Zoledronic acid-induced transient hepatotoxicity in a patient effectively treated for Paget’s disease of bone

Abstract

Bisphosphonate (BP)-induced hepatotoxicity is very rare. There are only a few reports of liver injury after BP treatment, including aledronate and risedronate in postmenopausal osteoporosis patients. We describe hereby the case of a patient with Paget's disease of bone accompanied by nonalcoholic fatty liver disease (NAFLD) who developed transient hepatotoxicity after zoledronic acid (ZOL) treatment. NAFLD had been diagnosed 1 year before presentation, based on liver ultrasonography (US). One day after infusion, serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and gamma-glutamyltransferase (GGT) were increased by 8.1, 6.7, and 6.7 times, respectively, compared with pretreatment values. Serum bilirubin remained normal. US revealed hepatic mild homogenous brightness without focal lesion of the liver or biliary ducts. Subsequent biochemical and serologic investigation did not reveal a specific liver or systematic disease. The patient remained asymptomatic, and ALT, AST, and GGT were normalized 7 days post-treatment. Although the mechanism by which ZOL may cause liver damage is elusive, physicians should be aware of this possible adverse effect and ZOL cautiously administered in NAFLD patients.

Zoledronic Acid: A Mischievous Suspect for Liver Injury

“…Earlier two case reports have been noted in female patients diagnosed with postmenopausal osteoporosis and Paget's disease, demonstrating the transient rise in liver enzymes. No serious liver injury was implicated [16,17]. Compared to earlier published cases, by our knowledge, it is the first report of zoledronic acid associated hepatic injury in a male patient suffering from cancer.…”

“…Whereas, hepatotoxicity is a very rare side effect seen due to bisphosphonates with only a few case reports to support this evidence [12][13][14][15]. As per the literature search, hepatic damage solely due to zoledronic acid is an unusual outcome; especially in the absence of any pre-existing liver disease, concomitant medication implicated to cause hepatotoxicity, evidence in favor of zoledronic acid as an attributing factor for hepatic dysfunction is scanty and so far only two case reports have been reported [16,17]. A pre-clinical study carried in rats has shown biopsy-confirmed hepatotoxicity due to zoledronic acid administration [18].…”

A network meta‐analysis on the short‐term efficacy and adverse events of different anti‐osteoporosis drugs for the treatment of postmenopausal osteoporosis

“…This results in increased BMD through several antiresorptive mechanisms including inhibition of osteoclast recruitment, osteoclast activity on the bone, induction of osteoclastic apoptosis, and alteration of the bone or bone mineral to reduce dissolution rate . Risedronate, a novel orally administered pyridinyl bisphosphonate prescribed for the prevention or treatment of postmenopausal and glucocorticoid‐induced osteoporosis and Paget's disease, can reduce bone turnover and decreases resorption chiefly through osteoclastic effects, with no undesirable effects on cortical porosity or thickness or on cancellous bone volume . However, gastrointestinal (GI) effects of oral bisphosphonates are well observed and recognized and vary from mild nausea and heartburn to erosive oesophagitis and ulceration .…”

“…60 Risedronate, a novel orally administered pyridinyl bisphosphonate prescribed for the prevention or treatment of postmenopausal and glucocorticoid-induced osteoporosis and Paget's disease, can reduce bone turnover and decreases resorption chiefly through osteoclastic effects, with no undesirable effects on cortical porosity or thickness or on cancellous bone volume. 61,62 However, gastrointestinal (GI) effects of oral bisphosphonates are well observed and recognized and vary from mild nausea and heartburn to erosive oesophagitis and ulceration. 63 Prolonged treatment with alendronate has been associated with adynamic bone disease and atypical long bone fractures in postmenopausal osteoporosis.…”

Recalcitrant Hyperkalaemia Associated with a Single Dose Administration of Zoledronic Acid for Treatment of Post-Menopausal Osteoporosis

“…While we may be familiar with more common side effects such as renal toxicity, flu-like symptoms (bone pain, arthralgia, fever, nausea, chills), atrial fibrillation and hypocalcaemia, there have been increasing number of case reports describing rare but significant complications associated with zoledronic acid use [5,6]. These include osteonecrosis of the jaw, orbital inflammatory disease, transient changes in thyroid function tests, transient hepatotoxicity, flare up of hand osteoarthritis and lifethreatening hyperkalaemia [7][8][9][10][11][12].…”