Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0221002 (primary hyperparathyroidism)
 4,921 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An enzyme-linked immunosorbent assay for measuring type I collagen degradation products in serum (S-ELISA) was developed. The assay uses a high affinity polyclonal antibody which reacts with an isomerized form of an 8 amino acid sequence of the C-telopeptides of type I collagen (EKAHD-beta-GGR). Cross-reactivity to a nonisomerized synthetic peptide form of the 8 amino acid sequence is less than 0.2%. Values obtained in a group of premenopausal women (age, 33.3 +/- 3.11 years) were 69 +/- 24 ng/ml(n = 22). In a group of early postmenopausal women (age, 51.8 +/- 1.88 years) values obtained were 125 +/- 43 ng/ml (n = 46), which represents an increase of 81% (p < 0.001). Values found in untreated patients with Paget's disease were 234 +/- 95 ng/ml (n = 15), and for primary hyperparathyroidism we found 335 +/- 82 ng/ml (n = 10). Intravenous administration of a bisphosphonate (Pamidronate) to Paget's disease patients for 3 days was reflected in the S-ELISA by a decrease in the values of 55% when compared with values before treatment (n = 15). Following treatment with another bisphosphonate (Alendronate) for 6 months, values were decreased to 48 +/- 19 ng/ml (n = 12), which corresponds to a 62% decrease. Clinical results presented in this context support that the assay is a sensitive and specific index of bone resorption. It may, therefore, prove useful in the follow up of treatment of patients with metabolic bone diseases and in the clinical investigation of osteoporosis.
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PMID:Measurement of bone degradation products in serum using antibodies reactive with an isomerized form of an 8 amino acid sequence of the C-telopeptide of type I collagen. 920 1

This study has been carried out in order to evaluate several bone metabolic markers after parathyroidectomy in patients with primary hyperparathyroidism (PHP) and secondary hyperparathyroidism (SHP). The subjects studied were 6 patients with PHP (5 females, 1 male, aged 64-83 years) and 5 patients with SHP on chronic maintenance hemodialysis with skeletal symptoms (2 females, 3 males, aged 57-67 years). In PHP, serum alkaline phosphatase (ALP) and procollagen type I carboxy-terminal propeptides (PICP) levels showed a trend to increase gradually after parathyroidectomy, changes which were statistically significant (ALP, p = 0.0375; PICP, p = 0.0006). The serum bone Gla protein (BGP) level showed no significant change throughout the pre- and postoperative periods (p = 0.7512). Urinary pyridinoline (Pyr.) and deoxypyridinoline (DPyr.) levels showed rapid decreases after parathyroidectomy (Pyr.; p = 0.0014, DPyr., p = 0.0087). In SHP, individual values of serum ALP in 3 patients with complete parathyroid resection and 1 patient with incomplete parathyroid resection showed a tendency to increase. Individual values of serum BGP and PICP increased after parathyroidectomy in 3 patients with complete parathyroid resection but not in the 2 patients with incomplete parathyroid resection. Individual values of the serum carboxy-terminal pyridinoline cross-linked telopeptide of type I collagen (ICTP) level showed no certain trend. The results obtained after surgery indicate that there is a positive uncoupling of the two processes of bone remodeling, and serum PICP and urinary pyridinium cross-links are good specific markers for the evaluation of potential recovery of bone damage after parathyroidectomy.
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PMID:Short-term effect of parathyroidectomy on biochemical markers in primary and secondary hyperparathyroidism. 925 75

In Paget's disease of bone, the normal lamellar bone is replaced by a woven structure with an irregular arrangement of collagen fibers. In this study, we investigated whether the degree of beta-isomerization within C-telopeptide of alpha 1 chain of type I collagen was altered in Paget's disease compared with other bone diseases with no alteration of bone structure. In Paget's disease (n = 26), but not in patients with primary hyperparathyroidism (n = 6) or hyperthyroidism (n = 17), the urinary excretion of nonisomerized (alpha) fragments derived from degradation of type I collagen C-telopeptide (CTX) was markedly increased compared with beta-isomerized CTX (+ 13-fold vs. + 3.5-fold over controls) resulting in an urinary alpha CTX/beta CTX ratio 3-fold higher than in controls (2.6 +/- 1.0 vs. 0.8 +/- 0.3, p < 0.001). In five pagetic patients in complete remission, as demonstrated by normal total alkaline phosphatase activity, the alpha CTX/beta CTX ratio was normal. The immunohistochemistry of normal and pagetic human bone sections showed a preferential distribution of alpha CTX within woven structure, while lamellar bone was intensely stained with an anti-beta CTX antibody, suggesting a lower degree of beta-isomerization of type I collagen in the woven pagetic bone. In collagenase digest of human bone specimens, we found a lower proportion of beta-isomerized type I collagen molecules in pagetic bone (40% of beta CTX) than in normal bone taken from trabecular (68%) and cortical compartments (71%). In conclusion, we found that in Paget's disease the alpha CTX/beta CTX ratio in bone and in urine is markedly increased. This altered beta isomerization can be accurately detected in vivo by measuring urinary degradation products arising from bone resorption.
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PMID:Decreased beta-isomerization of the C-terminal telopeptide of type I collagen alpha 1 chain in Paget's disease of bone. 928 56

