Ayse Kubat Uzum, Serpil Salman, Aysegul Telci, Harika Boztepe, Refik Tanakol, Faruk Alagol and Nese Colak Ozbey
Fibroblast growth factor 23 (FGF23), a phosphatonin, inhibits renal phosphate reabsorption and suppresses 1-α hydroxylase activity. Calcitriol stimulates FGF23 synthesis in bone. We aimed to determine the effect of vitamin D replacement therapy on serum FGF23 concentrations in vitamin D-deficient women and to compare the FGF23 concentrations of vitamin D-deficient patients with healthy subjects and patients with genetically determined hypophosphatemic rachitis.
Design and methods
The study group was composed of vitamin D-deficient females (n=18, mean age 29.1±9.9 years), vitamin D-sufficient healthy females (control group; n=19, mean age 28.5±5.2 years), and patients with genetically determined hypophosphatemic rachitis (n=13, mean age 26.5±15.1 years). The groups were compared for serum FGF23, 1,25-dihydroxyvitamin D3 (1,25(OH)2D), calcium, phosphate, bone turnover markers, intact parathyroid hormone (PTH), and urinary excretion of calcium and phosphate. The vitamin D-deficient group was re-evaluated after a standard treatment regimen.
Serum FGF23 concentrations were significantly lower in vitamin D-deficient patients than in vitamin D-sufficient women and hypophosphatemic rachitis group. Serum FGF23 and phosphate concentrations further decreased significantly during replacement of vitamin D (P<0.05). A significant negative correlation was evident between FGF23 and PTH before vitamin D replacement in the patients (r=−0.469, P<0.05).
Decreased FGF23 concentrations, which further decline during vitamin D replacement therapy, may have favorable action on bone mineralization by counterregulatory effect on phosphate homeostasis. Lower 1,25(OH)2D concentrations at baseline and hypophosphatemia during treatment may have dominating effects on FGF23 concentrations in vitamin D deficiency, leading to decreased FGF23 concentrations at baseline and during replacement therapy.
Fatma Sen, Mustafa Demirturk, Neslihan Abaci, Ebru Golcuk, Huseyin Oflaz, Ali Elitok, Faruk Kutluturk, Halim Issever, Nihan Erginel Unaltuna and Nese Colak Ozbey
Endothelial nitric oxide synthase (eNOS) intron 4a/b polymorphism is associated with plasma NO concentrations and coronary artery disease/hypertension in various populations. GH deficiency in adulthood predisposes to reduced NO concentrations and premature atherosclerosis. Our aim was to determine whether intron 4a/b polymorphism of eNOS gene influences endothelial function and early atherosclerotic changes in GH-deficient hypopituitary patients.
Thirty-three hypopituitary GH-deficient patients on conventional replacement therapy other than GH and 43 age-, sex-, and body mass index (BMI)-matched controls were studied in this cross-sectional case–control study.
Early atherosclerotic changes were determined by flow-mediated dilation (FMD) of brachial artery and carotid artery intima-media thickness (IMT). eNOS4a/b polymorphism was detected by PCR.
Hypopituitary patients had significantly higher total/low-density lipoprotein cholesterol and fat mass and lower IGF-I concentrations compared with controls. IMT was significantly higher in patients (0.777±0.23 vs 0.639±0.17 mm, P<0.01). No significant difference was observed with respect to FMD measurements. eNOS4a/b genotype frequencies were similar between patients and controls. Patients carrying ‘a’ allele (a/a and a/b) had significantly higher IMT compared with controls carrying ‘a’ allele and bb genotype (P<0.05). However, logistic regression analysis revealed that presence of hypopituitarism, age≥45 years, and BMI≥27.9 kg/m2 were significant independent predictors of IMT≥0.65 mm.
No compelling data are evident to suggest that eNOS4a/b polymorphism modifies the atherosclerotic process in GH-deficient situations. A large case–control study is needed to confirm our findings.