Inhibited osteoclastic bone resorption through alendronate treatment in rats reduces severe osteoarthritis progression

• Published in: Bone (New York, N.Y.) N.Y.), 2014-09, Vol.66, p.163-170
• Main Authors: Siebelt, M, Waarsing, J.H, Groen, H.C, Müller, C, Koelewijn, S.J, de Blois, E, Verhaar, J.A.N, de Jong, M, Weinans, H
• Format: Article
• Language: English
• Subjects: Alendronate; Alendronate - pharmacology; Alendronate - therapeutic use; Animals; Articular cartilage; Biological and medical sciences; Body Weight - drug effects; Bone and Bones - diagnostic imaging; Bone and Bones - drug effects; Bone and Bones - pathology; Bone Resorption - complications; Bone Resorption - drug therapy; Bone Resorption - pathology; Cartilage, Articular - drug effects; Cartilage, Articular - pathology; Disease Progression; Diseases of the osteoarticular system; Exercise; Fundamental and applied biological sciences. Psychology; Macrophage Activation - drug effects; Male; Medical sciences; Orthopedics; Osteoarthritis; Osteoarthritis - complications; Osteoarthritis - drug therapy; Osteoarthritis - pathology; Osteoclast; Osteoclasts - drug effects; Osteoclasts - pathology; Rats, Wistar; Skeleton and joints; Subchondral bone; Synovial Membrane - drug effects; Synovial Membrane - pathology; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Vertebrates: osteoarticular system, musculoskeletal system; X-Ray Microtomography
• ISSN: 8756-3282; 1873-2763
• DOI: 10.1016/j.bone.2014.06.009

Abstract Osteoarthritis (OA) is a non-rheumatoid joint disease characterized by progressive degeneration of extra-cellular cartilage matrix (ECM), enhanced subchondral bone remodeling, osteophyte formation and synovial thickening. Alendronate (ALN) is a potent inhibitor of osteoclastic bone resorption and results in reduced bone remodeling. This study investigated the effects of pre-emptive use of ALN on OA related osteoclastic subchondral bone resorption in an in vivo rat model for severe OA. Using multi-modality imaging we measured effects of ALN treatment within cartilage and synovium. Severe osteoarthritis was induced in left rat knees using papain injections in combination with a moderate running protocol. Twenty rats were treated with subcutaneous ALN injections and compared to twenty untreated controls. Animals were longitudinally monitored for 12 weeks with in vivo μCT to measure subchondral bone changes and SPECT/CT to determine synovial macrophage activation using a folate-based radiotracer. Articular cartilage was analyzed at 6 and 12 weeks with ex vivo contrast enhanced μCT and histology to measure sulfated-glycosaminoglycan (sGAG) content and cartilage thickness. ALN treatment successfully inhibited subchondral bone remodeling. As a result we found less subchondral plate porosity and reduced osteophytosis. ALN treatment did not reduce subchondral sclerosis. However, after the OA induction phase, ALN treatment protected cartilage ECM from degradation and reduced synovial macrophage activation. Surprisingly, ALN treatment also improved sGAG content of tibia cartilage in healthy joints. Our data was consistent with the hypothesis that osteoclastic bone resorption might play an important role in OA and may be a driving force for progression of the disease. However, our study suggest that this effect might not solely be effects on osteoclastic activity, since ALN treatment also influenced macrophage functioning. Additionally, ALN treatment and physical activity exercised a positive effect in healthy control joints, which increased cartilage sGAG content. More research on this topic might lead to novel insights as to improve cartilage quality.