This study was carried out in order to evaluate clinical usefulness of cross-linked N-telopeptides (NTx) of type I collagen determination, in patients with primary hyperparathyroidism. Twenty-six consecutive patients (6 males and 20 females, aged 56.3 +/- 15.0, SD, yrs) with primary hyperparathyroidism were studied in basal conditions and, ten of them, after surgical cure of the disease. Cross-linked collagen peptides were measured by enzyme-linked immunosorbent assay and conventional markers of bone turnover according to standard procedures. Bone densitometry at the lumbar spine and proximal femur was performed using dual-energy X-ray absorptiometry. Bone mineral density, was also assessed at the junction of the distal and middle third of the radius and at the ultradistal radius of the non-dominant arm by a dual photon densitometer. Mean urinary NTx values (194.2 +/- 121.9 pmoles bone collagen equivalents/mumoles creatinine) were significantly higher (p < 0.001) in respect to those found in normal subjects. The mean increase of Z score values of both serum tartrate resistant acid phosphatase activity (1.4 +/- 1.8) and the fasting hydroxyproline/creatinine ratio (1.45 +/- 2.0) was significantly lower (p < 0.02) in respect to that of NTx Z score values (3.3 +/- 3.3); the latter values were not significantly different than mean Z score values of serum osteocalcin (4.0 +/- 3.9), serum alkaline phosphatase activity (2.6 +/- 2.6) and urinary calcium/creatinine ratio (3.2 +/- 3.3). We found a significant inverse correlation between NTx values and both lumbar spine (p < 0.01) and ultradistal radius bone mineral density (p < 0.05); a modest inverse correlation was also observed between serum tartrate resistant acid phosphatase activity and lumbar spine bone mineral density (p < 0.04). Following successful adenoma removal, the percentage decrease of both NTx and hydroxyproline was similar in patients with increased bone turnover rate; major discrepancies were observed in patients with normal values of NTx, the telopeptide reduction being greater than that of hydroxyproline. Finally, in a hypercalcemic patient with metastatic parathyroid cancer, telopeptide excretion was shown to be more sensitive in respect to urinary hydroxyproline when evaluating the effects of antiresorptive therapy. Our results seem to indicate that amongst the markers with good sensitivity, NTx is the only one that is inversely related with bone mineral density at two different skeletal sites. This assay should therefore have a place in both the initial screening and medical follow-up of patients with this glandular disorder; in fact, in both situations an increased urinary excretion of this marker should warn about the possibility of hidden bone loss.
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PMID:The measurement of urinary amino-terminal telopeptides of type I collagen to monitor bone resorption in patients with primary hyperparathyroidism. 941 11

Biochemical markers of bone turnover are expected to have some different characteristics among bone metabolic disorders. We compared bone formation markers: serum total alkaline phosphatase (s-Alp), serum osteocalcin (s-OC) and serum carboxy-terminal propeptide of type I collagen (s-PICP); and bone resorption markers: serum carboxy-terminal telopeptide of type I collagen (s-ICTP), urinary pyridinoline (u-Pyr) and urinary deoxypyridinoline (u-Dpyr) to examine which marker is the most suitable and reliable to evaluate bone turnover in patients with osteoporosis (n = 29), osteomalacia (n = 10), primary hyperparathyroidism (n = 6) and renal osteodystrophy (n = 21). The value of s-Alp in the osteomalacia group was significantly higher than those in the normal control group and the osteoporosis group (p < 0.001), and T-score of s-Alp was significantly higher than those of s-OC and s-PICP in the osteomalacia group. The values of u-Pyr and u-Dpyr in the primary hyperparathyroidism group were significantly higher than those in the other groups (p < 0.001). S-PICP, which are not dependent upon renal function, was much higher in the renal osteodystrophy group than in all other groups. In the osteoporosis group, T-score of s-ICTP was significantly higher than those of s-OC. Thus, s-Alp was a good marker in osteomalacia, u-Pyr and u-Dpyr in primary hyperparathyroidism, s-PICP in renal osteodystrophy, and s-ICTP in osteoporosis.
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PMID:Characteristics of biochemical markers in patients with metabolic bone disorders. 955 54

