Tumor-Induced Osteomalacia: Treating the Phosphate While the Tumor Stays Hidden
A single patient whose actual cure is a tumor nobody can find yet. The disagreement is what to do about his bones and his pain for however long that search takes.
Baldwin R., a 52-year-old man, spent nearly two years being treated for what several doctors assumed was slowly worsening osteoarthritis, before progressive bone pain and a series of unexplained fractures — a rib, then a metatarsal, both from minimal trauma — finally prompted the lab workup that found it: severe hypophosphatemia driven by inappropriately elevated FGF23, the signature of tumor-induced osteomalacia. A phosphate of 1.2 mg/dL is not a mild deficiency being managed; it is a level at which bone cannot mineralize, which is what turns a rib and a metatarsal broken by nothing into a coherent picture rather than bad luck. Somewhere in his body, almost always a small benign mesenchymal tumor in these cases, something is secreting FGF23 and wasting that phosphate into his urine, and finding it is the only path to an actual cure.
Finding it is proving difficult. His initial whole-body imaging did not localize a culprit, and his endocrinologist is now coordinating a targeted search with somatostatin-receptor and FDG-PET imaging — a process that in cases like his can run months and does not always succeed. Meanwhile he is using a cane for the first time in his life, has missed most of the last two months of work as an electrician, and describes a level of bone pain he says he would not have believed possible from anything short of a broken bone. Treating the phosphate wasting directly while that search continues is squarely contemplated by the label rather than an improvisation: burosumab was approved in 2020 for FGF23-related hypophosphatemia in tumor-induced osteomalacia where the tumor cannot be curatively resected or localized, which describes him precisely today, and Jan de Beur and colleagues' phase 2 trial in TIO reported sustained increases in serum phosphate and improvement in osteomalacia on bone biopsy. What is genuinely uncertain is narrower and more specific: whether starting a drug that targets FGF23 could interfere with imaging studies being run to find an FGF23-secreting tumor. He has asked directly how long "months" might actually mean in practice, having already lost two years to a wrong diagnosis before anyone found the real one.
Treating the phosphate while the search continues
I'd start burosumab now as bridge therapy rather than wait for localization. This is squarely on-label: the FDA approved burosumab in 2020 for FGF23-related hypophosphatemia in tumor-induced osteomalacia where the tumor cannot be curatively resected or localized, which describes him exactly today. Jan de Beur and colleagues' phase 2 trial in TIO reported sustained increases in serum phosphate and improvement in osteomalacia on bone biopsy. His fracture risk and functional decline are severe enough right now that months of additional imaging shouldn't mean months of untreated disease.
My hesitation is the localization workup itself. Data on burosumab's interaction with the tumor-localization process are still limited, and I'd want to know whether altering FGF23-related signaling could theoretically complicate the very studies being used to find his tumor before starting it during an active search.
I'm not arguing to withhold treatment indefinitely — I'm raising a real, if unconfirmed, concern that deserves a direct answer before we start a drug that shares a target with what the imaging may be relying on.
I can answer that directly. His localization workup relies on somatostatin-receptor and FDG-PET imaging — both target tumor characteristics (receptor expression, metabolic activity) that are unrelated to FGF23 signaling itself. Burosumab's mechanism of action doesn't plausibly interfere with what these specific studies are actually detecting.
That reassurance is specific to these imaging modalities, not a blanket statement about every possible localization technique — but for the studies actually being used here, I don't see a mechanistic reason to delay starting burosumab while the search continues.
Agreed: start burosumab now as bridge therapy while the localization workup continues, given nuclear medicine's direct confirmation that the specific imaging modalities being used aren't mechanistically affected by FGF23 inhibition.
Not fully settled: what the plan becomes if the tumor still isn't found after the current round of imaging is exhausted — the endocrinologist raised long-term burosumab as one possibility and additional, more invasive localization techniques as another, without the group committing to either path in advance of that outcome.