Case report: primary osteonecrosis associated with thrombophilia-hypofibrinolysis and worsened by testosterone therapy

Michael Ian Jarman,Ali Huda,Ariel Kanevsky,Ilana Schlam,Charles J Glueck,Ping Wang,Chris Mahida,Sarah Min,Naila Goldenberg,Kevin Lee,Alexander Milgrom

doi:10.1186/s12878-017-0076-x

Abstract

BackgroundFamilial and acquired thrombophilia are often etiologic for idiopathic hip and jaw osteonecrosis (ON), and testosterone therapy (TT) can interact with thrombophilia, worsening ON.Case presentationCase 1: A 62-year-old Caucasian male (previous deep venous thrombosis), on warfarin 1 year for atrial fibrillation (AF), had non-specific right hip-abdominal pain for 2 years. CT scan revealed bilateral femoral head ON without collapse. Coagulation studies revealed Factor V Leiden (FVL) heterozygosity, 4G/4G plasminogen activator inhibitor (PAI) homozygosity, high anti-cardiolipin (ACLA) IgM antibodies, and endothelial nitric oxide (NO) synthase (eNOS) T786C homozygosity (reduced conversion of L-arginine to NO, required for bone health). Apixaban 5 mg twice daily was substituted for warfarin; and L-arginine 9 g/day was started to increase NO. On Apixaban for 8 months, he became asymptomatic. Case 2: A 32-year-old hypogonadal Caucasian male had 10 years of unexplained tooth loss, progressing to primary jaw ON with cavitation 8 months after starting TT gel 50 mg/day. Coagulation studies revealed FVL heterozygosity, PAI 4G/4G homozygosity, and the lupus anticoagulant. TT was discontinued. Jaw pain was sharply reduced within 2 months.ConclusionsIdiopathic ON, often caused by thrombophilia-hypofibrinolysis, is worsened by TT, and its progression may be slowed or stopped by discontinuation of TT and, thereafter, anticoagulation. Recognition of thrombophilia-hypofibrinolysis before joint collapse facilitates anticoagulation which may stop ON, preserving joints.

Highlights

Familial and acquired thrombophilia are often etiologic for idiopathic hip and jaw osteonecrosis (ON), and testosterone therapy (TT) can interact with thrombophilia, worsening ON.Case presentation: Case 1: A 62-year-old Caucasian male, on warfarin 1 year for atrial fibrillation (AF), had non-specific right hip-abdominal pain for 2 years
Our specific aim was to describe the association of familial thrombophilia (Factor V Leiden heterozygosity), acquired thrombophilia, and hypofibrinolysis (4G4G homozygosity for the plasminogen activator inhibitor −1 mutation) with hip and jaw ON, and the interaction of TT with familial thrombophilia in ON
Cases with idiopathic osteonecrosis and Controls To provide a frame of reference for the two cases in the current report, thrombophilia-hypofibrinolysis measures in 240 cases with idiopathic osteonecrosis sequentially referred to our center for coagulation studies are provided, along with comparisons to 110 previously reported healthy, normal controls [11] (48 men, 62 women)

Summary

Introduction

Familial and acquired thrombophilia are often etiologic for idiopathic hip and jaw osteonecrosis (ON), and testosterone therapy (TT) can interact with thrombophilia, worsening ON.Case presentation: Case 1: A 62-year-old Caucasian male (previous deep venous thrombosis), on warfarin 1 year for atrial fibrillation (AF), had non-specific right hip-abdominal pain for 2 years. Coagulation studies revealed Factor V Leiden (FVL) heterozygosity, 4G/4G plasminogen activator inhibitor (PAI) homozygosity, high anti-cardiolipin (ACLA) IgM antibodies, and endothelial nitric oxide (NO) synthase (eNOS) T786C homozygosity (reduced conversion of L-arginine to NO, required for bone health). The development of primary ON appears to follow a sequence of events initiated by familial or acquired thrombophilia [2,3,4], venous occlusion causing osseous venous outflow obstruction, leading to increased intraosseous venous pressure, reduced arterial flow, ischemia, bone infarction and eventual joint collapse [3,4,5,6,7]. Our specific aim was to describe the association of familial thrombophilia (Factor V Leiden heterozygosity), acquired thrombophilia (lupus anticoagulant, high anticardiolipin [ACLA] antibody IgM), and hypofibrinolysis (4G4G homozygosity for the plasminogen activator inhibitor −1 mutation) with hip and jaw ON, and the interaction of TT with familial thrombophilia in ON.

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Results

Conclusion