Tumor-Induced Osteomalacia: A Systematic Clinical Review of 895 Cases.

Tumor-induced osteomalacia (TIO) is a rare and largely underdiagnosed paraneoplastic condition. Previous reviews often reported incomplete data on clinical aspects, diagnosis or prognosis. The aim of this study was to present a systematic clinical review of all published cases of TIO. A search was conducted in Pubmed, Embase, Web of Science from inception until April 23rd, 2020. We selected case reports and case series of patients diagnosed with TIO, with information on tumor localization and serum phosphate concentration. Two reviewers independently extracted data on biochemical and clinical characteristics including bone involvement, tumor localization and treatment. 468 articles with 895 unique TIO cases were included. Median age was 46 years (range 9 months-90 years) and 58.3% were males. Hypophosphatemia and inappropriately low or normal 1,25-dihydroxyvitamin D levels, characteristic for TIO, were present in 98% of cases. Median tumor size was 2.7 cm (range 0.5 to 25.0 cm). Serum fibroblast growth factor 23 was related to tumor size (r = 0.344, P < 0.001). In 32% of the cases the tumor was detected by physical examination. Data on bone phenotype confirmed skeletal involvement: 62% of cases with BMD data had a T-score of the lumbar spine ≤ - 2.5 (n = 61/99) and a fracture was reported in at least 39% of all cases (n = 346/895). Diagnostic delay was longer than 2 years in more than 80% of cases. 10% were reported to be malignant at histology. In conclusion, TIO is a debilitating disease characterized by a long diagnostic delay leading to metabolic disturbances and skeletal impairment. Increasing awareness of TIO should decrease its diagnostic delay and the clinical consequences.

Lean mass and fat mass predict bone mineral density in middle-aged individuals with noninsulin-requiring type 2 diabetes mellitus.

OBJECTIVE: Despite high bone mineral density (BMD), persons with type 2 diabetes are at greater risk of fracture. The relationship between body composition and BMD in noninsulin-requiring diabetes is unclear. The aim was to examine how fat and lean mass independently affect the skeleton in this population. RESEARCH DESIGN AND METHODS: Subjects for this cross-sectional analysis were men (n = 78) and women (n = 56) aged 40-65 years (56 ± 6 years) with uncomplicated, noninsulin-requiring type 2 diabetes. Total body fat and lean mass, total body, hip and lumbar spine BMD were measured with dual energy X-ray absorptiometry. Magnetic resonance imaging measured total abdominal, visceral and subcutaneous (SQ) fat. RESULTS: Subjects had normal all-site BMD and were obese to overweight (body mass index 29-41 kg/m(2)) with controlled diabetes (HbA1c women 6·6 ± 1·2%, men 6·7 ± 1·6%). Lean mass was positively associated with total body, hip, femoral neck and hip BMD in both sexes. Fat mass, abdominal total and SQ fat were associated with total body and hip BMD in women. In multivariate analyses adjusted for sex, lean mass significantly predicted total, hip and femoral neck BMD in men and women. In unadjusted models, lean mass continued to predict BMD at these sites in men; fat mass also predicted total body, femoral and hip BMD in women. CONCLUSIONS: In men and women with uncomplicated, noninsulin-requiring diabetes, lean mass significantly predicted BMD at the total body, hip and femoral neck. Further research is needed to determine whether acquisition or maintenance of lean mass in T2DM can prevent hip fracture in this at-risk population.

Tumors associated with oncogenic osteomalacia express genes important in bone and mineral metabolism.

Oncogenic osteomalacia (OOM) is associated with primitive mesenchymal tumors that secrete phosphaturic factors resulting in low serum concentrations of phosphate and calcitriol, phosphaturia, and defective bone mineralization. To identify overexpressed genes in these tumors, we compared gene expression profiles of tumors resected from patients with OOM and histologically similar control tumors using serial analysis of gene expression (SAGE). Three hundred and sixty-four genes were expressed at least twofold greater in OOM tumors compared with control tumors. A subset of 67 highly expressed genes underwent validation with an extended set of OOM and control tumors using array analysis or reverse-transcription polymerase chain reaction (RT-PCR). Ten of these validated genes were consistently overexpressed in all OOM tumors relative to control tumors. Strikingly, genes with roles in bone matrix formation, mineral ion transport, and bone mineralization were highly expressed in the OOM tumors.