Skeletal involvement in tumor-induced osteomalacia

Tumor-induced osteomalacia (TIO) is an ultrarare paraneoplastic syndrome of abnormal phosphate and vitamin D metabolism secondary to the overproduction of fibroblast growth factor 23 by small-sized mesenchymal tumors typically located in soft tissues and bone. The tumor has adverse effects on bone and patients complain of skeletal symptoms and, in severe cases, they suffer multiple devastating fractures. Specific features may characterize the histology of tumors located in bone with respect to those found in extra-skeletal sites. Indeed, the matrix may contain foci resembling primitive cartilage and osteoid. Light microscopy of bone biopsy samples reveal accumulation of osteoid due to thickening of osteoid seams and, if tetracyclines were sequentially administrated, fluorescence microscopy reveals prolongation of the mineralization lag time. Areal BMD assessed by DXA is significantly lower at both the lumbar and femoral sites in patients with TIO and values of trabecular bone score are significantly reduced with respect to healthy individuals. Patients with TIO are also characterized by significant impairment in bone quality at both the trabecular and cortical compartment when evaluated by HR-pQCT. Successful surgical removal of the causative tumor completely reverts biochemical abnormalities. BMD accrual is impressive in the short term at the central (spine and hip) level but may take longer to improve, together with microstructural parameters, at peripheral sites (radius and tibia). Future studies should address effects of long-term treatment on quality-of-life outcomes related to irreversible events, such as vertebral fractures. This is particularly important in patients with a heavy burden due to a long-standing disease.