title: Changing bone patterns with progression of chronic kidney disease.
abstract: It is commonly held that osteitis fibrosa and mixed uremic osteodystrophy are the predominant forms of renal osteodystrophy in patients with chronic kidney disease. Osteitis fibrosa is a high-turnover bone disease resulting mainly from secondary hyperparathyroidism, and mixed uremic osteodystrophy is in addition characterized by a mineralization defect most often attributed to vitamin D deficiency. However, there is ancient and more recent evidence that in early chronic kidney disease stages adynamic bone disease characterized by low bone turnover occurs first, at least in a significant proportion of patients. This could be due to the initial predominance of bone turnover-inhibitory conditions such as resistance to the action of parathyroid hormone (PTH), reduced calcitriol levels, sex hormone deficiency, diabetes, and, last but not least, uremic toxins leading to repression of osteocyte Wnt/β-catenin signaling and increased expression of Wnt antagonists such as sclerostin, Dickkopf-1, and sFRP4. The development of high-turnover bone disease would occur only later on, when serum PTH levels are able to overcome peripheral PTH resistance and the other inhibitory factors of bone formation. Whether FGF23 and Klotho play a direct role in the transition from low- to high-turnover bone disease or participate only indirectly via regulating PTH secretion remains to be seen.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (Inserm) Unité 1018, Centre de recherche en épidémiologie et santé des populations, Equipe 5, Villejuif; Paris-Sud University and University of Paris-Ouest, Versailles-Saint-Quentin-en-Yvelines; Paris, France. Electronic address: tilman.drueke@inserm.fr.
authors.forename: Tilman B
authors.initials: TB
authors.lastname: Drüeke
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (Inserm) Unité 1018, Centre de recherche en épidémiologie et santé des populations, Equipe 5, Villejuif; Paris-Sud University and University of Paris-Ouest, Versailles-Saint-Quentin-en-Yvelines; Paris, France; Division of Nephrology, Ambroise Paré Hospital, Assistance Publique Hôpitaux de Paris, Boulogne-Billancourt/Paris; University of Paris-Ouest, Versailles-Saint-Quentin-en-Yvelines; Paris, France.
authors.forename: Ziad A
authors.initials: ZA
authors.lastname: Massy
mesh_terms: D001842:Bone and Bones / Q000473:pathology; D012080:Chronic Kidney Disease-Mineral and Bone Disorder / Q000097:blood / Q000209:etiology* / Q000473:pathology; D000089703:Fibroblast Growth Factor-23; D006801:Humans; D051436:Renal Insufficiency, Chronic / Q000097:blood / Q000150:complications* / Q000473:pathology
keywords: CKD progression; PTH resistance; Wnt/β-catenin; adynamic bone disease; indoxyl sulfate; renal osteodystrophy; sclerostin; uremic toxins