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A Diagnosis Delayed: Why Tumor- Induced Osteomalacia (TIO) Goes Unrecognized

Daniel M. Englert, MD

Vice Chair of Endocrinology and

Associate Fellowship Program Director

Ochsner Medical Center

New Orleans, LA

TIO, tumor-induced osteomalacia.

COMM-US-RDS-1078 July 2026

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Disclosures

The following presentation is sponsored by Kyowa Kirin, Inc.
The presenter is a paid consultant of Kyowa Kirin, Inc., and is presenting this information on the company’s behalf

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Agenda

Today’s presentation will cover

TIO, tumor-induced osteomalacia.

A TIO patient case

Identifying TIO and differentiating it from other renal phosphate wasting disorders

An overview of TIO

Recommendations for diagnosing TIO, including testing and evaluations that should be performed

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David: 66-year-old male with worsening pain

Hypothetical patient case study based on real patient data provided by Daniel M. Englert, MD. For education purposes only.

Image is not an actual patient.

MRI, magnetic resonance imaging; NSAID, nonsteroidal anti-inflammatory drug; PCP, primary care provider.

#2: +5 MONTHS�Orthopedics

#1: INITIAL VISIT�Primary Care

Patient followed up with orthopedics 5 months �after his initial visit with the PCP for continued �right ankle pain
MRI identified a stress fracture, which was treated �with rest and crutches

66-year-old male complaining of right shoulder pain, right ankle pain, and low back pain after performing heavy labor
He was treated with NSAIDs, but pain did not improve

Actor portrayal

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David: 66-year-old male with worsening pain

Ongoing right ankle pain and difficulty walking
Laboratory testing done
Intra-articular steroid injection given but provided no relief

Laboratory Test	Current Result �(Reference Range^a)
Creatinine, mg/dL	1.1 (0.5-1.4)
Calcium, ng/mL	10.1 (8.7-10.5)
ALP, U/L	152 (55-135)
Albumin, g/dL	4.0 (3.5-5.2)

Biochemical Testing

#3: +8 MONTHS�Primary Care

Actor portrayal

Hypothetical patient case study based on real patient data provided by Daniel M. Englert, MD. For education purposes only.

Image is not an actual patient.

^aReference ranges provided by Daniel M. Englert, MD.

ALP, alkaline phosphatase.

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David: Arthroscopy for ankle pain but begins presenting with knee pain

Ankle arthroscopy performed and repaired partial thickness �tear of talar dome cartilage

#4: +11 MONTHS�Orthopedics

Hypothetical patient case study based on real patient data provided by Daniel M. Englert, MD. For education purposes only.

Image is not an actual patient.

Persistent left knee pain
Cannot walk without crutches

#6: +13 MONTHS�Orthopedics

New pain in left mid-foot
Referred to rheumatology due to multiple joint arthropathies

#7: +14 MONTHS�Orthopedics

Knee arthroscopy performed for complaint of left knee pain
Repair of medial and lateral meniscus tear and chondroplasty

#5: +12 MONTHS�Orthopedics

Actor portrayal

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David: New pain develops but no evidence of rheumatologic disease

#8: +17 MONTHS�Rheumatology

Hypothetical patient case study based on real patient data provided by Daniel M. Englert, MD. For education purposes only.

Image is not an actual patient.

^aReference ranges provided by Daniel M. Englert, MD.

ALP, alkaline phosphatase; ANA, antinuclear antibody; CCP, cyclic citrullinated peptide; CRP, C‑reactive protein; NSAID, nonsteroidal anti-inflammatory drug; PTH, parathyroid hormone; SSA, Sjögren syndrome–related antigen A; TSH, thyroid‑stimulating hormone.

Laboratory Test	Current Result �(Reference Range^a)
Anti-SSA antibody, EU	2.11 (0-19.99)
Anti-SSA interpretation	Negative
TSH, uIU/mL	1.09 (0.40-4.00)
25(OH)D, ng/mL	18 (30-96)
ANA screen	Negative <1:160
Rheumatoid factor, IU/mL	10 (0-15)
CCP antibodies, U/mL	0.5 (<5.0)
Sedimentation rate, mm/h	22 (0-10)
CRP, mg/L	22.5 (0-8.2)
PTH, pg/mL	66 (9-77)

Other Biochemical Testing

Laboratory Test	Current Result�(Reference Range^a)
Initial visit, U/L	71 (55-135)
+8 months, U/L	152 (55-135)
+12 months, U/L	139 (55-135)
+17 months, U/L	138 (55-135)

ALP Testing

NSAIDs being taken for pain with �no improvement
Pain now involving top and bottom of feet

Patient unable to walk without pain
No other signs of rheumatologic disease

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David: DXA indicates mild osteopenia, but surgeon noted presence of soft bone after arthroplasty

DXA scan T-scores indicate osteopenia

#9: +17 MONTHS�Rheumatology

Hypothetical patient case study based on real patient data provided by Daniel M. Englert, MD. For education purposes only.

Image is not an actual patient.

DXA, dual-energy x-ray absorptiometry.

Left knee total arthroplasty due to persistent pain in the knee
Surgeon noted: “The bone had a rubber quality to it. It was a little more fibrous over on the medial femoral condyle, but it was diffuse throughout. The frozen section was bone and looked mostly like osteoid.”

#10: +17 MONTHS�Orthopedics

Pain in right knee and patient requesting right knee arthroplasty
Developed low back pain
Unable to walk

#11: +19 MONTHS�Orthopedics

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David: Patient received 2 additional arthroplasties and saw multiple providers but still has unresolved pain

Felt snap in right knee
Knee diffusely swollen
Subchondral tibial plateau fracture �with joint effusion

#12: +20 MONTHS�Emergency Room

Hypothetical patient case study based on real patient data provided by Daniel M. Englert, MD. For education purposes only.

Image is not an actual patient.

Initial pain clinic referral

#15: +26 MONTHS�Pain Clinic

Right knee total arthroplasty

#13: +21 MONTHS�Orthopedics

Still unable to walk due to ankle pain

#14: +22 MONTHS�Orthopedics

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David: ~3 years after initial pain, patient referred to endocrinologist for suspected metabolic bone disease

Bilateral genicular nerve ablation
No lasting improvement

#16: +31 MONTHS�Pain Clinic

Hypothetical patient case study based on real patient data provided by Daniel M. Englert, MD. For education purposes only.

Image is not an actual patient.

