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Drugs that block the mineralocorticoid receptor, like the hypertension medications spironolactone and eplerenone, may help to protect bones during ageing, according to a study published in the Journal of Bone and Mineral Research.
Scientists at Department of Cellular Biology and Anatomy at the Medical College of Georgia (MCG) have come to the conclusion that drugs like prednisone are glucocorticoids, which help to reduce inflammation in patients with arthritis, for example, can actually disrupt the healthy, ongoing dynamic of bone being made and destroyed.
“We think the mineralocorticoid receptor may explain a lot of what is going wrong in aging bone”
McGee-Lawrence, corresponding author of the study explains that glucocorticoids can coax stem cells to make bone-forming osteoblasts, but it also causes those osteoblasts to store more fat, and too much fat in the bone typically correlates with bone loss.
The scientists were surprised to find that in mice, the loss of functioning glucocorticoid receptors did not protect against bone loss and there was, in fact, increased fat accumulation in the bone marrow and worsened osteoporosis. The mice also had smaller muscle mass, chose to move around less and had higher blood pressure.
The scientist then used drugs to inhibit the mineralocorticoid receptor, and found that many of the problems were reversed. As Lawrence explains: “The only way we have found to get rid of that lipid storage by osteoblasts was to inhibit the mineralocorticoid receptor with drugs.”
She continues: “We thought that knocking out the glucocorticoid receptor would make things better, but it made them worse. We think the mineralocorticoid receptor may explain a lot of what is going wrong in aging bone.”
Scientists believe something from the bone is communicating with other body systems
McGee-Lawrence et al have some evidence that bone’s expression of mineralocorticoid receptors goes up, potentially significantly, as you age, and early mixed results on whether glucocorticoid receptors go down with age.
They are now considering what happens with both receptor levels as well as learning more about the role of mineralocorticoid receptors in ageing bone.
She explains: “We want to know what would cause bone cells to change which receptors they are expressing and how they are responding to these, but there are a lot of things that happen with ageing. We know inflammation changes with ageing, so there are a lot of different cues that could cause these things to change.”
She continues: “By changing glucocorticoid signalling in the bone, not only are we seeing changes in the bone, but we are seeing changes in the fat, muscle, adrenal glands, in physical activity. This means something from the bone is communicating with all these other body systems.”
McGee-Lawrence say the team will continue to explore why these changes are happening so they can “pick the right avenue to pursue for a treatment strategy”.