Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0005940 (bone disease)
 7,459 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We encountered 11 patients with aluminum-associated bone disease (AABD), and treated them with deferoxamine (DFO). In 3 patients, a second bone biopsy was done during DFO treatment. Clinical features of AABD were compared with surgically proven secondary hyperparathyroidism (2 degrees HPT) with osteitis fibrosa on X-ray. Patients with AABD had disabling bone pain. This disease showed radiological signs ranging from normal, localized bone atrophy, to multiple fractures. It was characterized by increased soft tissue activity and localized abnormal uptake of 99mTc-MDP, detected by skeletal scintigrams. Patients with AABD had low levels of parathyroid hormone and alkaline phosphatase, but high aluminum (Al) levels compared to those with 2 degrees HPT. Serum Al increased after DFO administration, and the patients improved both clinically and histologically. 1-alpha-Hydroxyvitamin D3 (1-alpha-OH D3) was not effective for AABD. We concluded that the administration of antacids containing Al should be minimized in dialysis patients.
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PMID:Clinical features of aluminum-associated bone disease in long-term hemodialysis patients. 394 60

Five patients with primary hyperparathyroidism (surgically verified) and one patient with probable normocalcaemic hyperparathyroidism were diagnosed in a series of 93 recurrent stone formers in general practice. The six case histories are presented. The initial diagnosis was based on repeated albumin corrected total serum calcium determinations. The condition had previously not been diagnosed in four of the six patients, despite one or more hospital admissions. The urinary calcium excretion index ad modum Peacock & Nordin is not recommended as a routine test for use in general practice. Serum immunoreactive parathyroidal hormone related to simultaneous serum calcium values did not give any further diagnostic information in 48 of these patients with, or without, formation of new stones during a mean follow-up period of 3.2 years. The clinical spectrum of primary HPT has apparently shifted during the last three decades from bone disease and renal calculi to more general symptoms.
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PMID:The diagnosis, occurrence and clinical aspects of primary hyperparathyroidism in patients with recurrent urolithiasis as registered in general practice. 408 2

Pseudohypoparathyroidism (pseudo HPT) is the prototype of a group of diseases with end organ unresponsiveness to parathyroid hormone (PTH). Patients with the classic form of this disease have both renal and osseous resistance to PTH. We describe a rare variant of pseudo HPT with classic renal unresponsiveness to PTH but normal skeletal responsiveness to this hormone. The latter patients develop metabolic bone disease in response to depressed calcium and elevated PTH levels. Skeletal abnormalities are histologically and radiologically indistinguishable from renal osteodystrophy and these patients frequently present in childhood with symptoms relating to slipped capital femoral epiphyses. The latter radiologic findings, in the face of normal renal function or the classic somatic features of the syndrome, are highly suggestive of pseudo HPT with normal skeletal responsiveness to PTH.
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PMID:Pseudohypoparathyroidism presenting as renal osteodystrophy. 746 16

Renal osteodystrophy in diabetic patients on maintenance hemodialysis is characterized by a higher prevalence of low bone turnover and is associated with a relative deficiency of parathyroid hormone (PTH) as compared with non-diabetic hemodialysis patients. The goal of the study was to evaluate how diabetes affected the development of secondary hyperparathyroidism (2 degrees HPT) and bone disease in azotemic rats. Three groups of 5/6 nephrectomized, pair-fed male Wistar rats maintained on a high phosphorus (1.2%) diet were studied: (1) the control group, non-diabetic azotemic rats (NDR); and two streptozotocin-induced diabetic azotemic groups, (2) poorly-controlled diabetic rats (PCDR) which received only enough NPH insulin to maintain the blood glucose between 300 and 400 mg/dl, and (3) well-controlled insulin-treated diabetic rats (IDR) which received a continuous insulin infusion for 14 days via a subcutaneously implanted miniosmotic pump. Serum calcium, phosphorus and creatinine levels were similar among the three groups. Blood glucose levels were greater in the PCDR group than the IDR and NDR groups (358 +/- 11 vs. 83 +/- 9 and 87 +/- 8 mg/dl, respectively; P < 0.001). Rats in the PCDR group weighed less at sacrifice as compared with the IDR and NDR groups (P < 0.05). Serum PTH levels (normal 47 +/- 2 pg/ml) were elevated, but not different among the three groups (136 +/- 34, 147 +/- 21 and 98 +/- 8 pg/ml in the PDCR, IDR and NDR groups, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Development of secondary hyperparathyroidism and bone disease in diabetic rats with renal failure. 764 45

