Disruptions in melatonin signaling may be the reason why some people develop osteoporosis at a young age, according to new research. Osteoporosis is a bone-weakening disease that affects about 0.4 people per 100,000 every year. It weakens bones, making them brittle and prone to fractures even from mild movements like coughing or bending over.
Idiopathic osteoporosis is a rare form of the disease that spontaneously occurs in young, otherwise healthy individuals. Researchers have identified a genetic cause for this condition, which is mutations in a gene that disrupts a protein called MTNR1A. This protein is a receptor for melatonin, a hormone that regulates the sleep-wake cycle in the body.
The study involved analyzing the genomes of 10 family members with idiopathic osteoporosis and 75 unrelated female patients with the condition. Specific mutations in the gene that codes for MTNR1A were found only in individuals with idiopathic osteoporosis. These mutations were more common in people of Ashkenazi Jewish ancestry, suggesting a genetic link to the disease.
Experiments using CRISPR gene editing in human bone cells and mice showed that these mutations led to a dysfunctional melatonin receptor, disrupting melatonin signaling and accelerating bone tissue aging. This resulted in a reduction in bone mass, indicating a potential treatment target for idiopathic osteoporosis.
While melatonin has shown promise in improving bone density and preventing bone loss in clinical trials, further research is needed to determine if restoring melatonin signaling could prevent bone loss and fractures in patients with idiopathic osteoporosis. The study does not currently provide a way to correct the genetic mutations associated with the disease.
In conclusion, this research sheds light on the role of melatonin in bone health and offers potential avenues for future treatment of idiopathic osteoporosis. More studies are needed to explore the therapeutic potential of melatonin in preventing bone loss and fractures in individuals with this rare form of osteoporosis.