Tumor-Induced Osteomalacia

Table of Contents

1. Tumor-Induced Osteomalacia in Brief
2. How a Small Tumor Drains Phosphate From the Body
3. The Tumor Behind the Disease
4. How Rare the Disease Is
5. Symptoms and the Long Road to a Diagnosis
6. The Blood and Urine Tests
7. How the Tumor Is Found
8. Surgery and How Often It Cures
9. When the Tumor Cannot Be Found or Removed
10. Burosumab: The Trials and the United States Label
11. What the 2023 Global Guidance States
12. What Is Not Known
13. Key Research Papers
14. Connections
15. Featured Videos

Tumor-Induced Osteomalacia in Brief

A 2023 global guidance document written by an international expert panel describes tumor-induced osteomalacia as a rare paraneoplastic syndrome (a disease caused by substances a tumor releases, rather than by the tumor pressing on anything) caused by mesenchymal tumors that secrete fibroblast growth factor 23 (FGF23). Patients, the guidance states, present with progressive bone pain, muscle weakness and fragility fractures (Jan de Beur 2023).

Four features shape the rest of this page:

• It is acquired. A Danish national registry study calls it a rare, acquired condition of phosphate wasting due to phosphaturic mesenchymal tumors (Abrahamsen 2021). Unlike X-linked hypophosphatemia, it is not passed down in families; the cause is a growth that appears during life.
• It is hard to recognise. A 2023 review in Endocrine Reviews describes the symptoms as usually nonspecific and reports an initial misdiagnosis rate of more than 95% (Minisola 2023).
• It is usually curable. A large Chinese surgical series calls the disease curable by removing the causative tumor (Li 2020), and the 2023 guidance names removal of the tumor as the recommended treatment (Jan de Beur 2023).
• Not every operation succeeds. In that same surgical series, nearly one patient in five either did not recover after the first operation or relapsed later (Li 2020). The details are in the surgery section below.

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How a Small Tumor Drains Phosphate From the Body

Phosphate is one of the two minerals, with calcium, that harden the soft protein scaffold of new bone. Each day the kidneys filter phosphate out of the blood and then pull most of it back, keeping just enough in the body. A hormone made in bone, fibroblast growth factor 23, sets how much the kidneys keep. How phosphate builds bone in general is laid out on the Phosphorus for Bone Mineralization page.

In tumor-induced osteomalacia the tumor makes this hormone on its own, without the body's usual controls. A review from the United States National Institutes of Health describes two effects at the kidney tubule, the fine tube where phosphate is reclaimed from the urine (Chong 2011):

• Phosphate leaks into the urine. Fibroblast growth factor 23 impairs the tubule's reabsorption of phosphate, so the kidneys keep throwing away phosphate the body is short of. The result is hypophosphatemia, a low level of phosphate in the blood.
• Active vitamin D falls. The hormone also blocks the kidney step that turns stored vitamin D into its active form, 1,25-dihydroxyvitamin D (also called calcitriol). The result is low levels of active vitamin D (Chong 2011).

Why the vitamin D effect matters. When blood phosphate is low for any ordinary reason, the kidneys normally make more active vitamin D so the gut absorbs more phosphate from food. In this disease that rescue is switched off. The 2023 guidance describes active vitamin D as low or "inappropriately normal" (Jan de Beur 2023): a level that looks normal on a lab sheet is still too low for a body that is short of phosphate. The body loses phosphate through the kidneys and takes in less through the gut at the same time.

What happens to bone. Bone-building cells keep laying down the soft scaffold, but without enough phosphate it does not harden. The bone fills with soft, unhardened tissue. This is osteomalacia, literally "soft bone", and it is why the bones ache and crack. The same hormone-driven leak occurs in X-linked hypophosphatemia, where an inherited gene change causes the excess hormone instead of a tumor (see the X-Linked Hypophosphatemia page).

A plain picture. Think of the kidneys as a sieve with a lid that a messenger opens and closes. Normally the messenger opens the lid only when the body has phosphate to spare. In tumor-induced osteomalacia a tiny, hidden tumor keeps shouting "open", so phosphate drains away day and night, and the gut's back-up supply line is cut at the same time. Remove the source of the shouting and the lid closes again.

