Case reportBurosumab in tumor-induced osteomalacia: A case report
Introduction
Hypophosphatemia is a cause metabolic bone disease and may rarely be acquired due to the paraneoplastic overproduction of fibroblast growth factor-23 (FGF-23), known as tumor-induced (or oncogenic) osteomalacia (TIO) [1], [2].
Phosphate metabolism is regulated primarily by parathyroid hormone, 1,25-dihydroxyvitamin D, and FGF-23 [3]. Overproduction of FGF-23 leads to hypophosphatemia via inappropriate urinary phosphate wasting [4]. When phosphate levels remain chronically low, osteomalacia develops due to insufficient bone mineralization.
The diagnosis of TIO can be challenging and often requires a functional imaging study, such as 111-indium octreotide scintigraphy or gallium-68 Dotatate PET/CT, as these tumors, often of mesenchymal origin, can be small and sometimes very difficult to detect. If detected, the surgical removal or ablation of the tumor is often curative. In patients whose tumors cannot be localized, or are unable to have or choose not to have surgery, medical treatment with phosphate supplementation and calcitriol is recommended [4]. Recently, burosumab (KRN23), a fully human monoclonal antibody directed at FGF-23, was approved for the treatment of X-linked hypophosphatemia [5].
We describe a patient diagnosed with TIO, in whom surgical resection was considered unsafe, and was treated medically with burosumab (KRN23).
Section snippets
Case Report
A 52-year-old Caucasian female was referred to the University of Alabama at Birmingham (UAB) Osteoporosis Clinic after an outside hospitalization for workup of multiple occult fractures in various stages of healing. She had a past medical history of hypertension and reported being in good health until seven years prior to consultation at UAB. At the time of symptom onset, she experienced generalized aches and pains, which were attributed to the development of fibromyalgia by the physicians who
Discussion
TIO was suspected in this case due to the history and laboratory values. Patients with TIO often present with non-specific symptoms such as bone pain, muscle pain, progressive weakness, and fractures [2], and these non-specific symptoms were seen in this patient. Patients may be misdiagnosed with a suspected inflammatory arthritis or fibromyalgia. Due to the often occult and rare nature of TIO, there may be a diagnostic delay.
One retrospective review of 144 cases of TIO estimated that average
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Disclosure of interest
The authors declare that they have no competing interest.
Acknowledgements
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Cited by (20)
Challenges in the management of tumor-induced osteomalacia (TIO)
2021, BoneCitation Excerpt :By Week 23, she was able to use a walker. Serum phosphate concentrations also normalized and were 4.3 mg/dL after 5 months [104]. Currently, burosumab is only licensed for the management of TIO in Japan and the USA.
Hiding in plain sight: Gene panel and genetic markers reveal 26-year undiagnosed tumor-induced osteomalacia of the rib concurrently misdiagnosed as X-linked hypophosphatemia
2021, Bone ReportsCitation Excerpt :In particular, Kyowa Kirin and Ultragenyx's Crysvita (burosumab-twza) has been approved for the treatment of TIO associated with PMTs that cannot be curatively resected or localized in adult and pediatric patients 2 years of age and older. Burosumab has been shown to improve serum phosphate levels and histomorphology of bone biopsies in patients with TIO, but mild side effects have been reported, including reactive overproduction of FGF23 and consequent Vitamin D deficiency (Day et al., 2020). For these reasons, monitoring FGF23 levels is not a reliable way to monitor patients on Burosumab; clinicians should focus on serum phosphorous, Alkaline phosphatase, renal phosphate wasting, 1,25 Dihydroxyvitamin D, and clinical signs/symptoms.
Effects of burosumab on osteocalcin and bone mineral density in patient with 15-year history of nonremission tumor-induced osteomalacia initially treated with conventional therapy: Case report
2020, Bone ReportsCitation Excerpt :In December 2019, burosumab, a recombinant fully human IgG1 monoclonal antibody that inhibits FGF23 activity, was first covered by insurance in Japan before the rest of the world for treatment of FGF23-associated hypophosphatemic osteomalacia by TIO. Unfortunately, except for a case report presented in the United States (Day et al., 2020) and an interim analysis of a phase 2 trial in Japan and Korea (Imanishi et al., 2020), little is known about the precise effects of burosumab in patients with nonremission TIO encountered in daily clinical practice. Herein, we report a patient with a 15-year history of nonremission TIO who had been treated with conventional therapy.
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