Refractory Rickets

Nutritional rickets, caused by vitamin D and/or calcium deficiency is by far the most common cause of rickets. In resource-limited settings, it is therefore not uncommon to treat rickets with vitamin D and calcium. If rickets fails to heal and/or if there is a family history of rickets, then refractory rickets should be considered as a differential diagnosis. Chronic low serum phosphate is the pathological hallmark of all forms of rickets as its low concentration in extracellular space leads to the failure of apoptosis of hypertrophic chondrocytes leading to defective mineralisation of the growth plate. Parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF23) control serum phosphate concentration by facilitating the excretion of phosphate in the urine through their action on the proximal renal tubules. An increase in PTH, as seen in nutritional rickets and genetic disorders of vitamin D-dependent rickets (VDDRs), leads to chronic low serum phosphate, causing rickets. Genetic conditions leading to an increase in FGF23 concentration cause chronic low serum phosphate concentration and rickets. Genetic conditions and syndromes associated with proximal renal tubulopathies can also lead to chronic low serum phosphate concentration by excess phosphate leak in urine, causing rickets. In this review, authors discuss an approach to the differential diagnosis and management of refractory rickets

Traditional Chinese Medicine Intervenes in Signaling Pathways Associated with CKD-MBD： A Review / 中国实验方剂学杂志

Traditional Chinese medicine （TCM） has certain advantages in the treatment of chronic kidney disease-mineral and bone disorder （CKD-MBD）. In recent years， there have been many studies on the treatment of CKD-MBD by Chinese medicinal compounds and monomers. As revealed by literature retrieval， the research on the mechanism of Chinese medicine in intervening in signaling pathways related to CKD-MBD was mainly based on self-made Chinese medicinal compounds， and the action pathways involved fibroblast growth factor 23/Klotho （FGF23/Klotho） signaling pathway， Wnt/β-catenin signaling pathway， receptor activator of nuclear factor-κB/receptor activator of nuclear factor-κB ligand/osteoprotegerin （RANK/RANKL/OPG） system， and other signaling pathways. TCM can improve calcium and phosphorus metabolism and bone metabolism disorder， and regulate inflammatory reaction， oxidative stress， apoptosis， and autophagy by regulating this series of signaling pathways for the treatment of CKD-MBD. This paper introduced the research results of these signaling pathways and the mechanism of TCM in the treatment of CKD-MBD in order to provide ideas and references for the related research of Chinese medicine in the treatment of CKD-MBD.

New treatments for rare bone diseases: hypophosphatemic rickets/osteomalacia

Abstract Phosphorus is one of the most abundant minerals in the human body; it is required to maintain bone integrity and mineralization, in addition to other biological processes. Phosphorus is regulated by parathyroid hormone, 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], and fibroblast growth factor 23 (FGF-23) in a complex set of processes that occur in the gut, skeleton, and kidneys. Different molecular mechanisms - overproduction of FGF-23 by tumors responsible for oncogenic osteomalacia, generation of an FGF-23 mutant that is resistant to cleavage by enzymes, and impaired FGF-23 degradation due to a reduction in or loss of the PHEX gene - can lead to FGF-23-stimulating activity and the consequent waste of urinary phosphate and low levels of 1,25(OH)2D3. Conventional treatment consists of multiple daily doses of oral phosphate salts and vitamin D analogs, which may improve radiographic rickets but do not normalize growth. Complications of the conventional long-term treatment consist of hypercalcemia, hypercalciuria, nephrolithiasis, nephrocalcinosis, impaired renal function, and potentially chronic kidney disease. Recently, burosumab, an antibody against FGF-23, was approved as a novel therapy for children and adults with X-linked hypophosphatemia and patients with tumor-induced osteomalacia. Burosumab showed good performance in different trials in children and adults. It increased and sustained the serum phosphorus levels, decreased the rickets severity and pain scores, and improved mineralization. It offers a new perspective on the treatment of chronic and disabling diseases. Arch Endocrinol Metab. 2022;66(5):658-65

Phosphaturic mesenchymal tumor: An underdiagnosed rare entity

Tumor-induced osteomalacia is a paraneoplastic syndrome resulting in renal phosphate wasting and decreased bone mineralization. Phosphaturic mesenchymal tumors represent a rare etiology of tumor-induced osteomalacia. They are exceptionally rare, probably accounting for < 0.01% of all soft tissue tumors. Most PMTs present as small inapparent lesions that require very careful clinical examination and radionucleotide scan for localization. Here we describe a case in a 65 years old woman with recurrent multiple bone fractures and subsequent detection of a tumor involving right femur and adjacent soft tissue, low phosphate level and elevated serum Fibroblast growth factor-23 (FGF-23).

