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Research Article: Unveiling the biochemical signature of tumor-induced osteomalacia: implications for distinguishing it from primary osteoporosis

Date Published: 2026-07-24

Abstract:
Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome caused by FGF23-secreting tumors, resulting in renal phosphate wasting and hypophosphatemic osteomalacia. Low bone mineral density (BMD) in TIO frequently leads to misdiagnosis as the more prevalent primary osteoporosis (POP) and subsequent diagnostic delay. This study characterizes the distinct biochemical profile of TIO and proposes a stepwise diagnostic approach to differentiate it from POP for timely clinical identification and appropriate management. We conducted a retrospective comparative analysis of 11 TIO patients and 12 POP patients managed at our institution over a 14-year period. Detailed clinical data were collected and compared between groups, including history, physical examination findings, laboratory results, imaging studies, and pathological outcomes. Comparative analysis revealed that, compared with POP patients, TIO patients had significantly lower serum calcium (2.19 ± 0.1 vs.2.3 ± 0.1 mmol/L, p < 0.05), serum phosphorus [0.46 (0.42, 0.6) vs. 1.15 (1.13, 1.23), p < 0.001], and the tubular maximum reabsorption of phosphate per glomerular filtration rate (TmP/GFR) (0.41 ± 0.2 vs.1.05 ± 0.15 mmol/L, p < 0.001). In contrast, ALP was significantly higher in the TIO cohort [317 (177.5, 344) vs. 79.5 (67.75, 86.75) U/L, p < 0.001]. No significant intergroup differences were observed in PTH levels or BMD. We recommend serum phosphate, alkaline phosphatase, and TmP/GFR tests for symptomatic patients (e.g., bone pain, muscle weakness). Confirmed hypophosphatemia warrants FGF23 testing after excluding other causes of elevation. Subsequent bone X-ray and BMD guides the need for molecular imaging. The diagnostic gold standard comprises: (1) histopathological confirmation of the causative tumor, (2) rapid postoperative serum phosphate normalization, and (3) significant clinical improvement.

Introduction:
Disorders of bone mineral metabolism serve as a frequent pathological basis for increased skeletal fragility and susceptibility to fractures. Primary osteoporosis (POP), a systemic skeletal disorder defined by diminished bone mass and impaired microarchitecture, represents a major global public health challenge owing to its elevated prevalence—notably among aging and postmenopausal female populations—and the considerable burden of resulting fractures. The diagnostic and therapeutic framework for POP is relatively…

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