THU0205 Targeting the Bone-Driven Phenotype of OA by A Novel Calcitonin Analogue, Kbp088, Affecting Both Bone and Cartilage Turnover as Well as Metabolic Health
Authors: D. Reker, S.T. Hjuler, K. Andreassen, M.A. Karsdal, K. Henriksen, A.C. Bay-Jensen
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Osteoarthritis (OA) may be segregated into different disease phenotypes based on disease drivers; cartilage damage, joint inflammation or subchondral bone remodelling. Each phenotype may require targeted treatments. Patients with a bone-driven OA may particularly benefit from a treatment with anti-resorptive and chondro-protective properties. Salmon calcitonin (sCT), a hormone acting through CT and amylin receptors, have in multiple preclinical models been demonstrated to improve bone homeostasis and attenuate joint destruction, in part through the anti-resorptive property. In addition, sCT have recently been shown to have a positive effect on obesity and diabetes, which may benefit certain OA subjects. Several CT analogues were characterized through a larger screening program; the KBP088 analogue was found to be particular interesting for OA, by showing higher potency for the receptors than sCT. <h3>Objectives</h3> To investigate the effect of KBP088 on bone and cartilage turnover <i>in vivo</i>, and secondary investigate the effect on body weight in rats fed with high fat diet (HFD). <h3>Methods</h3> Thirty male Sprague Dawley rats (Taconic, Ry, Denmark) were given HFD for 10 weeks before they were treated with defined doses of KBP088 (0.63, 1.3, 2.5, 5, 10 ug/Kg) or vehicle as subcutaneous injections. Blood was collected from overnight fasted rats immediately at baseline, 3 and 24 hours after first treatment. Rats were treated for 8 weeks. Body weight was recorded weekly. Biomarkers of bone and cartilage degradation were assessed in the blood using the ELISAs CTX-I (bone resorption) and CTX-II (cartilage degradation). CTX-I and -II were reported as fold change baseline levels, as means with standard error of mean (SEM) and compared using two-way ANOVA assuming normal distribution. Significance levels; *P&lt;0.05, **P&lt;0.01, ***P&lt;0.001. <h3>Results</h3> Serum levels of both CTX-I and -II decrease significantly 3 hours after treatment with KBP088, even at the lowest dose tested (<i>P</i>&lt;0.05, fig. 1). Moreover, a dose-dependent response by CTX-I still remained 24 hours after treatment, suggesting increased potency. KBP088 caused a 19% vehicle-corrected weight reduction for two highest doses at the end of the experiment. <h3>Conclusions</h3> The data presented here clearly indicate a protective effect of KBP088 on both bone and cartilage <i>in vivo</i>, when evaluated by biochemical markers. Furthermore, KBP088 has demonstrated positive effects on metabolic health (cause a weight decrease), and may therefore represent a possible treatment opportunity for bone-driven OA, with an unhealthy phenotype (e.g. high BMI). Many further studies are needed to match the optimal treatment opportunity with the right OA patient for a personalized health care approach for OA. <h3>Disclosure of Interest</h3> : None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.4027