The Potential Role of Ferritin in Relation to Inflammatory and Metabolic Syndrome Biomarkers in Patients Undergoing Total Joint Arthroplasty of the Hip or Knee
Authors: Wanderling Christopher , Liles Jeffrey , Carlsgaard Peter , Saluk Jennifer , Syed Daneyal , Timothy Schnettler , Guler Nil , Hopkinson William , Hoppensteadt Debra , Fareed Jawed 
Published: October 2019

Abstract
Introduction: Maintaining proper iron regulation systemically is crucial in preserving systemic homeostasis. Ferritin is known to be a key component in this regulation by acting as a buffer via the controlled binding and releasing of iron. Ferritin is not only crucial in iron regulation, but it has also been observed to be a biomarker of inflammation. Considering this observation, it may be possible that ferritin plays a role in the pathogenesis of degenerative joint diseases (DJD). It has been identified that patients who had underwent total joint arthroplasty (TJA) procedure had increased serum levels of ferritin both pre-operatively and post-operatively. The rate of TJA procedures has been progressively increasing and it is projected that TJA procedures will increase to over 4 million procedures performed by 2030. In consideration of this observation, it is becoming increasingly important to gain a more comprehensive understanding in the pathology of DJD that require TJA procedure. The aim of this study is to examine the levels of ferritin in TJA patients pre-operatively and compare this level with those of other inflammatory and metabolic syndrome biomarkers in the patient samples while comparing the ferritin measurement to that of healthy controls.
Study Design and Methods:
After approval of the Institutional Review Board (IRB), pre-operative day one and post-operative day one blood samples of 45 TJA patients who underwent total knee arthroplasty (TKA) or total hip arthroplasty (THA) procedure were obtained as de-identified samples. Blood samples were collected into tubes containing 3.2% (0.109M) sodium citrate, plasma was then isolated. Control citrated plasma samples from non-smoking, drug-free, volunteers (age 18-35 years old) were obtained from from a certified vendor (George King Biomedical, Overland Park, KS). Plasma samples were stored at -80O C. The plasma samples were profiled for ferritin, C-peptide, insulin, IL-6, resistin, IL-1a, and PAI-1 utilizing a biochip array technology (RANDOX, Antrim, UK). All individual results were compiled as mean+1 SD and are summarized in the following table. The Mann-Whitney U test and the Spearman correlation test were used to analyze patient and control samples.
Results: Table. Normal Mean + standard deviation Pre-op Mean + standard deviation Post-op Mean + standard deviation Ferritin (ng/ml) 68.44±74.23 125.0±121.0 73.79±71.29 C-peptide (ng/ml) 3.22±2.577 2.65±2.986 3.40±3.64 IL-6 (pg/ml) 0.818±0.5228 27.18±41.18 55.69±38.74 Resistin (ng/ml) 2.49±0.7406 5.34±4.976 6.39±4.95 Insulin (uIU/ml) 20.77±19.01 37.75±82.58 41.39±77.53 IL-1a (pg/ml) 0.418±0.1507 0.663±0.7824 1.29±1.39 PAI-1 (ng/ml) 3.21±4.127 14.98±9.836 17.89±11.58
There were significant increases in pre-operative levels of ferritin (p=0.0305), IL-6 (p<0.0001), resistin, (p<0.0001), IL-1a (p=0.0483), and PAI-1 (p<0.0001). There were insignificant alterations in the levels of C-peptide (decreased) and insulin (increased) in the pre-operative samples when compared with the healthy controls. Pre-operative correlations were observed between ferritin and each of the measured biomarkers; C-peptide (p=0.0043, R=0.324), IL-6 (p=0.00034, R=0.40), resistin (p=0.00043 R=0.394), insulin (p=0.00054, R=0.388), IL-1a (p=0.0256, R=-0.256), and PAI-1 (p<0.0001, R=0.460). Post-operative correlations were observed between ferritin and C-peptide (p=0.0008, R=0.529), as well as Insulin (p=0.0037, R=0.372). There was a correlation observed between pre-operative and post-operative levels of ferritin (p=0.0035, R=0.4943). Interestingly, the post-op values for ferritin dramatically decreased despite an increase in all other inflammatory and metabolic biomarkers.
Conclusions:
Understanding the factors that may affect ferritin regulation in TJA patients may be helpful in the management of DJD. Profiling inflammatory and metabolic syndrome biomarkers, including ferritin, may provide dynamic management options in the future that not only reduce adverse outcomes in these patients but also control the progression of degenerative processes.

Disclosures
No relevant conflicts of interest to declare.