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The Tumor Behind the Disease

The Endocrine Reviews summary states that phosphaturic mesenchymal tumors are the pathological cause in most affected patients, that these tumors are small and grow slowly, and that they can occur in all parts of the body "from head to toe", with a similar share arising in soft tissue and in bone (Minisola 2023). "Mesenchymal" means the tumor grows from connective tissue such as bone, cartilage, fat or blood vessel tissue; "phosphaturic" means it makes the body pass phosphate into the urine. A surgical series from Beijing describes the usual cause as a small, benign phosphaturic mesenchymal tumor (Wang 2015).

Where the tumors turn up. The places reported in the published series include:

• Head and neck. A systematic review of 163 published head-and-neck cases from 109 publications found the paranasal sinuses (the air spaces around the nose), the lower jaw, inside the skull, the upper jaw and the mouth to be the commonest sites, in that order. Only 44.1% of these patients had symptoms at the tumor site itself (Shah 2019).
• Long bones. In 17 Beijing patients with tumors in the long bones of the arms and legs, 82% of the tumors sat in the epiphysis, the rounded end of the bone next to the joint, and the tumors averaged 2.4 cm across (Wang 2015).
• The spine. The same hospital describes tumors in the vertebrae as rare, with a low detection rate and poorer results after surgery (Pang 2024).

A genetic signature in the tumor. In 2015 researchers found a fused gene, called FN1-FGFR1, in 9 of 15 phosphaturic mesenchymal tumors (60%). One gene's switch drives a growth-signal receptor, and the authors propose that the tumor's own hormone may help keep that receptor switched on (Lee 2015). The 2023 review reports that this fusion, or a related FN1-FGF1 fusion, is present in about half of the tumors that cause the disease (Minisola 2023).

Benign, mostly. Most tumors are benign, but not all. In a Beijing series of 230 operated patients, the malignant tumors did worse after surgery than the benign ones (Li 2020), and the head-and-neck review counted four patients with spread (metastatic) disease among its 163 cases (Shah 2019).

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How Rare the Disease Is

The disease has no code of its own in the International Classification of Diseases (ICD-10), which makes it hard to count. A Danish study got around this by combining national hospital and prescription registers from 2008 to 2018: a diagnosis of low phosphate or adult osteomalacia, plus the prescriptions used in early treatment, plus the advanced scans used to hunt for tumors (Abrahamsen 2021). It found:

• New cases of below 0.13 per 100,000 person-years in the whole population, and 0.10 per 100,000 for disease that began in adulthood.
• A prevalence (people living with the disease at one time) of no more than 0.70 per 100,000 in the whole population and 0.43 per 100,000 in adults.
• At most nine new adult cases in all of Denmark in 2018.
• Low mortality, but few patients met the study's cure criterion during the observation period (Abrahamsen 2021).

The authors note that the registers held no blood results and no information on phosphate supplements, which limits the estimate, and that because the patient group is so small and the delay to diagnosis and cure is known, care for suspected cases is best centralised in specialist centres (Abrahamsen 2021). The 2023 review calls the disease "ultrarare" and underdiagnosed (Minisola 2023), so the true number of people affected may be higher than any count shows.

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Symptoms and the Long Road to a Diagnosis

The symptoms come on slowly. The largest published series, 144 patients treated at Peking Union Medical College Hospital between 1982 and 2014, lists the main complaints as (Feng 2017):

• Bone pain
• Difficulty walking
• Pathological fractures (bones breaking under loads that would not break normal bone)
• Muscle weakness
• Loss of height

The deep, weight-bearing ache of soft bone, the tender bones and the small stress cracks called Looser zones are described in detail on the Bone Pain and Softening page, and the weakness of low phosphate on the Muscle Weakness page.

How long the diagnosis takes. In the 144-patient Beijing series (Feng 2017):

• The average time from the first symptoms to the correct diagnosis was 2.9 years, and to removal of the tumor 5.4 years.
• 137 of the 144 patients (95.1%) were first given a wrong diagnosis, and the group as a whole collected 240 wrong diagnoses along the way.
• The commonest wrong diagnoses were a slipped disc (intervertebral disc herniation), spondyloarthritis (including ankylosing spondylitis) and osteoporosis.
• In 62 of the 144 patients (43.1%), a low phosphate result was already printed on a lab sheet and was overlooked.

