One family's bones were remarkably hard to break

Researchers at Yale traced the trait through the family tree and found it followed one gene. Their spines and hips were far denser than normal.

The team sequenced LRP5, a receptor in the Wnt signaling pathway, and found one mutation, G171V, shared by every affected relative. It kept bone-building cells switched on long after they should have stopped, so new bone kept forming while old bone was cleared away at a normal rate.

The same pathway controls bone loss in everyone, not just this family, and the finding helped focus drug research on it; romosozumab, an osteoporosis drug approved in 2019, blocks sclerostin, another natural brake on the pathway. Unusual skeletons pointed to a drug used in clinics today.

One gene, and bones that were hard to break.