Biomarkers of bone and mineral disorders (FGF-23, fetuin-A) and vascular calcification scores as predictive tools for cardiovascular death in dialysis patients, at 10 years of follow-up / Biomarcadores del metabolismo mineral óseo (FGF-23, fetuína-A) y calcificaciones vasculares como herramientas predictivas de muerte cardiovascular de pacientes en diálisis, a 10 años de seguimiento

Abstract Cardiovascular disorders represent the leading cause of death in dialysis patients. Alterations of bone and mineral metabolism (BMM) and vascular calcifications play a fundamental role in it. The objective of this study was to evaluate the predictive role on cardiovascular mortality of the measurement of biomarkers of BMM and vascular calcifications. A prospective cohort study was performed. All prevalent patients on chronic dialysis in September 2009 at our institution, who completed the total of the complementary stud ies, were studied. BMM biomarkers were measured (FGF 23, fetuin A, PTH, calcium and phosphorus) and the vascular calcifications were evaluated using the Kauppila and Adragao scores. Follow-up was carried out until 1/1/2019, death or transplant. Of the 30 patients included, 7 (23.3%) died due to cardiovascular causes. The follow-up time was 44.1 ± 30.4 (range = 1.4-112) months. The Adragao score was the only predictive variable of long-term cardiovascular mortality (area under the curve = 0.82; 95% CI 0.64-0.94; p < 0.001). The best cut-off point was 5 (sensitivity = 85.7%; specificity = 78.3%). It was also an independent risk factor for cardiovascular mortality adjusted for age, diabetes mellitus, coronary heart disease, aortic calcifications, time spent on dialysis and follow-up time (adjusted OR = 1.77; 95% CI = 1.06-2.96; p = 0.028). The vascular calcifications quantified from the Adragao score were the only independent predictor of long-term cardiovascular mortality. This score represents a simple, useful and superior tool to the biomarkers of BMM.

Resumen Los trastornos cardiovasculares representan la primera causa de muerte en los pacientes en diálisis. Las alteraciones del metabolismo óseo y mineral (MOM) y las calcificaciones vasculares juegan un papel fundamental en la misma. El objetivo de este estudio fue evaluar el rol predictor sobre la mortalidad car diovascular de la medición de los biomarcadores del MOM y las calcificaciones vasculares. Se realizó un estudio de cohorte prospectivo. Se estudiaron todos los pacientes prevalentes en diálisis crónica en septiembre del 2009 en nuestra institución que completaron el total de los estudios complementarios. Se midieron biomarcadores del MOM (FGF 23, fetuína A, PTH, calcio y fósforo) y se evaluaron las calcificaciones vasculares mediante los scores de Kauppila y de Adragao. Se realizó un seguimiento hasta el 1/1/2019, la muerte o el trasplante. De los 30 pacientes incluidos, 7 (23.3%) fallecieron por causa cardiovascular. El tiempo de seguimiento fue de 44.1 ± 30.4 (rango = 1.4-112) meses. El score de Adragao fue la única variable predictiva de muerte cardiovascular a largo plazo (área bajo la curva = 0.82; IC95% = 0.64-0.94; p<0.001). El mejor punto de corte fue de 5 (sensibili dad = 85.7%; especificidad = 78.3%). Además, fue un factor de riesgo independiente de muerte cardiovascular ajustado por edad, diabetes mellitus, enfermedad coronaria, calcificaciones aorticas, tiempo de permanencia en diálisis y tiempo de seguimiento (OR ajustado = 1.77; IC95% = 1.06-2.96; p = 0.028). Las calcificaciones vasculares cuantificadas a partir del score de Adragao fueron el único predictor independiente de mortalidad cardiovascular a largo plazo. Este score representa una herramienta simple, útil y superior a los biomarcadores del MOM.

