Recent advances in understanding the phenotypes of osteoarthritis

Abstract

Recent research in the field of osteoarthritis (OA) has focused on understanding the underlying molecular and clinical phenotypes of the disease. This narrative review article focuses on recent advances in our understanding of the phenotypes of OA and proposes that the disease represents a diversity of clinical phenotypes that are underpinned by a number of molecular mechanisms, which may be shared by several phenotypes and targeted more specifically for therapeutic purposes. The clinical phenotypes of OA supposedly have different underlying etiologies and pathogenic pathways and they progress at different rates. Large OA population cohorts consist of a majority of patients whose disease progresses slowly and a minority of individuals whose disease may progress faster. The ability to identify the people with relatively rapidly progressing OA can transform clinical trials and enhance their efficiency. The identification, characterization, and classification of molecular phenotypes of rapidly progressing OA, which represent patients who may benefit most from intervention, could potentially serve as the basis for precision medicine for this disabling condition. Imaging and biochemical markers (biomarkers) are important diagnostic and research tools that can assist with this challenge.

Sustained Acoustic medicine; Sonophoresis for Nonsteroidal anti-inflammatory Drug Delivery in Arthritis

“…Arthritis is the pathology of the full joint, which leads to degeneration of cartilage, meniscus, tendon and bone due to a highly inflammatory environment over a long time [ 4 ]. COX-1/2 pathway regulates the most common inflammatory cytokines involved in the degradation of joints, which are known for joint destruction but also because of underlying pain associated with arthritis.…”

“…There are multiple kinds of arthritis, with osteoarthritis and rheumatoid arthritis being the two primary forms [ 1–3 ]. It is the disease of the whole joint, which involves activation of catabolic enzymes, nitric oxide synthase-2, cyclooxygenases-(COX)-2, degradation of the matrix through matrix metalloproteinases (MMP-1, MMP-3 and MMP-13), a disintegrin and metalloproteinase with thrombospondin-1 domains 4 and 5 and activation of cytokines, such as (IL-6, IL-1β and TNF-α), leading to the destruction of the total joint and chronic pain [ 4–7 ].…”

“…Currently, there is no cure for arthritis and arthritis-induced pain. The pain is managed through weight loss, physical therapy, hot/cold therapy, ultrasound therapy, compression therapy and either systemic or topical nonsteroidal anti-inflammatory drugs (NSAIDs) [ 4 , 8 , 9 ]. Ultimately most patients with moderate-to-severe arthritis progress onto surgical procedures to repair and/or replace the damaged joint [ 10 ].…”

Quantification of hip effusion-synovitis and its cross-sectional and longitudinal associations with hip pain, MRI findings and early radiographic hip OA

“…OA has been historically categorized as non-inflammatory arthritis [2,4]. However, synovitis plays a key role in cartilage damage and vice versa [1,2,5]. Occurring in either early or late stages of OA, synovitis leads to increase in catabolic and proinflammatory mediators such as cytokines, nitric oxide, prostaglandin E, and neuropeptides.…”

Blood levels of matrix metalloproteinase generated C-reactive protein metabolite (CRPM) are a sensitive measure of chronic inflammation in OA

“…Anti-in ammatory treatment options (anti-TNF-alpha and anti-IL-1R1) [3][4][5] have been tested interventional trial including patient populations with de ned OA, however with no or limited description to their phenotype that may indicate differential response across different sub-populations. It has been suggested that a drug like lutikizumab (monoclonal antibody against IL1α/β) would work in patients with an in ammatory phenotype, while sprifermin (recombinant and truncated form of broblast growth factor 18) would work in patients with cartilage repair endotype [6][7][8]. There is a clear medical need to identify phenotypes in OA to enable development of more e cacious drugs.…”