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)

Quantitative ultrasound (QUS) of bone and new markers of bone remodeling have been poorly investigated in mild primary hyperparathyroidism (PHPT). In this study 26 patients (20 females and 6 males) were evaluated. BUA and SOS were measured by QUS at the heel. Markers of bone remodeling assessed were bone alkaline phosphatase (BAP), osteocalcin (OC), procollagen type I N- and C-terminal propeptides (PINP et PICP), and procollagen type I C-terminal telopeptide in blood and urine (ICTP and CTX). Bone mineral density (BMD) was measured at the lumbar spine (LS), femoral neck (FN), and Ward's triangle (WT). The control group comprised 35 sex- and age-matched subjects. The statistically significant variables between the two groups were (P < 0.05) BUA, BMD(LS), BMD(FN), BMD(WT), BAP, and OC. Corresponding z-scores were -0.55 +/- 0.75, -0.66 +/- 0.77, -0.66 +/- 0.71, -0.67 +/- 0.52, 1.87 +/- 3.87, and 1.93 +/- 3.53, respectively. Although PICP and PINP levels were higher in PHPT patients as compared with controls, the difference was not significant. Several markers of bone turnover were moderately correlated with both QUS (r = -0.39 to -0.55) and BMD (r = -0.48 to 0.63). In conclusion QUS seems to be a relevant tool in the assessment of bone status for patients with mild PHPT.
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PMID:Bone ultrasonometry and turnover markers in primary hyperparathyroidism. 1060 38

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

We employed skeletally matured rats to study changes in biochemical markers of bone turnover, bone mineral density (BMD), and bone biomechanics produced by continuous elevation of parathyroid hormone (PTH) in estrogen-deplete and -replete rodents. Ninety-six 7-month-old virgin female rats were divided randomly into 12 groups (n = 8) and treated as follows. One group was killed on the day of surgery. The remaining groups were either bilaterally ovariectomized (Ovx) or sham-operated and left untreated for 8 weeks, at which point, two groups, one sham and one Ovx, were killed. The remaining nine groups were treated for 2 weeks or 4 weeks. One sham and two Ovx groups received subcutaneous implants of Alzet miniosmotic pumps with vehicle for PTH. Two Ovx groups were given pumps with vehicle as well as a subcutaneous implant of 17beta-estradiol, which delivered 10 microg/kg per day. Two Ovx groups were implanted with rat PTH(1-34) in Alzet miniosmotic pumps, which delivered 30 microg PTH/kg per day. Two Ovx groups were implanted with both estradiol pellets and PTH-loaded pumps. One group of Ovx animals from each treatment was killed after 2 weeks and the other after 4 weeks. Biochemical markers of bone turnover, serum osteocalcin and urinary free pyridinoline, BMD, and mechanical strength of excised bones were measured. As expected, there was a significant increase in N-terminal PTH and serum calcium levels in all PTH infusion groups. Both serum osteocalcin and urinary pyridinoline showed a rapid increase within the first 2 weeks of the PTH infusion and remained elevated at week 4. In estrogen-replete groups, osteocalcin increased by week 2 of PTH infusion but pyridinoline did not increase until week 4. BMD of the distal and proximal femur showed the expected decrease 8 weeks after ovariectomy but did not exhibit any further changes during the 4 weeks of treatment with vehicle. Four weeks of PTH infusion in Ovx animals resulted in BMD loss at the midshaft, distal, and proximal regions of the femur. Estrogen repletion by itself, beginning 8 weeks after ovariectomy, produced no change in BMD at any site when compared with from Ovx vehicle-treated rats. Estrogen repletion in PTH-infused Ovx animals resulted in significant improvements of BMD comparable with sham-operated animals at all three femoral regions. The indentation test at the cancellous bone of the distal femur, three-point bending test at the midshaft femur, and cantilever bending test at the femoral neck showed that the changes in mechanical strength in these sites were consistent to the changes found in BMD. Our results showed that (1) continuously elevated levels of PTH induced additional loss of BMD in estrogen-deficient animals beyond the rapid bone loss phase associated with ovariectomy, (2) estrogen repletion, given by implant, to PTH-infused Ovx animals, reversed these BMD changes increasing BMD to levels comparable with estrogen-sufficient rats, and (3) these changes were reflected in the mechanical strength determined at these sites. These results lend experimental support that hormone replacement therapy may benefit bone health in postmenopausal women with primary hyperparathyroidism (PHPT). In addition, it raises the possibility that a continuous elevation of PTH could exert anabolic effects on skeletal tissue if its catabolic component can be minimized.
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PMID:Skeletal effects of parathyroid hormone infusion in ovariectomized rats with or without estrogen repletion. 1078 Aug 65

