Can impaired diaphyseal fracture healing be predicted early?: A cohort study of biomarkers

Sabir Ali; Ajai Singh; Manish Yadav; Salma Siddiqui; Vaishnavi Pandey; Abbas Ali Mahdi; Rajeshwer Nath Srivastava

doi:10.1016/j.jcot.2019.04.026

Can impaired diaphyseal fracture healing be predicted early?: A cohort study of biomarkers

J Clin Orthop Trauma. 2019 Oct;10(Suppl 1):S37-S46. doi: 10.1016/j.jcot.2019.04.026. Epub 2019 Apr 29.

Authors

Sabir Ali¹, Ajai Singh¹, Manish Yadav¹, Salma Siddiqui¹, Vaishnavi Pandey¹, Abbas Ali Mahdi², Rajeshwer Nath Srivastava¹

Affiliations

¹ Department of Orthopaedic Surgery, King George's Medical University, Lucknow, India.
² Department of Biochemistry, King George's Medical University, Lucknow, India.

Abstract

Background: Currently, the clinico-radiological method was used to analyze the healing progression of fractures globally, but even they are also unable to presume the impaired healing early. Hence till date, no reliable methods are available to predict the impaired healing early, so that it could be interventionally managed as required within the time.

Methods: In this prospective observational study, a total of 121 adults fractured patients and 108 healthy controls were analyzed. Peripheral blood samples were taken from controls (at once) and fractured cases (at different follow-ups) to quantify the Osteocalcin and Osteopontin mRNA and protein expression using qRT-PCR and western blotting assay respectively. In parallel to that the clinico-radiological follow-up examinations also done at various specific follow-up intervals up to 24th post-fracture weeks.

Results: As per the clinico-radiological status at the 24th week, fracture patients were divided into normal healing (n = 102) and impaired healing (n = 19) groups. Mean RUST score between normal healing and the impaired healing group showed a significant statistical difference at each follow-up. In both groups, expressions of Osteocalcin (mRNA & protein) were gradually up-regulated from the baseline to end of follow-ups, whereas Osteopontin mRNA as well as protein gradually up-regulated from the baseline to a peak value at 10th day, then declined. In general, the Osteocalcin and Osteopontin mean fold expressions were higher in normal healing as compared to the impaired healing groups.A significant correlation was found between the mRNA expressions of Osteocalcin and Osteopontin with the RUST score at most of the follow-ups. However, the protein expressions were not shown any significant correlation.

Conclusions: The Osteocalcin and Osteopontin expression will provide an early prediction of the healing outcomes of tibial fractures. This may open a new horizon for innovations to deal with complications associated with impaired fracture healing, especially in tibial bone fractures.

Keywords: Biomarkers; Diaphyseal fracture; Osteocalcin; Osteopontin.