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Osteoarthritis (OA) is the leading cause of function loss and disability among the elderly, with significant burden on the individual and society. It is a severe disease for its high disability rates, morbidity, costs, and increased mortality. Multifactorial etiologies contribute to the occurrence and development of OA. The heterogeneous condition poses a challenge for the development of effective treatment for OA; however, emerging treatments are promising to bring benefits for OA management in the future. This narrative review will discuss recent developments of agents for the treatment of OA, including potential disease-modifying osteoarthritis drugs (DMOADs) and novel therapeutics for pain relief. This review will focus more on drugs that have been in clinical trials, as well as attractive drugs with potential applications in preclinical research. In the past few years, it has been realized that a complex interaction of multifactorial mechanisms is involved in the pathophysiology of OA. The authors believe there is no miracle therapeutic strategy fitting for all patients. OA phenotyping would be helpful for therapy selection. A variety of potential therapeutics targeting inflammation mechanisms, cellular senescence, cartilage metabolism, subchondral bone remodeling, and the peripheral nociceptive pathways are expected to reshape the landscape of OA treatment over the next few years. Precise randomized controlled trials (RCTs) are expected to identify the safety and efficacy of novel therapies targeting specific mechanisms in OA patients with specific phenotypes.

Uric acid (UA) is the end product of purine nucleotide metabolism in the human body. Hyperuricemia is an abnormally high level of UA in the blood and may result in arthritis and gout. The prevalence of hyperuricemia has been increasing globally. Epidemiological studies have shown that UA levels are positively correlated with cardiovascular diseases, including hypertension, atherosclerosis, atrial fibrillation (AF), and heart failure (HF). Hyperuricemia promotes the occurrence and development of cardiovascular diseases by regulating molecular signals, such as inflammatory response, oxidative stress, insulin resistance/diabetes, endoplasmic reticulum stress, and endothelial dysfunction. Despite extensive research, the underlying molecular mechanisms are still unclear. Allopurinol, a xanthine oxidase (XO) inhibitor, has been shown to improve cardiovascular outcomes in patients with HF, coronary heart disease (CHD), type 2 diabetes (T2D), and left ventricular hypertrophy (LVH). Whether febuxostat, another XO inhibitor, can improve cardiovascular outcomes as well as allopurinol remains controversial. Furthermore, it is also not clear whether UA-lowering treatment (ULT) can benefit patients with asymptomatic hyperuricemia. In this review, we focus on the latest cellular and molecular findings of cardiovascular disease associated with hyperuricemia and clinical data about the efficacy of ULT in patients with cardiovascular disease.