The authors put the misdiagnoses down to the disease's rarity, its slow onset, its nonspecific symptoms and poor recognition by doctors (Feng 2017). Other centres report the same pattern. An Italian rheumatology centre found an average delay of 6.6 years from the first symptoms to finding the tumor in 17 patients (Crotti 2021). In six Australian patients, every case showed a delayed diagnosis despite severe symptoms (Clifton-Bligh 2013), and in six Indian patients the time from symptoms to the scan that found the tumor ranged from 1.5 to 22 years (Agrawal 2015). In the head-and-neck review, the reported duration of symptoms ranged from 1 to 240 months (Shah 2019).

The 2023 guidance links the delay to limited awareness: because the disease is rare and its presentation puzzling, the right tests may not be ordered, which the guidance states leads to delayed diagnosis and poorer outcomes (Jan de Beur 2023).

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The Blood and Urine Tests

The disease is suspected from blood and urine tests long before any tumor is seen. The 2023 guidance describes three defining laboratory features: low blood phosphate, excess phosphate in the urine, and low or inappropriately normal active vitamin D (Jan de Beur 2023). The Endocrine Reviews summary adds the hormone itself: fibroblast growth factor 23 is increased or inappropriately normal, and active vitamin D is low to low-normal (Minisola 2023).

The priority tests named by the guidance. The 2023 guidance lists these as the first laboratory evaluations (Jan de Beur 2023):

• Phosphate and creatinine in both blood and urine, to work out how much filtered phosphate the kidneys reclaim. One common calculation is the tubular maximum reabsorption of phosphate per glomerular filtration rate (TmP/GFR), often called the kidney phosphate threshold.
• Alkaline phosphatase, an enzyme from bone-building cells that tends to rise when bone is soft.
• Parathyroid hormone.
• 25-hydroxyvitamin D, the stored form of vitamin D, to rule out plain vitamin D deficiency.
• 1,25-dihydroxyvitamin D, the active form.
• Fibroblast growth factor 23.

What the results looked like in practice.

• In the 144 Beijing patients, average blood phosphate was 0.48 mmol/L, alkaline phosphatase was raised at an average of 277.9 U/L, the kidney phosphate threshold was reduced (an average of 0.39), and fibroblast growth factor 23 was markedly raised, with a median of 302.9 pg/mL (Feng 2017).
• In the 17 Italian patients, average blood phosphorus was 1.3 mg/dL against a reference range of 2.5 to 4.6, and average intact fibroblast growth factor 23 was 358.9 pg/mL against a reference range of 25 to 45. Average active vitamin D was 31.8 ng/mL against a reference range of 25 to 86, which illustrates what "inappropriately normal" means (Crotti 2021).

A trap in the urine test. In the Italian series, a 24-hour urine phosphorus was raised in only 2 of the 17 patients, while the tubular reabsorption of phosphate, which compares urine with blood, was reduced in all of them, confirming that the kidneys were wasting phosphate (Crotti 2021). In that series it was the comparison of urine with blood, not the 24-hour total alone, that showed the leak.

The blood test that starts it all. The guidance states that serum phosphate be measured in people who present with chronic muscle pain or weakness, fragility fractures or bone pain (Jan de Beur 2023). The Beijing authors reached the same conclusion from their overlooked lab sheets (Feng 2017).

Other causes to separate. A raised or inappropriately normal fibroblast growth factor 23 with low phosphate is not specific to a tumor. Inherited forms exist, including X-linked hypophosphatemia, and a Japanese study points out that some adults with this blood picture and no tumor found may have a late-onset inherited form (Kato 2022). Certain intravenous iron products can raise the same hormone and lower phosphate (see Intravenous Iron and Low Phosphate), and vitamin D deficiency softens bone through a different route (see Vitamin D Deficiency: Bone Pain and Osteomalacia).

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How the Tumor Is Found

Once the blood tests point to a hormone-driven phosphate leak, the hunt for the tumor begins. This is often the hardest step: the tumors are small and, as an Australian case series puts it, often difficult to find with conventional imaging (Clifton-Bligh 2013). The 2023 guidance states that functional imaging, which shows what tissue is doing rather than only its shape, be used to localise the tumor (Jan de Beur 2023).

