Severe hypophosphatemia induced by denosumab in a patient with osteomalacia and tenofovir disoproxil fumarate-related acquired Fanconi syndrome

Abstract

Denosumab, a novel agent that inhibits osteoclasts, reduces the risk of fracture in patients with osteoporosis. However, worsening of hypophosphatemia and other symptoms may be induced by denosumab in patients with pre-existing hypophosphatemic osteomalacia. A 58-year-old man with hepatitis B presented with diffuse bone pain and muscle weakness. Denosumab was prescribed by the orthopedist according to documented low bone mass and spine compression fracture. After administering denosumab, the patient's bone pain worsened, and he later developed a right tibia stress fracture. His condition was diagnosed as adult-onset hypophosphatemic osteomalacia complicated by multiple bone fractures, which resulted from Fanconi syndrome with proximal tubulopathy due to tenofovir disoproxil fumarate (TDF) treatment for his hepatitis B. Denosumab use leads to aggressive hypophosphatemic osteomalacia and the complication of stress fractures, because of its effects on bone resorption. Physicians should be aware that in patients with chronic hepatitis B monoinfection who are administered TDF therapy, bone pain or fracture is possible but preventable by timely monitoring of serum phosphate levels. Denosumab should not be used in patients with untreated osteomalacia or vitamin D deficiency, as it may lead not only to hypocalcemia but also to hypophosphatemia in these patients.

Impact of Tenofovir Disoproxil‐Induced Fanconi Syndrome on Bone Material Quality: A Case Report

“…Consequently, denosumab can induce or worsen preexisting hypophosphatemia and osteomalacia in TDF‐acquired Fanconi syndrome, leading to severe bone pain and atraumatic fractures. ( 1 ) Similar effects were observed after zoledronic acid administration in a patient with undiagnosed TDF‐induced osteomalacia. In this case, a mild hypophosphatemia was already observed before the bisphosphonate administration, with a consecutive aggravation afterward accompanied by several fractures.…”

“…It has been reported repeatedly, that anti-resorptive treatment might lead to hypocalcemia and hypophosphatemia in patients with existing osteomalacia. Consequently, Denosumab can induce or worse pre-existing hypophosphatemia and osteomalacia in TDF acquired Fanconi syndrome, leading to severe bone pain and atraumatic fractures [1]. Similar effects were observed after zoledronic acid administration in a patient with undiagnosed TDF-induced osteomalacia.…”

“…Tenofovir disoproxil (TDF)-induced Fanconi Syndrome is a rare, but severe complication in hepatitis B and HIV patients, leading to osteomalacia, pain, multiple fractures and delayed fracture healing. Anti-resorptive agents including bisphosphonates and Denosumab even worsen the bone quality and clinical outcome [1]. Although TDF-induced osteomalacia can be reflected by low phosphate and high alkaline phosphatase in serum, bone biopsy assures the diagnosis and gives information on the magnitude of bone deterioration.…”

“…Antiresorptive agents including bisphosphonates and denosumab even worsen the bone quality and clinical outcome. ( 1 ) Although TDF‐induced osteomalacia can be reflected by low phosphate and high alkaline phosphatase in serum, bone biopsy assures the diagnosis and gives information on the magnitude of bone deterioration. Since information on bone biopsy findings in TDF‐induced osteomalacia is scarce, we accurately investigated the bone sample of an affected female patient including bone histomorphometry and quantitative backscattered electron imaging (qBEI) analyses.…”

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

“…Monitoring of the serum calcium level also is mandatory to prevent severe hypocalcemia when denosumab is initiated in all forms of osteomalacia. Very recently, there was another case report of hypophosphatemia osteomalacia secondary to Fanconi syndrome in which bone pain was worsened by administration of denosumab [15]. Unlike in these reports, we observed that 2 months after initiation of denosumab, hip and knee pain of our patient was relieved along with a decrease in serum ALP and some bone resorption markers.…”