“Patient has some unusual metabolic bone disease. No formal diagnosis has been made. Patient continues to have a lot of bone and leg pain”
Referred to endocrinology

#17: +33 MONTHS�Orthopedics

Actor portrayal

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David: 3 years after initial pain, serum phosphate measured by endocrinologist

Noted great difficulty walking due to pain
Noted muscle weakness of the lower extremities
5-inch height loss
Recognized patient has persistently low phosphate with elevated alkaline phosphatase

#18: +37 MONTHS�INITIAL VISIT

Endocrinology

Laboratory Test	+21 months	+22 months	+31 months	+37 months	Reference Range^a
Phosphate, mg/dL	2.5	-	-	-	2.7-4.5
25(OH)D, ng/mL	-	-	-	48	30-96
ALP, U/mL	152	-	204	217	55-135
Calcium, mg/dL	9.9	8.7	9.9	9.4	8.7-10.5

Biochemical Testing

Hypothetical patient case study based on real patient data provided by Daniel M. Englert, MD. For education purposes only.

Image is not an actual patient.

^aReference ranges provided by Daniel M. Englert, MD.

ALP, alkaline phosphatase.

Actor portrayal

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Understanding TIO

TIO, tumor-induced osteomalacia.

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TIO is a rare paraneoplastic disorder of renal phosphate wasting^1,2

FGF23, fibroblast growth factor 23; TIO, tumor-induced osteomalacia.

1. Dahir K, et al. J Endocr Soc. 2021;5(9):bvab099. 2. Rendina D, et al. J Clin Endocrinol Metab. 2022;107(8):e3428-e3436. 3. Álvarez-Rivas N, et al. Bone Rep. 2024;21:101772. 4. Jan de Beur SM, et al. �J Clin Endocrinol Metab. 2024;110(1):102-113. 5. Chong WH, et al. Endocr Relat Cancer. 2011;18(3):R53-R77. 6. Minisola S, et al. Endocrine Reviews. 2023;44(2):323-353.

TIO is an ultrarare disease, with approximately 2000 cases reported^3,4

Elevated FGF23 causes hypophosphatemia, which decreases bone mineralization¹

PO₄

Phosphate

Typically caused by small, benign, mesenchymal tumors that secrete FGF23¹

Tumors are often slow growing and can occur anywhere in the body^1,5,6
Other tumors, including malignancies, have also been described⁶

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Calcium and phosphate are critical for bone health

Hughes EAB, et al. J Mater Chem B. 2019;7(47):7460-7470.

PO^4-

+

Ca²⁺

PO^4-

Hydroxyapatite

Bone mineralization

Hydroxyapatite incorporated into collagen fibrils

Bone

Ionic calcium and phosphate

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Hypophosphatemia can have diverse causes¹

ADHR, autosomal dominant hypophosphatemic rickets; ARHR, autosomal recessive hypophosphatemic rickets; FD/MAS, fibrous dysplasia/McCune-Albright syndrome; HRHPT, hypophosphatemic rickets and hyperparathyroidism; IV, intravenous; XLH, X-linked hypophosphatemia.

1. Sharma S, et al. Hypophosphatemia. In: StatPearls [Internet]. Accessed May 26, 2026. https://www.ncbi.nlm.nih.gov/books/NBK493172/. 2. Bosman A, et al. Front Endocrinol (Lausanne). 2021;12:733793.

PO₄

Phosphate

Metabolic disorders^1,2

Hyperparathyroidism, �Cushing syndrome

Side effects from drugs such as¹

Diuretics, corticosteroids, bisphosphonates, IV iron formulations

Phosphate wasting disorders¹

TIO, XLH, ADHR, ARHR, Fanconi syndrome, FD/MAS, HRHPT

Decreased intestinal absorption¹

Malnutrition, malabsorption conditions (such as Crohn’s disease), chronic diarrhea, or alcoholism

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Speaker Notes:

Causes of hypophosphatemia include metabolic disorders, decreased intestinal absorption, side effects from drugs, and other phosphate wasting disorders^1,2
If hypophosphatemia is identified, a first step in reaching a diagnosis is to ascertain if the hypophosphatemia is due to nonrenal or renal causes; the latter can be FGF23 (fibroblast growth factor 23) mediated or non-FGF23 mediated³

References:

Bosman A, van den Beld AW, Feelders RA, Zillikens MC. Cortisol and phosphate homeostasis: Cushing’s syndrome is associated with reversible hypophosphatemia. Front Endocrinol (Lausanne). 2021;12:733793.
Sharma S, Hashmi HF, Kaur J, Castro D. Hypophosphatemia. In: StatPearls [Internet]. Updated February 12, 2024. Accessed May 26, 2026. https://www.ncbi.nlm.nih.gov/books/NBK493172/.
Imel EA, Econs MJ. Approach to the hypophosphatemic patient. J Clin Endocrinol Metab. 2012;97(3):696-706.

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Phosphate testing should be ordered in patients with unexplained musculoskeletal symptoms or fractures¹

1. Tebben PJ. Endocr Pract. 2022;28(10):1091-1099. 2. Berndt TJ, et al. Am J Physiol Renal Physiol. 2005;289(6):F1170-F1182. 3. Foster BL, et al. Birth Defects Res C Embryo Today. 2008;84(4):281-314. 4. Hayashibara T, et al. J Bone Miner Res. 2007;22(11):1743-1751 5. Pesta DH, et al. FASEB J. 2016;30(10):3378-3387.

Phosphate plays an essential role in human physiology, including �in bone mineralization and other processes²^-5

Phosphate is not routinely included in standard metabolic panels, which can contribute to delayed diagnosis of hypophosphatemia¹

Because chronic hypophosphatemia can lead to rickets in children and osteomalacia in adults, serum phosphate should be assessed in patients with unexplained musculoskeletal symptoms or fractures¹

Symptoms of hypophosphatemia are nonspecific, and disorders of phosphate wasting can sometimes go unrecognized for years—delaying accurate, timely diagnosis¹

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Speaker Notes:

Phosphate is involved in ATP synthesis, skeletal growth, bone and tooth mineralization, osteoclast differentiation, cell membrane structure, DNA/RNA structure, and cellular signal transduction^1-4

Low serum phosphate can result in impaired growth, poorly mineralized bones and teeth, and skeletal defects^1-5

Phosphate requirements change with age, with the highest levels needed in the neonatal period followed by childhood to accommodate growth and development^6,7
Because phosphate requirements change with age, it is important to consider age-appropriate reference ranges when monitoring serum phosphate levels⁸
While phosphate plays an essential role in human physiology, it is not routinely included in standard metabolic panels, which can contribute to delayed diagnosis of hypophosphatemia^9,10
Because chronic hypophosphatemia can lead to rickets in children and osteomalacia in adults, serum phosphate should be assessed in patients with unexplained musculoskeletal symptoms^9,10

