The predictive value of biochemical markers of bone turnover for bone mineral density in early postmenopausal women treated with hormone replacement or calcium supplementation

To compare the relative sensitivity and specificity of bone turnover indexes for bone loss or gain in early postmenopausal women, we performed a multicenter trial in 236 menopausal women (mean age, 51 yr), who were randomized to hormone replacement therapy (HRT) or calcium supplementation (CS; 500 mg/day) for 1 yr. Two markers of bone formation, osteocalcin (OC) and bone alkaline phosphatase (BSAP), and two markers of bone resorption, urinary N-telopeptide (NTx) and urinary free deoxypyridinoline (fDpd), as well as spine and femoral neck bone mineral density (BMD) were measured at baseline and 3, 6, and 12 months after treatment. Women receiving HRT (n = 105) showed a significant increase in spine BMD (+2.5%; P < 0.0001) and hip BMD (+1.0%; P = 0.02) compared to women receiving CS, who showed a decline at both sites (-1.1%; P < 0.01). All four markers showed time-dependent decreases in women receiving HRT (P < 0.001) and no change in women receiving CS alone. When baseline indexes of turnover were stratified by quartile, there was a significantly greater increase in BMD among those with the highest NTx, OC, and BSAP levels compared to that in those with the lowest NTx, OC, and BSAP levels (P < 0.05). The highest quartile for percent change from baseline to 6 months in fDpd, BSAP, and NTx was also associated with the greatest change in spine BMD at 1 yr. Receiver operator characteristic curves for percent change from baseline to 6 months in an individual marker to 1 yr change in BMD during HRT revealed that the percent change in NTx provided the greatest discrimination between gain and loss of BMD. When subjects receiving HRT were compared by their positive or negative skeletal response at 1 yr and their baseline turnover marker, initial NTx values were significantly higher in those that gained bone than in those that lost bone (P = 0.0002). CS women in the highest quartile for NTx at baseline had significantly greater decreases in spine BMD than subjects with the lowest NTx values (P < 0.005), although this was not true for fDpd (P < 0.20). In conclusion, for early postmenopausal women there are differential responses of biochemical markers to HRT and CS. Baseline urinary NTx and serum OC were the most sensitive predictors of change in spine BMD after 1 yr of either HRT or CS. Similarly, the percent change in NTx and OC from baseline to 6 months best predicted bone gain or loss. We conclude that markers of bone formation and resorption can be used clinically to predict future BMD in early postmenopausal women.     

Evaluation of bone turnover in type I osteoporosis using biochemical markers specific for both bone formation and bone resorption

Multivariate analysis was used to determine which characteristics: sex of the proband, sibling sex, severity of the proband's defect or family history, are the best predictors of recurrence risk among siblings of individuals with non-syndromic cleft lip with or without cleft palate (CL +/- P). Sibling recurrence risks are not significantly related to the sex of the proband. Severity of the proband's defect, classified by the extent of the lip defect (unilateral versus bilateral), was found to be a significant predictor of sibling recurrence, whereas involvement of the palate in the proband's defect was not. A positive family history of clefting (i.e. at least one affected first-degree relative in addition to the proband) and the sex of the sibling were also found to be significant predictors of sibling recurrence. The associations between sibling risk and family history, and sibling risk and bilaterality of the proband's defect appear to be mildly confounded. After adjusting for the effects of family history, the risk to siblings of probands with bilateral lip defects is twice the risk to siblings of probands with unilateral defects (O.R. = 2.00; 95% C.I. 1.25-3.19). A positive family history of clefting increases the risk to siblings by greater than 4-fold (O.R. = 4.49; 95% C.I. 2.74-7.35), after adjusting for the extent of the proband's lip defect. These results provide a rational strategy for identifying subsets of the 'at risk' population which have markedly different recurrence risks. This information is important for genetic counseling, since it allows for more precise estimation of sibling recurrence risks in individual cases.(ABSTRACT TRUNCATED AT 250 WORDS)     

Monitoring of bone turnover biological, preanalytical and technical criteria in the assessment of biochemical markers