Increased levels of intact parathyroid hormone (PTH) have been documented after surgery for primary hyperparathyroidism (pHPT) despite normocalcemia. The pathogenesis remains to be elucidated. Seventeen consecutive patients operated on for solitary parathyroid adenoma were investigated before and at 8 weeks and 1 year after surgery with serum levels of intact PTH, biochemical variables known to reflect PTH activity, and bone mineral content (BMC). In addition, an oral calcium loading test was performed 8 weeks after the operation. All patients had low or normal serum calcium levels during follow-up. Eight weeks after operation six patients (35%) had an increased serum PTH level. These patients (group I) preoperatively had higher serum levels of PTH and alkaline phosphatase than patients with normal PTH levels (group II). They also had lower BMC and larger parathyroid adenomas. They did not differ in renal function. At 8 weeks after operation group I showed higher mean serum levels of osteocalcin and propeptide of type I procollagen but lower urinary calcium excretion. In contrast to patients in group II, they also showed a lower calciuric response and a trend to a lower calcemic response during the oral calcium load. The two groups showed similar parathyroid sensitivity for calcium. Patients in group I demonstrated a significant increase in BMC the first year after the operation. Increased serum PTH 8 weeks after surgery for sporadic parathyroid adenoma was not due to persistent pHPT or impaired renal function. Instead, the results imply there is diminished calcium absorption and increased bone turnover with cortical bone remineralization.
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PMID:Postoperative elevated serum levels of intact parathyroid hormone after surgery for parathyroid adenoma: sign of bone remineralization and decreased calcium absorption. 1103 1

In a large proportion of the patients with primary hyperparathyroidism (PHPT), a variable degree of osteopenia is the only relevant manifestation of the disease. Low bone mineral density (BMD) in patients with PHPT is an indication for surgical intervention because successful parathyroidectomy results in a dramatic increase in BMD. However, low BMD values are almost an invariable finding in elderly women with PHPT, who are often either unwilling or considered unfit for surgery. Bisphosphonates are capable of suppressing parathyroid hormone (PTH)-mediated bone resorption and are useful for the prevention and treatment of postmenopausal osteoporosis. In this pilot-controlled study, we investigated the effects of oral treatment with alendronate on BMD and biochemical markers of calcium and bone metabolism in elderly women presenting osteoporosis and mild PHPT. Twenty-six elderly patients aged 67-81 years were randomized for treatment with either oral 10 mg alendronate on alternate-day treatment or no treatment for 2 years. In the control untreated patients a slight significant decrease was observed for total body and femoral neck BMD, without significant changes in biochemical markers of calcium and bone metabolism during the 2 years of observation. Urine deoxypyridinoline (Dpyr) excretion significantly fell within the first month of treatment with alendronate, while serum markers of bone formation alkaline phosphatase and osteocalcin fell more gradually and the decrease became significant only after 3 months of treatment; thereafter all bone turnover markers remained consistently suppressed during alendronate treatment. After 2 years in this group we observed statistically significant increases in BMD at lumbar spine, total hip, and total body (+8.6 +/- 3.0%, +4.8 +/- 3.9%, and +1.2 +/- 1.4% changes vs. baseline mean +/- SD) versus both baseline and control patients. Serum calcium, serum phosphate, and urinary calcium excretion significantly decreased during the first 3-6 months but rose back to the baseline values afterward. Increase in serum PTH level was statistically significant during the first year of treatment. These preliminary results may make alendronate a candidate as a supportive therapy in patients with mild PHPT who are unwilling or are unsuitable for surgery, and for whom osteoporosis is a reason of concern.
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PMID:Effects of oral alendronate in elderly patients with osteoporosis and mild primary hyperparathyroidism. 1114 74

