RESUMEN
BACKGROUND: Osteomalacia (OM) is frequently confused with various musculoskeletal or other rheumatic diseases, especially in patients with adult-onset widespread musculoskeletal pain because of its low prevalence and non-specific manifestations. AIM: To facilitate the early diagnosis and etiology-specific treatment of adult-onset hypophosphatemic OM. METHODS: A retrospective review of medical records was performed to screen adult patients who visited a physiatry locomotive medicine clinic (spine and musculoskeletal pain clinic) primarily presenting with widespread musculoskeletal pain at a single tertiary hospital between January 2011 and December 2019. We enrolled patients with hypophosphatemia, high serum bone-specific alkaline phosphatase levels, and at least one imaging finding suggestive of OM. RESULTS: Eight patients with adult-onset hypophosphatemic OM were included. The back was the most common site of pain. Proximal dominant symmetric muscle weakness was observed in more than half of the patients. Bone scintigraphy was the most useful imaging modality for diagnosing OM because radiotracer uptake in OM showed characteristic patterns. Six patients were diagnosed with adefovir (ADV)-induced Fanconi syndrome, and the other two patients were diagnosed with tumor-induced OM and light-chain nephropathy, respectively. After phosphorus and vitamin D supplementation and treatment for the underlying etiologies, improvements in pain, muscle strength, and gait were observed in all patients. CONCLUSION: Mechanical pain characteristics, hypophosphatemia, and distinctive bone scintigraphy patterns are the initial diagnostic indicators of adult-onset hypophosphatemic OM. ADV-induced Fanconi syndrome is the most common etiology of hypophosphatemic OM in hepatitis B virus-endemic countries.
RESUMEN
Osteomalacia is a metabolic bone disease that leads to softening of the bones and can be caused by hypophosphatemia. Large clinical studies of low-dose adefovir dipivoxil (adefovir) have found no evidence of renal tubular dysfunction leading to hypophosphatemia after 48 weeks of treatment. We report two cases of low-dose adefovir-induced hypophosphatemic osteomalacia that initially presented with diffuse musculoskeletal pain. The first patient was a 62-year-old man with a 2-year history of bone pain involving the dorsal mid-thorax, lower anterior chest wall, right sacroiliac joint area, and both knees. The patient had been receiving adefovir for 5 years before confirmation of hypophosphatemia and urinary phosphate wasting. Bone scintigraphy revealed multifocal lesions including multiple ribs, costochondral junctions, costovertebral junctions, sacrum, both posterior iliac bones, both proximal tibia, right calcaneus, and the left second metatarsophalangeal joint area, which were suggestive of metabolic bone disorder. Bone pain was significantly reduced within 3 months after supplementation with phosphate and calcitriol. The second patient was a 54-year-old male who presented with an 18-month history of severe bone pain of the right medial knee and low back. The patient had been taking adefovir for approximately 40 months before the development of bone pain. Laboratory data revealed hypophosphatemia and vitamin D deficiency. Bone scintigraphy showed increased uptake in bilateral ribs, sternum, both scapulae, both costovertebral junctions, both pelvic bones, medial cortex of the right proximal femur, right proximal tibia, and the left lateral tarsal bone. The symptoms improved by changing the antiviral agent from adefovir to entecavir. Because osteomalacia often presents with diffuse bone pain, non-specific radiologic findings and non-characteristic routine serum biochemical changes, the disease can be confused with various musculoskeletal diseases and a high index of suspicion is necessary for an early diagnosis in patients receiving adefovir therapy.