Adynamic bone disease

It is important to monitor vitamin D therapy aggressively to assure that PTH levels are not oversuppressed. Oversuppression of PTH levels can induce adynamic bone disease, which manifests as decreased osteoblast and osteoclast activity, decreased bone formation, and low bone turnover. 

ROD progresses insidiously for several years before the onset of symptoms such as bone pain and fractures. Skeletal complications include osteitis fibrosa cystica (high bone turnover), osteomalacia (low bone turnover) and adynamic bone disease. When ROD symptoms appear, the disease is not easily amenable to treatment. 

A less common circumstance leading to hypercalcemia is development of a form of bone disease characterized by a profound decrease in bone cell activity and loss of the calcium buffering action of bone (adynamic bone disease). In the absence of kidney function, any calcium absorbed from the intestine accumulates in the blood. Therefore, such patients are very sensitive to the hypercalcemic action of l,25(OH)2D. These individuals generally have a high serum calcium but... 

Much clinical and experimental experience has been obtained about the manifestation of bone diseases, especially in renal patients. Many patients with Al-induced bone disease remain asymptomatic. There are two distinct forms of Al bone disease. The most severe form is osteomalacia, with recurrent fractures and resistance to vitamin D therapy. This disease is characterized by an increase of osteoid due to a mineralization defect induced by Al that is localized at a critical site in the bone, i.e., the osteoid calcification front [250]. The adynamic bone disease is another form of Al-related bone disease, characterized by a reduced bone turnover [97]. Al can have a direct negative effect on the bone by deposition at the mineralization front, causing a defective calcification. This is due to the influence of Al on calcium-phosphorus precipitation, crystal formation and crystal growth [251]. There might also be a toxic effect on the proliferation of osteoblasts and on mature osteoblasts with a time- and dose-dependent effect on osteoblast growth and function [143]. 

Moriniere P, Cohen-Solal M, Belbrik S, Boudailliez B, Marie A, Westeel PF, Renaud H, Fievet P, Lalau JD, Sebert JL, et al. Disappearance of aluminic bone disease in a long term asymptomatic dialysis population restricting A1(0H)3 intake emergence of an idiopathic adynamic bone disease not related to aluminum. Nephron 1989 53(2) 93-101. 

Recent research on the speciation and protein binding characteristics of aluminum has led to a better insight in the mechanisms underlying the element s tissue distribution and toxicity [33,34]. In this context, the provocative hypothesis linking the widespread use of erythropoietin to the increasing prevalence of adynamic bone disease is of particular interest [35]. 

Low-turnover bone diseases include osteomalacia and adynamic (also known as aplastic) bone diseases. Osteomalacia and adynamic bone disease are distinguished by the extent of unmineralized bone matrix or osteoid osteoid is increased in osteomalacia and normal or low in adynamic bone disease. Osteomalacia in chronic renal failure may reflect vitamin D deficiency because of the decreased renal synthesis of l,25(OH)2D (see Osteomalacia and Rickets) or aluminum-related disease. In the 1970s and 1980s, aluminum intoxication was a significant contributing factor to the development of osteomalacia and adynamic bone... 

Renal osteodystrophy (ROD)—The condition resulting from sustained metabolic changes that occur with chronic kidney disease including secondary hyperparathyroidism, hyperphosphatemia, hypocalcemia, and vitamin D deficiency. The skeletal complications associated with ROD include osteitis fibrosa cystica (high bone turnover disease), osteomalacia (low bone turnover disease), adynamic bone disease, and mixed bone disorders. 

As patients live longer with dialysis treatment, they begin to develop yet another set of problems related to dialysis itself, and to the chronic accumulation of endogenous compounds (p2-microglobulin) and exogenous toxins (aluminum). P2-Microglobulin causes dialysis amyloidosis with the carpal tunnel syndrome and destructive arthropathy. Aluminum causes anemia, osteomalacia or adynamic bone disease, and encephalopathy. 

Hypocalcemia can be diminished by initiating therapy with a low dose and gradually titrating it as necessary or adjusting the dose when vitamin D and/or phosphate binders are admiiustered concomitantly. Patients on hemodialysis with low-calcium dialysate need to be monitored closely for hypocalcemia. Seizure threshold is lowered by significant reductions in serum Ca +, so patients with a history of seizure disorders should be monitored especially closely. Finally, adynamic bone disease may develop if the PTH level is less than 100 pg/mL, and the drug should be discontinued or the dose decreased if the PTH level falls below 150 pg/mL. 

In humans, Al is associated with a low-turnover osteomalacia and an adynamic bone disease. Both are associated with elevated bone Al, but different bone Al distribution (Nieboer et al. 1995). The potential for Al to cause neurotoxicity, which manifests as impaired motor and cognitive performance, has been well established in animals and humans (Cory-Slechta 1996, Yokel... 

Bone disease is a frequent consequence of chronic renal failure and dialysis. Pathologically, the lesions are typical of hyperparathyroidism, adynamic bone disease, deficiency of vitamin D (osteomalacia), or a combination of the above. The underlying defect reflects increased phosphate and decreased calcium, leading to secondary events that strive to preserve circulating levels of Ca at the expense of bone. 

The term chronic kidney disease-mineral and bone disorder (CKD-MBD) was introduced in a position statement by the Kidney Disease Foundation. According to the guidelines, CKD-MBD is a systemic disorder and patients with vascular or valvular calcification should be included in the group with the greatest cardiovascular risk. Therefore, the presence or absence of calcification is a key factor in strategy decisions for such patients. In particular, it is recommended that the use of calcium-based phosphate binders should be restricted in patients with hypercalcaemia, vascular calcification, low levels of parathyroid hormone or adynamic bone disease. 

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