Scientists Identify New Bone-Building Mechanism With Potential to Treat Osteoporosis

Osteoporosis weakens bones and increases the risk of fractures, but scientists may have identified a new way to strengthen weakened skeletons. Researchers at Leipzig University found that activating a little-known receptor called GPR133 increased bone strength in mice with and without osteoporosis-like bone loss.

GPR133 belongs to a family of cell-surface receptors that help cells respond to signals around them. The researchers found that mice with genetic changes affecting this receptor developed low bone density early in life. They then tested AP503, a compound identified through computer-assisted screening that stimulates GPR133.

In both healthy and osteoporotic mice, AP503 increased bone strength. Researchers suggest the receptor helps control the balance between osteoblasts, which build new bone, and osteoclasts, which break down old bone. Activating GPR133 appeared to encourage bone-forming activity while reducing bone-resorbing activity, shifting the balance towards stronger bone.

The findings could be particularly relevant to osteoporosis after menopause, when falling hormone levels can accelerate bone loss. However, the research has so far been conducted in mice, so it is not known whether AP503 will strengthen bones or safely treat osteoporosis in people.

The receptor may also have benefits beyond bone health. An earlier Leipzig University study found that activating GPR133 with AP503 could strengthen skeletal muscle. A treatment that supports both bone and muscle could potentially be useful for older adults, who commonly experience declines in both tissues and face increased risks of falls and fractures.

Researchers are now studying GPR133 and AP503 further, including their wider effects in the body and possible medical applications. Human studies will be needed to determine whether this approach can eventually become a safe and effective osteoporosis treatment. The findings offer an early lead, but much more research is needed before clinical testing.

REFERENCE: Juliane Lehmann, et al.; The mechanosensitive adhesion G protein-coupled receptor 133 (GPR133/ADGRD1) enhances bone formation. Signal Transduction and Targeted Therapy, 2025; 10 (1) DOI: 10.1038/s41392-025-02291-y