Somatostatin-receptor scans. Many of these tumors carry receptors for somatostatin, a natural hormone, on their surface. A scan using a radioactive tracer that sticks to these receptors (gallium-68 DOTATATE or gallium-68 DOTATOC), read with positron emission tomography combined with computed tomography (PET/CT), lights up tissue that carries them. The 2023 review states that these gallium-68 tracers have better sensitivity than other methods (Minisola 2023). What individual studies found:

• In six Australian patients, the gallium-68 DOTATATE scan showed high uptake and located the tumor with confidence in every case, and every tumor showed a high level of somatostatin receptor subtype 2 when examined under the microscope (Clifton-Bligh 2013).
• In six Indian patients, the gallium-68 DOTATATE scan found the tumor in 5 of 6 (83.3%). In the four who had both scans, the DOTATATE scan found the tumor in 3 and the sugar-tracer scan (18F-FDG, which shows tissue that burns a lot of glucose) in 2 (Agrawal 2015).
• In 35 Japanese patients with suspected disease, the gallium-68 DOTATOC scan detected the cause in 20 of 35 (57%); one further positive scan was judged a false positive. The level of fibroblast growth factor 23 in the blood did not differ between patients with positive and negative scans (Kato 2021).
• In 16 Beijing patients with tumors in the spine, the gallium-68 DOTATATE scan had a sensitivity of 100%, against 40% for an older octreotide scan (Pang 2024).
• At the Italian centre, the average delay to diagnosis fell from 8.6 years to 4.3 years after gallium-68 scans entered routine practice in 2013 (Crotti 2021).

Venous sampling. When scans show more than one suspicious spot, or none, blood can be drawn through a thin tube placed in veins draining different parts of the body, measuring fibroblast growth factor 23 in each. The vein nearest the tumor carries the highest level. In a Japanese study of 18 patients with a confirmed phosphaturic mesenchymal tumor, the tumor was located before surgery in 72% with the sugar-tracer scan, 72% with an older somatostatin-receptor scan (indium-111 pentetreotide), and 94% with systemic venous sampling; the combination of the sugar-tracer scan and venous sampling located it in 100% (Kato 2022). The National Institutes of Health review describes a step-wise approach of functional imaging, then anatomical imaging such as computed tomography or magnetic resonance imaging, and, if needed, selective venous sampling (Chong 2011).

Biopsy. The Italian centre observed relapses only in patients who had earlier had a closed (needle) biopsy of the tumor, and its authors advise against tumor biopsy because of the possibility of spilling tumor cells (Crotti 2021). This is the observation of one series of 17 patients.

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Surgery and How Often It Cures

The 2023 guidance names tumor resection, complete surgical removal, as the recommended treatment (Jan de Beur 2023), and the Endocrine Reviews summary calls surgery the treatment of choice (Minisola 2023).

How fast the body responds. In 17 Beijing patients with tumors in the long bones, fibroblast growth factor 23 returned to normal within 24 hours of successful removal, and blood phosphorus returned to normal after an average of 6.5 days (Wang 2015). In the Australian series, symptoms and blood phosphate resolved after removal except in one patient whose scan showed tumor left behind (Clifton-Bligh 2013).

How often surgery fails or the disease returns. The largest series on this question followed 230 patients who had surgery at one Beijing hospital (Li 2020):

• After the first operation, the disease persisted in 26 patients (11.3%) and came back later in 16 (7.0%), an overall "refractory" rate of 18.3%.
• The median time to recurrence was 33 months.
• The refractory rate was lowest for head-and-neck tumors (7.5%) and highest for spine tumors (77.8%).
• Tumors involving bone did worse than tumors in soft tissue only (32.7% versus 7.0% refractory).
• Malignant tumors did worse than benign ones: the disease persisted in 21.4% versus 9.7% and recurred in 28.6% versus 6.5%.
• Female sex, a spine tumor, bone involvement, malignancy and a lower phosphate level before surgery were risk factors for a poor result, and a higher fibroblast growth factor 23 level before surgery was also linked to it (Li 2020).