References:

Berndt TJ, Schiavi S, Kumar R. “Phosphatonins” and the regulation of phosphorus homeostasis. Am J Physiol Renal Physiol. 2005;289(6):F1170-F1182.
Pesta DH, Tsirigotis DN, Befroy DE, et al. Hypophosphatemia promotes lower rates of muscle ATP synthesis. FASEB J. 2016;30(10):3378-3387.
Hayashibara T, Hiraga T, Sugita A, et al. Regulation of osteoclast differentiation and function by phosphate: potential role of osteoclasts in the skeletal abnormalities in hypophosphatemic conditions. J Bone Miner Res. 2007;22(11):1743-1751.
Foster BL, Tompkins KA, Rutherford RB, et al. Phosphate: known and potential roles during development and regeneration of teeth and supporting structures. Birth Defects Res C Embryo Today. 2008;84(4):281-314.
Weber TJ, Quarles LD. Molecular control of phosphorus homeostasis and precision treatment of hypophosphatemic disorders. Curr Mol Biol Rep. 2019;5(2):75-85.
Penido MG, Alon US. Phosphate homeostasis and its role in bone health. Pediatr Nephrol. 2012;27(11):2039-2048.
Pettifor JM. What’s new in hypophosphataemic rickets? Eur J Pediatr. 2008;167(5):493-499.
Colantonio DA, Kyriakopoulou L, Chan MK, et al. Closing the gaps in pediatric laboratory reference intervals: a CALIPER database of 40 biochemical markers in a healthy and multiethnic population of children. Clin Chem. 2012;58(5):854-868.
Kritmetapak K, Kumar R. Phosphate as a signaling molecule. Calcif Tissue Int. 2021;108(1):16-31.
Tebben PJ. Hypophosphatemia: a practical guide to evaluation and management. Endocr Pract. 2022;28(10):1091-1099.

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FGF23 and 1,25(OH)₂D are primary regulators of phosphate homeostasis^1-3

1,25(OH)₂D, 1,25-dihydroxyvitamin D (calcitriol;) FGF23, fibroblast growth factor 23.

1. Penido MG, Alon US. Pediatr Nephrol. 2012;27(11):2039-2048. 2. Quarles LD. J Clin Invest. 2008;118(12):3820-3828. 3. Michigami T, et al. Physiol Rev. 2018;98(4):2317-2348.

Phosphate excretion

Dietary phosphate

Renal �phosphate excretion

FGF23

1,25(OH)₂D

production

Intestinal phosphate absorption

Renal phosphate reabsorption

Serum phosphate

Resorption

Formation

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Speaker Notes:

Phosphorus is present in the body as phosphate, and the 2 terms are commonly used interchangeably¹
Dietary phosphate is absorbed in the small intestine and excreted from the kidneys, although the majority of phosphate is reabsorbed from the proximal tubules of the kidney back into the circulation^1-3
Intestinal absorption and renal reabsorption of phosphate, as well as its release by bone resorption, contribute to phosphate homeostasis²
Phosphate homeostasis is essential to maintain healthy bones and is primarily regulated by FGF23, 1,25(OH)₂D, and parathyroid hormone (PTH)^1,4
FGF23
Reduces 1,25(OH)₂D, leading to decreased intestinal absorption of phosphate²
Decreases reabsorption of phosphate in renal tubules and increases urinary excretion of phosphate²
1,25(OH)₂D
Stimulates the production of FGF23 in the bone²
Increases intestinal absorption of dietary phosphate and phosphate release through bone resorption²
PTH also contributes to phosphate homeostasis
Increases 1,25(OH)₂D production and leads to increased intestinal absorption of phosphate²
Decreases renal phosphate reabsorption²
Net effect of PTH action is to decrease serum phosphate levels⁵

References:

Penido MG, Alon US. Phosphate homeostasis and its role in bone health. Pediatr Nephrol. 2012;27(11):2039-2048.
Michigami T, Kawai M, Yamazaki M, et al. Phosphate as a signaling molecule and its sensing mechanism. Physiol Rev. 2018;98(4):2317-2348.
Michigami T. Advances in understanding of phosphate homeostasis and related disorders. Endocr J. 2022;69(8):881-896.
Berndt TJ, Schiavi S, Kumar R. “Phosphatonins” and the regulation of phosphorus homeostasis. Am J Physiol Renal Physiol. 2005;289:F1170-F1182.
Bergwitz C, Jüppner H. Regulation of phosphate homeostasis by PTH, vitamin D, and FGF23. Annu Rev Med. 2010;61:91-104.

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TIO is an acquired form of hypophosphatemia caused by excess FGF23 produced by tumors^1-3

1,25(OH)₂D, 1,25-dihydroxy vitamin D (calcitriol); FGF23, fibroblast growth factor 23; TIO, tumor-induced osteomalacia.

1. Dahir K, et al. J Endocr Soc. 2021;5(9):bvab099. 2. Jan de Beur SM. JAMA. 2005;294(10):1260-1267. 3. Jan de Beur SM, et al. J Intern Med. 2023;293(3):309-328.

Serum�phosphate

Typically �small, benign �mesenchymal �tumor

Excess �FGF23

Renal phosphate reabsorption

1,25(OH)₂D

Intestinal phosphate absorption

Defective bone mineralization

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Speaker Notes:

Manifestations of TIO are caused by an increase in FGF23 levels brought about by FGF23 secretion from small, typically benign endocrine tumors¹
Increased FGF23 activity has 2 principal effects^1-3

First, it inhibits renal expression of sodium phosphate cotransporters, which leads to decreased renal phosphate reabsorption and increased urinary phosphate excretion
Second, it decreases renal expression of 1α-hydroxylase and increases expression of 24-hydroxylase, which leads to decreased or inappropriately normal 1,25-dihydroxyvitamin D levels

Decreased 1,25-dihydroxy vitamin D can lead to decreased intestinal phosphate absorption³

Impairments in phosphate reabsorption in the kidneys and phosphate absorption in the intestine lead to low serum phosphate levels, or hypophosphatemia, which results in defective bone mineralization, which manifests as osteomalacia³

References:

Dahir K, Zanchetta MB, Stanciu I, et al. Diagnosis and management of tumor-induced osteomalacia: perspectives from clinical experience. J Endocr Soc. 2021;5(9):1-12.
Jan de Beur SM. Tumor-induced osteomalacia. JAMA. 2005;294(10):1260-1267.
Jan de Beur SM, Minisola S, Xia W-B, et al. Global guidance for the recognition, diagnosis, and management of tumor-induced osteomalacia. J Intern Med. 2023;293(3):309-328.

