" fatigue (25% and 40% of total displacement to failure, respectively), were used on OVX forelimbs to examine microdamage creation. However, neither group showed increased damage burden as compared to non-loaded controls. Following fatigue loading rabbit ulnae had increased intracortical remodeling and periosteal lamellar bone formation in "moderate" fatigue limbs, although no basic multicellular units or microdamage-targeted remodeling was observed. In summary, we adapted the rabbit forelimb fatigue model to accommodate OVX animals. However, loading parameters that could induce repeatable microdamage burden were not identified. Thus, while increased intracortical remodeling and periosteal bone formation were induced by our fatigue loading regimen, this preliminary study did not establish conditions to allow future study of the interactions between microdamage accrual and repair.