Mechanism of Modified Liuwei Dihuangtang in Bone Protection of CKD-MBD Model Rats： An Exploration Based on Klotho-FGF23 Axis / 中国实验方剂学杂志

Objective:To observe the effects of modified Liuwei Dihuangtang on serum fibroblast growth factor 23 （FGF23）， full-length intact parathyroid hormone （iPTH）， and 1，25-dihydroxyvitamin D₃［1，25（OH）₂D₃］ levels and Klotho and FGF23 protein expression in renal and bone tissues of rats exposed to high phosphorus combined with adenine， so as to explore the mechanism of modified Liuwei Dihuangtang against renal osteopathy. Method:One hundred and thirty healthy adult SD rats were randomly divided into five groups， namely normal group（<italic>n</italic>=10），high phosphorus group（<italic>n</italic>=30），model group（<italic>n</italic>=30），modified Liuwei Dihuangtang group（<italic>n</italic>=30） ， and calcitriol group（<italic>n</italic>=30），and rats in each group were further classified based on three time points， namely 8，10， and 12 weeks. Rats in the normal group were fed with normal diet， the ones in the high phosphorus group with high phosphorus diet， and those in the other groups with adenine and high phosphorus diet for inducing renal osteopathy. Rats in the normal group，high phosphorus group， and model group were intragastrically administered with distilled water （10 mL·kg^-1·d^-1），the ones in the modified Liuwei Dihuangtang group with modified Liuwei Dihuangtang （2.556 g·kg^-1·d^-1） ， and those in the calcitriol group with calcitriol （0.09 μg·kg^-1·d^-1）. Result:Compared with the normal group and high phosphorus group at the weeks of 8，10 and 12，the model group displayed significantly elevated blood urea nitrogen（BUN），serum creatinine（SCr），serum phosphorus，iPTH，FGF23，renal interstitial fibrosis score， and FGF23 expression in renal and bone tissues， but lowered serum calcium and 1，25（OH）₂D₃ and Klotho protein expression in renal and bone tissues（<italic>P</italic><0.05 ，<italic>P</italic><0.01）. Compared with the model group at the weeks of 8，10 and 12， the modified Liuwei Dihuangtang and calcitriol both significantly decreased the serum BUN，SCr，serum phosphorus，iPTH， FGF23， tubulointerstitial semi-quantitative score， and FGF23 expression in renal and bone tissues， while increased the serum calcium，1，25（OH）₂D₃， and Klotho protein expression in renal and bone tissues （<italic>P</italic><0.05，<italic>P</italic><0.01）. There was no significant difference in the above-mentioned indexes between the modified Liuwei Dihuangtang group and the calcitriol group at the same time point. Conclusion:Klotho-FGF23 axis is probably involved in renal osteopathy. The modified Liuwei Dihuangtang effectively improves renal function，alleviates pathological changes in renal and bone tissues，and regulates calcium and phosphorus metabolism to protect the bone， which is related to its regulation of Klotho-FGF23 axis.

Management of X-linked hypophosphatemic rickets: a review

There are two types of management in X-linked hypophosphatemic rickets (XLH), out of which the main stay of treatment is conventional treatment which includes combination of oral phosphate supplements and active vitamin D (calcitriol or alfacalcidol) after the diagnosis is established. Although, conventional treatment with phosphate supplementation and active vitamin D might improve the rickets and control the renal phosphate excretion but it has significant risk of high calcium excretion in the urine and thereby increases the risk of nephrocalcinosis. The other emerging treatment is burosumab therapy which is human monoclonal IgG1 antibody against fibroblast growth factor 23 (FGF 23) for the treatment of XLH in children ≥1 year of age and in adolescents and is found to be effective in improving rickets without major adverse events. In this review, modalities for XLH treatment over the past and the near future will be discussed along with clinical manifestations and investigations.

