Elsevier

Joint Bone Spine

Volume 87, Issue 1, January 2020, Pages 81-83
Joint Bone Spine

Case report
Burosumab in tumor-induced osteomalacia: A case report

https://doi.org/10.1016/j.jbspin.2019.07.012Get rights and content

Highlights

  • Tumor-induced osteomalacia is a rare, paraneoplastic, cause of acquired osteomalacia.

  • Treatment typically involves surgical resection of the offending tumor after localization with functional imaging.

  • Burosumab, an anti-fibroblast growth factor-23 monoclonal antibody, is an emerging, promising treatment in those who cannot undergo surgery.

Abstract

Tumor-induced osteomalacia is a rare cause of acquired hypophosphatemia due to the paraneoplastic overproduction of fibroblast growth factor-23. Unlike many causes of osteomalacia, tumor-induced osteomalacia is curable by resection of the offending tumor. If a patient has a tumor that is unidentifiable, unresectable, or makes the decision to forgo surgery, medical treatment is recommended. Burosumab (KRN23) is a fully human monoclonal antibody against fibroblast growth factor-23 that was recently approved for the treatment of X-linked hypophosphatemia. We present a case of tumor-induced osteomalacia due to two somatostatin receptor avid meningiomas. The patient initially was wheelchair bound due to symptoms of diffuse bone and muscle pain with recurrent traumatic and nontraumatic fractures. Serum phosphate was 1.8 mg/dL (reference range: 2.4–5.0 mg/dL) with no other laboratory or historical cause. Workup revealed two widely separated intracranial meningiomas with typical magnetic resonance imaging characteristics. The duplicity of tumors precluded safe surgery and the potential delay in, or lack of, efficacy using radiosurgery prompted the treatment team to opt for medical treatment. Burosumab was initiated resulting in improvement in pain symptoms and mobility. Serum phosphate normalized. Trials are ongoing to assess the utility of burosumab in the treatment of tumor-induced osteomalacia.

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

Financial support and sponsorship

None.

Disclosure of interest

The authors declare that they have no competing interest.

Acknowledgements

None.

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