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

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

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

We present the case of a 55-year-old patient who underwent total parathyroidectomy for severe hyperparathyroidism unresponsive to medical therapy, 4 years after having started hemodialysis treatment. It was decided to perform total parathyroidectomy because at macroscopic evaluation the parathyroid glands appeared completely compromised. After surgery, the patient developed hungry bone disease, characterized by severe hypocalcemia and hypophosphatemia. After parathyroidectomy, serial measurements were made for the long-term monitoring of the calcemia, phosphatemia and the serum levels of intact parathormone and bone alkaline phosphatase, a marker of bone turnover that mainly expresses bone formation. There was initially a slight decrease in the circulating levels of bone alkaline phosphatase as the calcemia dropped dramatically, then a new increase that anticipated the subsequent calcemia increase and finally, 6 months later, a decrease to very low values. We believe that the calcemia and blood bone alkaline phosphatase could be useful for the laboratory monitoring of the hungry bone state, providing information which may be useful to avoid excessive calcium administration and the dangerous consequences such as soft-tissue calcification.
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PMID:Kinetics of the circulating levels of bone alkaline phosphatase in a case of hungry bone disease following total parathyroidectomy. 1552 40

Prevention and treatment of renal osteodystrophy (ROD) are great challenges for pediatric nephrologists. The strategies for prevention and treatment of ROD in children with chronic renal failure (CRF) should be created on an individual basis. The following factors should be considered: age, type of primary disease, rate of progression of CRF, nutrition, acidosis, type of dialysis, and drugs (corticosteroids, growth hormone, etc). The treatment should start very early in the course of renal insufficiency with close monitoring of serum calcium, phosphate, alkaline phosphatase and parathormone (PTH) levels. Maintenance of serum phosphate within age- appropriate limits is essential for prevention of secondary hyperparathyroidism. PTH levels should be kept within normal limits in predialysis children and 2-3 times over upper normal limit in those on dialysis. Aggressive treatment with calcium-based phosphate binders and vitamin D derivates should be avoided to prevent PTH oversuppression and development of adynamic bone disease. The advantage in this respect is the development of calcium- and aluminum-free phosphate binders, of which there is limited pediatric experience with sevelamer hydrochloride. Paricalcitol is a non-hypercalcemic vitamin D analogue, and preliminary favorable experience has been reported in children. Calcimimetics like cinacalcet hydrochloride, which directly stimulate calcium sensing receptor and potently suppress PTH secretion without increasing plasma calcium in adults, are very promising agents, but pediatric experience is lacking.
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PMID:Management of renal osteodystrophy in children. 1588 62

Skeletal involvement in chronic kidney disease manifests long before the initiation of dialysis. This study aimed at identifying the extent of renal bone disease among predialysis and on maintenance dialysis patients. Thirty-two patients (Group 1) on maintenance hemodialysis (MHD) for a variable period of time were compared with 20 newly detected irregularly treated advanced renal failure (immediately predialysis), patients (Group 2) for their clinical, biochemical and imaging features. The mean age of Group 1 and Group 2 patients was 45+/-14 vs. 34+/-15 years (p<0.05). Comparison of blood biochemistries between Groups 1 and 2 showed serum creatinine 9.9+/-2.9 vs. 13.4+/-4.4 mg/dL (p<0.01); calcium 10.1+/-1.8 vs. 7.8+/-1.2 mg/dL (p<0.001); phosphate 4.4+/-1.2 vs. 7.9+/-2.1 mg/dL (p<0.001); alkaline phosphatase 116.4+/-31.7 vs. 85.7+/-30.6 IU/L (p<0.05); and parathormone 71.7+/-48.2 vs. 146.9+/-92.1 pg/mL (p<0.05). Radiological changes present in the 2 groups were as follows: osteopenia 63% vs. 65% (ns); trabecular resorption 53% vs. 20% (p<0.05); soft tissue calcification 31% vs. 10% (p<0.05); bone cysts 16% vs. 26% (ns); and subperiosteal bone resorption 16% vs. 20% (ns). Technetium 99 methylene diphosphonate (Tc-99 MDP) bone scans in both groups of patients showed similar increased uptake in wrist joint, tibia-fibula, costochondral junction, vertebral column, sternum, radius-ulna and mandible. X-ray findings were positive for bone involvement in 59% of cases, and Tc-99 scan was positive in 80% (p<0.05). It is concluded that newly detected, irregularly treated patients with advanced renal failure who are predialysis may present with deranged calcium homeostasis and a high prevalence of bone involvement similar to MHD patients.
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PMID:Biochemical and imaging alterations of renal bone disease in newly detected predialysis and on maintenance dialysis patients. 1622 39

