Pharmacologic therapy for osteoarthritis—the era of disease modification

Abstract

Osteoarthritis (OA) is a prevalent and disabling condition for which few safe and effective therapeutic options are available. Current approaches are largely palliative and in an effort to mitigate the rising tide of increasing OA prevalence and disease impact, modifying the structural progression of OA has become a focus of drug development. This Review describes disease modification and discusses some of the challenges involved in the discovery and development of disease-modifying OA drugs (DMOADs). A variety of targeted agents are in mature phases of development; specific agents that are beyond preclinical development in phase II and III trials and show promise as potential DMOADs are discussed. A research agenda with respect to disease modification in OA is also provided, and some of the future challenges we face in this field are discussed.

Intraarticular Sprifermin (Recombinant Human Fibroblast Growth Factor 18) in Knee Osteoarthritis: A Randomized, Double‐Blind, Placebo‐Controlled Trial

“…The majority of previous clinical trials of treatments aimed at improving symptoms and reducing joint cartilage loss in OA used standardized acquisition and assessment of radiographs (14). MRI has the advantage of providing highly accurate and precise quantitative data on multiple synovial joint structures (30,31,38,39).…”

“…The potential of a combined beneficial effect on joint structure and symptoms in OA as a result of treatment with diacerein, glucosamine, doxycycline, risedronate, chondroitin sulfate, strontium ranelate, or cindunistat has been investigated (6)(7)(8)(9)(10)(11)(12)(13). However, no pharmacologic treatment or other treatment has been shown to have unequivocally beneficial effects on the structural characteristics of joint damage in OA that translate into clinical benefit (14). Accordingly, no structure-modifying treatment has yet been approved by regulatory agencies in the US or European Union.…”

“…Many studies have focused on use of anticatabolic agents to delay progression of cartilage breakdown (14). An alternative approach is to stimulate cartilage development and repair.…”

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.…”

Clinical Validation of Pain Management Manipulative Therapy for Knee Osteoarthritis With the Squeeze-Hold Technique: A Case Series

“…11 In conservative therapy, therapeutic exercises are considered an effective treatment for OA knee pain. 12,13 However, sustained effort is required for the analgesic effect to be obtained, and patients find it difficult to remain motivated.…”