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Disease Profile

Oncogenic osteomalacia

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.

Unknown

Age of onset

All ages

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ICD-10

M83.8

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

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Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

Tumor-induced osteomalacia; Oncogenic hypophosphatemic osteomalacia; TIO

Summary

Oncogenic osteomalacia is characterized by the development of a tumor that causes the bones to be weakened.[1] This occurs when a tumor secretes a substance called fibroblast growth factor 23 (FGF23). FGF23 inhibits the ability of the kidneys to absorb phosphate.[2] Phosphate is important for keeping bones strong and healthy. Therefore, this disease is characterized by a softening and weakening of the bones (osteomalacia). The disease also results in multiple biochemical abnormalities including high levels of phosphate in the urine (hyperphosphaturia) and low levels of phosphate in the blood (hypophosphatemia). The majority of tumors that cause oncogenic osteomalacia are small and slow-growing. These tumors most commonly occur in the skin, muscles, or bones of the extremities or in the paranasal sinuses around the head. Most of these tumors are benign, meaning they are not associated with cancer.[1]

The exact reason that the tumors associated with oncogenic osteomalacia develop is not known. The disease is diagnosed when a person experiences clinical features such as bone weakening and hyperphosphaturia and a tumor is found by imaging of the body. Treatment of the disease consists of surgical removal of the tumor. The symptoms of the disease, including the weakening of the bones, typically resolve once the tumor is removed.[1]

Symptoms

The first symptoms of oncogenic osteomalacia are typically fatigue, muscle weakness, bone pain, fractures, and weakening of the bones (osteomalacia).[2] When the blood and urine is tested, people with this disease have high levels of phosphate in the urine (hyperphosphaturia) and low levels of phosphate in the blood (hypophosphatemia). Additionally, people with this disease may have low levels of 1,25-dihydroxy vitamin D in their blood.[2] 

The majority of tumors that cause oncogenic osteomalacia are small, slow-growing tumors called phosphaturic mesenchymal tumors (PMT).[3] These tumors most commonly occur in the skin, muscles, or bones of the extremities or in the paranasal sinuses around the head. Most of these tumors are benign, meaning they are not associated with cancer.[1] Oncogenic osteomalacia can occur in children or adults. When the disease occurs in children, it may also be associated with rickets (muscle weakness causing bowing at the knees) and slow growth.[1]

Cause

Tumor-induced osteomalacia is caused by the development of a tumor that releases fibroblast growth factor 23 (FGF23). FGF23 is responsible for regulating levels of phosphate and vitamin D in the body by telling the kidneys how much phosphate to absorb and how much phosphate to release from the body in the urine. When there is too much FGF23 in the body, the kidneys are not able to absorb the appropriate amount of phosphate. This means that too much phosphate is released from the body in the urine.[2] Phosphate is important for keeping bones strong and healthy. Therefore, when there is not enough phosphate for the bones, they begin to soften and weaken, causing osteomalacia.[2] 

Exactly what causes the development of the tumors associated with tumor-induced osteomalacia is unknown. It is most likely that these tumors develop by chance.[4]

Diagnosis

Oncogenic osteomalacia is diagnosed when an individual has signs and symptoms consistent with the disease such as fractures, bone weakening, and low levels of phosphate in the blood (hypophosphatemia). A doctor should rule out other causes of these symptoms. Doctors can confirm that the low levels of phosphate in the blood are due to the kidneys being unable to absorb phosphate. This can be done by comparing the levels of phosphate in the blood to that in the urine. In some cases, people with oncogenic osteomalacia may be misdiagnosed as having other disorders such as rheumatic disorders or psychiatric disorders. A misdiagnosis can occur because oncogenic osteomalacia is very rare.[2] 

When oncogenic osteomalacia is suspected, the tumor that is causing the disease must be detected in order to confirm the diagnosis and plan a surgery to remove the tumor. A number of imaging techniques can be used to find the tumor including CT scanMRI, and MR angiography. In many cases, the tumor is too small to be detected using imaging of the whole body, so other kinds of imaging tests may be necessary. In some cases, it may be necessary to sample levels of FGF23 in multiple blood vessels throughout the body. Parts of the body where FGF23 levels are the highest are more likely to be closer to the tumor.[5]

Treatment

Treatment for oncogenic osteomalacia is focused on identifying and removing the tumor that is causing the disease. It is important that all of the tumor is removed to reduce the changes that it will come back again. For most people, removing the tumor cures symptoms of the disease because levels of phosphate and vitamin D are returned to normal. Improvement of symptoms typically occurs within the first weeks or months of surgery.[2]

Typically, the tumors associated with oncogenic osteomalacia are not malignant, meaning that they are unlikely to spread to other parts of the body. Therefore, chemotherapy and radiation therapy are not widely used to treat patients with this disease.[2] After the tumor is removed, it is important that affected individuals continue to receive frequent monitoring to make sure that the tumor does not grow back.[4] This monitoring can take place with frequent imaging and testing levels of FGF23 in the blood.[6]

When the tumor cannot be located or cannot be removed surgically, medications are available that can help increase the levels of phosphate and vitamin D in the blood. This is possible by taking phosphate supplements and calcitriol, which helps increase levels of vitamin D.[4]

Learn more

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

  • MedlinePlus was designed by the National Library of Medicine to help you research your health questions, and it provides more information about this topic.

In-Depth Information

  • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
  • PubMed is a searchable database of medical literature and lists journal articles that discuss Oncogenic osteomalacia. Click on the link to view a sample search on this topic.

References

  1. Kumar K and Halkar RK. Tumor-Induced Osteomalacia (TIO) (also Known as Oncogenic osteomalacia). Applied Radiology. 2008; 37(1):9-24. https://www.medscape.com/viewarticle/570120.
  2. Chong WH, Molinolo AA, Chen CC, and Collins MT. Tumor-induced osteomalacia. Endocrine-Related Cancer. June 2011; 18(3):R53-R77. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3433741/.
  3. Zuo Q, Wang H, Li W, Niu X, Huang Y, Chen J, You Y, Liu B, Cui A, and Deng W. Treatment and outcomes of tumor-induced osteomalacia associated with phosphaturic mesenchymal tumors: retrospective review of 12 patients. BMC Musculoskeletal Disorders. 2017; 18:403. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5609032/.
  4. Dadoniene J, Miglinas M, Miltiniene D, Vajauskas D, Seinin D, Butenas P, and Kacerguis T. Tumor-induced osteomalacia: a literature review and a case report. World Journal of Surgical Oncology. 2016; 14:4. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4705745/.
  5. Lee JY, Park HS, Han S, Lim JK, Hong N, Park S, and Rhee Y. Localization of Oncogenic osteomalacia by Systemic Venous Sampling of Fibroblast Growth Factor 23. Yonsei Medical Journal. September 1, 2017; 58(5):981-987. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5552653/.
  6. Chokyu I, Ishibashi K, Goto T, and Ohata K. Oncogenic osteomalacia associated with mesenchymal tumor in the middle cranial fossa: a case report. Journal of Medical Case Reports. 2012; 6:181. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3514377/.

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