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

Abstract

Excess fibroblast growth factor 23 (FGF23) causes hypophosphatemic osteomalacia, which is associated with impaired bone matrix mineralization. Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome caused by over-secretion of FGF23 from a tumor. Burosumab, a fully human monoclonal antibody with activities against FGF23, was initially approved in Japan before the rest of the world for treatment of FGF23-associated hypophosphatemic osteomalacia by TIO. We report here a patient with a 15-year history of non-remission TIO initially treated with conventional therapy who was then switched to burosumab treatment. Persistent hypophosphatemia and a relative low level of osteocalcin (bone Gla protein, BGP) compared with bone alkaline phosphatase (BAP) level, indicating poor matrix mineralization, developed during long-term conventional therapy. Repeated surgical and stereotactic body radiation treatments did not result in complete resection of the causable tumor, and bone mineral density (BMD) gradually decreased. Ultimately, burosumab treatment was administered and the serum Pi concentration immediately normalized, while both BGP and BMD also showed a good response. This is first known case report of the detailed efficacy of burosumab for nonremission TIO as an alternative to conventional therapy.

Favorable effects of burosumab on tumor-induced osteomalacia caused by an undetectable tumor

“…Miyaoka et al compared burosumab with conventional therapy for a recurrent TIO case [8] . Despite repeated surgery for multiple recurrences, improvements in symptoms including bone pain and resection were not completed.…”

“…Although subcutaneous burosumab administration has already been established as an effective treatment for X-linked hypophosphatemic rickets, its potential as a treatment for TIO has not been determined and only a few case reports and clinical trials have been presented. [6][7][8][9][10] Herein, we describe a case of TIO caused by an undetectable tumor that was effectively treated with burosumab.…”

Improvement in the mobility of a patient with fibroblast growth factor 23-related hypophosphatemic osteomalacia and decompensated liver cirrhosis in response to burosumab: a case report

“…Therefore, the increase in serum BGP concentration is consistent with the improvement in the osteomalacia of the present patient. It has been reported that the low BGP in a patient with TIO increased during the 2 weeks following the removal of an FGF23-producing tumor, peaked after 8 weeks, and then gradually decreased [19]; and also that a patient with TIO who had not entered remission had a similar clinical course during burosumab treatment [12]. The present patient showed a similar improvement in her serum 1,25(OH) 2 D concentration, and her low serum BGP increased during the first 12 weeks of burosumab treatment, and then gradually decreased.…”

“…There is no evidence that active vitamin D metabolites or analogs or oral phosphate supplementation increases the BMD of patients with TIO, but complete surgical removal of the causative tumor is known to increase BMD [20]. Previous studies have shown that LS-BMD increases after treatment with burosumab [10][11][12], but this has not been confirmed in larger numbers of patients. In addition, surgical resection and burosumab administration may accelerate the healing of fractures and pseudo-fractures, reduce the risk of new fractures, ameliorate pain, and improve physical function [3,10,11,[21][22][23].…”

“…TIO is a major cause of acquired FGF23-related hypophosphatemic osteomalacia [3]. The efficacy and safety of burosumab in patients with TIO have been demonstrated in two clinical trials performed in Asia [10] and the United States [11] and in three patients with TIO [12][13][14].…”