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

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.

Testosterone Therapy, Thrombophilia, Venous Thromboembolism, and Thrombotic Events

“…None of the 16 patients had osteonecrosis before starting TT. Idiopathic osteonecrosis, with intra-osseous venous thrombosis, is often caused by thrombophilia [21,27,49], often develops after starting TT, and its progression may be slowed or stopped by discontinuation of TT, and, thereafter, anticoagulation [18,50,51,52,53]. Of the 16 cases, 5 (31%) were FVL heterozygotes versus 4 of 48 patients who had osteonecrosis and were not receiving TT ( p = 0.04).…”

“…Of the 16 cases, 5 (31%) were FVL heterozygotes versus 4 of 48 patients who had osteonecrosis and were not receiving TT ( p = 0.04). Subsequently, we reported 2 additional cases [50] of osteonecrosis after starting TT, both found to be heterozygous for the FVL mutation.…”

Idiopathic Exposed Bone Lesions of the Jaw

“…Possible etiologic factors for exposed bone lesions were reported in the literature and consist of trauma, odontogenic infections, herpes zoster infection associated osteonecrosis, HIV-associated necrotizing ulcerative periodontitis, benign sequestration of the lingual plate [1], long-term corticosteroid usage [4], ischaemia, occlusion, and coagulopathies [5,6,7].…”

Osteonecrosis of the Femoral Head in Patients with Hypercoagulability—From Pathophysiology to Therapeutic Implications

“…The efficiency of direct oral anticoagulants was highlighted in other case reports, as well. One patient with important thrombophilic burden and history of deep venous thrombosis (anticoagulated with warfarin for atrial fibrillation and symptomatic for ONFH) showed complete resolution of symptoms after 8 months on apixaban 5 mg bid [111]. Milgrom et al [110] reported the case of a woman diagnosed at the age of 26 with primary multifocal ON, in context of complex thrombophilia (FV Leiden heterozygosity, C677T MTHFR homozygosity, and hypofibrinolytic 4G4G homozygosity for the PAI-1 gene).…”