How the tumor is removed matters. Two Beijing series compared scooping a tumor out of the bone (curettage) with cutting out the whole section of bone that contains it (segmental resection):

• In long bones, complete removal was achieved in 67% with curettage and 80% with segmental resection, but the disease recurred in 50% after curettage and 0% after segmental resection (Wang 2015).
• In the spine, recovery was 62.5% after segmental resection and 12.5% after curettage (Pang 2024).

Other centres. In the head-and-neck review, 97.5% of patients were treated first with surgery; 20 had persistent disease and 9 had a recurrence, more often with tumors inside the skull or in the mouth (Shah 2019). An Indian centre reported that, of 24 patients operated on first, 12 went into early remission, 3 into delayed remission and 9 had persistent disease at a median follow-up of 5 years; two had a few weeks of worse weakness after the operation (Memon 2024). At the Italian centre, after surgery or ablation, 8 patients were in complete remission, 3 had persistent disease and 3 relapsed over time (Crotti 2021). The Italian authors describe active watch for recurrence as always needed (Crotti 2021).

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When the Tumor Cannot Be Found or Removed

For some patients the tumor never shows up on any scan, sits where it cannot be safely removed, or comes back. The 2023 guidance lists two medical options for tumors that cannot be removed or identified: phosphate salts plus active vitamin D, or burosumab (Jan de Beur 2023).

Phosphate plus active vitamin D. This is the older approach: phosphate taken by mouth to replace what the kidneys lose, together with an active form of vitamin D (calcitriol or alfacalcidol) to restore gut absorption. The National Institutes of Health review states that this regimen is usually successful but can be cumbersome and associated with complications (Chong 2011). It treats the effect of the hormone; it does not remove its source. The complications of long-term phosphate and active vitamin D treatment are described on the X-Linked Hypophosphatemia page.

Ablation. Some tumors can be destroyed in place with a needle guided by imaging rather than cut out. In radiofrequency ablation, heat from an electrical current destroys the tumor tissue. An Indian centre noted that earlier data on ablation for this disease came only from case reports, about 11 patients. In its own series, 10 patients had radiofrequency ablation (9 as the first treatment); at a median follow-up of 5 years, 7 were in remission, two of the three with persistent disease had large tumors (5.6 and 3.6 cm), there were no ablation complications other than a local ulcer in one patient, and neither the ablation group nor the surgery group had a recurrence (Memon 2024). The authors describe the response to ablation as durable and similar to surgery (Memon 2024). These are 10 patients at one centre.

Radiation and radionuclide therapy. Small numbers of patients with persistent disease have been treated with radiation therapy or with peptide receptor radionuclide therapy, a radioactive drug that targets the same somatostatin receptors the scans detect (Shah 2019; Memon 2024). These are single-patient or few-patient reports.

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Burosumab: The Trials and the United States Label

Burosumab is a fully human monoclonal antibody, a laboratory-made immune protein, that binds fibroblast growth factor 23 and stops it acting on the kidney. The United States label lists it for both X-linked hypophosphatemia and tumor-induced osteomalacia. It does not remove the tumor; it blocks the hormone the tumor makes.

The United States trial. An open-label phase 2 study (everyone received the drug; there was no comparison group) reported on 14 adults with tumor-induced osteomalacia (Jan de Beur 2021):

• Blood phosphorus rose from 0.52 mmol/L at the start and stayed raised after the dose was adjusted, at 0.91 mmol/L at week 22 and 0.82 mmol/L at week 144.
• Most measures of soft bone on bone biopsies taken from the hip bone improved at week 48.
• Of 249 fractures and pseudofractures seen across the 14 patients at the start, 33% were fully healed and 13% partly healed at week 144.
• Patients reported less pain and fatigue and better physical health.
• Sixteen serious adverse events occurred in seven patients, and one patient died; all serious events were judged unrelated to the drug. Nine patients had 16 events judged treatment-related, all mild to moderate. Two patients stopped, one to treat tumor progression (Jan de Beur 2021).

The Japanese and Korean trial. An interim report of an open-label phase 2 study gave burosumab at 0.3 to 2.0 mg/kg every 4 weeks to 13 patients in Japan and Korea. The average dose after week 112 was about 1.0 mg/kg. Average blood phosphate rose and stayed in the normal range from week 14 to week 112; patients walked further on a 6-minute walk test, reported less pain, and showed a tendency toward healing of fractures and pseudofractures. Two patients stopped, one because of disease progression. There were no treatment-related serious adverse events (Imanishi 2021).

