Emerging drugs for osteoarthritis

Abstract

Introduction Osteoarthritis (OA), the most prevalent form of joint disease, affecting as much as 13% of the world’s population. In the United States, it is the leading cause of disability in people over age 65 and is characterized by progressive cartilage loss, bone remodeling, osteophyte formation and synovial inflammation with resultant joint pain and disability. There are no treatments marketed for structural disease modification; current treatments mainly target symptoms, with >75% of patients reporting need for additional symptomatic treatment. Areas covered Drugs in later development (Phase II-III) for osteoarthritis pain and joint structural degeneration are reviewed. Not covered are procedural (e.g. arthrocentesis, physical therapy), behavioral (e.g. weight loss, pain coping techniques) or device (e.g. knee braces, surgical implants) based treatments. Expert opinion More in depth understanding of the pathophysiology of the disease, as well as elucidation of the link between clinical symptomatology and structural changes in the joint will likely lead to development of novel target classes with promising efficacy in the future. Efficacy notwithstanding, there remain significant hurdles to overcome in clinical development of these therapeutics, inherent in the progression pattern of the disease as well as challenges with readouts for both pain and structure modification trials.

TGF-β Family Signaling in Connective Tissue and Skeletal Diseases

“…BMP-7 possesses cartilage-protective properties by enhancing the expression of cartilage ECM and counteracting catabolic enzyme synthesis (Huch et al 1997;Im et al 2003). Clinical application of BMP-7 as a treatment for OA is promising with greater symptomatic improvement in comparison to placebo treated group (Hunter et al 2010;Matthews and Hunter 2011).…”

Focused Low-intensity Pulsed Ultrasound Affects Extracellular Matrix Degradation via Decreasing Chondrocyte Apoptosis and Inflammatory Mediators in a Surgically Induced Osteoarthritic Rabbit Model

“…Although various management techniques are available for the treatment of OA, there are presently no therapies that modify the onset or progression of OA-induced structural damage (Matthews and Hunter 2011;Zhang et al 2010). Ultrasound (US) treatment has been used as a non-invasive modality for management of OA over the past 60 y because it relieves pain through thermal and non-thermal modalities (mechanical effects; Ter Haar 1999).…”

A rabbit model demonstrates the influence of cartilage thickness on intra‐articular drug delivery and retention within cartilage

“…[1][2][3] Many potential OA therapies have shown beneficial effects in animals but have failed in human clinical trials. [4][5][6] The translatability of preclinical research is largely dependent on the anatomical and biomechanical similarities between the animal models used and humans. 2,7 Small animals have commonly been used in OA research due to their lower costs and ease of manipulation relative to larger species; more recently, the development of transgenic mouse models have broadened their utility.…”