Scientists at Leipzig University have identified a little-known receptor, GPR133, as a key player in bone health. By stimulating GPR133 with a new compound called AP503, they were able to boost bone strength in mice, even reversing osteoporosis-like conditions. The potential breakthrough could provide an effective treatment for millions struggling with bone loss.
Stimulating bone growth
Osteoporosis is a major health concern and affects over three million people in the UK alone. The NHS says that half of women over 50 years old and a third of men over 60 will suffer a ‘low trauma fracture’ due to this common bone disease. It’s debilitating, life changing and potentially set to be a thing of the past.
That’s because the Leipzig team, led by Ines Liebscher, have discovered by computer modelling a receptor that’s critical to bone formation called GPR133. (That stands for G protein-coupled receptor 133 and is found on cell surfaces.)
After discovering the receptor’s impact on bone growth, they set about creating a compound, AP503, that would stimulate GPR133 with the aim of strengthening bones. And it worked.
“With this compound we were able to significantly increase bone strength in both healthy and osteoporotic mice,” said Liebscher.
In the study, AP503 triggered a signal that not only stimulated new bone-forming cells, known as osteoblasts, but also inhibited bone-resorbing cells, known as osteoclasts. The result was a band of mice with stronger, more resilient bones. The team is already working on follow-up projects that, if proved successful and safe, would result in human trials.
A ‘silent’ disease
Osteoporosis is often considered a ‘silent’ disease, as it typically presents no symptoms until a fracture occurs. It’s more common in the older population, as you gradually start losing bone density from around the age of 35. That said, it can affect younger people.
Declining sex hormones is one of the major causes, which is why women are more at risk of developing osteoporosis: the hormone changes that happen at the menopause, including falling oestrogen levels, directly affect bone density. An early menopause (under 45) is a greater risk factor, as is having a hysterectomy before 45.
In men, the cause of osteoporosis is often unknown, albeit there is a link between low levels of the male hormone testosterone and healthy bones.
Further risk factors for both sexes include an overactive thyroid gland, a low body mass index, having an eating disorder, heavy drinking, and some drugs used to treat breast cancer and prostate cancer that affect hormone levels.
Current therapies often focus on vitamin D and/or calcium supplementation, with equivocal results. There are pharmacological treatments but many are associated with severe side effects. For instance, post-menopausal oestrogen therapy strengthens bones but increases the risk of cancer and thrombosis.
If further trials into the efficacy of GPR133 on humans proves successful, the compound could have broader applications. It could be used to treat those with muscle-wasting disease or even help astronauts maintain bone density when faced with zero gravity in space.
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