We describe a sinus, referred to as a bone remodeling compartment (BRC), which is intimately associated with cancellous bone remodeling. The compartment is lined on its marrow side by flattened cells and on its osseous side by the remodeling bone surface, resembling a roof of flattened cells covering the bone surface. The flat marrow lining cells are in continuity with the bone lining cells at the margins of the BRC. We examined a large number of diagnostic bone biopsy specimens received during recent years in the department. Furthermore, 10 patients (8 women and 2 men, median age 56 [40-69] years) with the high turnover disease of primary hyperparathyroidism who were treated with parathyroidectomy and followed for 3 years were included in the histomorphometric study. Bone samples for the immuno-enzyme staining were obtained from an amputated extremity of child. The total cancellous bone surface covered by BRC decreases by 50% (p < 0.05) following normalization of turnover and is paralleled by a similar 50% decrease in remodeling surface (p < 0.05). The entire eroded surface and two-thirds of the osteoid surface are covered by a BRC. BRC-covered uncompleted walls are 30% (p < 0.05) thinner than those without a BRC. This indicates that the BRC is invariably associated with the early phases of bone remodeling, that is, bone resorption, whereas it closes during the late part of bone formation. Immuno-enzyme staining shows that the flat marrow lining cells are positive for alkaline phosphatase, osteocalcin, and osteonectin, suggesting that they are bone cells. The first step in cancellous bone remodeling is thought to be the lining cells digesting the unmineralized matrix membrane followed by their disappearance and the arrival of the bone multicellular unit (BMU). We suggest that the lining cell barrier persists during bone remodeling; that the old lining cells become the marrow lining cells, allowing bone resorption and bone formation to proceed under a common roof of lining cells; that, at the end of bone formation, new bone lining cells derived from the flattened osteoblasts replace the marrow lining cells thereby closing the BRC; and that the two layers of lining cells eventually becomes a single layer. The integrity of the osteocyte-lining cell system is reestablished by the new generation of lining cells. The BRC most likely serves multiple purposes, including efficient exchange of matrix constituents and minerals, routing, monitoring, or modulating bone cell recruitment, and possibly the anatomical basis for the coupling of bone remodeling.
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PMID:Cancellous bone remodeling occurs in specialized compartments lined by cells expressing osteoblastic markers. 1154 27

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

This study aimed to clinically validate the global skeletal uptake (GSU) of (99m)Tc-methylene diphosphonate ((99m)Tc-MDP), and to compare it with a marker of bone formation (i.e. serum osteocalcin or OC) and an index of bone resorption (i.e. urinary deoxypyridinoline or U-DPD) in different endocrine disorders affecting the skeleton. We studied 29 female patients with thyrotoxicosis (TT), 27 with primary hyperparathyroidism (PHPT), 16 with acromegaly (AC), 15 with Cushing's syndrome (CS), and altogether 110 healthy women matched for age, BMI and menstrual status. In all subjects total body digital scan images (TBDS) were acquired at 5 min and at 4 h after the administration of (99m)Tc-MDP; the whole body retention (WBR) of the tracer was measured by counting two identical sets of rectangular ROIs, and GSU was subsequently calculated by drawing an irregular ROI on 4 h TBDS images. Serum OC was assessed by IRMA and urinary DPD by fluorometric detection after reverse phase high pressure chromatography. In TT patients GSU (40.0 +/- 5.1 vs 36.5 +/- 4.8%), OC (19.1 +/- 11.8 vs 7.1 +/- 2.9 microg/l) and U-DPD (62.4 +/- 42.7 vs 19.5 +/- 5.3 pmol/pmol) were significantly ( p<0.01) higher than in controls. PHPT patients showed GSU (47.2 +/- 6.6 vs 37.8 +/- 5.3%), OC (38.6 +/- 40.9 vs 8.2 +/- 2.5 microg/l), and U-DPD (55.0 +/- 51.3 vs 21.9 +/- 6.1 pmol/pmol) values significantly ( p<0.001) higher than controls. In CS patients, GSU (39.6 +/- 6.4 vs 32.7 +/- 3.5%; p<0.01) and U-DPD (22.8 +/- 8.4 vs 16.5 +/- 2.7 pmol/pmol; p<0.05) were higher, whereas OC (3.6 +/- 2.4 vs 5.2 +/- 1.9 mg/l; p<0,05) was lower than in controls. In AC patients, GSU (34.9 +/- 5.3 vs 35.2 +/- 3.4%) did not differ significantly from controls, whereas OC (16.8 +/- 8.8 vs 6.9 +/- 2.9 microg/l; p<0.001) and U-DPD (30.9 +/- 13.6 vs 21.0 +/- 5.7 pmol/pmol; p<0.01) were higher. Stepwise multivariate linear regression analysis was performed with disease activity, creatinine clearance, age, and years since menopause as predictor variables and GSU or OC or U-DPD as dependent variables. The significant partial regression coefficients ( r) were: in TT, free triiodothyronine (fT3) with GSU ( r = 0.37; p<0.005), Ln OC ( r = 0.30; p = NS), Ln U-DPD ( r = 0.76; p<0.0001), respectively; in PHPT, PTH with GSU ( r = 0.74; p<0.001), Ln OC ( r = 0.50; p<0.05), Ln U-DPD ( r = 0.64; p<0.001); in CS Ln urinary free cortisol with OC ( r = -0.68; p<0.001) and U-DPD ( r = 0.66; p<0.05). Our data suggest that GSU could represent a valuable clinical tool for evaluating bone turnover rate in PHPT, CS, TT but not in AC. The behavior of GSU and OC and U-DPD is non-uniform in disorders characterized by a marked uncoupling between bone formation and resorption.
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PMID:Global skeletal uptake of 99mTc-methylene diphosphonate (GSU) in patients affected by endocrine diseases: comparison with biochemical markers of bone turnover. 1237 73

