Tumor-induced osteomalacia (TIO), also known as oncogenic osteomalacia, is a rare condition where a tumor causes bones to soften. This paraneoplastic syndrome is characterized by persistent low phosphate levels due to excessive phosphate loss through the kidneys. Symptoms can be misleading, making accurate and timely diagnosis a significant challenge.
Understanding Tumor-Induced Osteomalacia
TIO arises from specific, often benign, tumors that produce an excessive amount of Fibroblast Growth Factor 23 (FGF23, a hormone-like substance). Elevated FGF23 levels disrupt the body’s phosphate and vitamin D metabolism. This hormone acts primarily on the proximal renal tubules, decreasing phosphate reabsorption and inhibiting vitamin D activation.
The excessive loss of phosphate through the kidneys, combined with impaired vitamin D activation, leads to hypophosphatemia. Phosphate is a mineral that plays a role in bone mineralization, and its deficiency results in osteomalacia. These causative tumors are typically small mesenchymal tumors found in various parts of the body, including bone or soft tissue, which complicates their identification.
Recognizing the Signs
Individuals with TIO often experience a range of symptoms that develop gradually. Widespread bone pain is a common complaint, affecting areas such as the ribs, spine, and lower extremities. This pain can be debilitating.
Muscle weakness, particularly in the proximal muscles, is another frequent manifestation. This weakness can lead to difficulty walking. Patients may also experience frequent fractures, even from minor trauma. Chronic fatigue is also commonly reported.
Pinpointing the Cause
Diagnosing TIO involves a comprehensive approach, combining biochemical tests and advanced imaging studies. Blood tests typically reveal low serum phosphate levels, elevated FGF23 concentrations, and low or inappropriately normal levels of 1,25-dihydroxyvitamin D. Urine tests often show increased phosphate excretion.
Locating the causative tumor presents a significant diagnostic challenge. Specialized imaging techniques, including whole-body MRI and CT scans, are used to identify anatomical locations. Functional imaging methods such as Octreoscan or PET scans, including Gallium-68 DOTATATE PET/CT, help pinpoint these FGF23-secreting tumors. Finding the tumor is essential for treatment.
Treatment Approaches
The definitive treatment for TIO involves surgical removal of the tumor, which typically leads to rapid resolution of the condition. Accurate tumor localization through advanced imaging is important for successful surgery.
For cases where the tumor cannot be located or completely removed, medical management options are available to alleviate symptoms and correct biochemical abnormalities. These options include oral phosphate supplementation and active vitamin D analogs. Newer medications, such as burosumab, specifically target and block the action of FGF23, managing the disease when surgical resection is not feasible.