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Osteomalacia is characterized by impaired bone mineralization resulting in the accumulation of osteoid^1,2

Osteomalacia, or bone softening, is characterized by accumulation of unmineralized bone matrix (or osteoid) and impaired new bone formation^1,2

1. Parfitt AM. Osteomalacia and related disorders. In: Avioli LV, Krane SM, eds. Metabolic Bone Disease and Clinically Related Disorders. 3rd ed. Academic Press; 1998:327-386. 2. Bhan A, et al. Bone Rep. 2018;8:125-134. 3. Arboleya L, et al. J Clin Med. 2023;12(7):2714.

Histomorphometric changes in osteomalacia

Normal bone

Osteomalacia

Osteoid

New bone

Old bone

Increased osteoid�(volume and thickness)

Less new bone

Old bone

>10

%

INCREASED OSTEOID³

>10% osteoid in the cancellous bone area (normal: <4%)

>15

μm

INCREASED OSTEOID WIDTH³

Osteoid width >15 μm (normal: 4-12 μm)

>100

days

DELAYED TIME TO MINERALIZATION³

>100 days (normal: 9-20 days)

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Speaker Notes:

Osteomalacia, which is often described as a disorder of bone softening, is characterized by impaired bone mineralization resulting in the accumulation of osteoid tissue and impaired new bone formation^1,2

In osteomalacia, there is an increase in the osteoid and a dramatic delay in time to osteoid mineralization³
In terms of clinical manifestations, osteomalacia may present as vague and diffuse bone pain, progressive muscle weakness, and difficulty walking²
The Looser’s zone is a key radiographic feature of osteomalacia. The Looser’s zone appears on a radiograph as a lucent band adjacent to the periosteum, representing an unhealed insufficiency-type stress fracture. Looser’s zones are commonly associated with local tenderness and pain on activity¹

References:

Parfitt AM. Osteomalacia and related disorders. In: Avioli LV, Krane SM, eds. Metabolic Bone Disease and Clinically Related Disorders. 3rd ed. Academic Press; 1998:327-386.
Bhan A, Qiu S, Rao SD. Bone histomorphometry in the evaluation of osteomalacia. Bone Rep. 2018;8:125-134.
Arboleya L, Braña I, Pardo E, Loredo M, Queiro R. Osteomalacia in adults: a practical insight for clinicians. J Clin Med. 2023;12(7):2714.

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Tumor size can pose a challenge for diagnosing, locating, and successfully resecting the tumor^1,2

Tumors associated with TIO

Often benign and slow growing^2,3

In a systematic review of 895 cases of TIO, �only 9.7% (56/579) of tumors were reported as malignant⁴

Produce FGF23²
Size may be as small as 0.5 cm⁴
Typically appear in adulthood³
Frequently found in the lower extremities, but may occur anywhere in the body⁵
>85% are localized⁶

In a systematic review of 895 cases of TIO, prevalence of tumors in the following 5 regions⁴
	Lower limbs	46.4%
	Head and neck	25.7%
	Pelvis	10.3%
	Trunk	9.7%
	Upper limbs	6.9%

TIO can be cured if the causative tumor �is found and completely removed^3,5

FGF23, fibroblast growth factor 23; TIO, tumor-induced osteomalacia. �1. Feng J, et al. Endocr J. 2017;64(7):675-683. 2 Chong WH, et al. Endocr Relat Cancer. 2011;18(3):R53-R77. 3. Ruppe MD, Jan de Beur SM. In: Rosen CJ, et al, eds. Primer on the Metabolic Bone Disease and Disorders of Mineral Metabolism. 8th ed. John Wiley & Sons, Inc; 2013. 4. Bosman A, et al. Calcif Tissue Int. 2022;111:367-369. 5. Dahir K, et al. J Endocr Soc. 2021;5(9):bvab099. 6. Hartley IR, Roszko KL. Calcif Tissue Int. 2025;116(1):24.

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Speaker Notes:

TIO diagnosis is challenging because of the tumor size and variable location, both of which impact successful resection of the lesion^1,2
As shown in the table, soft tissue or skeletal tumors found in patients with TIO are often located in the lower extremities, but they can be found anywhere: in the head/neck, pelvis, trunk, and upper extremities³
The tumors are typically small and benign and frequently occur in adulthood³
Given that tumor location and size can make diagnosis of TIO difficult, it is important to note that, if these tumors that cause hypophosphatemia and osteomalacia are not successful resected, patients are not cured and will likely need medical treatment to manage the symptoms⁴

References:

Chong WH, Molinolo AA, Chen CC, Collins MT. Tumor-induced osteomalacia. Endocr Relat Cancer. 2011;18(3):R53-R77.
Feng J, Jiang Y, Wang O, et al. The diagnostic dilemma of tumor induced osteomalacia: a retrospective analysis of 144 cases. Endocr J. 2017;64(7):675-683.
Bosman A, Palermo A, Vanderhulst J, et al. Tumor‑induced osteomalacia: a systematic clinical review of 895 cases. Calcif Tissue Int. 2022;111:367-369.
Ruppe MD, Jan de Beur SM. In: Rosen CJ, Bouillon R, Compston JE, Rosen V, eds. Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism. 8th ed. John Wiley & Sons, Inc; 2013.

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TIO is difficult to diagnose as symptoms are nonspecific

The most common symptoms of TIO are^1-3

TIO, tumor-induced osteomalacia.

1. Jan de Beur SM, et al. J Intern Med. 2023;293(3):309-328. 2. Feng J, et al. Endocr J. 2017;64(7):675-683. 3. Dahir K et al. J Endocr Soc. 2021;5(9):bvab099.

Patients may present with any combination of symptoms that overlap with various musculoskeletal ailments and rheumatologic or neurologic disorders³

Bone pain

Difficulty walking

Spinal deformity

Fractures/�pseudofractures

Height loss

Thoracic deformity

Local lumps

Muscle weakness

Tooth loss or loose teeth

21

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Speaker Notes:

Time from symptom onset to diagnosis ranges from 0.1 to 42 years¹
Because symptoms are nonspecific and overlap with various musculoskeletal ailments and neurologic disorders,the path to diagnosis of TIO is characterized by frequent misdiagnosis^2,3
Potential misdiagnoses for patients with TIO can include^2,3

Osteoporosis
Intervertebral disc herniation
Spondyloarthritis
Rheumatoid arthritis
Osteoarthritis
Connective tissue diseases
Fibromyalgia
Bone metastases
Vitamin D deficiency
XLH
Other genetic diseases

References:

Bosman A, et al. Tumor-induced osteomalacia: a systematic clinical review of 895 cases. Calcif Tissue Int. 2022;111(4):367-379.
Dahir K et al. Diagnosis and management of tumor-induced osteomalacia: perspectives from clinical experience. J Endocr Soc. 2021;5(9):bvab099.
Feng J, et al. The diagnostic dilemma of tumor induced osteomalacia: a retrospective analysis of 144 cases. Endocr J. 2017;64(7):675-683.

