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Query: UMLS:C0005940 (bone disease)
 7,459 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Vitamin D is an important hormone for mineral homeostasis and the proper formation and maintenance of bone. In addition, vitamin D has broader functions in the body that expand its traditionally known role in mineral balance. In chronic renal failure, calcitriol deficiency contributes to the development and progression of secondary hyperparathyroidism, bone disorders, and altered mineral metabolism. Recent revelations of the broader role of vitamin D also suggest calcitriol deficiency may contribute to decreased cardiac and immune function in chronic renal failure patients. Research on vitamin D has led to a more complete understanding of the actions of vitamin D at the transcriptional level and with respect to the clinical use of vitamin D and its analogs to control parathyroid hormone overactivity and to replace the other D hormone-dependent actions in patients with renal failure. Limitations of vitamin D and its metabolites include hypercalcemia, hyperphosphatemia and suppression of bone turnover with the risk of adynamic bone disease. Vitamin D analogs may offer greater selectivity and potentially greater safety as compared to calcitriol because of their altered relative potency on calcium and phosphorus metabolism. This review focuses on the current understanding of the biological actions of vitamin D and its analogs and the rationale for treating patients with chronic renal failure.
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PMID:Update on vitamin D and its newer analogues: actions and rationale for treatment in chronic renal failure. 1263 80

Most patients with renal failure maintained on chronic dialysis have elevated parathyroid hormone (PTH) levels and PTH-mediated bone disease (secondary hyperparathyroidism [sHPT]). Elevated PTH production in this setting represents a progressive, exaggerated physiologic response to hypocalcemia by the parathyroid glands, and generalized growth of the parathyroids is an adaptive response to chronic stimulation. Effective medical strategies to reduce PTH secretion and PTH-mediated bone turnover in sHPT (eg, controlling hyperphosphatemia, normalizing serum calcium, and administering vitamin D analogs) has decreased the need for parathyroidectomy in recent years. However, failure of medical therapy because of inadequate treatment, persistent hyperphosphatemia, or acquired parathyroid neoplasia still leads to recommendations for parathyroidectomy in select patients. Furthermore, increased awareness of potential long-term, irreversible cardiovascular effects of uncorrected hyperparathyroidism has led some to advocate parathyroidectomy earlier in the course of this disease. This monograph will review parathyroidectomy for secondary and tertiary hyperparathyroidism.
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PMID:Surgical management of secondary hyperparathyroidism. 1220 3

Bone disease develops relatively early in the development of chronic renal failure. Much of what is known about the evaluation and management of renal osteodystrophy in chronic renal failure is based on knowledge obtained in the dialysis population. The classic bone lesion found in the dialysis population is osteitis fibrosa, the high turnover lesion of secondary hyperparathyroidism. Clearly, hypocalcemia, hyperphosphatemia, and calcitriol deficiency play major roles in the development and maintenance of the high turnover disease. Interestingly, in both the dialysis and nondialysis patients, the incidence of adynamic bone disease, a low turnover lesion, is increasing. It is postulated that the aggressive use of calcium-containing phosphate binders and the use of calcitriol and other vitamin D analogs to treat secondary hyperparathyroidism may contribute to this shift in bone lesions. Treatment in the nondialysis kidney disease patient remains aggressive correction of hypocalcemia and hyperphosphatemia. The use of calcitriol and other agents to maintain serum calcium and to suppress elevated parathyroid hormone remains well supported. However, the increase in extraskeletal calcifications and incidence of adynamic bone disease in these patients raises concern about current management techniques.
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PMID:Renal osteodystrophy in chronic renal failure. 1243 93