A review is given summarizing the present knowledge of bone turnover markers with special emphasis on biological, preanalytical and technical criteria in the proper judgement of efficacy and limitations of the methods employed. The marker substances may be either measures of bone formation or bone resorption. Markers of bone formation are bone alkaline phosphatase, osteocalcin and the carboxyl-terminal propeptide of procollagen type I. Bone alkaline phosphatase has proved to be superior to total alkaline phosphatase activity with respect to diagnostic sensitivity and specificity. Immunochemical techniques for measuring bone alkaline phosphatase show a cross-reactivity of 14-20% with liver alkaline phosphatase. However, this does not compromise the clinical usefulness of these assays except for patients with severe liver diseases. Osteocalcin is strictly bone-specific but shows numerous disadvantages with respect to apparent instability and discordant results as obtained by different methods; however, in certain diagnostic situations (corticosteroid-induced osteopenia, absence of destroyed bone architecture) osteocalcin may serve as a sensitive bone turnover marker. The carboxyl-terminal propeptide of procollagen type I generally shows low discriminating power in the diagnosis of bone diseases. The urinary excretion of pyridinium "cross-links' has been carefully evaluated so far with respect to analytical performance and clinical usefulness. This marker may be a substitute for 4-hydroxyproline measurements as the method of choice for assessment of bone resorption. There are other degradation products from the telopeptide regions of bone-derived collagen type I which are excreted into the urine (N-telopeptides, CrossLapsTM); these analytes are promising tools in the assessment of bone resorption but require further evaluation, in particular with respect to their extraskeletal clearance and putative origin outside bone. Moreover, their clinical usefulness may vary depending on the patient group examined. In contrast, the serum concentration of the cross-linked telopeptide region of collagen type I seems to lack both diagnostic specificity and sensitivity in the majority of patient groups. Tartrate-resistant acid phosphatase (as determined by the presently available methods) cannot be recommended as a routine tool for assessment of bone resorption.     

Quantification of biochemical markers of bone turnover by kinetic measures of bone formation and resorption in young healthy females

The quantification of biochemical markers of bone formation and resorption with kinetic measures of bone turnover is an essential step in their validation. Some biochemical markers have been validated by quantification against formation and resorption rates measured by calcium kinetics in adults with bone disease. However, none has been validated in healthy individuals who are undergoing skeletal growth and bone consolidation. Therefore, we have measured biochemical markers of bone formation (serum osteocalcin [OC], bone-specific alkaline phosphatase [BAP], and total alkaline phosphatase [ALP]) and resorption (serum tartrate resistant acid phosphatase [TRAP], urinary cross-linked N teleopeptides of type I collagen/creatinine [NTx/Cr], and hydroxyproline/creatinine [OHP/Cr]) in healthy females aged 11-32 years (n = 31) after an overnight fast to determine their relationship with bone formation (Vo+) and bone resorption (Vo-) as measured by calcium kinetics and balance. All biochemical markers were highly intercorrelated (r > 0.6, p < 0.001) as were Vo+ and Vo- (r = 0.91, p < 0.001). Highly significant correlations were present between bone formation measured by calcium kinetics (Vo+) and serum levels of bone biochemical markers (OC, r = 0.82, p = 0.001; ALP, r = 0.92, p = 0.001; and BAP, r = 0.90, p = 0.001) and between bone resorption measured by calcium kinetics (Vo-) and fasting serum levels and urine creatinine ratios of biochemical markers (TRAP, r = 0.77, p < 0.001; OHP/Cr, r = 0.79, p < 0.001; and NTx/Cr, r = 0.70, p < 0.001). Thus, biochemical markers of bone formation and resorption can be used to predict calcium kinetic rates during skeletal growth and the early years of formation of peak bone mass, ages at which strategies to build peak bone mass are important. Biochemical markers of formation and resorption are equally useful in predicting either the bone formation rate or the resorption rate.     

Identification of metabolic bone disease in patients with endogenous hyperthyroidism: role of biological markers of bone turnover

Active hyperthyroidism is associated with reduced bone mass. Nevertheless, not all patients show the same risk for developing osteoporosis. Our aim was to analyze some clinical and biochemical potential predictors of low bone mass in hyperthyroid patients. We studied 127 consecutive hyperthyroid patients (110 females, 17 males; aged 42 +/- 16 years). Bone mineral density (BMD) was measured by dual X-ray absorptiometry (DXA) at lumbar spine (LS; L2-L4) and femoral neck (FN). Data were expressed as g/cm2 and T-score. Patients were placed into two groups based on recent WHO criteria: Group A, no osteoporosis (n = 98); and group B, lumbar or femoral osteoporosis (n = 29). Study protocol included evaluation of osteoporosis risk factors, anthropometrical variables, thyroid function, and bone turnover markers. Receiver-operating characteristic (ROC) plots for the precision of bone markers and multivariate analysis for the prediction of BMD and osteoporosis were performed. Group B showed greater age and proportion of menopausal females; lower weight, height, and calcium intake; longer duration of menopause; and greater levels of total and bone alkaline phosphatase and of urine hydroxyproline. No differences in thyroid function, osteocalcin, tartrate-resistant acid phosphatase, and type I collagen C-telopeptide (ICTP) were found. The best predictive model accounted for 46% and 62% of the variability of lumbar and femoral BMD respectively and correctly classified 89% of the osteoporotic hyperthyroid patients. No significant difference in ROC plots was observed. It is concluded that hyperthyroid patients with lumbar or femoral osteoporosis show a typical clinical and biochemical profile illustrating that the relationship between BMD and bone markers is better in high turnover states. Classical bone turnover markers show high performance in the evaluation of hyperthyroid bone disease.     

