Tumor-induced osteomalacia (TIO) is an acquired form of hypophosphatemia resulting in osteomalacia caused by excess fibroblast growth factor 23 (FGF23) secreted by tumors1

Untreated hypophosphatemia leads to osteomalacia and fractures2

Mineralization of the bone matrix (osteoid) is a critical step during bone formation. During this process, minerals are deposited to allow the “hardening” of the matrix into bone, hence the term mineralization.

Osteomalacia is a disease characterized by the increased presence of osteoid, which is indicative of defective bone mineralization.3

Mineralized bone and unmineralized osteoid in normal bone and normal mineralization in femur bone

Mineralized bone is shown in green, and unmineralized osteoid is shown in orange or red.

    In normal bone:

  • The osteoid layer represents a small proportion of total bone volume
  • Mineralization of the bone matrix occurs shortly after the matrix is formed
Mineralized bone and unmineralized osteoid in patient with osteomalacia and pseudofracture in patient with osteomalacia

Mineralized bone is shown in green, and unmineralized osteoid is shown in orange or red.

    In osteomalacia:

  • The proportion of unmineralized osteoid is greater than in mineralized bone
  • Mineralization of bone matrix is slower than the formation of unmineralized osteoid

Up to 95% of patients with TIO are misdiagnosed4

Time from symptom onset to accurate diagnosis may range from 2.5 to 28 years.1 If you have a patient with osteomalacia, consider TIO if they also have low serum phosphorus, reduced active vitamin D, and elevated intact serum FGF23.4

Delayed diagnosis

The symptoms associated with TIO are often mistaken for other, more common conditions such as osteoporosis or inflammatory arthritis. The time from symptom onset to correct diagnosis of TIO often takes more than 2 years, during which period patients may lose the ability to function independently.

Disease burden

Many patients with TIO develop multiple bone abnormalities and require assistance with walking. Patients with TIO experience substantial disease burdens from muscle pain, bone pain, and fatigue.

Symptoms

Many patients with TIO present with bone pain, muscle pain, and fatigue.

Tumor locations

Tumors can occur anywhere in the body and can be found in bones and soft tissue. Often, tumors are located in the extremities.

Tumor removal

Tumor removal can be curative. However, tumors often recur after surgical removal and cause the patient's symptoms to return. Some tumors can be as small as 1 cm in diameter and are difficult to locate. Additionally, tumors can occur in locations that preclude surgery.

Tumor removal can be curative, but may not be possible under certain circumstances1

References

  1. Minisola S, Peacock M, Fukumoto S, et al. Tumor-induced osteomalacia. Nat Rev Dis Primers. 2017;3(17044):2-15.

  2. Ruppe MD, Jan de Beur S. Disorders of phosphate homeostasis. In: Clifford J, Bouillon R, Compston JE, Rosen V, eds. Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism. 8th ed. Ames, Iowa: John Wiley & Sons, Inc; 2013.

  3. Ott S. Histomorphometric measurements of bone turnover, mineralization, and volume. Clin J Am Soc Nephrol. 2008;3(suppl 3):S151-S156.

  4. 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.

  5. Florenzano P, Gafni R, Collins MT. Tumor-induced osteomalacia. Bone Rep. 2017;7:90-97.