Rare cause of pathological fracture in adults as hypophosphatemic rickets

Hypophosphatemic rickets is a disorder of defective bone minerlization due to defect in renal phosphate handling process. It is characterised by increased phosphate excretion accompanied by increased phosphatonins like fibroblast growth factor 23. It can be hereditary form of X linked, autosomal dominant, autosomal recessive type of hypophosphatemic rickets. It is associated with low serum phosphorus, normal serum calcium, inappropriately low to normal vitamin D level. Correct identification of these disorders is important for determining therapy. Early diagnosis and management prevent subsequent complication of the disease.

A study on FGF23 among chronic renal failure patients in Perambluar District

Background: Fibroblast growth factor 23 (FGF23) is a phosphate-regulating hormone primarily secreted by osteocytes. Levels of FGF23 increase as kidney function declines as a physiologic response to maintain normal serum phosphate levels and neutral phosphate balance. Although FGF23 helps to prevent hyperphosphatemia, elevated circulating levels are independently associated with vascular dysfunction, left ventricular hypertrophy, increased risk for ESRD, and death in patients with CKD. Aim of the study: To evaluate the FGF23 and eGFR levels in chronic kidney disease patients to compare them with healthy controls. Materials and methods: Totally 100 patients were included in the study. The study was conducted from June 2018 – November 2018 over a period of 6 months at Nephrology department of DSMCH, Perambalur. Group – I (50) who were in CKD stage - IV. Group - II (50) healthy controls were included in the study. Fibroblast growth factor 23 (FGF23) was estimated by standard techniques and results are analyzed accordingly. Results: The mean value of FGF23 in Group – I was 730.7 ± 492.72 pg/ml was higher than that of the Group – II whose mean value was 39.49 ± 12.47 pg/ml and this difference was statistically significant( p<0.05). Group – I had very low mean eGFR levels than Group - II and this difference was statistically significant. Conclusion: Higher FGF23 levels are independently associated with higher levels of inflammatory markers in patients with CKD and with significantly greater odds of severe inflammation. Future studies should evaluate whether inflammation modifies the association between FGF23 and adverse outcomes in CKD.

The FGF metabolic axis / 医学前沿

Members of the fibroblast growth factor (FGF) family play pleiotropic roles in cellular and metabolic homeostasis. During evolution, the ancestor FGF expands into multiple members by acquiring divergent structural elements that enable functional divergence and specification. Heparan sulfate-binding FGFs, which play critical roles in embryonic development and adult tissue remodeling homeostasis, adapt to an autocrine/paracrine mode of action to promote cell proliferation and population growth. By contrast, FGF19, 21, and 23 coevolve through losing binding affinity for extracellular matrix heparan sulfate while acquiring affinity for transmembrane α-Klotho (KL) or β-KL as a coreceptor, thereby adapting to an endocrine mode of action to drive interorgan crosstalk that regulates a broad spectrum of metabolic homeostasis. FGF19 metabolic axis from the ileum to liver negatively controls diurnal bile acid biosynthesis. FGF21 metabolic axes play multifaceted roles in controlling the homeostasis of lipid, glucose, and energy metabolism. FGF23 axes from the bone to kidney and parathyroid regulate metabolic homeostasis of phosphate, calcium, vitamin D, and parathyroid hormone that are important for bone health and systemic mineral balance. The significant divergence in structural elements and multiple functional specifications of FGF19, 21, and 23 in cellular and organismal metabolism instead of cell proliferation and growth sufficiently necessitate a new unified and specific term for these three endocrine FGFs. Thus, the term "FGF Metabolic Axis," which distinguishes the unique pathways and functions of endocrine FGFs from other autocrine/paracrine mitogenic FGFs, is coined.

Design and expression of FGF23 inhibitor in Pichia pastoris / 药学学报

Hypophosphatemia is a common metabolism disease in humans. Fibroblast growth factor 23 (FGF23) inhibits phosphate reabsorption by targeting on the renal tubules. FGF23C-tail contains 73 amino acids from C-terminus of FGF23, serves as an inhibitor of FGF23, and can increase phosphate reabsorption. Therefore, FGF23C-tail is an important drug for hypophosphatemia. In this paper, we constructed a fusion protein of FGF23C-tail with HSA, and investigated the expression of the fusion protein in the Pichia pastoris system. The recombinant gene was constructed by fusion PCR. A high-yield strain was selected by G418 resistance and fermentation yield, and the expression yield was 43.7 mg·L-1 in flask. In 5 L fermenters, the highest expression yield could reach 265.6 mg·L-1. FGF23C-tail-HSA could be used as an inhibitor for FGF23, and could significantly increase blood phosphorus levels in rats. The procedures for care and use of animals were approved by the Ethics Committee of YiChun University. This paper provided a basis research for further studying physiological activity of FGF23C-tail-HSA.