What the United States label states. The burosumab label on DailyMed (version published July 2026) gives the following:

• Approved use. Treatment of fibroblast growth factor 23-related low phosphate in tumor-induced osteomalacia caused by phosphaturic mesenchymal tumors that cannot be curatively removed or located, in adults and children 2 years of age and older.
• Dosing as the label gives it. For adults, a starting dose of 0.5 mg/kg every 4 weeks, which may be increased up to 2 mg/kg, not to exceed 180 mg, given every 2 weeks. For children 2 years and older, a starting dose of 0.4 mg/kg every 2 weeks, with the same maximum. It is given as an injection under the skin by a healthcare provider.
• Before starting. Oral phosphate and active vitamin D are stopped for one week, and fasting blood phosphorus is below the reference range.
• Contraindications. Use together with oral phosphate or active vitamin D, because of the risk of high phosphate; blood phosphorus already within or above the normal range; and severe kidney impairment or end-stage kidney disease.
• Warnings. Serious allergic (hypersensitivity) reactions; high phosphate, which may raise the risk of calcium deposits in the kidneys (nephrocalcinosis); raised blood calcium; and injection-site reactions. If the tumor is treated by surgery or radiation, the label states that burosumab is interrupted and blood phosphorus rechecked afterwards.
• Boxed warning. The label carries none.
• Side effects in the tumor-induced osteomalacia studies. In 27 adults pooled from two single-arm studies, the commonest adverse reactions were tooth abscess (19%), muscle spasms (19%), dizziness (15%), constipation (15%), injection-site reactions (15%), rash (15%) and headache (11%). Hypersensitivity reactions occurred in 22%, most often eczema (11%) and rash (11%), all mild or moderate. High phosphate occurred in 2 patients (7%) and was managed by lowering the dose.
• Effect on phosphate in the label's studies. In the 14-patient study, average fasting phosphorus rose from 1.60 mg/dL to 2.64 mg/dL averaged through week 24, with 7 of 14 patients (50%) above the lower limit of normal; in the 13-patient study it rose from 1.62 mg/dL to 2.63 mg/dL, with 9 of 13 (69%) above the lower limit of normal. The kidney phosphate threshold rose from 1.12 to 2.12 mg/dL and from 1.15 to 2.30 mg/dL at week 48 in the two studies.

The label, as quoted above, limits the approved use to tumors that cannot be curatively removed or located; it does not present the antibody as a replacement for removing a tumor that can be found and taken out. Decisions about any of these medicines belong with the specialist team treating the disease.

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What the 2023 Global Guidance States

In 2023 an international panel of specialists published global guidance in the Journal of Internal Medicine. They reviewed the literature and ran a three-round Delphi survey of experts (a structured process of repeated anonymous voting), and kept as final recommendations only statements that reached at least 70% agreement (Jan de Beur 2023). As reported in the guidance's summary:

• Who gets tested. Serum phosphate is measured in patients who present with chronic muscle pain or weakness, fragility fractures or bone pain.
• The examination. A physical examination looks for signs of muscle disease (myopathy) and for lumps that could be the tumor.
• The first laboratory tests. Urine and serum phosphate and creatinine, to assess the kidneys' reabsorption of phosphate and the kidney phosphate threshold; alkaline phosphatase; parathyroid hormone; 25-hydroxyvitamin D; 1,25-dihydroxyvitamin D; and fibroblast growth factor 23.
• Referral. Patients with clinical or laboratory suspicion of the disease are referred to a specialist to confirm the diagnosis.
• Finding the tumor. Functional imaging is used to localise the causative tumor or tumors.
• Treatment. Tumor resection; or, with tumors that cannot be removed or identified, phosphate salts plus active vitamin D, or burosumab (Jan de Beur 2023).