Musculoskeletal problems remain among the main limitations of the quality of life of renal failure patients, in particular of those treated with long-term maintenance dialysis. Renal osteodystrophy continues to receive great attention. The mechanisms of uremic skeletal resistance to parathormone (PTH) are further investigated. The assay used for the dosage of "intact PTH" has been found to detect 7-84 fragments with an inhibitory effect on the action of the whole hormone. A decrease in the density of PTH receptor on osteoblasts is another recently evidenced factor. Investigations of the recently described RANK-RANKL system have demonstrated an increase in serum osteprotegerin levels, which, together with the two above-mentioned abnormalities, may explain bone resistance to PTH. These are important advances in the understanding of renal osteodystrophy as skeletal resistance to PTH appears to play an important part in the pathophysiology of secondary hyperparathyroidism and of adynamic bone disease. Because of this skeletal resistance, it has been recommended for several years that serum PTH level be monitored and kept twofold to threefold above the upper value of the normal level to maintain normal bone turnover in dialysis patients. Relative hypoparathyroidism has recently been found to be associated with increased spontaneous fracture rate and mortality, so this recommendation appears to hold adequate, despite the demonstration that serum PTH levels in this range are a poor predictor of bone turnover and that chronic parathyroid gland hyperplasia is likely to favor parathyroid gland autonomization. Recent publications have insisted on the role that hyperphosphatemia plays not only in the development of secondary hyperparathyroidism, but also of vascular, especially coronary, calcification and as a predictor of mortality. This "silent killer" of uremic patients is one of the main targets for therapeutic intervention. Extensive use of calcium-containing phosphate binders has been recently criticized as calcium overload appears to favor vascular calcification. Sevelaner (RenaGel) is a calcium- and aluminum-free phosphate binder that is an important advance in the management of renal osteodystrophy, especially in patients with extraskeletal calcification and hypercalcemia. The use of vitamin D derivatives has also raised concern because they enhance calcium and phosphorus absorption and reduce bone turnover. New metabolites with fewer hypercalcemic effects have been developed. Calcium-sensing receptor agonists are stimulating interest and are likely to take an important place in the future management of renal osteodystrophy. Uremic myopathy has received recent attention. Impaired muscle capillary oxygen transfer has been identified as a pathophysiologic factor, and progressive resistance training has been shown to improve the condition. Finally, a new entity, nephrogenic fibrosing dermopathy, has been described, which must be distinguished from calciphylaxis and scleromyxedema.
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PMID:Musculoskeletal manifestations of chronic renal failure. 1249 10

Hyperphosphataemia is prevalent among chronic renal failure and dialysis patients. It is known to stimulate parathyroid hormone and suppress vitamin D3 production, thereby inducing hyperparathyroid bone disease. In addition, it may independently contribute to cardiac causes of death through increased myocardial calcification and enhanced vascular calcification. Hyperphosphataemia is also associated with cardiac microcirculatory abnormalities. Therefore, phosphate control is of prime importance. It is important to control phosphate levels early in the course of chronic renal failure in order to avoid and treat secondary hyperparathyroidism, and cardiovascular and soft tissue calcifications. Dietetic restrictions are often difficult to follow long term. Because of its large sphere of hydration and the complex kinetics of phosphate elimination, phosphate is not easily removed by dialysis. Long, slow dialysis may be effective, but this needs logistics and acceptance by patients. Thus, oral phosphate binders are generally required to control serum levels. None of the existing phosphate binding agents is truly satisfactory. Aluminium-containing agents are highly efficient but many clinicians have abandoned their use because of the potential toxicity. Despite of the wide use of calcium-containing agents, there was a link with hypercalcaemia and soft tissue calcifications. Novel phosphate binders in the form of polyallylamine hydrochloride, polyuronic acid derivatives and lanthanum carbonate appear promising. In this review, we discuss causes of hyperphosphataemia, pathological consequences and modalities of treatment.
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PMID:Hyperphosphataemia in renal failure: causes, consequences and current management. 1265 55

