Background

Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome of acquired hypophosphatemic osteomalacia caused by increased secretion of fibroblast growth factor 23 (FGF23) by a tumor. These tumors are of mesenchymal origin, and patients with TIO can be cured completely if the tumor is properly localized and subsequently completely removed. However, localization of these tumors is often challenging, and in case of severe complaints but without a clear tumor, Burosumab treatment, a human monoclonal antibody inhibiting FGF23, could be considered.

Patient Case

A 44-year old male was seen because of severe hypophosphatemia with since 3 years complaints of severe fatigue, myalgia, muscle weakness, and decreased activity tolerance. Laboratory results revealed hypophosphatemia (0.40 mmol/L; reference range: 0.80–1.40 mmol/L), relatively high FGF23 levels (90 RU/ml; reference range: <125 RU/ml), and a reduced TmP-GFR (0.37 mmol/L; reference range: 0.8–1.4 mmol/L). These results combined with his complaints were suggestive for TIO. However, Gallium-PET/CT showed no increased uptake that would fit with a FGF23 producing tumor, while genetic testing was negative. Treatment with alfacalcidol 1.25mcg once daily and liquid phosphate 10mmol four times daily was initiated, but serum phosphate levels remained low (0.46 mmol/L) and complaints persisted. Therefore, he was discussed within the indication committee for treatment with Burosumab, and started on monthly 90mg. Within a few weeks his complaints almost completely resolved, and because of high levels of serum phosphate (1.46 mmol/L), the Burosumab dose could be tapered to monthly 30mg. Treatment was well-tolerated and serum phosphate levels remained normal (0.81 mmol/L). Questionnaires showed better quality of life, and the physical tests also improved significantly.

Conclusions

We demonstrated the first patient in The Netherlands treated with Burosumab for a suspected TIO. After initiating treatment, normalization of phosphate metabolism combined with a remarkable recovery of his complaints was seen.