The concept that the PTH-calcium curve is representative of parathyroid function has been discussed. Comparisons of parathyroid function have been made between normal humans and hemodialysis patients and also between hemodialysis patients with different forms of renal osteodystrophy. From these comparisons, it is apparent that the magnitude of HPT is much greater in patients with renal failure than in normal humans, and as represented by the ratio of basal to maximal PTH, the parathyroid gland appears to be stimulated at basal serum calcium levels in hemodialysis patients. Similarly, based on an analysis of the PTH-calcium curve, we were able to determine that several differences in parathyroid function were present in hemodialysis patients with different forms of renal osteodystrophy. As compared to hemodialysis patients with LTAABD and aplastic bone disease, patients with osteitis fibrosa have a greater magnitude of hyperparathyroidism, a greater sensitivity of the parathyroid cell (slope), a higher set point of calcium, and greater PTH stimulation at basal serum calcium (ratio of basal to maximal PTH). Calcitriol treatment of hemodialysis patients with osteitis fibrosa resulted in a significant decrease in PTH throughout the PTH-calcium curve and also reduced the sensitivity (slope) of the PTH-calcium curve. The concept of hysteresis has been discussed as well as the role that the ambient basal serum calcium concentration may have on the determination of the PTH-calcium curve. Finally, the effect that successful renal transplantation has on HPT has been examined. In conclusion, we believe that the PTH-calcium curve provides a reliable assessment of parathyroid function, and as such, has considerable application for the study of parathyroid disorders in the clinical setting.
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PMID:Parathyroid gland function in chronic renal failure. 847 13

Serum vitamin D metabolites and PTH were measured in seven subjects with a history of previous partial gastrectomy (PGX) and metabolic bone disease. The elimination t1/2 of [3H]25-hydroxyvitamin D3 ([3H]25OHD3) in serum was assessed after an iv pulse dose of 5 microCi [26,27-3H]25OHD3. Median serum 25OHD3 was 37.5 (27.5-101.3) nmol/L, [normal range (NR) 10.8-58.5 nmol/L], mean serum 1,25-dihydroxyvitamin D [1, 25-(OH)2D3] was raised at 175 +/- 72 pmol/L, (NR 48-120 pmol/L) and mean PTH was also high, 67 +/- 27 ng/L, (NR 10-60 ng/L). Serum t1/2 [3H]25OHD3 ranged from 10.9-21.2 days. A strong negative correlation existed between t1/2 [3H]25OHD3 and serum 1,25-(OH)2D3 [Spearman's rank correlation coefficient (r = -0.82, P = 0.002)] and PTH [Spearman's rank correlation coefficient (r = -0.81, P = 0.001)]. Four subjects who had high initial PTH concentrations (60-115 ng/L) and elevated 1,25-(OH)2D levels (162-300 pmol/L) were reassessed after calcium supplementation to suppress secondary hyperparathyroidism (2 degrees HPT). In this subgroup, after-treatment PTH fell from 82 +/- 24 to 52 +/- 24 ng/L (mean +/- SD), not significant; 1,25-(OH)2D fell from 210 +/- 61 to 116 +/- 28 pmol/L, P = 0.015; and t1/2 [3H]25OHD3 increased from 13.2 +/- 1.9 to 18.9 +/- 3.1 days, P = 0.012. Patients with PGX and evidence of 2 degrees HPT with elevated 1,25-(OH)2D have a reduced t1/2 [3H]25OHD3, and this may explain the increased susceptibility of the subjects to osteomalacia. Calcium supplementation suppresses 2 degrees HPT, increases t1/2 [3H]25OHD3 and may protect against PGX osteoporosis and osteomalacia.
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PMID:Increased catabolism of 25-hydroxyvitamin D in patients with partial gastrectomy and elevated 1,25-dihydroxyvitamin D levels. Implications for metabolic bone disease. 898 60

Nearly all patients with chronic renal failure exhibit some degree of secondary hyperparathyroidism (sHPT), defined as parathyroid hyperplasia and elevated serum parathyroid hormone (PTH) levels. Despite improvements in the medical management of patients with sHPT continue to develop progressive bone disease manifested by osteitis fibrosa cystica, soft tissue calcification and myopathy, pruritus, bone and joint pain and calciphylaxis may accompany the bone disorder. When medical therapy fails, parathyroidectomy becomes necessary. This is not sufficiently explained by the failure to administer calcitriol to control serum phosphate and calcium concentration or to deliver sufficient dialysis. The continuous increase of the proportion of patients exhibiting severe uncontrolled HPT with increasing time of dialysis points to a more basic underlying biological problem; an even higher proportion of patients shows also nodular, rather than diffuse hyperplasia. It was commonly believed that after restoration of normal renal function with successful transplantation, the hyperplastic parathyroid glands would involute and return to normal function state. After renal transplantation some patients continue to have a HPT. This disease entity is recognized and termed as tertiary Hyperparathyroidism (tHPT). After establishing a diagnosis of hyperparathyroid bone disease, in patients with sHPT and tHPT a parathyroidectomy (PTX) frequently becomes necessary to decrease the mass of the hyperplastic parathyroid tissue. The surgical procedure remains controversial. Some surgeons prefer subtotal PTX, others prefer total PTX with autotransplantation of a small amount of tissue to the arm, because the transplanted tissue can be removed in the event of a recurrent HPT. Successful surgical intervention for sHPT and tHPT significantly reduces preoperative symptoms and leeds to restoration of bone disease and therefore supports PTX for patients with s and tHPT. In our experience total PTX with autograft has proven to be a satisfactory procedure. Subtotal PTX is also an effective procedure and the choice of operative technique should be left to the surgeon.
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PMID:[Treatment of secondary and tertiary hyperparathyroidism--surgical viewpoints]. 1055 Mar 38

