This could result in a higher incidence of cardiovascular events, stroke, and is an important cause of mortality in CKD patients. Blood vessel calcifications can increase wall stiffness and pulse pressure, along with chronic hypertension. Vascular calcifications are an important complication and can lead to site-specific manifestations. Patients with ABD are likely to have an overly-suppressed PTH along with an inability to buffer calcium onto the bone leading to hypercalcemia. Proximal muscle and axial skeleton involvement point towards aluminum toxicity and the resulting osteomalacia. The higher incidence of fractures in these patients can also be attributed to the poor structural integrity of the bones in patients with ABD. This is seen in patients with adynamic bone disease who have bone pain as the predominant symptom. Low turnover states leading to defective mineralization and the inability to repair any ongoing damage, are more commonly symptomatic. It is not uncommon for patients with renal osteodystrophy to be asymptomatic, although some may present with bone pain or fractures. On the other hand, low bone turnover states have lower than normal PTH levels, which renders the bone incapable of integrating calcium into the new bone that is being formed.

High bone turnover states involving an increased PTH act through the RANK complex to activate more osteoclasts. Patients suffering from chronic kidney disease (CKD) have an accelerated disease process due to the alteration in levels of other factors like phosphate, calcium, and vitamin D along with PTH. The derangement in the levels of these factors mentioned, especially PTH, is the culprit in renal osteodystrophy. Osteoprotegerin is an osteoclastogenesis inhibitory factor and ultimately decrease bone resorption. This will increase serum calcium levels by increasing bone resorption. Interleukins like IL-1,6, tumor necrosis factor, and MIF-1 alpha also activate osteoclasts. In reality, this complex first activates osteoclasts precursor cells, which in turn provoke the gene transcription by nuclear factor kappa B leading to an increase in osteoclasts and bone resorption.įactors that stimulate the complex and aim to increase osteoclasts formation are PTH, vitamin D, and acidosis. The process begins with the resorption of bone by the osteoclasts, which are activated by osteoblasts through a RANK-RANK ligand complex and intricately regulated by several factors like PTH, vitamin D, osteoprotegerin (OPG), etc. Osteoblasts produce the organic matrix of the bone consisting of type 1 collagen along with other non-collagenous proteins like alkaline phosphatase and osteocalcin. The two main cells in this process are osteoclasts that cut down or resorb the bone and osteoblasts that build-up or form new bone. It is important to understand the ongoing bone remodeling that takes place and the elements involved in it to get a more complete picture of the pathophysiology of renal osteodystrophy. Other metals implicated include iron and cadmium.Īdynamic bone disease (ABD): The pathogenesis of adynamic bone disease mainly revolves around the suppression of PTH, leading to low bone turnover and inadequate bone mineralization but no accumulation of excess osteoid in contrast to osteomalacia. A defect in bone mineralization due to the dysfunctional osteoblast leads to an excess of accumulated bone matrix. Osteomalacia: Heavy metal intoxication, mainly aluminum, can lead to dysfunction of both osteoblasts and osteoclasts. The important factors that play a role in the pathogenesis are: Low bone turnover states: Diseases included here are mainly osteomalacia and dynamic bone disease, both seen in patients with end-stage renal disease (ESRD).

Along with the PTH level, secondary factors that play a role in the development of osteitis fibrosa include interleukins 1, 6, and TNF-alpha. The predominant histological bone pattern in renal osteodystrophy is osteitis fibrosa, which is a product of high bone turnover due to secondary hyperparathyroidism. Fibroblast growth factor 23: FGF-23 is responsible for decreasing phosphate levels in the body, and a decrease in FGF-23 can lead to secondary hyperparathyroidism.

Metabolic turnover definition