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TIO is differentiated from other renal phosphate wasting disorders by age of onset and curability

ADHR, autosomal dominant hypophosphatemic rickets; ARHR, autosomal recessive hypophosphatemic rickets; DMP1, dentin matrix acidic phosphoprotein 1; ENPP1, ectonucleotide pyrophosphatase/phosphodiesterase 1; FGF23, fibroblast growth factor 23; GNAS, Guanine Nucleotide binding protein, Alpha Stimulating activity polypeptide; PHEX, phosphorus-regulating endopeptidase homolog X-linked; TIO, tumor-induced osteomalacia; XLH, X-linked hypophosphatemia.

1. Orphanet. Disease database. Accessed May 26, 2026. https://www.orpha.net. 2. Ruppe MD, Jan de Beur SM. In: Rosen CJ, et al, eds. Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism. 8th ed. John Wiley & Sons, Inc; 2013. 3. DeCorte J, et al. JBMR Plus. 2022;6(2):e10580. 4. Hamilton AA, et al. J Endocr Soc. 2022;6(8):bvac086. 5. Carpenter TO. Endotext. Updated June 7, 2022. Accessed April 1, 2026. www.endotext.org. �6. Sawalha NA et al. Calcif Tissue Int. 2026;117:40

	Prevalence	Source of excess FGF23	Disease origin	Curability
TIO	1-9 per 1,000,000¹	Typically small, often benign tumors²	Can occur at any age but more common in adults²	If tumor can be localized and resected, a cure is possible²
XLH	1-9 per 100,000¹	Variant in PHEX gene leading to excess production from bone²	Present from birth³	Lifelong genetic disease; no available cure⁴
ADHR	<1 per 1,000,000¹	FGF23 gain‑of‑function mutation⁵	Present from birth¹	Lifelong genetic disease; no available cure¹
ARHR 1 and 2	Unknown¹	DMP1 or ENPP1 loss of function mutations⁵	Present from birth¹	Lifelong genetic disease; no available cure⁶
McCune‑�Albright syndrome	1-9 per 1,000,000¹	Postzygotic GNAS mutation⁵	Present from birth¹	Lifelong genetic disease; no available cure¹

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Speaker Notes:

Although TIO and other renal phosphate wasting disorders are similar, there are distinguishing characteristics between them¹
For patients with TIO¹

Source of the FGF23 is from the tumors
Onset of symptoms occurs more often in adulthood

Of note, TIO is curable, but this is dependent on successful tumor resection¹
Most FGF23-mediated renal phosphate wasting disorders have genetic causes²

Children and young adults suspected of having TIO should undergo genetic testing to exclude genetic causes of renal phosphate wasting³

References:

Ruppe MD, Jan de Beur SM. In: Rosen CJ, et al, eds. Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism. 8th ed. John Wiley & Sons, Inc; 2013.
Carpenter TO. Primary disorders of phosphate metabolism. In: Feingold KR, Anawalt B, Blackman MR, et al, eds. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000–. Updated June 7, 2022. Accessed April 1, 2026. https://www.endotext.org.
Jan de Beur SM, et al. Global guidance for the recognition, diagnosis, and management of tumor-induced osteomalacia. J Intern Med. 2023;293(3):309-328.

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Diagnosing TIO

TIO, Tumor-Induced Osteomalacia.

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Diagnosis of TIO depends on recognizing clinical signs and symptoms that raise suspicion for TIO

TIO, tumor-induced osteomalacia; XLH, X-linked hypophosphatemia.

Jan de Beur SM, et al. J Intern Med. 2023;293:309-328.

Medical history and physical examination

Biochemical workup

(including serum phosphate)

Refer to specialist

Genetic testing

Tumor identified

No tumor identified

Surgical resection/�ablation

Medical management

Generalized musculoskeletal pain or weakness should prompt suspicion �of a hypophosphatemic disorder and trigger phosphate testing

Imaging

Perform genetic testing before imaging in children, young adults, or those with suggestive family history. Perform genetic testing in adults without family �history and negative �functional imaging

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Medical history should assess age of onset, symptoms, medication history, and family history

XLH, X-linked hypophosphatemia.

Jan de Beur SM, et al. J Intern Med. 2023;293:309-328.

Imaging

Medical history

Medication history

Family history

Medical history �and physical examination

Biochemical workup

(including serum phosphate)

Refer to specialist

Genetic testing

Perform genetic testing before imaging in children, young adults, or those with suggestive family history. Perform genetic testing in adults without family �history and negative �functional imaging

Should include:

Age of onset
Symptoms

Bone pain in the distal extremities
Diffuse/generalized bone pain
Fractures commonly occurring in the ribs, vertebral bodies, femoral neck or shaft, and pelvis
Lower bone mineral density and strength than people with XLH

25

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Speaker Notes:

Medical history should include

Age of onset: TIO can occur at any age but typically occurs in those who are older¹
Accompanying symptoms¹

The most common initial symptom in adults is bone pain in the distal extremities, especially ankles and feet¹
Indicators of osteomalacia may include tenderness in the anterior tibia, sternum, and where the ribs connect to the sternum²
Generalized bone pain is common, as is back, neck and, shoulder pain¹
The most common locations for fractures to occur are the ribs, vertebra, femur, and pelvis¹
Individuals with TIO often have lower bone mineral density and reduced bone strength than people with XLH¹

References:

Jan de Beur SM, Minisola S, Xia WB, et al. Global guidance for the recognition, diagnosis, and management of tumor-induced osteomalacia. J Intern Med. 2023;293(3):309-328.
Oh RC, Johnson JD. Chest pain and costochondritis associated with vitamin D deficiency: a report of two cases. Case Rep Med. 2012;2012:375730.

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Medical history should assess age of onset, symptoms, medication history, and family history

Jan de Beur SM, et al. J Intern Med. 2023;293:309-328.

Medical history

Medication history

Family history

Medical history �and physical examination

Biochemical workup

(including serum phosphate)

Should be assessed for medications that may cause hypophosphatemia

Imaging

Refer to specialist

Genetic testing

Perform genetic testing before imaging in children, young adults, or those with suggestive family history. Perform genetic testing in adults without family �history and negative �functional imaging

26

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Medical history should assess age of onset, symptoms, medication history, and family history

TIO, tumor-induced osteomalacia.

