This 2015 narrative review by Einhorn and Gerstenfeld synthesizes the biology of fracture healing from the cellular level to clinical trials. It covers the phases of repair, immune regulation, stem cell origins, and the biophysical and pharmacological interventions tested to enhance healing. The central clinical question: what actually works to augment fracture repair, and when?
When a patient with an open tibial fracture asks about adjuncts to their nail fixation, this paper is the evidence base: high-dose BMP-2 cuts the reoperation rate by 44% and has FDA approval specifically for this indication.
For closed tibial fractures, however, BMP-2 offers no benefit — a phase II-III RCT was terminated early after 180 patients showed no improvement in time to union. Knowing this distinction prevents inappropriate off-label use.
For the fragility fracture patient who needs faster healing (distal radius, pelvic insufficiency fracture in an osteoporotic woman), teriparatide at 20 µg daily is supported by RCT data showing roughly a 2-week acceleration in cortical bridging.
Electromagnetic stimulation and low-intensity pulsed ultrasound both have weak, conflicting evidence; the electromagnetic meta-analysis pooled RR of 1.76 did not reach significance (P=0.15). Do not rely on these as primary interventions.
The paper also establishes why massive soft tissue injury predisposes to nonunion: periosteal stripping shifts callus cell origin to muscle, and if muscle is also severely damaged, the stem cell supply is exhausted.
This 2015 narrative review by Einhorn and Gerstenfeld synthesizes the biology of fracture healing from the cellular level to clinical trials. It covers the phases of repair, immune regulation, stem cell origins, and the biophysical and pharmacological interventions tested to enhance healing. The central clinical question: what actually works to augment fracture repair, and when?
When a patient with an open tibial fracture asks about adjuncts to their nail fixation, this paper is the evidence base: high-dose BMP-2 cuts the reoperation rate by 44% and has FDA approval specifically for this indication.
For closed tibial fractures, however, BMP-2 offers no benefit — a phase II-III RCT was terminated early after 180 patients showed no improvement in time to union. Knowing this distinction prevents inappropriate off-label use.
For the fragility fracture patient who needs faster healing (distal radius, pelvic insufficiency fracture in an osteoporotic woman), teriparatide at 20 µg daily is supported by RCT data showing roughly a 2-week acceleration in cortical bridging.
Electromagnetic stimulation and low-intensity pulsed ultrasound both have weak, conflicting evidence; the electromagnetic meta-analysis pooled RR of 1.76 did not reach significance (P=0.15). Do not rely on these as primary interventions.
The paper also establishes why massive soft tissue injury predisposes to nonunion: periosteal stripping shifts callus cell origin to muscle, and if muscle is also severely damaged, the stem cell supply is exhausted.