title: Case report: primary osteonecrosis associated with thrombophilia-hypofibrinolysis and worsened by testosterone therapy.
abstract: BACKGROUND
  Familial and acquired thrombophilia are often etiologic for idiopathic hip and jaw osteonecrosis (ON), and testosterone therapy (TT) can interact with thrombophilia, worsening ON.
  
  
  METHODS
  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. 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.
  
  
  CONCLUSIONS
  Idiopathic 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.
authors.affiliation: Jewish Hospital, Internal Medicine Resident Graduate Medical Education Department, 4777 East Galbraith Road, Cincinnati, OH 45236 USA.
authors.forename: Michael Ian
authors.initials: MI
authors.lastname: Jarman
authors.affiliation: Jewish Hospital, Internal Medicine Resident Graduate Medical Education Department, 4777 East Galbraith Road, Cincinnati, OH 45236 USA.
authors.forename: Kevin
authors.identifier: 0000-0003-0162-5574
authors.initials: K
authors.lastname: Lee
authors.affiliation: Jewish Hospital, Internal Medicine Resident Graduate Medical Education Department, 4777 East Galbraith Road, Cincinnati, OH 45236 USA.
authors.forename: Ariel
authors.initials: A
authors.lastname: Kanevsky
authors.affiliation: Jewish Hospital, Internal Medicine Resident Graduate Medical Education Department, 4777 East Galbraith Road, Cincinnati, OH 45236 USA.
authors.forename: Sarah
authors.initials: S
authors.lastname: Min
authors.affiliation: Jewish Hospital, Internal Medicine Resident Graduate Medical Education Department, 4777 East Galbraith Road, Cincinnati, OH 45236 USA.
authors.forename: Ilana
authors.initials: I
authors.lastname: Schlam
authors.affiliation: Jewish Hospital, Internal Medicine Resident Graduate Medical Education Department, 4777 East Galbraith Road, Cincinnati, OH 45236 USA.
authors.forename: Chris
authors.initials: C
authors.lastname: Mahida
authors.affiliation: Jewish Hospital, Internal Medicine Resident Graduate Medical Education Department, 4777 East Galbraith Road, Cincinnati, OH 45236 USA.
authors.forename: Ali
authors.initials: A
authors.lastname: Huda
authors.affiliation: Jewish Hospital, Internal Medicine Resident Graduate Medical Education Department, 4777 East Galbraith Road, Cincinnati, OH 45236 USA.
authors.forename: Alexander
authors.initials: A
authors.lastname: Milgrom
authors.affiliation: Jewish Hospital, Internal Medicine Resident Graduate Medical Education Department, 4777 East Galbraith Road, Cincinnati, OH 45236 USA.
authors.forename: Naila
authors.initials: N
authors.lastname: Goldenberg
authors.affiliation: Jewish Hospital, Internal Medicine Resident Graduate Medical Education Department, 4777 East Galbraith Road, Cincinnati, OH 45236 USA.
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Glueck
authors.affiliation: Jewish Hospital, Internal Medicine Resident Graduate Medical Education Department, 4777 East Galbraith Road, Cincinnati, OH 45236 USA.
authors.forename: Ping
authors.initials: P
authors.lastname: Wang
keywords: Anticoagulation; Hypofibrinolysis; Osteonecrosis; Testosterone; Thrombophilia