Jan de Beur SM, et al. J Intern Med. 2023;293:309-328.

Medical history

Medication history

Family history

Medical history �and physical examination

Biochemical workup

(including serum phosphate)

TIO should be suspected in patients with suggestive symptoms and no personal or family history of hereditary hypophosphatemia

Imaging

Refer to specialist

Genetic testing

Perform genetic testing before imaging in children, young adults, or those with suggestive family history. Perform genetic testing in adults without family �history and negative �functional imaging

27

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Physical examination should look for abnormalities that would indicate genetic causes to rule out other diseases

TIO, tumor-induced osteomalacia.

Jan de Beur SM, et al. J Intern Med. 2023;293:309-328.

Medical history �and physical examination

Biochemical workup

(including serum phosphate)

Assess

Height
Body proportions
Spine for vertebral fractures
Gait
Indicators of genetic causes, such as

Shorter than expected stature
Limb deformity
Craniofacial anomalies
Dental abnormalities

Examine entire body for masses

Genetic causes of hypophosphatemia are more common than TIO. As such, it is important to exclude genetic causes of hypophosphatemia when diagnosing TIO. Perform genetic testing before imaging in children, young adults, or those with suggestive family history. Perform genetic testing in adults without family history and negative functional imaging

Imaging

Refer to specialist

Genetic testing

Perform genetic testing before imaging in children, young adults, or those with suggestive family history. Perform genetic testing in adults without family �history and negative �functional imaging

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Measuring serum phosphate is essential for assessing renal phosphate wasting

1,25(OH)₂D, 1,25-dihydroxy vitamin D (calcitriol); ALP, alkaline phosphatase; FGF23, fibroblast growth factor 23; PTH, parathyroid hormone; TmP/GFR, ratio of tubular maximum reabsorption of phosphate to glomerular filtration rate; TIO, tumor-induced osteomalacia.

Jan de Beur SM, et al. J Intern Med. 2023;293:309-328.

Serum phosphate may need to be ordered separately as it is not routinely included �in standard chemistry panels

Medical history �and physical examination

Biochemical workup

(including serum phosphate)

Laboratory Test	TIO
Fasting serum phosphate
TmP/GFR
ALP
1,25(OH)₂D
PTH
Serum intact FGF23
Serum calcium

or inappropriately normal

or normal

or inappropriately normal

or normal

Imaging

Refer to specialist

Genetic testing

Perform genetic testing before imaging in children, young adults, or those with suggestive family history. Perform genetic testing in adults without family �history and negative �functional imaging

29

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Speaker Notes:

Reference ranges may vary based on assay and instrument used. It is important to use the reference range provided by the laboratory conducting the test to ensure accuracy¹
Use age- and sex-appropriate reference ranges when assessing laboratory test results²

Phosphate levels vary by age, with levels highest in infancy^3,4

TmP/GFR reflects the kidney’s capacity to reabsorb phosphate^5,6

Calculated using paired serum and urine phosphate and creatinine levels⁵
Low TmP/GFR signifies renal phosphate wasting in the setting of hypophosphatemia^6,7
Samples are obtained in the morning after fasting overnight to minimize the impact of circadian changes in urine and serum phosphate and postprandial changes in urine and serum phosphate and creatinine⁸

Samples should be from the second void of the day⁸
Patients should not be receiving oral phosphate prior to sample collection⁹

References:

Abadie J. Laboratory reference ranges. Merck Manual Professional Edition. Reviewed/revised May 2026. Accessed June 11, 2026. https://www.merckmanuals.com/professional/resources/normal-laboratory-values/laboratory-reference-ranges.
Colantonio DA, Kyriakopoulou L, Chan MK, et al. Closing the gaps in pediatric laboratory reference intervals: a CALIPER database of 40 biochemical markers in a healthy and multiethnic population of children. Clin Chem. 2012;58(5):854-868.
Pettifor JM. What's new in hypophosphataemic rickets? Eur J Pediatr. 2008;167:493-499.
Penido MG, Alon US. Phosphate homeostasis and its role in bone health. Pediatr Nephrol. 2012;27(11):2039-2048.
Haffner D, Emma F, Eastwood DM, et al. Clinical practice recommendations for the diagnosis and management of X-linked hypophosphataemia. Nat Rev Nephrol. 2025;21(5):330-354.
Manghat P, Sodi R, Swaminathan R, et al. Phosphate homeostasis and disorders. Ann Clin Biochem. 2014;51(Pt6):631-656.
Ackah SA, Imel EA. Approach to hypophosphatemic rickets. J Clin Endocrinol Metab. 2022;108(1):209-220.
Payne RB. Renal tubular reabsorption of phosphate (TmP/GFR): indications and interpretation. Ann Clin Biochem. 1998;35(Pt 2):201-206.
Dahir K, Zanchetta MB, Stanciu I, et al. Diagnosis and management of tumor-induced osteomalacia: perspectives from clinical experience. J Endocr Soc. 2021;5(9):bvab099.

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David: Patient has low phosphate and TmP/GFR and elevated alkaline phosphatase

Hypothetical patient case study based on real patient data provided by Daniel M. Englert, MD. For education purposes only.

Image is not an actual patient.

^aReference ranges provided by Daniel M. Englert, MD.

Noted great difficulty walking due to pain
Noted muscle weakness of the lower extremities
5-inch height loss
Recognized patient has persistently low phosphate with elevated alkaline phosphatase

Laboratory Test	Current Result �(Reference Range^a)
Fasting serum phosphate (mg/dL)	1.5 (2.7-4.5)
Serum 1,25(OH)₂D, pg/mL	16 (20-79)
Serum FGF23, RU/mL	352 (≤180)
Urine creatinine, mg/hr	53.5 (40.0-75.0)
Urine phosphorus, mg/hr	20.9 (0-53.9)
TmP/GFR (calculation)	1.09

Biochemical Testing

#18: +37 MONTHS�INITIAL VISIT

Endocrinology

Actor portrayal

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Biochemical findings for TIO are identical to other renal phosphate wasting disorders

1,25(OH)₂D, 1,25-dihydroxy vitamin D (calcitriol); ALP, alkaline phosphatase; FGF23, fibroblast growth factor 23; PHEX, phosphate regulating endopeptidase X-linked; PTH, parathyroid hormone; TmP/GFR, ratio of tubular maximum reabsorption of phosphate to glomerular filtration rate; TIO, tumor-induced osteomalacia; XLH, X-linked hypophosphatemia.