An adynamic bone disorder (ABD) is an important complication of chronic kidney disease (CKD) of unknown etiology for which there is no adequate treatment. Reported is an animal model of ablative CKD complicated by an ABD characterized by the absence of secondary hyperparathyroidism and its successful treatment with a skeletal anabolic factor, bone morphogenetic protein-7 (BMP-7). Adult mice were subjected to electrocautery of the right kidney followed by left nephrectomy. Animals were randomized into groups fed normal chow or fed low-phosphate chow supplemented with calcitriol to maintain normophosphatemia in CKD. All groups were maintained on the regimens for 12 wk. Hyperphosphatemia, secondary hyperparathyroidism, and a mild osteodystrophy developed in the CKD/chow-fed group, as expected. When dietary phosphorus was restricted and calcitriol was administered in the CKD low-phosphate/calcitriol group (ABD), Ca, PO(4), and parathyroid hormone levels were maintained normal. A significant ABD developed in the ABD group characterized by significant depressions in osteoblast number, perimeters, bone formation rates, and mineral apposition rates when compared with the sham-operated, chow-fed group. The abnormal skeletal histomorphometry was reversed by BMP-7 therapy to normal values and significantly improved from the ABD group (P < 0.05). The sham-operated low-phosphate/calcitriol-fed control group and the CKD low-phosphate/calcitriol/BMP-7 groups had reduced phosphate levels compared with the other groups (P < 0.05). ABD produced in mice with CKD in the absence of hyperparathyroidism was successfully reversed with a bone anabolic, BMP-7, associated with a reduction in plasma phosphorus.
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PMID:Successful treatment of an adynamic bone disorder with bone morphogenetic protein-7 in a renal ablation model. 1474 82

Paricalcitol [Zemplar: Abbott Laboratories, Abbott Park, IL, U.S.A.] is efficient for treating secondary hyperparathyroidism in patients on maintenance hemodialysis (HD). Zemplar is thought to be more potent than calcitriol and has been reported to cause less hypercalcemia and hyperphosphatemia. Here, we report a 1-year follow-up on patients from one inner-city dialysis unit. We reviewed the charts of 100 patients and collected data for 1 year. Patients were stratified into four groups depending upon their intact parathormone (iPTH) levels. Hemoglobin (Hb) and erythropoietin (EPO) doses were determined. More than 50% of patients had iPTH levels greater than 300 pg/mL. Mean Ca and PO4 levels were not significantly different, but Zemplar doses were significantly different in all groups. None of the patients had symptomatic bone disease. Seven patients were changed to low-Ca dialysate (1.0 mEq/L) secondary to hypercalcemia (Ca > 11.5 mg/dL) and severe secondary hyperparathyroidism. Interestingly, patients with low iPTH (< 100 pg/microL) showed relative EPO resistance, and patients with high iPTH (> 600 pg/microL) required smaller EPO doses. An inverse relationship was observed between Zemplar and EPO dose. The effect of Zemplar on EPO responsiveness needs to be confirmed in a larger study. Our data suggest that severe secondary hyperparathyroidism is frequent despite aggressive paricalcitol therapy in our inner-city HD population. To control severe secondary hyperparathyroidism in these patients, dietary and medication compliance may need to be supplemented with more effective non-calcium phosphate binders or calcimimetic agents, or both.
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PMID:Severe hyperparathyroidism despite paricalcitol therapy: one-year follow-up. 1476 69

