THU0413 New Formulation with Potential for the Prevention and Treatment of Osteoporosis and Osteoarthritis
Authors: A. Torrent, E. Montell, J. Vergés, R. Ruhí, P. Dalmau, M. Carceller, A. Blanco, M. Terencio, M. Ferrándiz, M. Alcaraz
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Osteoarthritis (OA) is a multidimensional disease that affects all anatomical joint structures, particularly cartilage, synovium and subchondral bone. In turn, osteoporosis (OP) is a skeletal disorder characterized by a compromised bone strength which substantially increases the risk of fracture. Both are common disorders which affect quality of life in elderly. Despite this, there is not any drug at the moment for the simultaneous prevention and treatment of osteoporosis and osteoarthritis. <h3>Objectives</h3> The aim of this study was to investigate the effect of a new formulation in a combined rat model of OP and OA. The formulation (BIS076) contains Vitamin D3, Hydroxyapatite as a source of calcium and a natural extract from porcine cartilage. The latter is rich in bioactive substances due to the mild conditions used in the manufacturing process. <h3>Methods</h3> OP was induced by ovariectomy in female Wistar rats (180-200g body weight, n= 15 rats/group) (week 0) and 2 weeks after (week 2) OA was induced by Anterior Cruciate Ligament Transection (ACLT). All surgical procedures were carried out under deep anaesthesia with isofluorane which was followed by the subcutaneous injection of butorphanol. Animals were maintained at a temperature of 21±2ºC, with a 12 hour light/dark cycle and with free access to food and tap water. BIS076 was administerd daily (oral gavage) at two doses from week 0 until wek 12 after ovariectomy. The low dose was 163.5 mg/kg/day and the high dose 245 mg/kg/day which correspond approximately to 1400 mg/day and 2100 mg/day in humans. A Control Group and an ovariectomized + ACLT Group (Vehicle Group) were also included. After week 12, animals were sacrificed. For the assessment of OA, histology was performed and cartilage degeneration was evaluated by means of the OARSI score. Synovitis degree was estimated according to the score proposed by Krenn et al. Bone microarchitecture and density were assessed by microCT. <h3>Results</h3> The preparation BIS076 has been shown to induce, at the 2 doses tested, a significant reduction (approximately 50%) of the cartilage degradation according to the OARSI score. Synovial inflammation was strongly reduced as well. In addition, microCT revealed that BIS076 treatment exerted a positive effect in bone structure, especially at the high dose: Significant increase in bone volume (p&lt;0.05), bone surface density (p&lt;0.01), trabecular number (p&lt;0.01) and significant reduction in the trabecular bone pattern factor (p&lt;0.01) compared to the Vehicle Group. <h3>Conclusions</h3> Our data demonstrate that treatment with BIS076 could be an effective strategy to control the progression of experimental Osteoarthritis and Osteoporosis. This approach holds promise for the development of improved therapies targeting these chronic and disabling diseases. <h3>Disclosure of Interest</h3> A. Torrent Employee of: Bioiberica, E. Montell Employee of: Bioiberica, J. Vergés Employee of: Bioiberica, R. Ruhí Employee of: Bioiberica, P. Dalmau Employee of: Bioiberica, M. Carceller: None Declared, A. Blanco: None Declared, M. Terencio: None Declared, M. Ferrándiz: None Declared, M. Alcaraz: None Declared