^aALP is elevated in pediatric patients but may be elevated or normal in adult patients.²

1. Jan de Beur SM, et al. J Intern Med. 2023;293:309-328. 2. Dahir K, et al. J Endocr Soc. 2020;4(12):bvaa151.

Medical history �and physical examination

Biochemical workup

(including serum phosphate)

Genetic testing such as PHEX, �is key to differentiate XLH from TIO¹

Laboratory Test	TIO¹	XLH²
Fasting serum phosphate
TmP/GFR
ALP
1,25(OH)₂D
PTH
Serum intact FGF23
Serum calcium

or inappropriately normal

or normal

or inappropriately normal

or normal

or inappropriately normal

or normal

or inappropriately normal

Normal

^a

Imaging

Refer to specialist

Genetic testing

Perform genetic testing before imaging in children, young adults, or those with suggestive family history. Perform genetic testing in adults without family �history and negative �functional imaging

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David: Genetic testing is negative for renal phosphate wasting disorders

Genetic panel ordered.

Patient tested negative for

PHEX (XLH)
FGF23 (ADHR)
DMP1 (ARHR)

Noted great difficulty walking due to pain
Noted muscle weakness of the lower extremities
5-inch height loss
Recognized patient has persistently low phosphate with elevated alkaline phosphatase

#18: +37 MONTHS�INITIAL VISIT

Endocrinology

Genetic testing results ruled out �XLH, ADHR, and ARHR

Hypothetical patient case study based on real patient data provided by Daniel M. Englert, MD. For education purposes only.

Image is not an actual patient.

ADHR, autosomal dominant hypophosphatemic rickets; ALP, alkaline phosphatase; ARHR, autosomal recessive hypophosphatemic rickets; DMP1, dentin matrix acidic phosphoprotein 1; FGF23, fibroblast growth factor 23; PHEX, phosphorus-regulating endopeptidase homolog X-linked; XLH, X-linked hypophosphatemia.

Actor portrayal

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A stepwise approach combining functional and anatomical imaging is recommended for the localization of tumors¹

Functional imaging of the entire body should be performed first¹

Guidelines recommend prioritizing functional imaging in the following order²

⁶⁸Ga-based or ⁶⁴Cu-based PET/CT �(⁶⁸Ga/⁶⁴Cu-DOTATATE, -DOTANOC, or -DOTATOC)
⁹⁹mTc- or ¹¹¹In-pentetreotide scan
FDG-PET

¹¹In, Indium-111; CT, computed tomography; Cu, Copper; FDG, fluorodeoxyglucose; Ga, Gallium; mTc, magnetization transfer contrast; PET, positron emission tomography; SSTR, somatostatin receptor; TIO, tumor-induced osteomalacia.

1. Yin Z, et al. Osteoporos Sarcopenia. 2018;4(4):119-127. 2. Jan de Beur SM, et al. J Intern Med. 2023;293:309-328. 3. Aligail K, et al. J Med Case Rep. 2022;16(1):22.

Most TIO tumors express a series of somatostatin receptors, �making SSTR imaging a practical tool for tumor localization¹

Tumor in the right humeral head detected by �⁶⁸Ga-DOTANOC PET/CT.³ Reprinted with permission �from Aligail K, et al. J Med Case Rep. 2022;16(1):22.

Medical history �and physical examination

Biochemical workup

(including serum phosphate)

Imaging

Refer to specialist

Genetic testing

Perform genetic testing before imaging in children, young adults, or those with suggestive family history. Perform genetic testing in adults without family �history and negative �functional imaging

33

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Speaker Notes:

Routine nuclear imaging often excludes the extremities, but because TIO tumors can occur anywhere in the body, it is important to include the extremities¹
According to 2023 expert global guidance, ⁶⁸Ga-based or ⁶⁴Cu-based PET/CT (⁶⁸Ga/⁶⁴Cu-DOTATATE, -DOTANOC, or -DOTATOC) should be used as first-line functional imaging²

⁶⁸Ga-DOTATATE, a ⁶⁸Ga-labeled somatostatin analog, localizes tumors by binding to SSTR expressed by the tumor³
⁶⁸Ga-DOTATATE-PET/CT has a higher sensitivity than Octreoscan SPECT/CT³

When unavailable, octreotide scan (^99mTc- or ¹¹¹In-pentetreotide scan) or fluorodeoxyglucose-PET (FDG-PET) can be used as alternatives, in that order²

Conventional Octreoscan SPECT/CT imaging (eg, ⁹⁹mTc-octreotide SPECT/CT imaging or ¹¹¹In-octreotide SPECT imaging) has limited spatial resolution but improved tumor detection³

References:

Chong WH, Yavuz S, Patel SM, Chen CC, Collins MT. The importance of whole body imaging in tumor-induced osteomalacia. J Clin Endocrinol Metab. 2011;96(12):3599-3600.
Jan de Beur SM, Minisola S, Xia WB, et al. Global guidance for the recognition, diagnosis, and management of tumor-induced osteomalacia. J Intern Med. 2023;293(3):309-328.
Tao H, Deng Z, Chen L, Wang W, Zhou Y, Wu Y. Case report with literature review: tumor-induced osteomalacia from a soft-tissue phosphaturic mesenchymal tumor of the trunk. Front Endocrinol (Lausanne). 2025;16:1655376.

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A stepwise approach combining functional and anatomical imaging is recommended for the localization of tumors¹

CT, computed tomography; MRI, magnetic resonance imaging.

1. Yin Z, et al. Osteoporos Sarcopenia. 2018;4(4):119-127. 2. Minisola S, et al. Nat Rev Dis Primers. 2017;3:17044. 3. Aligail K, et al. J Med Case Rep. 2022;16(1):22.

Lesions identified on functional imaging should be confirmed using anatomical imaging (either contrast-enhanced CT or MRI)²

Anatomical imaging may be helpful in planning subsequent surgery²

Tumor in the right humeral head detected by �MRI.³ Reprinted with permission from Aligail K, et al. J Med Case Rep. 2022;16(1):22.

Medical history �and physical examination

Biochemical workup

(including serum phosphate)

Imaging

Refer to specialist

Genetic testing

Perform genetic testing before imaging in children, young adults, or those with suggestive family history. Perform genetic testing in adults without family �history and negative �functional imaging

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David: Imaging findings are in alignment with a diagnosis of TIO despite lack of clear primary lesion

NM bone scan

Scintigraphy evidence of multiple fractures in the ribs, left femoral neck, ankles
Degenerative changes in the SI joints, lower lumbar spine, and right hip joints
Status post bilateral knee replacements

#18: +37 MONTHS�Endocrinology

Hypothetical patient case study based on real patient data provided by Daniel M. Englert, MD. For education purposes only.

Image is not an actual patient.