Is FGF-23 an early indicator of atherosclerosis and cardiac dysfunction in patients with gestational diabetes?

ABSTRACT Objective: Fibroblast growth factor 23 (FGF-23) is a phosphorus-regulating hormone and plays a role in the pathogenesis of myocardial hypertrophy. The aim of this study was to evaluate the association of FGF-23 levels with echocardiographic parameters and insulin resistance (IR) in patients with gestational diabetes. Subjects and methods: Fifty-four pregnant patients with gestational diabetes mellitus (GDM) (age, 31.12 ± 5.72 years) and 33 healthy pregnant women (age, 29.51 ± 4.92 years) were involved in the study. Fasting insulin, fasting plasma glucose (FPG), lipid profile, oral glucose tolerance test (OGTT), FGF23, echocardiographic parameters, and carotid artery intima-media thickness (CIMT) were evaluated in the two groups. Results: The two groups were not significantly different in age, sex, body mass index, lipid profile, or blood pressure. Insulin, homeostatic model assessment-insulin resistance (HOMA-IR), FGF-23 levels, CIMT, left ventricular (LV) mass, LV mass index and myocardial performance index (MPI) were significantly higher in the GDM group. HOMA-IR was positively correlated with FGF-23, and insulin was positively correlated with FGF-23. Additionally, FGF-23 was positively correlated with CIMT, LV mass index, and MPI. Conclusion: Our findings suggest that monitoring serum FGF-23 may be useful as a non-invasive indicator of subclinical atherosclerosis in patients with GDM.

Research on relationship of FGF-23 and sKL with cardiac valve calcification in CAPD patients / 上海交通大学学报（医学版）

Objective: To explore the relationship of fibroblast growth factor-23 (FGF-23) and soluble klotho (sKL) with cardiac valve calcification in patients with continuous ambulatory peritoneal dialysis (CAPD). Methods: 147 CAPD patients from the dialysis center of the First Affiliated Hospital of Soochow University were enrolled. The concentrations of FGF-23 and sKL were measured by enzyme-linked immunosorbent assays (ELISA). Echocardiography was applied to evaluate cardiac valve calcification. The patients were divided into normal cardiac valve group (group A) and cardiac valve calcification group (group B). SPSS 23.0 software was used for data analysis. Results: The incidence of cardiac valve calcification in CAPD patients was 54.42%. The risk of cardiac valve calcification showed positive correlation with age, dialysis age, serum creatinine, corrected calcium, serum phosphorus, serum alkaline phosphatase, parathyroid hormone, and the level of FGF-23 (P=0.045, P=0.022, P=0.006, P=0.024, P=0.000, P=0.017, P=0.022, P=0.000), and negative correlation with urea clearance index, the level of sKL and residual renal function (P=0.045, P=0.000, P=0.011). Multivariate Logistic regression analysis showed that the increase of FGF-23 (OR=5.007, 95% CI 1.446-17.339, P=0.011) and serum phosphorus (OR=7.433, 95% CI 1.558-35.470, P=0.012) were two independent risk factors for cardiac valve calcification in CAPD patients, and the decrease of sKL (OR=0.310, 95% CI 0.108-0.891, P=0.030) was another independent risk factor as well. Receiver operator characteristic curves (ROC) indicated that to predict cardiac valve calcification in patients with CAPD, the optimal cut off points of FGF-23 and sKL were 2 172.64 pg/mL (sensitivity was 91.3%, specificity was 91%) and 231.88 pg/mL (sensitivity was 88.8%, specificity was 92.5%), respectively. Conclusion: The high level of FGF-23 and low level of sKL are two independent risk factors for cardiac valve calcification in CAPD patients. FGF-23 and sKL can be used to diagnose cardiac valve calcification in CAPD patients.

