BACKGROUND/RATIONALE: Introducing new or testing existing drugs in an attempt to modify the progress of osteoarthritis (OA) is of paramount importance.QUESTIONS/PURPOSES: This study aims to determine the effect exerted by Calcitonin on the progress of early-stage osteoarthritic lesions.METHODS: We used 18, skeletally mature, white, female, New Zealand rabbits. OA was operatively induced in the right knee of each animal by the complete dissection of the anterior cruciate ligament, complete medial meniscectomy and partial dissection of the medial collateral ligament. Postoperatively, animals were divided into two groups. Starting on the ninth postoperative day and daily thereafter, group A animals (n = 9) received 10 IU oculus dexter (o.d.) of synthetic Calcitonin IntraMuscularly (I.M.); group B animals (n = 9) received equal volume of saline o.d. Three animals from each group were sacrificed at 1, 2 and 3 months following treatment's initiation. The extent and the grade of OA were assessed macroscopically, histologically and by radiographs, Computed Tomography (CT) and Magnetic Resonance Imaging (MRI)-scans. The Osteoarthritis Research Society International (OARSI) score, incorporating histological and macroscopic information, was calculated for each knee.RESULTS: Osteoarthritic changes in group A animals were less severe and progressed less rapidly when compared with those of group B animals (sham). This difference was statistically significant in the first and second month (P = 0.05), but not in the third month (P = 0.513).CONCLUSIONS: I.M. administration of Calcitonin seems to delay the progress of early-stage osteoarthritic lesions induced by mechanical instability in a rabbit experimental model.