Estrogen replacement therapy (ERT) decreases total serum calcium by about 0.5 mg/dl in postmenopausal women with primary hyperparathyroidism (PHPT). We investigated the ability of raloxifene, which has skeletal antiresorptive properties similar to those of ERT, to decrease serum calcium concentrations and markers of bone turnover in PHPT. Eighteen postmenopausal women with asymptomatic PHPT were randomized to 8 wk of raloxifene (60 mg/d) or placebo, followed by a 4-wk washout. At baseline, the groups were well matched. The calcium concentration decreased significantly by 8 wk of raloxifene administration (10.8 +/- 0.2 to 10.4 +/- 0.2 mg/dl; P < 0.05), as did markers of bone resorption and formation [osteocalcin, 11.4 +/- 1.6 to 9.9 +/- 1.6 nmol/liter (P < 0.05); serum N-telopeptide, 21.2 +/- 3.4 to 17.3 +/- 2.8 nmol bone collagen equivalents/liter (P < 0.05)]. Four weeks after raloxifene was discontinued, indices were indistinguishable from baseline. Raloxifene administration did not affect serum PTH, 1,25-dihydroxyvitamin D, total alkaline phosphatase, or urinary calcium excretion. Calcium and bone marker changes were therefore similar to those observed with ERT in PHPT. This short-term study suggests that raloxifene may be a useful approach to the treatment of postmenopausal women with mild PHPT.
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PMID:Raloxifene lowers serum calcium and markers of bone turnover in postmenopausal women with primary hyperparathyroidism. 1262 2

The effect of parathyroid hormone (PTH) on the production of osteoprotegerin (OPG) remains controversial. Most in vitro studies indicate that PTH decreases OPG secretion by the osteoblast, but in vivo observations are conflicting. In primary hyperparathyroidism (PHPT), hypersecretion of PTH leads to enhanced bone resorption and formation with increased risk of fracture. Patients with PHPT are cured by surgery, resulting in normalization of PTH levels and bone metabolism, but the concomitant effects on OPG production are not known. The hypothesis of the present study was that the circulating level of OPG is diminished in patients with PHPT and increases with successful parathyroidectomy. We also speculated that serum OPG may determine the magnitude of bone loss up to the time of surgery. In the present study, 20 patients (17 women and 3 men, mean age 62 y) with PHPT who were candidates for surgical cure were examined before and 12 months after surgery. Bone turnover markers decreased and BMD increased significantly after surgery. Serum OPG did not correlate with PTH before surgery (r = 0.07, P = 0.77) and was not affected by parathyroidectomy (P = 0.79). After normalization of PTH, bone formation markers showed significant (P1NP) and near-significant (osteocalcin) correlations with serum OPG. In conclusion, serum OPG is not decreased in patients with PHPT, nor is serum OPG to any demonstrable extent regulated by PTH pre- or postoperatively.
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PMID:Osteoprotegerin levels in primary hyperparathyroidism: effect of parathyroidectomy and association with bone metabolism. 1466 32


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