Abstract
Patients with β-thalassemia have an increased risk of developing chronic kidney disease which is associated with osteoporosis and periodontitis. The purpose of this study was to evaluate mandibular and femoral bone change in heterozygous β-globin knockout (BKO) mice following 5/6 nephrectomy (Nx). Female and male BKO mouse blood smears demonstrated microcytic hypochromic anemia. Serum urea nitrogen, creatinine, calcium, and phosphorus levels were not changed in BKO mice. Nx increased the serum levels of urea nitrogen in both wild type (WT) and BKO mice and the level was much higher in BKO males. Serum level of creatinine was increased in Nx WT but not BKO mice. However, serum calcium and phosphorus levels were not altered. Nx induced comparable renal fibrosis in BKO mice and WT controls. Bone loss was observed in mandibular cancellous bone but not cortical bone of both male and female BKO mice. Nx decreased cancellous bone volume and cortical thickness in WT. Interestingly, BKO mice were resistant to Nx-induced cancellous bone loss. However, cortical thickness and cortical bone mineral density were reduced in Nx male BKO mice. Nx increased mRNA levels of type I collagen, Osx and Trap in WT but not BKO mice. Similarly, Nx reduced cancellous bone volume in femurs and increased osteoblast number and osteoclast number in WT not BKO mice. Serum FGF23 and erythropoietin levels were markedly increased in BKO mice. Nx decreased serum erythropoietin but not FGF23 levels. Since WT treated with erythropoietin exhibited a significant reduction in cancellous bone volume, it was possible that lower level of erythropoietin in Nx BKO mice prevented the Nx-induced cancellous bone loss.
Highlights
Β-thalassemia is an inherited disorder of hemoglobin synthesis in which point mutations of the β-globin gene cause defective β-chain production leading to an imbalance in α- and β-globin chain synthesis. β-thalassemia is characterized by ineffective erythropoiesis, hemolysis, splenomegaly, iron overload, anemia, growth retardation, frontal bossing with the early signs of abnormal thalassemic facies and skeletal deformity[1]
Red blood cell (RBC), hemoglobin (Hb), hematocrit (Hct), and mean corpuscular hemoglobin (MCH) values were lower, whereas red cell distribution width-coefficient of variation (RDW-CV) and red cell distribution width-standard deviation (RDW-SD) were higher in sham bone change in heterozygous β-globin knockout (BKO) mice compared to wild type (WT) controls of both genders
red blood cell (RBC) and Hb levels were decreased in female Nx WT and BKO compared to their corresponding controls
Summary
Β-thalassemia is an inherited disorder of hemoglobin synthesis in which point mutations of the β-globin gene cause defective β-chain production leading to an imbalance in α- and β-globin chain synthesis. β-thalassemia is characterized by ineffective erythropoiesis, hemolysis, splenomegaly, iron overload, anemia, growth retardation, frontal bossing with the early signs of abnormal thalassemic facies and skeletal deformity[1]. Patients with β-thalassemia major present in the first year of life with profound anemia and subsequently require regular blood transfusions and iron chelation therapy for survival and end-organ damage prevention. In β-thalassemia patients, chronic anemia, iron overload from long-term blood transfusions, and specific iron chelation therapy are associated with renal impairment. CKD-MBD causes altered bone remodeling and bone loss throughout the skeleton and is associated with increased morbidity and mortality[5]. These patients have a high risk of bone fracture due to their low bone mineral density[6]. Several studies have reported increases in prevalence and severity of periodontal diseases, including gingivitis, and periodontitis in patients with CKD10,11
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