Delayed Irreversible Fanconi Syndrome Associated With Vertebral Fracture After Tenofovir Discontinuation

Abstract

The use of tenofovir disoproxil fumarate (TDF) as an antiretroviral agent has been reported to adversely affect both renal tubules and bone health, leading to pathological fractures. While such an effect is largely reversible, substituting TDF with tenofovir alafenamide (TAF) might result in lower rates of adverse events with the preservation of tenofovir effectiveness. We report a case of a 40-year-old lady with HIV infection who had a vertebral fragility fracture secondary to TDF-associated Fanconi syndrome. The syndrome developed four years after TDF cessation and switching to TAF. Other etiologies for decreased bone mass were excluded, and the diagnosis of Fanconi syndrome was established based on her bone mineral density (BMD) and urine parameters. She was treated conservatively with active vitamin D, calcium, and progesterone/estrogen combination, but her phosphate wasting persisted despite switching to TAF; this likely represents a delayed irreversible effect of TDF on the patient's bone remodeling. This case report highlights the chronic sequelae of TDF therapy and the importance of monitoring for and early detection of renal tubulopathy and osteoporotic fractures in this patient population.

Keywords: bone mineral density (bmd); human immunodeficiency virus (hiv); osteoporotic fractures; tenofovir alafenamide (taf); tenofovir disoproxil fumarate (tdf).

Figure 1. Ultrasound of the abdomen and pelvis and magnetic resonance cholangiopancreatography (MRCP) of the reported patient

Figure 1A: An ultrasound of the abdomen and pelvis reveals an enlarged liver measuring 18 cm and homogeneous parenchyma with no focal lesions or intrahepatic biliary dilatation. The portal vein and common bile duct are unremarkable. The gallbladder is surgically removed. The pancreas and both kidneys are unremarkable. The spleen is enlarged, measuring 18 cm, with no focal lesions. There is no ascites. Figure 1B: The MRCP shows two focal areas of cholangitis in the right liver lobe associated with a beaded appearance, suggestive of sclerosing cholangitis with multiple unchanged liver lesions, which represents mostly hepatic abscesses; however, cystic neoplasm could not be totally excluded. There are no radiological signs of pancreatitis.

Figure 2. Radiological studies of the reported patient

Figures 2A-2C: Lumbar spine x-ray revealing osteopenia with narrowed intra-vertebral spaces (A: lumbar spine lateral x-ray with flexion, B: lumbar spine lateral x-ray with extension, and C: lumbar spine anteroposterior x-ray). Figure 2D: The MRI confirmed a 12th-thoracic vertebral-first-lumbar vertebra (T12-L1) compression fracture with biconcave deformity of their endplates, illustrating the classical codfish radiological sign appearance (yellow arrows).