Osteoarthritis is the most common joint condition and the leading cause of disability in older people. We have thought of osteoarthritis as a wear and tear disease just like we think of aging, but there is more to it. Look at the joint next to the fingernail in the middle of the picture. One of the joints is very swollen. It is not just worn. It is swollen. It has gotten bigger.
Aging, weight, obesity, the metabolic syndrome, and genetic mutations increase the risk of OA development. Metabolic changes play a key role in osteoarthritis. There is increased risk of osteoarthritis and it is more severe in patients with the metabolic syndrome, obesity, insulin resistance, and high cholesterol with elevated triglycerides. We think of osteoarthritis as related to weight, wear, and tear, but the joint in the fingers are also involved. These are not load-bearing joints that would be affected by extra weight. That means there are other factors to consider.
In the metabolic diseases associated with obesity, AMPK is switched off and mTOR is abnormally switched on. AMPK activity plays a key role in maintaining the normal joint. There is a striking decrease in AMPK activity in joints with osteoarthritis which means mTOR would be abnormally switched on. Metformin switches on AMPK and switches off mTOR which reduces inflammation and protects against osteoarthritis in mice.
This has real implications for patients. In a study of patients with osteoarthritis of the knee, patients on metformin lost cartilage at half the rate and half as many patients had a knee replacement over six years compared with patients not on metformin. If you look at the slide below, the interventions of optimal medical therapy should be even more protective. All green box interventions switch off mTOR and activate AMPK. We have had no disease modifying therapies for osteoarthritis. Optimal medical therapy deserves a serious look and controlled trials that examine the impact vs usual care.
Hi, Bill. Can you site the reference on metformin slowing osteoarthritis of the human knee, please? I’d like to share is with my rheumatologist and see if she will prescribe metformin for me. As you know, I have had two hip replacements, left and right. And now my left knee is giving me trouble that is all too familiar. I remain very active, and do put a lot of strain on my joints on a daily basis. But this activity in fact seems to help my symptoms, as long as I don’t overdo it. Best, David
Bill, Hearing anecdotally from pediatricians about a substantial rise in arthritis diagnosis in young teenagers post COVID vaccine. Any thoughts about this? Is metformin contra-indicated at this early age?