Detection of biomarkers for impaired fracture healing: A prospective multicentre cohort study

Fracture healing is a unique and complex repair process. However, impaired
fracture healing remains a common problem and its pathophysiology is poorly
understood. Plain radiography and CT scans remain the standard method of
monitoring fracture healing, but it documents impaired healing only late in the
course. Depending on several factors 5-30% of fractures will fail to heal
adequately. Numerous proteins have been described having a significant role in
bone regeneration, fracture healing and wound healing. An abnormal expression
or abnormal circulating levels of these proteins could possibly be associated
with the development of non- or delayed union. Systemic alterations of these
proteins are detectable in the circulation and can therefore serve as a
biological marker (biomarker) for the prognosis and the extent of fracture
healing. Secondly, it is possible that genetic mutations impair the expressions
of these proteins leading to abnormal circulating levels. Early detection of
impaired expression of these parameters could lead to personalized treatment of
the patients.

The aim of this project is to determine the possible use of biomarkers for non
or delayed union in long bone fractures of the diaphyseal femur and tibia.

Observational prospective multicentre cohort study.
Protein levels and the genetic variations causing the systemic alterations will
be determined.

From all participating patients a total of 6 peripheral blood samples will be
collected. The logistic burden associated with participation will be minimal
because 5 of the 6 bloodsamples will be collected during standard follow up
procedures at the outpatient department. Only the final and 6th blood sample
will not be combined with a checkup at the outpatient department. Radiographs,
other research investigations or the nature of the physical examination or
interview will be according to the standard treatment management.