Research on relationship of FGF-23 and sKL with cardiac valve calcification in CAPD patients / 上海交通大学学报（医学版）

Objective· To explore the relationship of fibroblast growth factor-23 (FGF-23) and soluble klotho (sKL) with cardiac valve calcification in patients with continuous ambulatory peritoneal dialysis (CAPD).Methods· 147 CAPD patients from the dialysis center of the First Affiliated Hospital of Soochow University were enrolled.The concentrations of FGF-23 and sKL were measured by enzyme-linked immunosorbent assays (ELISA).Echocardiography was applied to evaluate cardiac valve calcification.The patients were divided into normal cardiac valve group (group A) and cardiac valve calcification group (group B).SPSS 23.0 software was used for data analysis.Results· The incidence of cardiac valve calcification in CAPD patients was 54.42％.The risk of cardiac valve calcification showed positive correlation with age,dialysis age,serum creatinine,corrected calcium,serum phosphorus,serum alkaline phosphatase,parathyroid hormone,and the level of FGF-23 (P=0.045,P=0.022,P=0.006,P=0.024,P=0.000,P=0.017,P=0.022,P=0.000),and negative correlation with urea clearance index,the level of sKL and residual renal function (P=0.045,P=0.000,P=0.011).Multivariate Logistic regression analysis showed that the increase of FGF-23 (OR=5.007,95％ CI 1.446-17.339,P=0.011) and serum phosphorus (OR=7.433,95％ CI 1.558-35.470,P=0.012) were two independent risk factors for cardiac valve calcification in CAPD patients,and the decrease of sKL (OR=0.310,95％ CI 0.108-0.891,P=0.030) was another independent risk factor as well.Receiver operator characteristic curves (ROC) indicated that to predict cardiac valve calcification in patients with CAPD,the optimal cut off points of FGF-23 and sKL were 2 172.64 pg/mL (sensitivity was 91.3％,specificity was 91％) and 231.88 pg/mL (sensitivity was 88.8％,specificity was 92.5％),respectively.Conclusion· The high level of FGF-23 and low level of sKL are two independent risk factors for cardiac valve calcification in CAPD patients.FGF-23 and sKL can be used to diagnose cardiac valve calcification in CAPD patients.

Research progress of hypophoshatemic rickets / 国际儿科学杂志

Hypophosphatemic rickets is a disorder of renal tublular reabsorption of phosphorus,which resulting in bone dysplasia.It is characterized by hypophosphatemia,rickets and limb deformity.Hypophosphatemic rickets may be mainly due to congenital / genetic or secondary to the tumor and other renal tubular disease.Phosphorus is an important element in cell metabolism.Extracellular phosphorus ions maintain the phosphorus concentration at a low level by dietary absorption,kidney regulation and various phosphorus-regulating factors.With the development of molecular biological technologies,forms of renal phosphate wasting diseases have been identified in past years,and FGF23 plays an important role in the disease mechanism.This review aims to overview the studies of the treatment and physiopathology of hypophosphatemic rickets and to enhance the recognition of hypophosphatemic rickets.

Eje somatotrópico y marcadores moleculares del metabolismo mineral en niños en diálisis / Somatotropic axis and molecular markers of mineral metabolism in children undergoing chronic peritoneal dialysis

