To the Editor:

We appreciated the recently published paper of Crotti and coworkers in which the authors reported a patient with tumor-induced osteomalacia (TIO) treated with burosumab for over 2 years for a tumor located in the pre-sacral region that recurred 18 months after excision [1]. Recurrence was associated with decline of serum phosphate (SP) and increase of serum FGF23. After 4 years of treatment with calcitriol and phosphorus supplements without SP normalization, burosumab was started “at the dose of 0.3 mg/kg/month.” The starting dose of burosumab used in this patient was the same used in two previous trials on TIO adult patients [2, 3]. However, in these studies, the overall effects were not completely satisfactory. For example, tubular reabsorption of phosphate remained low, mean SP was barely in the normal range, fractures persisted after 2 years of treatment, new fractures developed, and the osteoid surface/bone surface remained elevated. In addition, pain relief was moderate in one study2 and absent in the other3. As noted by Hartley and Collins [4], these findings contrast with the effects of burosumab (starting dose, 1 mg/kg/month) in adults with X-linked hypophosphatemia (XLH), in which, compared to TIO, baseline SP and intact FGF23 are higher and lower, respectively, and normalization of SP and fracture healing occur faster [4, 5]. In the patient described by Crotti and coworkers [1], burosumab at the starting dose of 0.3 mg/kg/month failed to normalize SP and, when increased to 0.6 mg/kg/month, the patient showed a “new and persistent decline of SP” that resolved in 2 months after the increase of the dose to 0.8 mg/kg/month4. It is likely that, in TIO patients with unresectable/unlocalizable tumors, higher doses are required at the onset to achieve the desired effects (i.e., normalization of SP and resolution of symptoms). Doses up to 2 mg/kg Q2W have been approved for these patients [4].