Hypophosphatemic Osteomalacia and Osteoporosis Associated with Adefovir Dipivoxil
Overview
A 67-year-old postmenopausal woman on long-term adefovir dipivoxil therapy for chronic hepatitis B developed hypophosphatemic osteomalacia due to Fanconi syndrome. Discontinuation of adefovir and supplementation corrected metabolic abnormalities and improved bone mineral density (BMD), but BMD remained below age-matched norms, indicating concomitant postmenopausal osteoporosis requiring further treatment.
Background
Adefovir dipivoxil (ADV) is a nucleotide analogue widely used for chronic hepatitis B treatment, effective against wild-type and lamivudine-resistant strains. Prolonged ADV therapy can cause nephrotoxicity leading to Fanconi syndrome and hypophosphatemic osteomalacia, which clinically mimics osteoporosis and is often misdiagnosed. Patients may present with decreased BMD, bone pain, fractures, and impaired mobility. Identifying and managing osteomalacia first is critical before evaluating for underlying osteoporosis, especially in postmenopausal women.
Data Highlights
Parameter
Findings
Bone Mineral Density (DXA T-scores)
Lumbar spine: -5.3; Left femoral neck: -4.1; Left total hip: -4.6
Laboratory abnormalities
Hypophosphatemia, hypokalemia, total hypocalcemia, hyperchloremia, elevated alkaline phosphatase, elevated fractional excretion of phosphate (FEP)
Imaging
Compression deformities of lumbar vertebrae; left femoral-neck fracture; multiple skeletal pseudofractures on bone scintigraphy
Key Findings
Long-term ADV therapy can induce Fanconi syndrome causing hypophosphatemic osteomalacia with severe bone pain and multiple fractures.
Discontinuation of ADV and supplementation with phosphate and vitamin D normalize biochemical markers and improve symptoms.
BMD improves significantly after osteomalacia correction but may remain below normal in patients with underlying osteoporosis risk factors.
Postmenopausal osteoporosis can coexist with drug-induced osteomalacia, necessitating further evaluation and anti-osteoporotic treatment after metabolic stabilization.
Early recognition of ADV-induced osteomalacia is essential to prevent misdiagnosis and inappropriate management.
Clinical Implications
Clinicians should monitor patients on long-term adefovir dipivoxil for signs of renal tubular dysfunction and bone disease. Upon diagnosis of hypophosphatemic osteomalacia, prompt discontinuation of ADV and correction of metabolic abnormalities are critical. Persistent low BMD after osteomalacia resolution warrants evaluation for osteoporosis and initiation of appropriate anti-osteoporotic therapy, especially in postmenopausal women.
Conclusion
Adefovir dipivoxil-induced hypophosphatemic osteomalacia is reversible with timely intervention, but underlying osteoporosis may persist, requiring additional treatment. Comprehensive assessment and management strategies are essential to optimize bone health in affected patients.
References
Case Study and Literature Review, 2024 -- Hypophosphatemic Osteomalacia and Osteoporosis Associated with Adefovir Dipivoxil
