Circulating bone morphogenetic protein levels and delayed fracture healing

Int Orthop. 2013 Mar;37(3):523-7. doi: 10.1007/s00264-012-1750-z. Epub 2012 Dec 28.


Objective: Despite adequate treatment 5-30% of bone fracture patients experience delayed union. During normal fracture union, bone morphogenetic proteins (BMPs) induce healing through a sequential cascade of events. Improved fracture healing after BMP-2 or -7 supplementation in patients with impaired fracture union suggests a deficiency of one or more of these factors. We postulated that low levels of circulating BMPs may result in delayed bone healing. The aim of this study was to quantify differences in levels of circulating BMP-2, -4, -6, -7, and -9 in patients that have demonstrated normal or delayed fracture healing.

Patients and methods: Blood samples were collected from an unselected cohort of 65 patients that had been treated for a diaphyseal tibia or femur fracture. Patients were divided into a group with fracture healing within nine months after injury and a group with delayed fracture union. BMP plasma concentrations were quantified using ELISAs and compared between these two groups.

Results: Circulating plasma levels of BMP-2, -4, -6, and -7 did not differ between 34 patients with normal fracture healing and 31 patients with delayed fracture healing. Also the median BMP-9 plasma levels were not statistically different between the two groups of patients. However, the distribution in the patients with normal union showed a wider range (72-2496 pg/ml) compared with the delayed union group (120-816 pg/ml).

Conclusion: In general, circulating BMP concentrations are not statistically different between patients who demonstrated normal or delayed fracture healing. High circulating BMP-9 levels seem to be associated with faster fracture healing, but are apparently not decisive.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Bone Morphogenetic Proteins / blood*
  • Female
  • Femoral Fractures / blood
  • Femoral Fractures / physiopathology*
  • Fracture Healing / physiology*
  • Growth Differentiation Factor 2 / blood
  • Humans
  • Male
  • Middle Aged
  • Retrospective Studies
  • Tibial Fractures / blood
  • Tibial Fractures / physiopathology*


  • Bone Morphogenetic Proteins
  • Growth Differentiation Factor 2