Denosumab improves clinical manifestations of hypophosphatemic osteomalacia by adefovir-induced Fanconi syndrome: a case report

Abstract

Background Adefovir dipivoxil is a nucleotide analogue that is approved for treatment of chronic hepatitis B. Adefovir dipivoxil is associated with proximal tubular dysfunction, resulting in Fanconi syndrome, which can cause secondary hypophosphatemic osteomalacia. We describe a case of a patient with hypophosphatemic osteomalacia secondary to Fanconi syndrome induced by adefovir dipivoxil concomitantly with osteoporosis in whom clinical symptoms were improved by adding denosumab (a human monoclonal antibody targeting the receptor activator of nuclear factor-κB ligand) to preceding administration of vitamin D 3 . Case presentation A 60-year-old Japanese man had been receiving low-dose adefovir dipivoxil (10 mg/day) to treat chronic hepatitis B for approximately 5 years. He presented to an orthopedic surgeon with severe pain of the right hip and no trauma history, and fracture of the neck of the right femur was identified. In addition, 99m Tc-hydroxymethylene diphosphate scintigraphy revealed significantly abnormal uptake in the bilateral ribs, hips, and knees, and he was therefore referred to our university hospital for evaluation of multiple pathological fractures. We diagnosed hypophosphatemic osteomalacia due to Fanconi syndrome induced by adefovir dipivoxil therapy. Although we reduced the patient’s adefovir dipivoxil dose and added calcitriol (active vitamin D 3 ), he did not respond and continued to complain of bone pain. Several bone resorption markers and bone-specific alkaline phosphatase were also persistently elevated. Therefore, we added denosumab to vitamin D 3 supplementation for treatment of excessive bone resorption. Two months after initiation of denosumab, his hip and knee pain was relieved, along with a decrease in serum alkaline phosphatase and some bone resorption markers. Conclusions Although denosumab is not generally an appropriate treatment for acquired Fanconi syndrome, it may be useful for patients who have hypophosphatemic osteomalacia due to adefovir dipivoxil-induced Fanconi syndrome associated with excessive bone resorption. However, clinicians should keep in mind that if denosumab is administered to patients with hypophosphatemic osteomalacia accompanied by excessive bone resorption, adequate vitamin D and/or phosphate supplementation should be done before administration of denosumab.

A bedridden young lady with hypophosphatemic rickets treated with denosumab: a case report

“…The patient did not develop any side effects from the denosumab such as hypocalcemia most likely due to the associated primary hyperparathyroidism in this patient. On reviewing the literature there were no cases reported on using denosumab for hypophosphatemic rickets but is has been used in a case of hypophosphatemic osteomalacia which was drug induced [ 6 ] it also has been reported to be used in cases of osteogenesis imperfecta [ 7 ]. Denosumab, in addition to other drugs are currently being investigated in phase III trials for use in hypophosphatemic rickets, hypophosphatasia and fibrodysplasia ossificans progressiva [ 8 ].…”

Fanconi syndrome induced by adefovir dipivoxil: a case report and clinical review

“…The main characteristics of 32 patients with ADV-induced FS, including eight patients in our institution and 24 published cases, are summarized in Table 4 . 5 , 18 , 22 , 23 , 36 – 43 …”

“…According to a case report, denosumab improves clinical manifestations of HO, which results from ADV-induced FS. 37 In addition, mitochondrial protection may be useful against ADV-induced FS and nephrotoxicity, and some chemicals such as glycine, coenzyme Q10, l -carnitine, N-acetyl cysteine, carnosine, and taurine have nephroprotective effects. These chemicals have been studied in patients and different experimental models, 32 and they may be applied for prevention and treatment.…”

Fanconi syndrome induced by the long-term use of tenofovir disoproxil fumarate: a case report and literature review

“…Heavy metals (e.g., lead, cadmium, mercury, copper), L-arginine and L-ornithine, aristolochic acid (a cause of herbal nephropathy), and fumaric acid are some other factors that cause FS. [3][4][5][6][7][8][9][10][11] Of these, drugs are the most frequent cause of FS. 7 Tenofovir disoproxil fumarate (TDF) is an NRTI antiviral drug.…”