The Study Of Clinical Profile Of Tumor-induced Osteomalacia And The Study Of Population Genetics Of Polymorphisms In LGR4

Aims: Tumor-induced osteomalacia(TIO)is a rare acquired form of hypophosphatemic osteomalacia,which is attributed to the overproduction of FGF-23 of neoplasms.The clinical manifestations include extensive bone pain,proximal muscle weakness and pseudo-fractures(Looser's zone),even fracture.The incidence of the TIO is low.The localization of the TIO associated tumor is challenging.The objective of the present study is to investigate the clinical data,diagnostic and treatment methods,and follow-up after the tumor resection of a cohort of patients with TIO.Through potentiating Wnt/?-catenin signaling,LGR4 could affect differentiation of osteoblasts and bone mass.LGR4 is also relevant to glycolipid metabolism.The present study aims to explore the relationship between SNPs and haplotypes in LGR4 gene and peak bone mineral density and body composition phenotypes in Chinese male-offspring nuclear families.Methods: Altogether,23 patients with adult-onset hypophosphatemia osteomalacia were enrolled.After taking a medical history and performing physical examination,we analyzed the preoperative and postoperative laboratory results(including the serum phosphorus,ALP and FGF-23 levels).To establish reference range of FGF-23,we also enrolled 95 healthy individuals.Basing on database of the male-offspring nuclear families,we used QTDT analysis explore the relationship between SNPs(22 SNPs)and haplotypes in LGR4 gene and p BMD and body composition phenotypes.Results: 17 patients were ultimately diagnosed as TIO.All patients presented with decreased serum phosphorus and elevated ALP.FGF-23 elevated in 16 patients.After tumor resection,serum phosphorus normalized in all patients in 4-21 days,FGF-23 levels in 9 patients in 2-7 days.For QTDT analysis,rs12796247 and rs2219783 were observed being associated with lumbar spine BMD in the within-family association.rs12787344,rs4128868 and rs7936621 were observed in significant association with BMI in within-family association.Conclusions: Measurement of serum phosphorus and FGF-23 on patients with suspected TIO is of paramount importance for making the diagnosis of TIO.TIO associated tumors were more frequently located in lower extremities than in other places.Complete surgical resection results in a cure of the TIO.The polymorphisms of LGR4 gene were associated with variation of peak bone mineral density and BMI variation in young men of Chinese Han.