Calcium supplementation prevents seasonal bone loss and changes in biochemical markers of bone turnover in elderly New England women: a randomized placebo-controlled trial

Elderly women are at increased risk for bone loss and fractures. In previous cross-sectional and longitudinal studies of women residing in northern latitudes, bone loss was most pronounced during winter months and in those consuming less than 1 g calcium per day. In this study we sought to test the hypothesis that calcium supplementation by either calcium carbonate or dietary means would prevent seasonal bone loss and preserve bone mass. Sixty older postmenopausal women without osteoporosis were randomized to one of three treatment arms: Dietary milk supplementation (D-4 glasses of milk/day), Calcium carbonate (CaCO3-1000 mg/day in two divided doses), or placebo (P). After 2 yr, placebo-treated women consumed a mean of 683 mg/day of calcium and lost 3.0% of their greater trochanteric (GT) bone mineral density (BMD) (P < 0.03 vs. baseline); Dietary supplemented women averaged a calcium intake of 1028 mg/day and sustained minimal loss from the GT (-1.5%; P = 0.30), whereas CaCO3-treated women (total Ca intake, 1633 mg/day) suffered no bone loss from the GT and showed a significant increase in spinal and femoral neck BMD (P < 0.05). Femoral bone loss occurred exclusively during the two winters of the study (i.e. total loss, -3.2%; P < 0.02 in placebo-treated women) with virtually no change in GT BMD during summer. Serum 25-OH vitamin D declined by more than 20% (P < 0.001) in all groups during the winter months but returned to baseline in summer; PTH levels rose approximately 20% (P < 0.001) during winter but did not return to baseline during the summers. Urine N-telopeptide and osteocalcin levels increased significantly but only in the P-treated women and only during winter. Serum insulin growth factor binding protein 4, an inhibitory insulin growth factor binding protein, rose 15% (P < 0.03) from summer to winter, but this increase was significant only in those women consuming <1000 mg/day of calcium. By multivariate analysis, total calcium intake was the strongest predictor of bone loss from the hip. Urinary N-telopeptide also closely correlated with GT BMD but only during winter (P = 0.003). We conclude that calcium supplementation prevents bone loss in elderly women by suppressing bone turnover during the winter when serum 25-OH vitamin D declines and serum PTH increases. The precise amount of calcium necessary to preserve BMD in elderly women requires further studies, although in this study, at least 1000 mg/day of supplemental calcium was adequate prophylaxis against femoral bone loss.     

A longitudinal study of markers of bone turnover in Graves'' disease and their value in predicting bone mineral density

Alterations of chromosome 8, including deletions of 8p, occur frequently in many tumors. In this study, fluorescence in situ hybridization was used to study the relationship between 8p deletions, 8q gains, and phenotype in bladder cancer. Cells from 87 tumors were examined by dual-labeling fluorescence in situ hybridization with a centromere 8 probe (pJM12) and P1 probes for 8p22, 8p12, 8q12, and 8q24. Both 8p22 deletions and 8q24 gains were strongly associated with tumor phenotype. There was a marked difference in 8p22 deletions between noninvasive (pTa) tumors (3/33) and minimally invasive (pT1) tumors (8/19; P = 0.005) whereas there was no significant difference between pT1 and muscle-invasive (pT2-4) tumors (19/35; P = 0.3926). Six tumors with 8p22 deletion were examined at 8p12. Three of these tumors showed no 8p12 deletion, narrowing down the site of a putative tumor suppressor gene distal to 8p12. In one other case, there was a marked increase in 8p12 copy number (> 40 per cell; amplification), suggesting the presence of an oncogene involved in bladder cancer at 8p12. The marked difference in 8p22 deletions between noninvasive (pTa) and minimally invasive (pT1) tumors is consistent with a role of a putative tumor suppressor gene on 8p for development of invasive tumor phenotype.     

