Two Cases of Hypophosphatemic Osteomalacia After Long-term Low Dose Adefovir Therapy in Chronic Hepatitis B and Literature Review

Abstract

Adefovir dipivoxil (ADV) is a nucleotide used as long-term therapy of chronic hepatitis B. Many published reports have shown that long-term high-dose therapy with adefovir can be associated with proximal renal tubular dysfunction resulting in significant hypophosphatemia, renal insufficiency and osteomalacia. We have encountered two patients who developed evidence of hypophosphatemic osteomalacia while on long-term low-dose adefovir therapy for chronic hepatitis B. We report on its clinical features and its potential resolution with cessation of the drug and supplementation with phosphate. We also reviewed the other published cases associated with hypophosphatemic osteomalacia after low-dose adefovir therapy. The symptoms and the hypophosphatemia improved after cessation of the drug and supplementation with phosphate in most cases. Patients taking adefovir long-term should receive regular investigation of the phosphate level and renal function.

Nucleotide Analogue-Related Proximal Renal Tubular Dysfunction during Long-Term Treatment of Chronic Hepatitis B: A Cross-Sectional Study

“…Osteoporosis and osteopenia were found in 10 (66.7%) patients who had proximal RTD, which was very close to the prevalence of the reduction of bone mineral density in patients who were treated with nucleotide analogues in a previous report [31]. Long-term hypophosphatemia with decreased renal phosphate absorption can lead to osteomalacia and impaired bone health [29]. …”

“…In addition, the problem of severe tubular phosphate loss in subclinical and overt proximal RTD was confirmed with low TmPO 4 /GFR (<2.8 mg/dL) in our study. Nucleotide analogue-related Fanconi syndrome, which is an extreme degree of proximal RTD, has a particularly low incidence in CHB treatment as shown from a few case reports [29, 30]. In this study, acid loading test and the investigation of aminoaciduria were not done to confirm the diagnosis of Fanconi syndrome, although some patients with overt proximal RTD shared many features of Fanconi syndrome.…”

809 Reversal of Proximal Renal Tubular Dysfunction After Nucleotide Analogue Withdrawal in Chronic Hepatitis B

“…Chronic phosphate depletion can cause hypophosphatemic osteomalacia, diffused bone pain, and bone fracture [7-9, 11, 12]. Prolonged hypophosphatemia with decreased renal phosphate absorption can lead to impaired bone health [37]. In this study, the prevalence of osteoporosis and osteopenia was 62.5%, which was close to the prevalence of nucleotide analogue-related bone demineralization reported from a previous study [38].…”

Adult-onset hypophosphatemic osteomalacia associated with Sjogren syndrome

“…[5–8] In clinical practice, this disorder cannot be only induced by phosphaturic mesenchymal tumor, [9,10] but also secondary to SS [4,11,12] or hyperparathyroidism, [13] even related to the adefovir therapy. [2,14] Although the clinical symptoms of HO are unspecific or noncharacteristic, it is very important and valuable to reveal etiological cause of this disorder to provide appropriate therapy.…”