Paraneoplastik Osteomalazi
Özet
Onkojenik osteomalazi olarak da bilinen tümör ilişkili osteomalazi (TİO), teşhisi oldukça güç ve nadir rastlanan bir paraneoplastik sendromdur. Hastalık, genellikle küçük, yavaş büyüyen ve vücudun farklı bölgelerindeki kemik ya da yumuşak dokularda yerleşen iyi huylu fosfatürik mezenkimal tümörlerden (FMT) kaynaklanır. Bu tümörlerin kontrolsüz şekilde fibroblast büyüme faktörü 23 (FGF-23) salgılaması, böbreklerden aşırı fosfat kaybına ve aktif D vitamini sentezinin bozulmasına yol açarak şiddetli hipofosfatemi ile sonuçlanır. Hastalar klinike genellikle kemik ağrısı, ilerleyici kas güçsüzlüğü ve çoklu patolojik kırıklar gibi özgül olmayan semptomlarla başvururlar; bu durum tanı süresinin ortalama 2-3 yıl gecikmesine ya da yanlış teşhisler konulmasına neden olur. TİO'nun kesin ve küratif tek tedavisi, tümörün geniş sınırlarla cerrahi olarak tamamen çıkarılmasıdır. Operasyonun ardından FGF-23 ve serum fosfat düzeyleri hızla normale döner. Cerrahi rezeksiyonun mümkün olmadığı durumlarda ise fosfat ve aktif D vitamini takviyesini içeren medikal tedaviler, kriyoablasyon veya son yıllarda geliştirilen burosumab ve FGFR inhibitörleri gibi hedefe yönelik monoklonal antikor ve ajanlar devreye girmektedir.
Tumor-induced osteomalacia (TIO), also known as oncogenic osteomalacia, is a rare and diagnostically challenging paraneoplastic syndrome. The disease typically originates from small, slow-growing, benign phosphaturic mesenchymal tumors (PMTs) located in bone or soft tissues across various bodily sites. Autonomous hypersecretion of fibroblast growth factor 23 (FGF-23) by these tumors leads to renal phosphate wasting and impaired vitamin D activation, resulting in severe hypophosphatemia. Patients commonly present with non-specific symptoms such as bone pain, progressive muscle weakness, and multiple pathological fractures, which frequently delays accurate diagnosis by an average of 2-3 years or leads to misdiagnoses. Complete surgical resection of the tumor with wide margins remains the only definitive curative treatment for TIO, leading to a dramatic normalization of FGF-23 and serum phosphate levels postoperatively. When tumors are unresectable, medical management involving phosphate and active vitamin D supplements is required, while targeted therapies such as burosumab (an anti-FGF-23 monoclonal antibody) and FGFR inhibitors represent promising medical alternatives.
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