El retraso del crecimiento de los niños con enfermedad renal crónica es de origen multifactorial, incluyendo la resistencia a hormona de crecimiento (GH) y alteraciones en el metabolismo mineral óseo. Objetivos: 1) Caracterizar marcadores del metabolismo mineral: FGF23-Klotho y del eje somatotrópico: IGF1, IGFBP3 y GHBP, en niños en diálisis peritoneal (DP); 2) Evaluar la evolución de la talla en aquellos pacientes tratados con rhGH. Pacientes y Método: Niños prepuberales en DP seguidos durante 12 meses. Criterios exclusión fueron Tanner > 1, síndrome nefrótico activo, tratamiento esteroidal, malabsorción gastrointestinal, enfermedades endocrinas, síndromes genéticos, uso de rhGH al ingreso del estudio. Se evaluaron variables demográficas, antropométricas: Z talla/edad, (ZT/E), velocidad de crecimiento (VC), bioquímicas (calcio, fósforo, PTH), marcadores del metabolismo mineral (25OHvitD, 1,25OHvitD, FGF23, Klotho), y de crecimiento (IGF-1, IGFBP-3, GHBP). Resultados: Quince pacientes, 7 varones, edad 6,9 ± 3,0 años, tiempo en DP 14,33 ± 12,26 meses. Puntaje ZT/E al mes 1= -1,69 ± 1,03. FGF23: 131,7 ± 279,4 y Klotho: 125,9 ± 24,2 pg/ml. Durante los 12 meses de seguimiento no hubo diferencia significativa en el promedio de las variables. El uso de rhGH en 8 pacientes no mostró mejoría significativa del ZT/E ni la VC. El análisis bivariado mostró correlación positiva entre niveles de Klotho y delta ZT/E, y entre GHBP y VC (p < 0,05). Conclusiones: Los valores de FGF23 se encuentran elevados y los de Klotho disminuidos en niños con enfermedad renal crónica en DP en comparación con niños sanos. Las variables de eje somatotrópico, se encuentran normales o elevadas. rhGH tiende a mejorar la talla y GHBP se correlaciona positivamente con VC en estos niños.

Growth failure is one of the most relevant complications in children with chronic kidney disease (CKD). Among others, growth hormone (GH) resistance and bone mineral disorders have been identified as the most important causes of growth retardation. Objectives: 1. To characterize bone mineral metabolism and growth hormone bio-markers in CKD children treated with chronic peritoneal dialysis (PD). 2. To evaluate height change with rhGH treatment. Patients and Method: A longitudinal 12-month follow-up in prepuberal PD children. Exclusion criteria: Tanner stage >1, nephrotic syndrome, genetic disorders, steroids, intestinal absorption disorders, endocrine disturbances, treatment with GH to the entry of the study. Demographic and anthropometric data were registered. FGF23, Klotho, VitD, IGF-1, IGFBP3, and GHBP were measured to evaluate mineral and growth metabolism. Results: 15 patients, 7 male, age 6.9 ± 3.0 y were included. Time on PD was 14.33 ± 12.26 months. Height/age Z score at month 1 was -1.69 ± 1.03. FGF23 and Klotho: 131.7 ± 279.4 y 125.9 ± 24.2 pg/ml, respectively. 8 patients were treated with GH during 6-12 months, showing a non-significant increase in height/age Z-score during the treatment period. Bivariate analysis showed a positive correlation between Klotho and delta ZT/E, and between GHBP vs growth velocity index (p < .05). Conclusions: FGF23 values were high and Klotho values were reduced in children with CKD in PD, comparing to healthy children. Somatotropic axis variables were normal or elevated. rhGH tends to improve height and there is a positive correlation of GHBP and growth velocity in these children.

FGF23-Klotho and its correlation with abnormal bone metabolism / 中华检验医学杂志

Skeletal metabolic disorder refers to multi-factors caused by bone tissue calcium, phosphorus and other minerals,osteoblasts and(or)osteoclast dysfunction.The FGF23-Klotho axis plays an important role in the bone-kidney-parathyroid axis and is involved in the regulation of bone mineral metabolism.At the same time, FGF23-Klotho axis affects the synthesis and secretion of vitamin D and parathyroid hormone.With the deepening of research,the FGF23-Klotho axis is promising to be the target of diagnosis and treatment of bone metabolic disorders.

Effect of Qigui Ershen Granules on Serum FGF23 and Klotho Protein Levels in Carotid Atherosclerosis Patients / 广州中医药大学学报

