Tissue Repair & Musculoskeletal
Delayed Union and Nonunion
Delayed union is fracture healing slower than expected for the site, while nonunion is a fracture that has stopped progressing toward healing and will not unite without intervention.
Most fractures heal through secondary bone healing: haematoma and inflammation, a soft cartilaginous callus bridging the gap, conversion to woven bone as hard callus, then remodelling toward lamellar bone along lines of load. Delayed union means the sequence is running slower than expected for that bone and pattern; nonunion means it has arrested. The regulatory definition used for device trials treats a fracture as a nonunion when it is not healed by nine months and has shown no radiographic progression across three consecutive months.
Rates are low overall but concentrated: single-digit percentages across all fractures, and substantially higher with open tibial shaft fractures, segmental bone loss, infection, smoking and diabetes. The most instructive biologic here is recombinant BMP-2, approved in the 2000s for lumbar interbody fusion and for acute open tibial shaft fractures. Independent reanalyses of the individual patient data published in 2013 found smaller benefits and more adverse events than the original industry-sponsored publications had reported.
For decisions the distinction that matters is mechanical versus biological failure. Hypertrophic nonunion, with abundant callus, signals adequate blood supply and too much motion, and needs better stabilisation rather than more growth factor; atrophic nonunion needs vascularity and graft. A systemic agent aimed at bone formation addresses only one of those.
The persistent error is calling any slow fracture a nonunion. Union is defined by absence of progression on serial imaging, not by a date on a calendar, and radiographic union routinely lags painless functional loading. Claims that a compound accelerates fracture healing should be checked against whether the comparator was given the time a normal fracture takes.