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Pediatric renal osteodystrophy is characterized by skeletal mineralization defects, but the role of osteoblast and osteocyte maturation in the pathogenesis of these defects is unknown. We evaluated markers of osteocyte maturation and programmed cell death in iliac crest biopsy samples from pediatric dialysis patients and healthy controls. We evaluated the relationship between numbers of fibroblast growth factor 23 (FGF23)-expressing osteocytes and histomorphometric parameters of skeletal mineralization. We confirmed that chronic kidney disease (CKD) causes intrinsic changes in bone cell maturation using an in vitro model of primary osteoblasts from patients with CKD and healthy controls. FGF23 co-localized with the early osteocyte marker E11/gp38, suggesting that FGF23 is a marker of early osteocyte maturation. Increased numbers of early osteocytes and decreased osteocyte apoptosis characterized CKD bone. Numbers of FGF23-expressing osteocytes were highest in patients with preserved skeletal mineralization indices, and packets of matrix surrounding FGF23-expressing osteocytes appeared to have entered secondary mineralization. Primary osteoblasts from patients with CKD retained impaired maturation and mineralization characteristics in vitro. Addition of FGF23 did not affect primary osteoblast mineralization. Thus, CKD is associated with intrinsic changes in osteoblast and osteocyte maturation, and FGF23 appears to mark a relatively early stage in osteocyte maturation. Improved control of renal osteodystrophy and FGF23 excess will require further investigation into the pathogenesis of CKD-mediated osteoblast and osteocyte maturation failure., (Copyright © 2018 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Osteocytes regulate bone turnover and mineralization in chronic kidney disease. As osteocytes are derived from osteoblasts, alterations in osteoblast function may regulate osteoblast maturation, osteocytic transition, bone turnover, and skeletal mineralization. Thus, primary osteoblast-like cells were cultured from bone chips obtained from 24 pediatric ESKD patients. RNA expression in cultured cells was compared with RNA expression in cells from healthy individuals, to RNA expression in the bone core itself, and to parameters of bone histomorphometry. Proliferation and mineralization rates of patient cells were compared with rates in healthy control cells. Associations were observed between bone osteoid accumulation, as assessed by bone histomorphometry, and bone core RNA expression of osterix, matrix gla protein, parathyroid hormone receptor 1, and RANKL. Gene expression of osteoblast markers was increased in cells from ESKD patients and signaling genes including Cyp24A1, Cyp27B1, VDR, and NHERF1 correlated between cells and bone cores. Cells from patients with high turnover renal osteodystrophy proliferated more rapidly and mineralized more slowly than did cells from healthy controls. Thus, primary osteoblasts obtained from patients with ESKD retain changes in gene expression ex vivo that are also observed in bone core specimens. Evaluation of these cells in vitro may provide further insights into the abnormal bone biology that persists, despite current therapies, in patients with ESKD.

Background: The authors review the pathophysiology, epidemiology, course of disease, dental findings and dental treatment of patients who developed atherosclerosis of the carotid artery after having received therapeutic radiation to the neck for squamous-cell carcinoma of the oral cavity, pharynx or larynx; salivary gland tumors; and lymphomas involving the cervical lymph nodes., Type of Studies Reviewed: The authors conducted a MEDLINE search for 1997 through 2002 using the key terms "radiation therapy," "carotid artery" "atherosclerosis," "cancer" and "dentistry." The articles selected for further review included those published in English in peer-reviewed journals, with preference given to articles reporting randomized, controlled trials., Results: Recent advances in the delivery of radiation therapy to malignancies of the head and neck have resulted in the prolonged survival of increasing numbers of patients. However, the therapy has been implicated as causing atherosclerotic lesions in the cervical component of the carotid artery, which predisposes patients to an increased risk of developing stroke. Panoramic radiography can identify some of these lesions before they can cause a stroke. Radiation-induced atherosclerosis is common, with approximately 40 percent of patients developing hemodynamically significant carotid artery plaques within 10 years of having received irradiation., Clinical Implications: Dentists treating patients who have received therapeutic radiation to the neck should examine the patients' panoramic radiographs for evidence of atheromalike calcifications, which appear 1.5 to 2.5 centimeters posterior and inferior to the angle of the mandible. Patients with evidence of such lesions should be referred to their physician for an ultrasound examination of their carotid arteries.

Therapeutic irradiation of the neck is frequently used to treat patients with head and neck carcinoma. The irradiation, however, has been implicated as the cause of cervical carotid artery atherosclerotic lesions and subsequent stroke. Panoramic radiography previously shown capable of demonstrating isolated lesions was used to assess their development over time. Individuals with a pre-irradiation radiograph free of atheromas were enrolled for study. The prevalence rate of atheroma formation on post-irradiation (bilateral portals at >/=45 Gy) radiographs obtained at an interval of >/=36 months was determined. A control group of non-irradiated patients having similar risk factors for head and neck carcinoma and atherosclerosis and having an initial radiograph free of atheroma formation were likewise enrolled for study. The prevalence rate of atheroma formation on a second radiograph obtained from these individuals at an interval of >/=36 months was determined. The study population consisted of 17 patients, with a mean age of 56.5 (range 21.5-77.8) years who received a mean therapeutic irradiation dose of 53.2 Gy (range 45-71) to each side of their neck. The prevalence rate of atheromas manifested on the post-irradiation radiographs was 53%. These radiographs were obtained, on average, 69.7 (range 37-133) months after completion of radiation therapy. The prevalence rate of atheromas manifested on the second radiograph of patients in the control group was 5.9%. These radiographs were obtained, on average, 53.5 (range 52-55) months after the first. The difference in prevalence rates was statistically significant (p=0.0003). Individuals who have received therapeutic irradiation to the neck are more likely to develop carotid artery atheromas after treatment than are risk-matched control patients who have not been irradiated. These lesions can be detected by panoramic radiography.