New Insights in Osteoporosis
Most of us know a woman who has had painful problems with osteoporosis. It is a very common problem of aging that causes spine and hip fractures. I have always been puzzled by this fact: calcium leaves bone and moves to arteries as we age. I have seen chest x-rays in women where there was less calcium in the spine than there was in the aorta. I always thought these problems must be related.
Oxidants play a central role in osteoporosis and artery disease. As we age, we produce more oxidants and antioxidant defenses decline dramatically. This imbalance kills the cells that maintain healthy strong bones. This insight can be very valuable, and it should inform the way that we treat patients.
Glucocorticoids are used very commonly in clinical practice. Sometimes they are used too casually. I have seen them used to help someone with a viral bronchitis get better faster. Osteoporosis is very common in patients on long term cortisone treatment. Changes in bone can be observed within weeks of starting steroid treatments for other chronic illnesses. Check out the mineralocorticoid receptor (MR) in a clear box in the upper right corner of the diagram. As you can see, aldosterone activates MR and that leads to increased oxidant production which in turn activates the master metabolic genetic switches EGFR and mTOR. Cortisone type steroids also activate MR and generate oxidants. That is a big part of the way cortisone produces osteoporosis. Interestingly, high aldosterone levels are also associated with osteoporosis. Look at the diagram again. This paper tied it all together for me.
On the other hand, metformin reduces the risk of osteoporosis by 30-40%. Benefits increased with higher metformin dose and a longer duration of treatment. A couple of reasons for this are immediately obvious when looking at the diagram. Metformin decreases oxidant production by blocking the effects of ADMA. Metformin reduces oxidants via other mechanisms. Eplerenone also reduces bone loss by blocking MR activation. Other diabetes medications like thiazolidinediones increase osteoporosis risk. Optimal medical treatment reduces oxidant effects and signaling. It should slow osteoporosis.
This post is another example of how chronic diseases and aging are related. Optimal medical therapy has multiple benefits beyond patients with heart disease and diabetes. I hope this is all coming together for you, and I welcome your comments and questions.