(1) Patients who require dialysis for chronic renal failure develop phosphocalcium metabolic disorders that often lead to secondary hyperparathyroidism. Standard treatment consists of a phosphate chelator and vitamin D, along with the use of an appropriate calcium concentration in the dialysis bath, but is difficult to manage. (2) Parathyroid cancer is a rare malignancy frequently associated with hypercalcaemia. (3) Cinacalcet is a calcimimetic agent that reduces the parathormone level. Clinical evaluation includes more than a dozen dose-finding studies and clinical trials. The optimal dose seems to range from 30 to 180 mg/day and varies widely from one patient to another. (4) 3 double-blind placebo-controlled trials, lasting for a maximum of one year and involving a total of 1136 dialysis patients with chronic renal failure, showed no improvement in quality of life with cinacalcet. The target parathormone level was reached by 40% of patients on cinacalcet versus 5% of patients on placebo, while the effects of cinacalcet on calcium levels (-7%) and phosphate levels (-8%) were modest. No impact on bone complications is mentioned in available reports. (5) The assessment of treatment of parathyroid cancer is limited to one ongoing non comparative trial involving 21 patients. (6) During clinical trials, 11% of dialysis patients had low parathormone levels, creating a risk of adynamic bone disease and fractures, but available data are sparse. (7) Two-thirds of patients receiving cinacalcet have episodes of hypocalcaemia, which may in part account for reports of seizures (1.4% of patients), nausea (31%) and vomiting (27%). Many adverse effects seen in animal studies have not been adequately investigated in the clinical setting, such as an increase in the QT interval, thyroid disorders, and sexual dysfunction. Cinacalcet is a powerful CYP 2D6 inhibitor and is also metabolised by isoenzymes CYP 3A4 and CYP 1A2, creating an increased risk of drug interactions. (8) In practice, treatment with cinacalcet seems difficult to manage and to provide only limited benefits. Available assessment reports leave many questions unanswered, and this is a further reason not to use this product outside of clinical trials, either after failure of phosphate chelator and vitamin D therapy (especially as an alternative to surgery) or in parathyroid cancer.
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PMID:Cinacalcet: new drug. Secondary hyperparathyroidism: where are the clinical data? 1676 95

Renal osteodystrophy (ROD), which is most evident in patients on renal replacement therapy (RRT), usually begins when the kidney function starts to deteriorate. The spectrum of skeletal abnormalities seen in ROD is classified according to the state of bone turnover. In the past two decades, the prevalence of high turnover ROD has decreased while low bone turnover has become increasingly recognized. Secondary hyperparathyroidism represents a common disorder in patients with chronic kidney disease (CKD); it develops as a result of hyperphosphatemia, hypocalcemia and impaired synthesis of renal vitamin D with reduction in serum calcitriol levels. Patients with secondary hyperparathyroidism have a range of symptoms that affect their quality of life. The aim of treatment of ROD is to reduce the incidence of uremic bone disease as well as cardiovascular morbidity and mortality caused by elevated serum levels of parathormone (PTH) and calcium X phosphorus product. Treatment measures include control of phosphorus retention and prevent hyperphosphatemia, maintaining serum calcium concentrations within the normal range and prevent excess PTH secretion.
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PMID:Renal osteodystrophy: review of the disease and its treatment. 1697 Feb 58