The parathyroid hormone/parathyroid hormone-related peptide (PTH/PTHrP) receptor (denoted as PTH-1R) is a key signaling factor through which calcium-regulating hormones PTH and PTHrP exert their effects on bone. There are contradictory reports regarding the capability of osteoclasts to express PTH-1R. To address this issue in humans, bone biopsy specimen samples from 9 normal controls and 16 patients with moderate to severe secondary renal hyperparathyroid bone disease (2 degrees HPT) with elevated PTH levels were studied to determine whether osteoclasts in the bone microenvironment express PTH-1R messenger RNA (mRNA) and protein. We report that osteoclasts express the PTH-1R mRNA but the protein is detected only in patients with 2 degrees HPT. The PTH-1R mRNA and protein also were found in osteoblasts, osteocytes, and bone marrow cells. Receptor expression was higher in osteoclasts and osteoblasts of patients with 2 degrees HPT than normal controls (98.0 +/- 1.1% vs. 65.7 +/- 14.3% and 65.8 +/- 3.4% vs. 39.1 +/- 6.2%; p < 0.01, respectively). Approximately half of osteoclasts found in bone of patients with 2 degrees HPT have the PTH-1R protein. In patients with 2 degrees HPT, a positive relationship exists between erosion depth, a parameter of osteoclastic activity, and the percentage of osteoclasts with PTH-1R protein (r = 0.58; p < 0.05). In normal controls, an inverse relationship exists between the percentage of osteoblasts with receptor mRNA, mRNA signals/cell, and serum PTH levels (r = -0.82 and p < 0.05 and r = -0.78 and p < 0.01, respectively). The results provide the novel evidence of PTH-1R in human osteoclasts and suggest a functional role for the receptors in 2 degrees HPT.
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PMID:Parathyroid hormone/parathyroid hormone-related peptide type 1 receptor in human bone. 1127 62

The term "osteoporosis" must be applied with caution to the uremic population, which has a complex range of metabolic bone disease. Trials of therapeutic interventions to prevent fractures in non uremic populations with osteoporosis cannot be generalized to uremic patients. It is unclear what, if any, role systematic bone densitometry measurement can play in the management of uremic patients who suffer "fragility" fractures--either for diagnostic purposes or to determine the effectiveness of therapy. Estrogen therapy--and perhaps SERMs (raloxifene)--appear to be a reasonable addition to conventional management of secondary HPT with calcium salts and vitamin D analogs. Using bisphosphonates to manage patients who have pre-existing fractures should be considered experimental at best. In certain circumstances, such treatment may be harmful. While the evidence is better that early therapy with intravenous pamidronate in the peri-transplant interval may mitigate the steroid-induced bone loss seen in those patients during the first 12 postoperative months, even that indication needs to be subjected to systematic clinical studies to develop appropriate clinical practice guidelines.
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PMID:Fragility fractures in dialysis and transplant patients. Is it osteoporosis, and how should it be treated? 1188 31

A trial on the long-term administration of 22-oxacalcitriol (maxacalcitol, OCT) was conducted among 124 patients with chronic renal failure on maintenance hemodialysis (HD) complicated with secondary hyperparathyroidism (2 degrees HPT ). In the trial, OCT was administered 3 times weekly for 26 weeks subsequent to a 26-week pre-trial. As a result, intact-parathyroid hormone (PTH) levels fell significantly after the start of administration and were well controlled for one year. The levels of markers of bone metabolism such as bone alkaline phosphatase were decreased significantly compared with those at the start of administration, suggesting a correction of high-turnover bone disease. Serum calcium (Ca) levels rose significantly following OCT administration, but were successfully maintained within a physiological range. Hypercalcemia, in 33.1% of patients, was found to resolve or ameliorate immediately after the withdrawal or dose reduction of OCT. The final doses ranged from 2.5 mg to 20 mg/HD, and the optimal dose varied among patients depending on the intact-PTH and serum Ca levels. These results clearly suggest that OCT is a highly effective drug for the treatment of 2 degrees HPT, and is an overall safe drug if the dosage is adjusted for serum Ca and intact-PTH levels.
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PMID:[Long-term clinical effect of maxacalcitol on hemodialysis patients with secondary hyperparathyroidism]. 1577 67


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