Objective To observe the effect of Qi-strengthening and blood-activating Chinese patent medicine Qigui Ershen Granules on the carotid intima-media thickness(IMT ) , atheromatous plaque scores, serum fibroblast growth factor 23 (FGF23) and Klotho protein levels, and oxidation- and inflammation-associated indicators in carotid atherosclerosis patients. Methods Fifty-two carotid atherosclerosis patients were randomized into Chinese medicine group and western medicine group, 26 cases in each group. Chinese medicine group was treated with Qigui Ershen Granules orally, and western medicine group was treated with Atorvastatin Calcium Tablets orally. The mediation for the two groups lasted for 24 continuous weeks. Carotid ultrasonography was performed before and after treatment for the examination of carotid IMT and plaque Crouse scores. Double antibody sandwich enzyme-linked immunosorbent assay(ELISA) was applied for the detection of serum Klotho, FGF23, interleukin 1(IL-1) and tumor necrosis factorα(TNF-α) levels, and radio-immuno-precitation method was used for the assay of serum reactive oxygen species (ROS), malondialdehyde (MDA) and superoxide dismutase (SOD) levels. The clinical efficacy of the two groups was evaluated by the scores of Qi deficiency syndrome and blood stasis syndrome before and after treatment. Results (1) In western medicine group, 5 cases dropped out and were excluded, and a total of 21 cases completed the trial; in Chinese medicine group, 3 cases dropped out and were excluded, and a total of 23 cases completed the trial.(2) After treatment for 24 continuous weeks, IMT and Crouse scores of the plaque in the two groups were obviously reduced(P 0.05). (3) Serum Klotho protein level was increased while FGF23 was decreased in Chinese medicine group after treatment (P 0.05). The effects of Chinese medicine on increasing Klotho protein level and decreasing FGF23 level were superior to those of western medicine (P 0.05).(5) The scores of Qi deficiency syndrome and blood stasis syndrome in Chinese medicine were decreased after treatment (P 0.05). Chinese medicine group had better effect on improving the scores of Qi deficiency syndrome and blood stasis syndrome than western medicine group(P < 0.01).(6) After treatment, the total effective rate for improving Qi deficiency syndrome and blood stasis syndrome in Chinese medicine group was 82.61%, 78.26%, and that in western medicine group was 28.57%, 14.28%respectively, the difference being significant (P<0.01). Conclusion Qi-strengthening and blood-activating Qigui Ershen Granules have certain effects on counteracting atherosclerosis, inflammatory aging and oxidation.

Case report of tumour-induced osteomalacia with parotid gland tumour as a focus / Journal of the ASEAN Federation of Endocrine Societies

@#<p style="text-align: justify;">Tumour-induced osteomalacia (TIO) is a rare paraneoplastic syndrome, which is characterized by overproduction of FGF23 as a phosphaturic agent leading to chronic phosphaturia and hypophosphatemia, associated with inappropriately normal or low levels of vitamin D. We describe a rare case of a 57-year-old Indian female who presented with bone pains, muscle pains and lower limb weakness. On examination she was found to have hypophosphatemia. Our work up led to the identification of a FGF23 secreting parotid tumour. The tumour responsible for symptoms was a pleomorphic adenoma of the parotid gland. Its complete resection resulted in normalisation of patient's symptoms. Laboratory parameters and microsopic examination further revealed a mesenchymal tumour of mixed connective tissue type.</p>

Effects of high phosphorous intake and jump training on the developing rat tibia / 体力科学

The extensive use of food additives has increased the phosphorous content of the modern diet, while calcium intake has remained similar to past levels according to the national standards of nutrient intake. Although exercise increase bone mineral content, the intake of phosphorus may change the exercise effect. The purpose of this study was to examine the effects of jump exercise on bone and phosphate-calcium metabolism in rats consuming high levels of dietary phosphorous. Forty-two male Wistar rats aged 8 weeks were fed either a high-phosphorus diet with a 2.0 P/Ca ratio or a normal diet with a 1.0 P/Ca ratio. Rats from each dietary group were then further assigned to undergo 8 weeks of jump exercise or to be sedentary controls. Two-way analysis of variance (ANOVA) revealed that the bone mineral content (P<0.001), strength (P<0.001), transverse thickness (P<0.001), and longitudinal thickness (P<0.001) of the tibial diaphysis were increased by jump exercise in both dietary groups. The concentrations of serum inorganic phosphorus (P<0.001), FGF23 (P<0.001), and 1-25 (OH) vitamin D (P<0.001) were increased by a high phosphorus diet, and the concentrations of serum total calcium (P<0.05) and 1-25 (OH) vitamin D (P<0.05) were increased by jump exercise in both groups. In conclusion, exercise is important to increase bone mass and bone strength in a high phosphorus intake state.