Intracardiac thrombosis following intravenous zoledronate treatment in a child with steroid-induced osteoporosis

Abstract

Objectives Bisphosphonates are used in childhood osteoporosis but can cause an acute phase reaction (APR) and hypocalcemia. We present a child with cardiac thrombosis following zoledronate, a previously unreported complication. Case Presentation An 11-year-old with Duchenne muscular dystrophy and steroid-induced osteoporosis presented 48 h after first zoledronate infusion with fever, tachycardia, tachypnoea and hypoglycaemia. This was managed as acute adrenal crisis and possible sepsis. He also had hypocalcemia, hypophosphatemia, hyponatraemia and hypokalaemia. Echocardiography performed due to persistent chest pain and tachycardia revealed a left ventricular thrombus. Conclusions Potential causes for intracardiac thrombosis in this patient include ventricular dysfunction due to acute adrenal crisis or electrolyte disturbance, and hypercoagulability due to the APR. Echocardiography should be considered in children with acute cardiovascular compromise following zoledronate. Stress-dose steroids to cover the APR and a reduced starting dose of zoledronate might have reduced the risk of this complication.

Bisphosphonates in Glucocorticoid-Treated Patients With Duchenne Muscular Dystrophy

“…The database searches resulted in the identification of 163 unique publications ( Figure 1 ). Of these, 18 full-text articles 4 , 10 - 26 and 1 editorial letter (reporting previously unpublished case series data) 27 were included for extraction, synthesis, and grading. Summary data of the included publications are listed in Table 1 .…”

“…Individual study samples comprised between 1 and 520 cases, and the age of patients ranged between 5 and 23 years (5 studies did not report minimum and maximum ages). 4 , 13 , 17 , 20 , 22 Two (11%) studies reported results from randomized controlled trials, 24 , 25 8 (42%) from retrospective cohort studies, 4 , 11 , 13 , 17 , 18 , 20 , 21 , 23 5 (26%) from case studies/series, 10 , 14 , 15 , 19 , 27 2 (11%) from prospective cohort studies, 16 , 26 1 (5%) from a case-control trial, 22 and 1 (5%) from an uncontrolled before-and-after trial. 12 …”

“…In total, 10 (53%) publications 10 , 14 - 16 , 20 , 21 , 24 - 27 reported evidence from studies of intravenous (IV) bisphosphonates and 6 (32%) of orally administered bisphosphonates 12 , 13 , 18 , 19 , 22 , 23 (2 studies reported oral and IV administration, 4 , 26 and 1 did not disclose the bisphosphonate administration route 11 ). Details of the reported methods for the quantification of osteoporosis clinical outcomes are summarized in Table 2 .…”

“…A summary of reported adverse events of bisphosphonates in glucocorticoid-treated patients with DMD is detailed in Table 3 . Reported events were largely due to the known “acute phase reaction” associated with the first dose; however, additional less common side effects were also reported, including rhabdomyolysis with myoglobinuria (IV zoledronate), 14 , 15 intracardiac thrombosis (IV zoledronate), 10 and memory loss (oral alendronate). 12 …”

Anti-RANKL Therapy Prevents Glucocorticoid-Induced Bone Loss and Promotes Muscle Function in a Mouse Model of Duchenne Muscular Dystrophy

“…While intravenous bisphosphonates are recommended following fractures to prevent bone loss in GC-treated DMD boys [ 14 ], there are significant side effects which includes nausea, vomiting, and pyrexia particularly following first infusion but could also occur in subsequent infusions [ 53 ]. Serious complications like rhabdomyolysis and intra-cardiac thrombosis have been reported in people with DMD treated with intravenous bisphosphonates [ 54 – 56 ]. In pre-clinical studies, RANKL inhibition by a human monoclonal anti-RANKL IgG2 antibody prevented GC-induced loss of bone mass and strength in hRANKL-knockin mice [ 57 ].…”