With the increasing demand for clinically useful biomarkers of bone turnover, a number of assays for the measurement of bone resorption markers have been developed. In the present study, automated (ACS: 180 DPD, Chiron Diagnostics, USA) and manual (DPD-ELISA, Pyrilinks-D, Metra Biosystems, USA) immunoassays for free DPD, and a manual immunoassay for the aminoterminal telopeptide of type I collagen (NTX, Osteomark, Ostex International, USA) were compared to the automated HPLC method for free DPD. Urine samples from a total of 538 healthy and diseased subjects aged 20 to 80 years were analyzed. The age and sex stratified reference ranges were essentially identical for the HPLC, ACS: 180 and the DPD-ELISA, but differed from the NTX assay. Individual values for free DPD as generated by HPLC and immunoassay techniques were highly correlated with each other, whereas correlations between assays measuring free and peptide-bound crosslink components were less pronounced. Precision of the automated techniques (HPLC and ACS: 180) was superior to that of the manual immunoassays. Disease-specific changes in crosslink excretion were similar for all assays and most pronounced in metastatic osteopathy, primary hyperparathyroidism and untreated Paget's disease of bone. We conclude that the automated assays for free DPD in urine, i.e. the HPLC and the ACS: 180 assay, show better analytical performance than the manual immunoassays studied. All techniques used in the present study appear to provide similar or identical clinical information. Therefore, the decision which assay to use largely depends on the laboratory set-up, the number of samples to be analysed, the turn-around time required, and the application for which the test should be used.
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PMID:Automated and manual assays for urinary crosslinks of collagen: which assay to use? 962 47

Although urinary measurements of collagen degradation provide valid estimates of bone resorption, their clinical application is hampered by pronounced analytical and biological variability. Therefore, immunoassays for the determination of such parameters in serum have been developed. In this study, we assessed the performance of three new serum markers of bone turnover, i.e., C-terminal and N-terminal telopeptides of type I collagen (S-CTX and S-NTX) and bone sialoprotein. Results were compared with urinary total pyridinoline, total deoxypyridinoline, and urinary C-terminal telopeptides of type I collagen (U-CTX) and urinary N-terminal telopeptides of type I collagen (U-NTX). The study population included healthy men (n = 27), premenopausal (n = 30) and postmenopausal (n = 31) women, patients with hepatic dysfunction (HF, n = 24), renal failure (RF, n = 30), breast cancer without (BC-, n = 24) and with (BC+, n = 30) bone metastases, primary vertebral osteoporosis (OPO, n = 27), primary hyperparathyroidism (PHPT, n = 16), active Paget's disease of bone (n = 18), multiple myeloma (MM, n = 18), and patients with hypercalcemia of malignancy before and after treatment with pamidronate (HOM, n = 28). Changes in urinary and serum markers were similar in most metabolic bone diseases. However, differentiation between healthy controls and OPO, or PHPT, was improved by the serum markers. In MM, all serum and urinary markers were elevated (p < 0. 05 vs. controls). In BC+, skeletal involvement was reflected by significant increments in all indices (p < 0.01 vs. BC-), except U-CTX and S-CTX. In HOM, pamidronate-induced changes in biomarkers were most pronounced for U-CTX and S-CTX and S-NTX. HF and RF were associated with elevated levels of all serum markers (p < 0.05 vs. controls). In conclusion, measurements in serum reflect bone resorption to the same extent as the urinary indices. Since serum markers circumvent some of the limitations of urinary measurements, their use potentially improves the assessment of skeletal disorders.
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PMID:Novel serum markers of bone resorption: clinical assessment and comparison with established urinary indices. 1032 May 28

