High Prevalence of Prothrombotic Abnormalities in Multifocal Osteonecrosis

Abstract

Multifocal or multiple osteonecrosis (ON), defined by the involvement of 3 or more anatomic sites, is unusual, being observed in only 3%–10% of patients diagnosed with ON. We report the clinical characteristics of a cohort of 29 patients with multifocal ON from a single center and evaluate the prevalence of associated prothrombotic abnormalities in 26 of these patients. We conducted a retrospective study of all patients diagnosed with multifocal ON evaluated in our institution during the last 20 years. We recorded clinical manifestations and underlying diagnoses. A wide thrombophilic profile was performed, including antithrombin, protein C, protein S, lupus anticoagulant, anticardiolipin antibodies, activated protein C resistance, factor V Leiden, mutation G-20210-A of the prothrombin gene, and factor VIII. Coagulation test results were compared with those in a healthy control group and a group of patients with history of lower-extremity deep venous thrombosis.The mean age of the patients was 49.2 ± 15 years (range, 28–81 yr). The mean number of ON localizations per patient was 5.2 ± 2.3 (range, 3–11). Hips were the most commonly affected joint (82%), followed by knees (58%), shoulders (37%), and ankles (13%). Most patients had an underlying disease process, and 12 of 25 (48%) patients had coagulation test abnormalities. The most common alterations were high factor VIII levels and antiphospholipid antibody (aPL) positivity in 24% and 20% of cases, respectively. These abnormalities were more prevalent in patients with multifocal ON compared with patients in the control groups.Sixty-one percent of patients had a history of corticosteroid treatment. Patients with coagulation abnormalities had a higher number of ON localizations per patient (6.5 ± 2.7 vs. 3.88 ± 0.8; p = 0.002) and a higher prevalence of atypical ON localizations (25% vs. 0%; p = 0.05).In conclusion, in the present cohort of patients with multifocal ON, 48% of the patients had at least 1 prothrombotic factor, especially high levels of factor VIII and aPL. These findings have major implications for the diagnosis and treatment of multifocal ON and clearly indicate the need to perform a thrombophilic profile in these patients.

Testosterone, thrombophilia, thrombosis

“…High factor VIII was more common in the 11 men (36%) than in normal male controls (2%) (P ¼ 0.005), and more common than in T-controls (4%) (P ¼ 0.023). The factor V Leiden mutation [17] and high factors VIII [18][19][20] and XI [17,21] are recognized familial thrombophilias associated with thrombotic events. The increased incidence of high factor VIII levels and the factor V Leiden mutation in men who took T and sustained DVT-pulmonary embolism-osteonecrosis points to a thrombosis-enhancing effect of exogenous T when given to men with previously undiagnosed thrombophilia-hypofibrinolysis, as in this and our other studies [1][2][3][4].…”

Clinical translation of a mesenchymal stromal cell-based therapy developed in a large animal model and two case studies of the treatment of atrophic pseudoarthrosis

“…Both ovine and human tissues were harvested, fixed in 4% formalin at room temperature, decalcified in 5% formic acid (Decalcifier I; Surgipath Canada Inc., Winnipeg, Canada), and embedded in paraffin for subsequent histological and immunohistochemical procedures Oliver-Vila et al, 2016). Microtome sections 4 μm thick were either stained with H&E or immunostained for the detection of macrophages (CD68, KP-1; Dako, Glostrup, Denmark), and vessels (endothelial cells, CD31, JC70A, Dako), as reported elsewhere (Gomez-Puerta et al, 2013). Images were taken using a bright field microscope (Olympus, Tokyo, Japan).…”

Clinical characteristics of multifocal osteonecrosis in Korean patients with rheumatic disease

“…Although we were unable to retrieve their exact doses, 17 patients from the literature review had been treated with corticosteroids, with the exception of two patients diagnosed with SSc and primary APS, respectively. However, there are several reports of ON in patients with rheumatic diseases (including SLE, primary APS and SSc) after little or no exposure to corticosteroids . These observations indicate that rheumatic disease is an important risk factor associated with ON.…”

“…One study reported that APA may play a role in the pathogenesis of ON, even in the absence of other predisposing factors . Patients with multifocal ON have also been found to have a statistically significant higher prevalence of APA . Another study reported that elevated titers of anti‐cardiolipin (aCL) antibody might increase the number of ON lesions .…”