Phosphorus control remains a relevant clinical problem in dialysis patients. With age, however, serum phosphorus level decreases significantly because of a spontaneous decrease in protein intake. Older patients usually need lower doses of phosphorus binders. Nevertheless, hyperphosphataemia is observed in a quarter of patients aged >65 years. Phosphorus retention is related to an imbalance between phosphorus intake and removal by dialysis, and is usually aggravated when vitamin D analogues are employed. Hyperphosphataemia induces secondary hyperparathyroidism and the development of osteitis fibrosa. Recent publications describe an association between phosphorus retention and increased calcium and phosphorus product (Ca2+ x P), with significant progression of tissue calcification and higher mortality risk. Dietary intervention, phosphorus removal during dialysis and phosphorus binders are current methods for the management of hyperphosphataemia. However, the phosphorus removed by standard haemodialysis is insufficient to achieve a neutral phosphorus balance when protein intake is >50 g/day. Additional protein restriction may impose the risk of a negative protein balance. More frequent dialysis may help to control resistant hyperphosphataemia. Phosphorus binders constitute the mainstay of serum phosphorus level control in end-stage renal disease patients. Aluminium-based phosphorus binders, associated with toxic effects, have largely been substituted by calcium-based phosphorus binders. However, widespread use of calcium-based phosphorus binders has evidenced the frequent appearance of hypercalcaemia and long-term progressive cardiovascular calcification. Sevelamer, a relatively new phosphorus binder, has proved efficacious in lowering serum phosphorus and parathyroid hormone (PTH) levels without inducing hypercalcaemia. Furthermore, several investigators have reported that sevelamer may prevent progression of coronary calcification. However, its efficacy in severe cases of hyperphosphataemia remains to be confirmed in large series. There are no specific guidelines for phosphorus control in the elderly. Until more information is available, levels of mineral metabolites should be targeted in the same range as those recommended for the general population on dialysis (calcium 8.7-10.2 mg/dL, phosphorus 3.5-5.5 mg/dL and Ca2+ x P 50-55 mg2/dL2). PTH values over 120 ng/L help to avoid adynamic bone disease. Since elderly patients have a higher incidence of adynamic bone (which buffers less calcium) and vascular calcification, sevelamer should be the phosphorus binder of choice in this population; but sevelamer is costly and its long-term efficacy has not been definitively validated. Patients with low normal levels of calcium may receive calcium-based phosphorus binders with little risk. Patients with low values of PTH and high normal calcium should receive sevelamer. Tailored combinations of calcium-based phosphorus binders and sevelamer should be considered, and calcium dialysate concentration adjusted accordingly.
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PMID:Management of hyperphosphataemia in dialysis patients: role of phosphate binders in the elderly. 1497 34

Secondary hyperparathyroidism, a characteristic manifestation of chronic kidney disease (CKD), arises from a series of abnormalities in the interrelated cascade that controls bone and mineral metabolism. Although bone disease is the most recognized consequence of secondary hyperparathyroidism (HPT), it also precipitates a series of potentially devastating effects on the cardiovascular, nervous, endocrine, and erythropoietic systems. Optimal management of secondary hyperparathyroidism should allow control of serum parathyroid hormone levels while preventing hyperphosphatemia, maintaining normal calcium levels, and providing adequate vitamin D supplementation. Current therapeutic approaches are frequently unsuccessful in achieving these goals and may, in fact, exacerbate risk factors that increase morbidity and mortality in the dialysis population. Development of new therapeutic approaches may provide improved control of secondary hyperparathyroidism in the future.
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PMID:Secondary hyperparathyroidism in chronic kidney disease: clinical consequences and challenges. 1511 99

Hyperphosphatemia is associated with soft-tissue calcification and bone disease. Nephrologists prescribe phosphate binders to decrease dietary phosphate absorption, reduce serum phosphorus concentrations, and minimize the risk for soft-tissue calcification and bone disease. Recent data suggest that the dose of calcium used as a phosphate binder may contribute to the risk for cardiovascular calcification. Chronic positive calcium balance from diet, dialysis, and calcium-based phosphate binders or intermittent hypercalcemia may favor precipitation of calcium and phosphate into tissues. Calcium suppresses parathyroid hormone (PTH) secretion and bone turnover, limiting the ability of bone to incorporate calcium and phosphorus. Sevelamer, a non-absorbed polymer, allows physicians to bind dietary phosphate and decrease serum phosphorus without unwanted absorption of metals or calcium or over-suppression of PTH. In a comparative trial, calcium-based phosphate binders were associated with progressive coronary artery and aortic calcification that was attenuated by sevelamer. The optimal phosphate binder is one that controls hyperphosphatemia prevents soft-tissue calcification and preserves bone health.
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PMID:Arterial calcification in chronic kidney disease. 1549 Mar 99


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