April 11, 2019

Keeping bone in its place

Jonathan Schoenecker and colleagues have discovered a new mechanism for the formation of bone in soft tissues — a complication of severe injuries that causes pain and limits mobility.

Heterotopic ossification (HO) is the formation of bone within soft tissue such as muscle, leading to pain and potentially the inability to use a limb. Once thought to be primarily a genetic disease, the cause of most trauma-induced HO is unknown.

Reporting this month in the journal Calcified Tissue International, Jonathan Schoenecker, MD, PhD, and colleagues led by Stephanie Moore-Lotridge, PhD, suggest a new paradigm for HO formation.

In an animal model, they discovered that injured muscle can produce microscopic nanohydroxyapatite, the main crystal of bone. Surprisingly, these crystals are ingested by macrophages before reparative cells heal the injured muscle. If the macrophage cannot clear the crystal, the reparative cells transform into bone instead of muscle.

If confirmed clinically, this paradigm would support new therapeutic interventions that target muscle-produced nanohydroxyapatite or enhance the “eating” capacity of macrophages to prevent the consequences of HO while preserving normal bone formation.

This research was supported by the Vanderbilt University Medical Center Department of Orthopaedics and Rehabilitation, the Caitlin Lovejoy Fund, and the James O’Loughlin PXE Research Fund through PXE International.