This study is aimed at evaluating the attitude of physicians in dialysis centers in the Kingdom of Saudi Arabia (KSA) towards the management of bone disease. We sent a questionnaire to 168 physicians who jointly cared for 7214 chronic hemodialysis (HD) patients. A total of 134 physicians (79.8%) answered the questionnaire from 134 dialysis centers (91.7%) that cumulatively catered to 7030 dialysis patients (97.6%). Of them, 71 (53.4%) had a protocol for management of bone disease at their centers, while 87 (67.4%) believed that the current results of management of bone disease were satisfactory. About 84.2% and 82.7% of the physicians checked serum calcium and phosphorus levels respectively monthly, while only 24.6% would check parathormone (PTH) once every three months; 32.8% did not have this latter test available in their centers. Bone x-rays of the hands and clavicles were being performed once every year by 47.4%, while 38.4% would perform the x-rays as indicated by the clinical status. Therapy would be aimed to achieve mid-normal calcium and phosphorus levels by 64.9% and 56.8 % of the respondents respectively, while only 29.3% would try to achieve three times the normal level of the PTH. Only 43.3% of the respondents believed that sevelamer would be a safer phosphate binder than calcium or metal based one. Almost all the respondents used vitamin D, mostly by daily oral administration. Fifty-nine respondents (44.4%) believed that sevelamer plus vitamin D was better to control PTH than calcium-based phosphate binder plus vitamin D, while 51 (38.3%) had no idea about this issue. There were 57 respondents (42.5%) who believed that high intake of calcium would increase the risk of vascular and metastatic calcifications without hypercalcemia, while 43 (32.1%) had no idea. There were a significantly lower percentage of MOH centers having a protocol for management of bone disease in the dialysis patients. Also, there was a higher percentage of non-availability of PTH assay, lower tendency of the physicians to target low normal level of phosphorus and higher percentage to target normal levels of PTH in MOH centers. In addition, MOH physicians had significantly lesser tendency to consider sevelamer the best phosphate binder for the dialysis patients. Our study suggests that the current practices concerning the management of bone disease in dialysis centers in the KSA require refinement and a protocol to guide the management is required.
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PMID:Attitude of Physicians towards the Management of Bone Disease in Hemodialysis Patients: A Questionnaire Based Survey. 1729 31

Renal osteodystrophy is a complication of chronic kidney disease (CKD) that present in low and high turnover patterns. This disorder has a key role in the disability of CKD patients in whom early diagnosis and treatment can result in better outcome. We studied hyperparathyroidism prevalence and its relationship with renal osteodystrophy in our advanced CKD population. We included 80 patients (of whom 44 (55%) were diabetic) during 6 months period. The patients answered a questionnaire about symptoms related to bone disease and blood levels of parathormone (PTH), calcium, phosphorus, and alkaline phosphatase were obtained, in addition to hand and skull radiographs in all the study patients. Prevalence of clinically evident hyperparathyroidism in our patients was 45%. Hyperparathyroidism had significant relationship with alkaline phosphatase and radiological findings, but did not have a significant relationship with dialysis duration, age, sex, familial history, diabetes mellitus, or hypertension. We conclude that secondary hyperparathyroidism is prevalent in our dialysis population and has high correlation with serum alkaline phosphatase levels and radiological changes.
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PMID:Evaluation of secondary hyperparathyroidism in patients undergoing hemodialysis. 1808 40

The extent of aluminum related bone disease was evaluated in 41 patients on regular maintenance hemodialysis in two dialysis centers in Riyadh, Saudi Arabia. There were 22 males and 19 females aged 20 to 70 years (mean 35.5+11.2 years). Thirty eight of the patients were on aluminum based oral phosphate binders. Investigations performed included serum calcium, magnesium, aluminum and parathormone and radiological investigations including skeletal survey and dual photon absorptiometry. All the patients underwent bone biopsy and the biopsy material was subjected to morphometric studies, including staining for aluminum deposits. The patients were divided into two groups: group 1, (16 patients, 39%) with negative aluminum staining in the bone biopsy tissue, and group 2, (25 patients, 61%) with positive aluminum staining. Bone pain and its distribution as well as fractures were similarly prevalent in both groups. The levels of aluminum in the blood was significantly higher in group 2 (32.9 + 20.2 vs 17.9 + 11.2 ug/L P< 0.05), though it was lower than the lowest accepted toxic level (40 ig/L). There was no significant difference between the two groups in the biochemical or hormonal data, frequency of abnormal radiological signs and pattern of bone histology. Our study indicates that increased aluminum deposition in the bone is prevalent in patients on maintenance hemodialysis using aluminum based phosphate binders, but adynamic bone disease is not prevalent. Further studies may be needed on a larger scale to assess the magnitude of the problem.
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PMID:Is aluminum related bone disease common in hemodialysis units using aluminum based phosphate binders? 1858 39


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