Exercise reverses pain-related weight asymmetry and differentially modulates trabecular bone microarchitecture in a rat model of osteoarthritis

There is great interest in developing and utilizing non-pharmacological/non-invasive forms of therapy for osteoarthritis (OA) pain including exercise and other physical fitness regimens. Aims: The present experiments determined the effects of prior wheel running on OA-induced weight asymmetry and trabecular bone microarchitecture. Main methods: Wheel running included 7 or 21 days of prior voluntary access to wheels followed by OA induction, followed by 21 days post-OA access to wheels. OA was induced with monosodium iodoacetate (MIA), and weight asymmetry was measured using a hind limb weight bearing apparatus. Bone microarchitecture was characterized using ex vivo mu CT. Key findings: Relative to saline controls, MIA (3.2 mg/25 mu l) produced significant weight asymmetry measured on post-days (PDs) 3, 7, 14, 21 in sedentary rats. Seven days of prior running failed to alter MIA-induced weight asymmetry. In contrast, 21 days of prior running resulted in complete reversal of MIA induced weight asymmetry on all days tested. As a comparator, the opioid agonist morphine (3.2-10 mg/kg) dose-dependently reversed weight asymmetry on PDs 3, 7, 14, but was ineffective in later stage (PD 21) OA. In runners, Cohen's d (effect sizes) for OA vs. controls indicated large increases in bone volume fraction, trabecular number, trabecular thickness, and connective density in lateral compartment, and large decreases in the same parameters in medial compartment. In contrast, effect sizes were small to moderate for sedentary OA vs. controls. Significance: Results indicate that voluntary exercise may protect against OA pain, the effect varies as a function of prior exercise duration, and is associated with distinct trabecular bone modifications. (C) 2017 Elsevier Inc. All rights reserved.