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

During pregnancy, calcium is continuously transferred directly from the maternal intestine to the fetal bone, a transfer that is mainly induced by the interrelated actions of the calcium-regulating hormones parathyroid hormone (PTH), 1,25-dihydroxyvitamin D (1,25(OH)2D) and calcitonin. It has recently been demonstrated in animals that PTH-related protein (PTHrP) is the fetal equivalent of PTH. Human PTHrP, originally described as a product of a human lung cancer cell line and implicated in the pathogenesis of humoral hypercalcemia of malignancy, is a protein with 141 amino acids, and it has biochemical actions similar to PTH. It is believed that fetal PTHrP is mainly derived from the placenta during early gestation and from the fetal parathyroid glands during further development and that this protein has the role of maintaining the maternal-fetal calcium gradient either alone or in concert with 1,25(OH)2D. With birth, the placental supply of calcium ceases abruptly, stimulating the increase of PTH and 1,25(OH)2D, which are the main regulators of postnatal calcium metabolism. Alterations in the placental calcium (and phosphate) gradient may be caused by maternal hypo- or hypercalcemia and placental insufficiency and may be followed by transient disorders of calcium metabolism in the newborn. Due to abrupt cessation of the calcium and phosphate supply after delivery at a time when mineral demands are the highest, preterm infants are especially prone to hypocalcemia and osteopathy. If bone disease of prematurity is to be prevented, the amounts of calcium and phosphate must be adequate, as demonstrated by laboratory tests, the most important being calcium and phosphate in urine and alkaline phosphatase activity in serum.
 ...
PMID:[Perinatal calcium metabolism. Physiology and pathophysiology]. 143 20

Using repeat bone biopsies, we studied whether 1) subtotal parathyroidectomy (PTX) enhances aluminum (Al) deposition in bone and 2) whether pretransplant PTX affects Al removal from bone after kidney transplantation. Twenty-four kidney graft recipients, 10 subjected to PTX 9-44 months prior to transplantation and 14 controls matched for dialysis duration, had bone biopsies taken at transplantation. Serum calcium and parathyroid hormone levels had decreased after PTX in all 10. At transplantation, eroded bone surface was lower in PTX-recipients, while extent of Al-stained bone surface and prevalence of symptomatic Al-related bone disease were similar in both groups (PTX: 2/10; non-PTX: 4/14). Hence, PTX did not enhance accumulation of stainable bone Al nor increase prevalence of clinical bone disease during dialysis. Fourteen (7 PTX) recipients with functioning grafts had a second biopsy 12 months after transplantation. Symptomatic Al-related bone disease was cured regardless of pretransplant PTX, and Al-stained surface had decreased in all but one (PTX) recipient.
 ...
PMID:Pretransplant parathyroidectomy in renal failure: effects on bone histology and aluminum deposits during dialysis and after kidney transplantation. 143 4

The effects of a very low-protein diet (VLPD) supplemented with amino acids and ketoanalogues (KA) and with 1 g of calcium carbonate and 1000 IU of vitamin D2, were studied in 17 patients with advanced renal failure (GFR < or = 20 ml/min) over a period of one year. The protein intake was 0.3 g protein/kg body wt/day. Daily phosphorus and calcium intake were respectively 1,500 mg and 300 mg. Sequential bone densitometry was performed and bone histomorphometry after double tetracycline labeling was evaluated, before and after one year of diet. Calcium and phosphate metabolism parameters were monitored every two months. In spite of a significant decrease of GFR, phosphorus, parathyroid hormone (1-84) and osteocalcin plasma levels decreased significantly, while low plasma bicarbonate normalized, and calcitriol and calcium levels remained respectively low and normal. Before the diet, histological study disclosed four cases of mixed osteopathy: osteomalacia associated with osteitis fibrosa (OM/OF), nine pure osteitis fibrosa (OF) and four with normal bone remodeling (NB). After one year of diet, the OM component of OM/OF disappeared, as evidenced by a normalization of the mineral apposition rate and osteoid thickness. In the patients presenting pure OF, a significant decrease in osteoblastic and osteoclastic surfaces, in the number of osteoclasts, and in the bone formation rate (BFR) were found. Vertebral mineral density measured by quantitative computerized tomodensitometry did not change significantly. In conclusion, this study not only confirms the beneficial effects of VLPD + KA + calcium on uremic hyperparathyroid bone disease in advanced renal failure assessed using static bone histomorphometry, but also shows a correction of histodynamic bone parameters.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Ketodiet, physiological calcium intake and native vitamin D improve renal osteodystrophy. 145 6