Changes in skeletal remodeling (biochemical bone markers) and regional bone mineral density (spine, hip, and forearm bone mineral density [BMD]) were observed for 3 years in 20 patients (15 women and 5 men; age 54 +/- 11 years, range 29-69 years) after successful surgery for primary hyperparathyroidism (PHPT). Fifteen PHPT patients were compared with 15 normal controls who were exactly matched with respect to age, gender, and menopausal status (10 women and 5 men; age 53 +/- 12 years, range 29-65 years [PHPT] and 29-66 years [controls]). All bone markers (serum osteocalcin, bone alkaline phosphatase, and type I collagen telopeptide [ICTP], and urinary hydroxyproline and NTx/creatinine ratio) declined significantly and reached normal levels within 6 months. No major changes took place during the remaining 2.5 years, apart from urine hydroxyproline, which disclosed a small peak around 12 months with a further decline towards study end (p < 0.05). Bone mineral density increased significantly in all regions (p < 0.001). At all locations, except the intertrochanteric region of the hip, the increase continued from 6 months until study end (p < 0.05). The increase in BMD was unequally distributed among regions (p < 0.001). The increase at the proximal forearm was less than in the spine (p < 0.05), the trochanteric region of the hip (p < 0.05), and the distal forearm (p < 0.05). No difference in BMD increase was observed between men, and pre- and postmenopausal women. Compared with the matched control group, PHPT patients had significantly lower BMD at baseline in the proximal (p < 0.02) and distal (p < 0.05) forearm. Furthermore, during the 3-year follow-up period, the PHPT patients showed a significant increase in BMD compared with controls in the spine (p < 0.005), the trochanteric and intertrochanteric regions of the hip (p < 0.005 and p < 0.05, respectively), and the distal forearm (p < 0.005). In conclusion, bone remodeling is normalized within the first 6 months after successful parathyroid surgery, with no major changes during the following 2.5 years. Bone mineral density increases at both cancellous and cortical sites, but in predominantly cortical bone, the recovery in BMD is less than in cancellous bone-rich areas.
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PMID:Primary hyperparathyroidism: effect of parathyroidectomy on regional bone mineral density in Danish patients: a three-year follow-up study. 1057 80

In 19 patients with primary hyperparathyroidism (PHPT) (14 women and 5 men; age 53 +/- 11 years, range 29-69 years), bone densitometry, biochemical markers of bone turnover, and iliac crest bone biopsies were obtained before and 3 years after successful surgical treatment. A significant increase in bone mineral content (BMC) was observed in both the lumbar spine (p < 0.001) and the proximal part of the distal forearm (p < 0.001), whereas the increase in BMC in the femoral neck was insignificant. Biochemical markers of bone formation (serum alkaline phosphatase, serum bone alkaline phosphatase and serum osteocalcin) and resorption (serum pyridinoline cross-linked telopeptide of type I collagen and urine N-telopeptide of type I collagen) all decreased following treatment. In cortical bone, relative cortical width increased following surgery (p < 0.05) and cortical porosity decreased (p < 0.01). No changes were observed in core width or cortical width. In cancellous bone, no significant changes were observed in any of the measured structural parameters. However, significant reductions in the extent of osteoid- (p < 0.01) and tetracycline-labeled surfaces (p < 0.001), and in bone formation rate (p < 0.001) and activation frequency (p < 0.001), were found. The numerical decrease in the extent of eroded surfaces did not reach significance (p = 0.057). No changes were observed in mineral appositional rate and adjusted appositional rate. The amount of bone resorbed (expressed as the resorption depth) and the amount of bone reformed (expressed as wall thickness) per remodeling cycle seemed unaffected by the treatment. Consequently, no effect on bone balance per remodeling cycle could be detected. The present study of PHPT patients showed that, within 3 years after surgery, BMC of both cancellous and cortical bone areas had increased. At the same time, bone turnover decreased markedly, as judged from biochemical as well as histomorphometric data, but no changes were seen in trabecular bone structure. In cortical bone, the relative cortical width increased and the cortical porosity decreased.
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PMID:Primary hyperparathyroidism: bone structure, balance, and remodeling before and 3 years after surgical treatment. 1077 96

The most common clinical presentation of primary hyperparathyroidism (PHPT) is nowadays characterized by a slight skeletal involvement. We studied 5 consecutive female patients with PHPT presenting with bone turnover marker levels within the reference range of our Center and whose bone mineral density values were above the usual fracture risk threshold. In each patient we measured, both in basal conditions and daily, for the first 5 days after surgery, the following indexes: serum total (T-ALP) and bone-specific (B-ALP) alkaline phosphatase activity, osteocalcin (BGP, by two different assays), together with the 24-hour urinary excretions of total pyridinoline (Pyr/Cr) and deoxypyridinoline (DPyr/Cr), free deoxypyridinoline (FD-Pyr/Cr), cross-linked N-telopeptide of type I collagen (NTx/Cr), and type I C-telopeptide (CTx/Cr). The markers of both bone formation and resorption significantly decreased after surgery (p<0.001 by multiple ANOVA). Individual post-surgical markers changes were all significant but T-ALP and FD-Pyr, the most pronounced percent reductions being shown by NTx and CTx. The time-course of such variations substantially differed among the various indexes. These results show that bone formation and resorption markers are up-regulated also in PHPT patients with mild skeletal involvement; acute removal of parathyroid hormone excess differently affected the markers of bone turnover in terms of both entity and time-course.
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PMID:Short-term effects of surgery in post-menopausal patients with primary hyperparathyroidism and normal bone turnover. 1168 39


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