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What Is Not Known

• How common it really is. The Danish figures are upper limits built from prescriptions and scans, without blood results (Abrahamsen 2021), and the disease is described as underdiagnosed (Minisola 2023). Nobody knows how many people live with it undiagnosed.
• Why the tumor forms. A gene fusion is found in about half of the tumors (Minisola 2023); what drives the other half is not established.
• What to do when no tumor is found. Some adults with the blood picture of this disease never have a tumor located, and a Japanese study notes that some of them may have a late-onset inherited form instead (Kato 2022). How often that is the case is not known.
• The best scan. Detection rates for gallium-68 scans range from 57% in one Japanese series (Kato 2021) to every patient in small Australian and Beijing spine series (Clifton-Bligh 2013; Pang 2024). The imaging studies cited here are small and mostly from single centres.
• Long-term results of the antibody. The burosumab trials enrolled 14 and 13 patients without a comparison group (Jan de Beur 2021; Imanishi 2021). How it performs over many years, and in children with the disease, rests on small numbers; the label states that use in children 2 years and older is supported by the adult studies plus modelling from other patient groups.
• Ablation versus surgery. The ablation data come mostly from one Indian centre and earlier case reports (Memon 2024). None of the studies cited here is a randomised comparison of ablation with surgery.
• Whether biopsy seeds relapses. The link between needle biopsy and relapse comes from one series of 17 patients (Crotti 2021).