Calcium carbonate (CaCO3) is an effective phosphate (PO4) binder in uremics, and its use reduces aluminum (AI) intake. By maintaining high serum Ca2+ levels, it decreases serum parathyroid hormone (PTH) levels. Hypercalcemia, however, often limits the dosage. To evaluate the effects of a low Ca2+ peritoneal dialysis solution (PDS; 1.25 mmol/L) on calcium metabolism, the following were studied in continuous ambulatory peritoneal dialysis (CAPD) patients with hypercalcemia (six with high PTH levels, and high turnover bone disease [Group 1], and six with low PTH levels, and low turnover bone disease [Group 2] documented by bone biopsies): 1) serum Ca2+ and PO4 levels; 2) serum PTH levels; 3) serum AI levels; and 4) bone morphology. The follow-up was 12 months. In both groups, within the third month, there was a decrease in serum Ca2+. In Group 2, serum PTH increased, reaching the norm, and in Group 1 it further increased, exceeding the norm. Because in both groups serum Ca2+ was normal, it was possible to give oral CaCO3 (10.5 +/- 2.5 g/day) to control PO4 levels while stopping AI gels. This did not induce any increase in serum Ca2+, whereas serum AI fell significantly. In Group 1, to avoid a further rise of serum PTH, the low Ca2+ PDS was supplemented with calcitriol (mean 3.5 +/- 0.5 microgram/day); this was followed by a reduction in serum PTH with no increase in serum Ca2+ or PO4.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Low calcium peritoneal dialysis solution. Effects on calcium metabolism and bone disease in CAPD patients. 145 29

Chronic metabolic acidosis results in metabolic bone disease, calcium nephrolithiasis, and growth retardation. The pathogenesis of each of these sequelae is poorly understood in humans. We therefore investigated the effects of chronic extrarenal metabolic acidosis on the regulation of 1,25-(OH)2D, parathyroid hormone, calcium, and phosphate metabolism in normal humans. Chronic extrarenal metabolic acidosis was induced by administering two different doses of NH4Cl [2.1 (low dose) and 4.2 (high dose) mmol/kg body wt per d, respectively] to four male volunteers each during metabolic balance conditions. Plasma [HCO3-] decreased by 4.5 +/- 0.4 mmol/liter in the low dose and by 9.1 +/- 0.3 mmol/liter (P < 0.001) in the high dose group. Metabolic acidosis induced renal hypophosphatemia, which strongly correlated with the severity of acidosis (Plasma [PO4] on plasma [HCO3-]; r = 0.721, P < 0.001). Both metabolic clearance and production rates of 1,25-(OH)2D increased in both groups. In the high dose group, the percentage increase in production rate was much greater than the percentage increase in metabolic clearance rate, resulting in a significantly increased serum 1,25-(OH)2D concentration. A strong inverse correlation was observed for serum 1,25-(OH)2D concentration on both plasma [PO4] (r = -0.711, P < 0.001) and plasma [HCO3-] (r = -0.725, P < 0.001). Plasma ionized calcium concentration did not change in either group whereas intact serum parathyroid hormone concentration decreased significantly in the high dose group. In conclusion, metabolic acidosis results in graded increases in serum 1,25-(OH)2D concentration by stimulating its production rate in humans. The increased production rate is explained by acidosis-induced hypophosphatemia/cellular phosphate depletion resulting at least in part from decreased renal tubular phosphate reabsorption. The decreased serum intact parathyroid hormone levels in more severe acidosis may be the consequence of hypophosphatemia and/or increased serum 1,25-(OH)2D concentrations.
 ...
PMID:Chronic metabolic acidosis increases the serum concentration of 1,25-dihydroxyvitamin D in humans by stimulating its production rate. Critical role of acidosis-induced renal hypophosphatemia. 146 97

We performed a prospective study of 30 patients undergoing chronic hemodialysis to determine which of 6 generally available diagnostic procedures provided the most useful information for the assessment of bone disease in hemodialysis patients. The 6 procedures were: routine biochemical measurements, N-terminal parathyroid hormone (N-PTH), radiographic analysis of hands and clavicles, bone density determination by dual photon absorptiometry (DPA), deferoxamine stimulation test, and iliac crest bone biopsy. Serum N-PTH was elevated in 83% of patients but was not significantly associated with abnormalities of other biochemical parameters. No significant relationship was demonstrated between biochemical data and radiographic findings or between biochemical data and bone density by DPA. All patients with abnormal DPA had an elevation of N-PTH; therefore, DPA did not reveal any unsuspected disease. Bone biopsies were done in 20 patients and findings in each were consistent with uremic osteodystrophy, including osteitis fibrosa cystica in 11 patients and aluminum-associated bone disease in 2 patients. Six patients had mixed disease, and 1 patient had osteoporosis. Despite 11 positive deferoxamine tests, bone biopsy revealed aluminum deposition in only 7 of these patients, suggesting extraosseous aluminum accumulation in the remaining 4. Evaluation of the positive and negative predictive accuracies of DPA, x-ray analysis, N-PTH levels, and aluminum bone deposition revealed that normal DPA or x-ray findings do not exclude bone disease, that N-PTH level is a good marker for secondary hyperparathyroidism, and that a negative deferoxamine test excludes aluminum-associated bone disease. Discriminant analysis also reinforced these conclusions.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Assessment of renal osteodystrophy in hemodialysis patients. 152 4

