Abstract
RATIONALE: Zoledronic acid (ZA) is a potent third-generation bisphosphonate widely used to manage bone metastases in prostate cancer. Although effective, ZA is associated with nephrotoxicity, which in rare cases may lead to Fanconi syndrome (FS): a form of acquired proximal renal tubular dysfunction. Clinicians may overlook early signs of FS, especially in patients receiving long-term bisphosphonate therapy. PATIENT CONCERNS: We report 2 cases of prostate cancer complicated by FS following ZA administration. Patient #1, a 74-year-old male without prior renal dysfunction, developed hypouricaemia 4 months after initiating ZA, and was diagnosed with FS 2 years later. Patient #2, a 66-year-old male with chronic hepatitis B and long-term low-dose adefovir use, exhibited progressive tubular injury shortly after ZA initiation and was diagnosed with FS 4 years later. DIAGNOSES: Both patients were diagnosed with acquired FS based on laboratory abnormalities including hypophosphatemia, hypouricaemia, glycosuria, proteinuria, and metabolic acidosis. Differential diagnoses including hereditary FS and other nephrotoxic exposures were excluded. INTERVENTIONS: In both patients, ZA was discontinued. Patient #1 was switched to denosumab, and received oral phosphate, potassium, and bicarbonate replacement. Patient #2 also discontinued adefovir and was transitioned to entecavir, alongside targeted supportive therapy with phosphate and vitamin D supplementation. OUTCOMES: Renal tubular function improved in both patients following drug withdrawal. Hypouricaemia, glycosuria, electrolyte abnormalities, and acid-base imbalance gradually resolved over 1 to 3 months, supporting a causal relationship between ZA and FS. LESSONS: These cases highlight the importance of early recognition and close monitoring of renal tubular function in patients receiving ZA. Screening for FS, including urinalysis, blood gas analysis, and serum electrolytes, should be considered within the first month of therapy and repeated regularly thereafter. Clinicians should maintain high vigilance for FS, especially when ZA is used concurrently with other nephrotoxic agents such as adefovir.