A dual amylin and calcitonin receptor agonist inhibits pain behavior and reduces cartilage pathology in an osteoarthritis rat model

Abstract

Pain and disability are the main clinical manifestations of osteoarthritis, for which only symptomatic therapies are available. Hence, there is a need for therapies that can simultaneously alter disease progression and provide pain relief. KBP is a dual amylin- and calcitonin-receptor agonist with antiresorptive and chondroprotective properties. In this study we investigated the effect of KBP in a rat model of osteoarthritis. Medial meniscectomy (MNX) was performed in 39 rats, while 10 underwent sham surgery. Rats were treated with KBP and/or naproxen. Nociception was assessed by mechanical and cold allodynia, weight bearing asymmetry, and burrowing behavior. Blood samples were collected for biomarker measurements, and knees for histology. Cartilage histopathology was evaluated according to the advanced Osteoarthritis Research International (OARSI) score and KBPs invitro antiresorptive effects were assessed using human osteoclasts cultured on bone. The MNX animals displayed an increased nociceptive behavior. Treatment with KBP attenuated the MNX-induced osteoarthritis-associated joint pain. The cartilage histopathology was significantly lower in rats treated with KBP than in MNX animals. Bone and cartilage degradation, assessed by CTX-I and CTX-II plasma levels, were decreased in all KBP-treated groups and KBP potently inhibited bone resorption invitro. Our study demonstrates the effectiveness of KBP in ameliorating osteoarthritis-associated joint pain and in protecting the articular cartilage, suggesting KBP as a potential drug candidate for osteoarthritis.