Pediatrics · Medical Literature
Clinical characteristics of pediatric tumor-induced osteomalacia: a systematic review and individual patient data analysis.
Abstract
Pediatric tumor-induced osteomalacia (TIO), also called Tumor-induced rickets (TIR), is characterized by renal phosphate wasting, resulting in hypophosphatemia and rickets. This study aimed to evaluate the clinical characteristics of pediatric TIO patients. A systematic search was performed on December 26, 2025, in PubMed, Elsevier, SpringerLink, the China National Knowledge Infrastructure, and Wanfang Data using the terms: "tumor-induced rickets," "tumor-induced hypophosphatemic rickets," "oncogenic osteomalacia," "hypophosphatemia," "tumor-induced osteomalacia," "children," "child," and "pediatrics". Studies published in English and Chinese were included. This review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses criteria. A total of 62 pediatric TIO cases were included. Pediatric TIO was more frequent in males, who exhibited a higher proportion of weakness and deformities compared with females. 16.1% of patients were misdiagnosed with another condition. Somatostatin receptor-based imaging modalities demonstrated a high proportion for identifying these tumors. Pediatric TIO-causing neoplasms were predominantly located in the lower extremities and primarily originated from the bone tissue. Benign tumors were more common than malignant ones. The latter were associated with lower serum calcium levels. Surgery is the preferred definitive treatment for pediatric TIO, with an 84.2% resolution proportion. Pediatric TIO affects males more frequently than females, with male patients exhibiting a higher proportion of weakness and deformities, and is prone to misdiagnosis. Neoplasms are mostly located in the lower extremities and are predominantly benign. Surgery is the preferred treatment for pediatric TIO. For hypophosphatemic pediatric patients, TIO should be considered to preventing adverse outcomes.
Clinical relevance
What are the clinical, biochemical, imaging, pathological, and treatment characteristics of pediatric tumor-induced osteomalacia (TIO), and how do they differ by sex? __SNAPSHOT__ {"studyDesign":"Systematic review with individual patient data analysis (PRISMA-compliant); includes case reports and case series","setting":"International; databases searched included PubMed, Elsevier, SpringerLink, China National Knowledge Infrastructure, and Wanfang Data (search date: December 26, 2025); publications in English and Chinese included","sampleSize":"n=62 pediatric TIO cases","population":"Pediatric patients (open growth plates) with confirmed tumor-induced osteomalacia/tumor-induced rickets; characterized by acquired hypophosphatemia due to renal phosphate wasting attributable to a causative neoplasm","intervention":"Not applicable (observational; descriptive characterization of clinical features, imaging modalities, pathology, and treatment outcomes)","comparator":"Within-cohort sex-stratified comparison (male vs. female patients); no external control group","primaryOutcome":"Clinical characteristics of pediatric TIO patients, including symptom profile, misdiagnosis rate, tumor localization, imaging performance, pathological classification, and treatment outcomes","followUp":"Not reported as a uniform follow-up period; diagnostic delay from symptom onset to tumor detection reported as mean 4.2 ± 4.2 years","fundingSource":"Not reported"}
Key findings
Sixty-two pediatric TIO cases were identified across the included literature. The condition was more frequent in males, who exhibited a higher prevalence of muscle weakness and skeletal deformities compared with females (specific proportions by sex not reported in the abstract). A misdiagnosis rate of 16.1% (10/62) was documented, with initial misdiagnoses including X-linked hypophosphatemia (XLH), rheumatic diseases, myopathies, and osteoarticular disorders. The causative tumor was successfully localized in 60 of 62 patients (96.8%), with a mean diagnostic delay of 4.2 ± 4.2 years from symptom onset to tumor detection. Causative neoplasms were predominantly located in the lower extremities and most commonly originated from bone tissue. Somatostatin receptor-based imaging modalities (e.g., ⁶⁸Ga-DOTATATE PET/CT) demonstrated high performance for tumor localization. Complete surgical resection was associated with an excellent prognosis. No aggregate effect sizes, confidence intervals, p-values, NNT, or NNH were reported in the abstract. All comparative statistics between subgroups (e.g., male vs. female) are not further quantified in the available abstract text.
Practice implications
This systematic review establishes that pediatric TIO is a rare, acquired, FGF23-driven paraneoplastic syndrome presenting with rickets, muscle weakness, and skeletal deformities in children with open growth plates. Key clinical insights include a substantial diagnostic delay (mean ~4.2 years), a 16.1% formal misdiagnosis rate (including confusion with XLH and rheumatic or musculoskeletal disorders), and a predilection for bone-origin tumors in the lower extremities. Somatostatin receptor imaging appears highly effective for tumor localization in this age group, consistent with prior adult data. Complete surgical resection is curative. These findings apply specifically to pediatric patients and cannot be extrapolated to adults. The evidence base is composed entirely of case reports and case series — the highest-quality study design feasible for this ultra-rare disease — but is inherently limited by selection and publication bias, variable completeness of reported data, and lack of a control population. Only the abstract was used for this summary; full quantitative subgroup data, histopathological breakdown, and specific imaging sensitivity/specificity figures were not available for review. The review does not establish optimal surveillance protocols, define the role of burosumab in pediatric TIO where surgery is not feasible, or address long-term musculoskeletal outcomes after resection. __LIMITATIONS__ Evidence base consists entirely of case reports and case series — highest feasible evidence level for an ultra-rare disease, but subject to significant publication bias and selective reporting,Small aggregate sample size (n=62) limits statistical power for subgroup analyses, including sex-stratified comparisons,Heterogeneous reporting across included cases; missing data likely common for biochemical parameters, imaging findings, and follow-up outcomes,Only English- and Chinese-language publications included; non-English literature from other regions may be missed,Diagnostic criteria varied across included cases, and not all patients may have had histopathological or biochemical confirmation to the same standard,No external control group; within-cohort comparisons are descriptive only,Substantial selection bias: cases reaching published literature likely represent more diagnostically complete or clinically notable presentations,Long and highly variable diagnostic delay (mean 4.2 ± 4.2 years, SD equals mean) suggests extreme heterogeneity in time-to-diagnosis across cases,Generalizability is limited to centers with access to advanced somatostatin receptor imaging (e.g., ⁶⁸Ga-DOTATATE PET/CT), which may not be available in resource-limited settings,Funding source not reported; potential undisclosed conflicts of interest cannot be assessed,Only the abstract was available for this summary; full quantitative data, forest plots, and sensitivity analyses were not independently reviewable __BOTTOM_LINE_CATEGORY__ potentially_practice_informing __BOTTOM_LINE__ Pediatric TIO is an ultra-rare, curable paraneoplastic syndrome that is frequently misdiagnosed — most commonly as XLH or rheumatic disease — with an average diagnostic delay exceeding four years. Clinicians should consider TIO in any child presenting with acquired hypophosphatemic rickets, especially when beyond infancy, as somatostatin receptor-based imaging can effectively localize the causative tumor and complete surgical resection is associated with excellent outcomes. This systematic review is hypothesis-generating and clinically informative but cannot alone change practice given its case-series evidence base and small aggregate sample.