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Key Research Papers

1. Jan de Beur SM, Minisola S, Xia WB, Abrahamsen B, Body JJ, Brandi ML, Clifton-Bligh R, Collins M, Florenzano P, Houillier P, Imanishi Y, Imel EA, Khan AA, Zillikens MC, Fukumoto S. Global guidance for the recognition, diagnosis, and management of tumor-induced osteomalacia. J Intern Med. 2023;293(3):309-328. PubMed PMID: 36511653
2. Minisola S, Fukumoto S, Xia W, Corsi A, Colangelo L, Scillitani A, Pepe J, Cipriani C, Thakker RV. Tumor-induced Osteomalacia: A Comprehensive Review. Endocr Rev. 2023;44(2):323-353. PubMed PMID: 36327295
3. Feng J, Jiang Y, Wang O, Li M, Xing X, Huo L, Li F, Yu W, Zhong DR, Jin J, Liu Y, Qi F, Lv W, Zhou L, Meng XW, Xia WB. The diagnostic dilemma of tumor induced osteomalacia: a retrospective analysis of 144 cases. Endocr J. 2017;64(7):675-683. PubMed PMID: 28450684
4. Abrahamsen B, Smith CD, Minisola S. Epidemiology of Tumor-Induced Osteomalacia in Denmark. Calcif Tissue Int. 2021;109(2):147-156. PubMed PMID: 33818653
5. Chong WH, Molinolo AA, Chen CC, Collins MT. Tumor-induced osteomalacia. Endocr Relat Cancer. 2011;18(3):R53-77. PubMed PMID: 21490240
6. Lee JC, Jeng YM, Su SY, Wu CT, Tsai KS, Lee CH, Lin CY, Carter JM, Huang JW, Chen SH, Shih SR, Mariño-Enríquez A, Chen CC, Folpe AL, Chang YL, Liang CW. Identification of a novel FN1-FGFR1 genetic fusion as a frequent event in phosphaturic mesenchymal tumour. J Pathol. 2015;235(4):539-45. PubMed PMID: 25319834
7. Clifton-Bligh RJ, Hofman MS, Duncan E, Sim IeW, Darnell D, Clarkson A, Wong T, Walsh JP, Gill AJ, Ebeling PR, Hicks RJ. Improving diagnosis of tumor-induced osteomalacia with Gallium-68 DOTATATE PET/CT. J Clin Endocrinol Metab. 2013;98(2):687-94. PubMed PMID: 23295468
8. Agrawal K, Bhadada S, Mittal BR, Shukla J, Sood A, Bhattacharya A, Bhansali A. Comparison of 18F-FDG and 68Ga DOTATATE PET/CT in localization of tumor causing oncogenic osteomalacia. Clin Nucl Med. 2015;40(1):e6-e10. PubMed PMID: 24999675
9. Kato A, Nakamoto Y, Ishimori T, Hayakawa N, Ueda M, Temma T, Sano K, Shimizu Y, Saga T, Togashi K. Diagnostic performance of (68)Ga-DOTATOC PET/CT in tumor-induced osteomalacia. Ann Nucl Med. 2021;35(3):397-405. PubMed PMID: 33582980
10. Kato H, Koga M, Kinoshita Y, Hidaka N, Hoshino Y, Takashi Y, Arai M, Kobayashi H, Katsura M, Nakamoto Y, Makise N, Ushiku T, Hoshi K, Nangaku M, Makita N, Fukumoto S, Ito N. Utility of Multimodality Approach Including Systemic FGF23 Venous Sampling in Localizing Phosphaturic Mesenchymal Tumors. J Endocr Soc. 2022;7(2):bvac181. PubMed PMID: 36540156
11. Li X, Jiang Y, Huo L, Wu H, Liu Y, Jin J, Yu W, Lv W, Zhou L, Xia Y, Wang O, Li M, Xing X, Chi Y, Jiajue R, Cui L, Meng X, Xia W. Nonremission and Recurrent Tumor-Induced Osteomalacia: A Retrospective Study. J Bone Miner Res. 2020;35(3):469-477. PubMed PMID: 31643101
12. Wang H, Zhong D, Liu Y, Jiang Y, Qiu G, Weng X, Xing X, Li M, Meng X, Li F, Zhu Z, Yu W, Xia W, Jin J. Surgical Treatments of Tumor-Induced Osteomalacia Lesions in Long Bones: Seventeen Cases with More Than One Year of Follow-up. J Bone Joint Surg Am. 2015;97(13):1084-94. PubMed PMID: 26135075
13. Pang Q, Zhou R, Ni X, Liu Y, Jin J, Wu H, Huo L, Yu W, Chi Y, Li X, Wang O, Li M, Xing X, Jiang Y, Jiajue R, Xia W. Clinical characteristics and surgical outcomes of vertebral lesions associated with tumor-induced osteomalacia: report of 16 patients and review of the literature. Osteoporos Int. 2024;35(11):1951-1962. PubMed PMID: 39093437
14. Shah R, Lila AR, Jadhav RS, Patil V, Mahajan A, Sonawane S, Thadani P, Dcruz A, Pai P, Bal M, Kane S, Shah N, Bandgar T. Tumor induced osteomalacia in head and neck region: single center experience and systematic review. Endocr Connect. 2019;8(10):1330-1353. PubMed PMID: 31505461
15. Crotti C, Bartoli F, Coletto LA, Manara M, Marini E, Daolio PA, Parafioriti A, Armiraglio E, Zucchi F, Sinigaglia L, Caporali R, Varenna M. Tumor induced osteomalacia: A single center experience on 17 patients. Bone. 2021;152:116077. PubMed PMID: 34175499
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17. Jan de Beur SM, Miller PD, Weber TJ, Peacock M, Insogna K, Kumar R, Rauch F, Luca D, Cimms T, Roberts MS, San Martin J, Carpenter TO. Burosumab for the Treatment of Tumor-Induced Osteomalacia. J Bone Miner Res. 2021;36(4):627-635. PubMed PMID: 33338281
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19. United States prescribing information for burosumab injection, DailyMed, National Library of Medicine (version published July 2026). DailyMed setid 102f96a0-6e3a-4fc1-b204-34d604683af6

PubMed Topic Searches

1. PubMed: tumor-induced osteomalacia
2. PubMed: phosphaturic mesenchymal tumor
3. PubMed: tumor-induced osteomalacia and gallium-68 somatostatin-receptor scans
4. PubMed: tumor-induced osteomalacia surgery and recurrence
5. PubMed: burosumab in tumor-induced osteomalacia

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Connections

• Endocrinology — the parent section for hormone diseases
• X-Linked Hypophosphatemia — the inherited form of the same hormone-driven phosphate loss
• Hypophosphatemia: Bone Pain and Softening — what soft bone feels like and how it is investigated
• Hypophosphatemia (Low Phosphate) — all the causes and effects of low phosphate
• Hypophosphatemia: Muscle Weakness — the weakness that often comes with the bone pain
• Phosphorus for Bone Mineralization — how phosphate hardens bone
• Vitamin D Deficiency: Bone Pain and Osteomalacia — the commoner route to soft bone
• Intravenous Iron and Low Phosphate — another cause of a raised phosphate-wasting hormone

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