Serial prospective observations were made on 40 patients with end-stage renal failure who transferred voluntarily from long-term maintenance hemodialysis (MHD) to continuous ambulatory peritoneal dialysis (CAPD). Adequate data were available through 6 months on CAPD in 26 participants, whereas 20 completed the study (1 year on CAPD). There were 12 (30%) treatment failures, including two deaths. Standard CAPD (four 2-L exchanges per day) proved to be inadequate therapy in large, young males with low total urea clearances (Ktu) on MHD. There was a large variation in Ktu within MHD and CAPD therapies that employed apparently similar or identical dialysis prescriptions; this underscores the need to quantify dialysis by a measure such as Ktu. Hematocrit, white blood cell (WBC) and platelet counts, and serum bicarbonate levels were significantly higher, whereas blood urea nitrogen (BUN) and serum potassium levels were significantly lower on CAPD than on MHD. While body weight, blood pressure, bone disease, parathyroid hormone (PTH) levels, and lipid profile did not change significantly, nutritional indices tended to decline with time on CAPD. Urea generation rate (Gu) decreased significantly after transfer to CAPD and correlated with Ktu regardless of treatment modality. Central nervous system (CNS) function reflecting uremic symptomatology and as indexed by average quantified electroencephalogram (EEG) discriminant scores did not change significantly. Hospitalization rates and stays were similar during equal time intervals on both therapies. Sufficiently diverse responses followed the MHD to CAPD therapy change to warrant more extended observations on larger numbers of patients.
 ...
PMID:Multicenter study of change in dialysis therapy-maintenance hemodialysis to continuous ambulatory peritoneal dialysis. 155 69

Breast and prostate carcinomas are the tumors most commonly associated with skeletal metastases, and the skeleton is the most common site of metastatic disease and of first distant relapse in breast cancer. Bone metastases are the source of considerable morbidity, including pain and functional disability, fractures, hypercalcemia, and epidural compression. The classical radionuclide bone scan remains the most effective tool for the screening of metastatic bone disease, but X-rays are more specific and remain the essential tool for the diagnosis and characterization of bone metastases. Computed tomography is much more useful to diagnose early metastatic involvement of bone, particularly of the spine. Patients with exclusive skeletal metastatic involvement are still frequently excluded from classical therapeutic trials because of the difficulties in the assessment of response. Recalcification of osteolytic lesions is indeed required when defining an objective response, but this criterion is insensitive and not quantitative. Moreover, the development of new osteoblastic lesions is often of difficult interpretation. A concomitant bone scan will help, but the absence of quantification of the changes and the "flare" phenomenon limit the usefulness of the technique. Pain and quality of life constitute simple, but frequently neglected, parameters of response to therapy. The clinical utility of tumor markers and of biochemical markers of bone turnover should also be more fully investigated. Neoplastic osteolysis is essentially mediated by the osteoclasts, which seem to be activated, maybe indirectly through the osteoblasts, by some tumor products. Various substances of tumoral origin have been proposed as mediators for this osteoclast activation, such as transforming growth factors, prostaglandins, and, more recently, products of the immune cells or parathyroid hormone-related peptide.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Metastatic bone disease: clinical and therapeutic aspects. 158 Nov 21

Recent advances in renal osteodystrophy deal with the pathogenesis of the disease, in particular in early renal failure, with the mechanisms of skeletal resistance to parathyroid hormone, with the potential role of iron, and with increased knowledge of adynamic bone disease. For the control of phosphatemia, aluminum-containing phosphate binders are more and more avoided, whereas calcium acetate or carbonate are more and more prescribed. X-linked hyphophosphatemia continue to cause great interest as well as the various iatrogenic osteomalacias.
 ...
PMID:Renal osteodystrophy, disorders of vitamin D metabolism, and hypophosphatasia. 159 20

Between October 1987 and October of 1989, we conducted a prospective study to evaluate non-invasive test strategies for predicting aluminum bone disease (ABD) in a group of largely unselected dialysis patients based on their deferoxamine (DFO) test alone, or the combined results of their DFO test and intact 1-84 parathyroid hormone (PTH) levels. These test parameters were evaluated against the pathological diagnosis of ABD based on bone biopsy ("gold standard"). A total of 445 patients in three dialysis centers in Toronto were serially followed for their clinical, laboratory and risk parameters for renal osteodystrophy during the study, and 259 (142 PD and 117 HD) patients underwent a series of investigations which included the DFO test, measurement of intact 1-84 PTH levels, and an iliac crest bone biopsy. Serum aluminum ([Al]) level greater than or equal to 3700 nM (or 100 micrograms/liter) had a positive predictive value (PPV) of 75% for ABD in our PD and 88% in our HD patients, but its sensitivity was low (10 and 37%). Delta [Al] (that is, incremental rise of serum [Al] from baseline post-DFO) was useful in predicting ABD in our PD but not HD patients. Test combination based on delta [Al] greater than or equal to 5550 nM (or 150 microgram/liter) and PTH levels less than 20 pM (or 200 pg/ml) yielded the best PPV greater than or equal to 95% for ABD in both PD and HD patients. This test cut-off would remain highly predictive of ABD even if the prevalence of ABD decreases to as low as 5% for the PD patients and 10% for the HD patients.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Non-invasive prediction of aluminum bone disease in hemo- and peritoneal dialysis patients. 161 52


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>