NM, nuclear medicine; PET, positron emission tomography; SI, sacroiliac; TIO, tumor-induced osteomalacia.

NM PET CT whole body: negative

#19: +41 MONTHS�Endocrinology

NM Octreoscan: negative

#20: +42 MONTHS�Endocrinology

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David: Imaging findings are in alignment with a diagnosis of TIO despite lack of clear primary lesion

Hypothetical patient case study based on real patient data provided by Daniel M. Englert, MD. For education purposes only.

Image is not an actual patient.

NM, nuclear medicine; PET, positron emission tomography; TIO, tumor-induced osteomalacia.

NM DOTATATE PET

Multiple areas of hypermetabolic focal �activity scattered throughout the �osseous structures with corresponding �sclerotic/lytic lesions

#21: +55 MONTHS�Endocrinology

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David: Summary of key findings suggestive of TIO

Persistently low phosphate with elevated ALP

BIOCHEMICAL WORKUP

Hypothetical patient case study based on real patient data provided by Daniel M. Englert, MD. For education purposes only.

Image is not an actual patient.

ALP, alkaline phosphatase; DMP1, dentin matrix acidic phosphoprotein 1; FGF23, fibroblast growth factor 23; PHEX, phosphorus-regulating endopeptidase homolog X-linked; TIO, tumor-induced osteomalacia.

Multiple fractures
Bone pain
Difficulty walking
Muscle weakness
Height loss

MEDICAL �HISTORY

Negative for PHEX, FGF23, DMP1

GENETIC �TESTING

Multiple areas of hypermetabolic activity in the skeleton consistent with osteomalacia on NM DOTATATE PET
Arthroplasty results consistent with osteomalacia

IMAGING

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David: Summary of key findings suggestive of TIO

Persistently low phosphate with elevated ALP

BIOCHEMICAL WORKUP

Multiple fractures
Bone pain
Difficulty walking
Muscle weakness
Height loss

MEDICAL �HISTORY

Negative for PHEX, FGF23, DMP1

GENETIC �TESTING

Phosphate testing upon development of any of these symptoms could have shortened the time to diagnosis by up to 4 years

Hypothetical patient case study based on real patient data provided by Daniel M. Englert, MD. For education purposes only.

Image is not an actual patient.

ALP, alkaline phosphatase; DMP1, dentin matrix acidic phosphoprotein 1; FGF23, fibroblast growth factor 23; PHEX, phosphorus-regulating endopeptidase homolog X-linked; TIO, tumor-induced osteomalacia.

Actor portrayal

Multiple areas of hypermetabolic activity in the skeleton consistent with osteomalacia on NM DOTATATE PET
Arthroplasty results consistent with osteomalacia

IMAGING

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Managing TIO

TIO, tumor-induced osteomalacia.

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Multidisciplinary management of TIO-related symptoms may be needed for as long as tumors are present¹

Example diagnostic and management pathway:

TIO, tumor-induced osteomalacia.

1. Dahir K, et al. J Endocr Soc. 2021;5(9):bvab099. 2. Jan de Beur SM, et al. J Intern Med. 2023;293:309-328. 3. Minisola S, et al. Nat Rev Dis Primers. 2017;3:17044.

ENDOCRINOLOGY/�NEPHROLOGY²

Performs �biochemical testing
May identify tumor location on �physical exam
Refers to a radiologist for imaging

SURGICAL ONCOLOGY²

If tumor can be resected

PRIMARY CARE²

Identifies symptoms and refers to specialist

Scan performed and tumor identified via imaging^2,3

ENDOCRINOLOGY/�NEPHROLOGY/ORTHOPEDICS/�PHYSICAL THERAPY^1-3

Management of TIO-related �symptoms if tumor cannot �be resected³

SURVEILLANCE�every 3-6 months²

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Speaker Notes:

Identification of tumors in TIO is done first by physical examination and functional imaging followed by anatomical imaging¹
Surgically remove the tumor in its entirety, with wide margins, if possible; note that TIO can persist, and relapses may occur¹

Serum phosphate should be measured frequently until normalization and then annually²
Occupational therapy or physical therapy may be beneficial post-surgery, especially in severe cases³

If the tumor cannot be successfully removed, medical management should be considered¹

The goal of medical management is to ease clinical symptoms, restore phosphate homeostasis and normalize ALP and PTH levels²
For patients who experience pain, referral to occupational therapy or physical therapy should be considered to address functional deficits³

References:

Minisola S, Peacock M, Fukumoto S, et al. Tumour-induced osteomalacia. Nat Rev Dis Primers. 2017;3:17044.
Jan de Beur SM, Minisola S, Xia WB, et al. Global guidance for the recognition, diagnosis, and management of tumor-induced osteomalacia. J Intern Med. 2023;293:309-328.
Dahir K, Zanchetta MB, Stanciu I, et al. Diagnosis and management of tumor-induced osteomalacia: perspectives from clinical experience. J Endocr Soc. 2021;5(9):bvab099.

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Summary

FGF23, fibroblast growth factor 23; TIO, tumor-induced osteomalacia.

1. Dahir K, et al. J Endocr Soc. 2021;5(9):bvab099. 2. Rendina D, et al. J Clin Endocrinol Metab. 2022;107(8):e3428-e3436. 3. Feng J, et al. Endocr J. 2017;64(7):675-683. 4. Jan de Beur SM, et al. J Clin Endocrinol Metab. 2025;110(1):102-113. 5. Jan de Beur SM, et al. J Intern Med. 2023;293:309-328.

TIO is a paraneoplastic syndrome of abnormal phosphate metabolism caused by tumors secreting excess FGF23^1,2
Symptoms of TIO are nonspecific and often mimic musculoskeletal, rheumatologic, or neurologic disorders, leading to diagnostic delays and multiple specialist referrals^3,4
TIO is differentiated from other disorders of renal phosphate wasting by evaluating family history and performing genetic testing⁵
Imaging is essential to localize the tumor and assess resectability⁵
When resection is not feasible, multidisciplinary management is required for optimal care^1,5

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Learn more about TIO

TIO HCP education website to access resources for your practice or request a rep�tiolinkhcp.com

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UNBRANDED EDUCATIONAL PRESENTATION FOR HCP AUDIENCES. NOT FOR PROMOTIONAL USE. NOT FOR DUPLICATION WITHOUT KYOWA KIRIN’S CONSENT.

COMM-US-RDS-1078 July 2026

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UNBRANDED EDUCATIONAL PRESENTATION FOR HCP AUDIENCES. NOT FOR PROMOTIONAL USE. NOT FOR DUPLICATION WITHOUT KYOWA KIRIN’S CONSENT.