BMP-2 Dependent Increase of Soft Tissue Density in Arthrofibrotic TKA

Abstract

Arthrofibrosis after total knee arthroplasty (TKA) is difficult to treat, as its aetiology remains unclear. In a previous study, we established a connection between the BMP-2 concentration in the synovial fluid and arthrofibrosis after TKA. The hypothesis of the present study was, therefore, that the limited range of motion in arthrofibrosis is caused by BMP-2 induced heterotopic ossifications, the quantity of which is dependent on the BMP-2 concentration in the synovial fluid.Eight patients with arthrofibrosis after TKA were included. The concentration of BMP-2 in the synovial fluid from each patient was determined by ELISA. Radiologically, digital radiographs were evaluated and the grey scale values were determined as a measure of the tissue density of defined areas. Apart from air, cutis, subcutis and muscle, the soft-tissue density in the area of the capsule of the suprapatellar pouch was determined. The connection between the BMP-2 concentration and the soft-tissue density was then investigated.The average BMP-2 concentration in the synovial fluid was 24.3 ± 6.9 pg/ml. The density of the anterior knee capsule was on average 136 ± 35 grey scale values. A linear correlation was shown between the BMP-2 concentration in the synovial fluid and the radiological density of the anterior joint capsule (R=0.84, p = 0.009).We were able to show that there is a connection between BMP-2 concentration and soft-tissue density in arthrofibrosis after TKA. This opens up the possibility of conducting a prophylaxis against arthrofibrosis in risk patients by influencing the BMP-2 pathway.

Correlation of Bone Morphogenetic Protein-2 Levels in Serum and Synovial Fluid with Disease Severity of Knee Osteoarthritis

“…There have been studies showing that BMP-2 was detected in the serum of patients with degenerative joint disease requiring total arthroplasty [ 30 ] and SF of patients with arthrofibrosis after total knee arthroplasty [ 31 , 32 ]. However, to the best of our knowledge, thus far there are no published data on the relationship between BMP-2 levels in the serum and SF of knee OA patients and disease severity.…”

“…Second, we did not measure the BMP-2 levels in SF of healthy controls because of ethics concerns. Although there were several studies reporting BMP-2 levels in SF of control groups, these controls underwent a diagnostic arthroscopy for unspecific knee complains [ 36 ] or referred pain [ 31 , 32 ], who were excluded from the present study. Also, we did not find any published data regarding the baseline SF levels of BMP2 in non-diseased patients that we can refer to.…”

Stiffness after Total Knee Arthroplasty

“…Interventions that block the cellular pathway through which BMP-2 exerts its effects, are being explored as a potential strategy for prevention of arthrofibrosis. 44 Arthrofibrosis has also been seen to correlate with a hypoxic-associated oxidative stress. As demonstrated by Freeman et al, 40 this process initiates mast cell proliferation with fibroblast growth factor secretion that promotes fibroblast proliferation and fibrous tissue formation followed by heterotopic ossification.…”

Arthrofibrosis After Total Knee Arthroplasty

“…A vicious cycle occurs in which myofibroblasts are activated and secrete TGF-beta, perpetuating scarring. Other molecules implicated in arthrofibrosis include interleukin (IL)-1 [108][109][110] , IL-6 111,112 , IL-17 [113][114][115] , tumor necrosis factor-alpha 116 , plateletderived growth factor 116 , beta-catenin 76 , and BMP-2 96 . Profibrogenic mediators potentially at play include nuclear factor kappa B (NF-kB) and xylosyltranferases.…”

“…Diagnostic biomarkers for arthrofibrosis after TKA are lacking. Both animal 83-90 and human 48,49,80,91-97 studies have sought to elucidate markers to identify high-risk patients and targets for potential therapeutics 53 . Wyatt et al provide a systematic review of relevant arthrofibrosis biomarker studies 53 .…”