Osteoarthritis is a progressive inflammatory-dependent deterioration of one or more joints (knees, hips, hands, elbow, spine) that robs the older adult of mobility and independence. “Osteoarthritis is the most common form of arthritis, affecting 1 in 3 people over age 65 and women more so than men” (Hawker, 2019). After diabetes and dementia, osteoarthritis ranks third in disability prevalence among older adults.
Overview
Osteoarthritis, robber of mobility and independence, begins as an illness characterized by joint pain, joint stiffness (especially when sitting for prolonged periods), muscle weakness, and reduced quality of life. Over time, structural changes develop in potentially all components of the affected joint. With permanent damage, osteoarthritis progresses to a disease state that severely limits range of motion, especially walking, leading to a serious disability. Additionally, it reduces exercise ability, fragments sleep, impairs productivity, encourages early retirement and steals independence. Sadly, osteoarthritis remains a major disability without an approved disease-modifying therapy. Symptoms may be minimized with over-the-counter pain/anti-inflammatory medications or injections of steroids into the joint (intra-articular). Eventually, surgical intervention with total joint replacement is required.
Modifiable Risk Factors
There are two modifiable risk factors strongly associated with osteoarthritis. They are obesity (adiposity) and joint injury (high impact and/or repetitive mechanical stress). Additionally, there are several non-modifiable risk factors associated with osteoarthritis. They include age, gender (female), and genetics (skeletal structure and alignment; uncorrected deformities).
The data suggests that maintenance of a normal body weight and reduction of joint injury, for example, in high stress occupations and elite sports, with proper physical preparations (e.g. exercises to strengthen muscles around joints) would reduce the risk of osteoarthritis. At present, the actual clinical support for this is minimal because there has been little interest, hence few studies.
One study on the effect of weight loss and exercise on knee osteoarthritis found that those who adhered to the recommended diet and exercise program had a lower incidence of knee osteoarthritis at 30 months out and those that lost 5% of their body weight has reduced joint injury at 6.5 years compared to controls. On the effect of exercise alone on the prevention of osteoarthritis, there are a number of clinical trials, but of poor quality. It appears that prevention of osteoarthritis by reduction of modifiable risk factors has to date received little clinical attention.
However, it is still important to re-emphasize the wealth of clinical data supporting the multiple benefits of exercise (Insight 2: Skeletal muscles, aging and consequences, Insight 3: Ways to retard skeletal muscle aging, Insight 4: Anti-aging benefits of aerobic and stretch exercises). For example, an exercise program reduces the risks for numerous other morbidities e.g. cardiovascular disease, and diabetes. A comorbidity with osteoarthritis accelerates joint deterioration. Exercise also reduces the risk of weight gain, promotes stable movements and stabilizes joints, thereby reducing mechanical stress.
Pathological Changes
There is growing interest in defining the pathological changes that occur during development of osteoarthritis. This research effort could potentially give rise to novel and effective disease-altering therapies.
Components of the Joint
The joint brings two bones together. The end of each bone is called the subchondral portion. It is covered by hyaline cartilage (articular) composed of fibrous proteins such as collagen, lots of water, and a few collagen-secreting cells called chondrocytes. There is no nerve or blood supply or lymphatic drainage making damage repair difficult. The synovial membrane that secretes the synovial fluid covers the articular cartilage. Ligaments (bone to bone) and tendons (muscle to bone) secure the joint.
Identified pathology
1) Breakdown of cartilage – harmful enzymes slowly destroy collagen and other matrix proteins; the low number of chondrocytes retards repair.
2) Inflammation in synovial fluid. Mechanical injury activates innate and immune responses with production of numerous pro-inflammatory mediators that destroy tissue.
3) Fibrosis – production of extra matrix proteins that contributes to synovial membrane thickness and stiffness.
4) Subchondral bone changes – bone supporting joint cartilage remodels in unfavorable ways.
5) Senescent cells – Chondrocytes senesce and exacerbate the inflammation by production of pro-inflammatory mediators and loss of normal function e.g. collagen repair. (See Blog 23 on senescent cells)
Current Therapies
Osteoarthritic pain is generally treated with topical or oral anti-inflammatory drugs. Specifically, education, exercise programs (strengthening, cardiovascular, mind-body i.e. Yoga) and weight loss strategies are encouraged. If seriously practiced, this approach consistently reduces joint pain.
As symptoms worsen, intra-articular injections of steroids provide additional relief. However, progression to structural damage (radiological confirmation) requires total joint replacement called arthroplasty surgery. The consensus to date is that arthroplasty surgery for the treatment of osteoarthritis is a successful therapy.
Future Therapies
Chemical entities that target one of the five pathological changes mentioned above are in development. Most, such as the senolytics, are effective in animal models of the disease. A potential future therapy, pirfenidone, an anti-fibrotic drug, used to treat pulmonary fibrosis, may decrease fibrosis in osteoarthritis. Another future therapy, now in clinical trials for pain relief in osteoarthritis is the intra-articular injections of a growth factor (portion of FGF-18 termed psrifermin).
Another therapy gaining considerable interest is intra-articular injection or implantation of stem cells. The approach is to harvest and inject mesenchymal stem cells (multipotent adult cells obtained from tissues such as bone marrow, fat, umbilical cord). In a critique of clinical trials using stem cell therapy for osteoarthritis, Diego de Carvalho Carneiro et al., (2023) reported findings that “indicate that intra-articular injections of mesenchymal stem cells are efficacious in the treatment of osteoarthritis and the regeneration of cartilage, but that they may be insufficient for the full repair of articular cartilage defects.” Additional large rigorous clinical trials would be of value.
Conclusions
Osteoarthritis is a debilitating joint illness/disease that robs an individual of independence. It desperately needs effective disease-modifying therapy. Fortunately, potentially valuable therapies are on the horizon. However, until these therapies are validated, it seems reasonable to establish common sense policies for the prevention of osteoarthritis beginning in childhood and continuing throughout the lifespan. These policies would include the maintenance of normal body weight throughout life, engagement in proven injury prevention for high impact sports and careers and a continuous exercise program to eliminate the development of co-morbidities and assure normal stresses on all joints.
References (Pubmed)
Aubourg G et al., Genetics of osteoarthritis. Osteoarthritis and Cartilage 30: 636-649, 2022.
Diego de Carvalho Carneiro et al., Clinical Trials with Mesenchymal Stem Cell Therapies for Osteoarthritis: Challenges in the Regeneration of Articular Cartilage. Int. J. Mol. Sci. 2023, 24, 9939.
Hawker GA. Osteoarthritis is a serious disease. Clin Exp Rheumatol 37 (Suppl. 120): S3-S6,2019.
Jiang Y et al., Osteoarthritis year in review 2021: biology Osteoarthritis and Cartilage 30 (2022) 207e215
Katz JN et al., Diagnosis and treatment of hip and knee osteoarthritis: A review JAMA. 2021 February 09; 325(6): 568–578.
Kun E et al., The genetic architecture and evolution of the human skeletal form. Science. 2023 Jul 21;381(6655)
Thoene M et al., The Current State of Osteoarthritis Treatment Options Using Stem Cells for Regenerative Therapy: A Review. Int. J. Mol. Sci.2023, 24, 8925.
Vincent TL et al., Osteoarthritis pathophysiology – therapeutic target discovery may require a multi-faceted approach. Clin Geriatr Med. 38(2): 193–219, 2022.
Whittaker JL et al., A lifespan approach to osteoarthritis prevention. Osteoarthritis and Cartilage 29 (2021) 1638e1653