The clinical usefulness of urinary pyridinoline and deoxypyridinoline as potential markers of bone metastasis in patients with prostate cancer

The aims of this study were to investigate the effects of paracentesis on uterine and intraovarian haemodynamics by colour Doppler ultrasound and the influences of repeated paracentesis on pregnancy outcome in severe ovarian hyperstimulation syndrome (OHSS). Forty-one abdominal paracenteses were performed on seven pregnant women with tense ascites and eight thoracocenteses were performed on three pregnant women with pleural effusion. Pulsatility index (PI) and maximum peak systolic velocity (MPSV) of uterine and intraovarian arteries were measured before and after each intervention. The mean PI of uterine arteries was decreased significantly after paracentesis, but not after thoracocentesis. Furthermore, uterine PI was decreased in 13 out of 14 (92.9%) paracenteses with <2500 ml ascites removed, compared with eight out of 13 (61.5%) with >2500 ml ascites removed. After paracentesis, there were no significant changes in the intraovarian PI and MPSV in either group. The 24-hour urine output increased significantly in the paracentesis group, but not in the thoracocentesis group. There were no significant changes in haematocrit and electrolytes as a result of paracentesis. However, gradual falls in serum total proteins and albumin concentrations were observed in all patients after repeated paracentesis, necessitating post-paracentesis albumin infusion. There was no significant difference in miscarriage rates between the two groups. We conclude that repeated abdominal paracentesis increases uterine perfusion and has no adverse effects on pregnancy outcome in severe OHSS. Extraction of 2500 ml of ascitic fluid did not impair uterine perfusion.     

High prevalence of adynamic bone disease diagnosed by biochemical markers in a wide sample of the European CAPD population

BACKGROUND: Adynamic bone disease (ABD) has been described in the current dialysis population to have an unexpectedly high prevalence. Moreover, it is clearly more prevalent in CAPD patients, compared to haemodialysis patients. Recently we demonstrated that both a low (< or = 27 U/1) level of bone alkaline phosphatase (BAP) as determined by an optimized agarose gel electrophoretic technique and a low (< or = 150 pg/ml ) level of iPTH are good markers of ABD with sensitivities of 78.1% and 80.6% and specificities of 86.4% and 76.2% respectively. METHODS: In this study (n = 212), the prevalence of ABD in the European CAPD population was evaluated by means of these biochemical markers. Clinical data on the patients included were recorded at the moment of blood sampling. In patients under CAPD treatment for longer than 9 months, we calculated an index of calcium exposure through PD fluid. RESULTS: In this population with a low exposure to aluminium, the prevalence of ABD as indicated by either a low level of BAP or PTH was 43%. The following risk factors could be identified: advanced age, shorter time on renal replacement therapy, male gender, and high calcium content of PD fluid. The index of calcium exposure was significantly higher in the patients with low BAP and low iPTH levels compared to those with either BAP > or = 27 U/1 or iPTH > 150 pg/ml. The latter finding gives further support to the hypothesis that a high calcium load administered to renal failure patients may lead to 'oversuppressed' parathyroids in ABD. In a subgroup of patients with a high level of BAP associated with a low iPTH level a profile previously shown to be associated in the presence of aluminium overload, significantly higher serum aluminium levels were noted. suggesting that even in patients with low exposure to aluminium, this element still can affect bone metabolism. CONCLUSION: A high prevalence of ABD--as diagnosed by biochemical markers--was observed in the European CAPD population. A number of risk factors could be put forward. The aetiology and pathogenesis of this type of renal osteodystrophy remain to be elucidated, but appear, however, to be multifactorial.     

Early changes in biochemical markers of bone turnover predict the long-term response to alendronate therapy in representative elderly women: a randomized clinical trial

Although the antiresorptive agent alendronate has been shown to increase bone mineral density (BMD) at the hip and spine and decrease the incidence of osteoporotic fractures in older women, few data are available regarding early prediction of long-term response to therapy, particularly with regard to increases in hip BMD. Examining short-term changes in biochemical markers incorporates physiologic response with therapeutic compliance and should provide useful prognostic information for patients. The objective of this study was to examine whether early changes in biochemical markers of bone turnover predict long-term changes in hip BMD in elderly women. The study was a double-blind, placebo-controlled, randomized clinical trial which took place in a community-based academic hospital. One hundred and twenty community-dwelling, ambulatory women 65 years of age and older participated in the study. Intervention consisted of alendronate versus placebo for 2.5 years. All patients received appropriate calcium and vitamin D supplementation. The principal outcome measures included BMD of the hip (total hip, femoral neck, trochanter, and intertrochanter), spine (posteroanterior [PA] and lateral), total body, and radius. Biochemical markers of bone resorption included urinary N-telopeptide cross-linked collagen type I and free deoxypyridinoline; markers of bone formation included serum osteocalcin and bone-specific alkaline phosphatase. Long-term alendronate therapy was associated with increased BMD at the total hip (4.0%), femoral neck (3.1%), trochanter (5.5%), intertrochanter (3.8%), PA spine (7.8%), lateral spine (10.6%), total body (2.2%), and one-third distal radius (1.3%) in elderly women (all p < 0.01). In the placebo group, bone density increased 1.9-2.1% at the spine (p < 0.05) and remained stable at all other sites. At 6 months, there were significant decreases in all markers of bone turnover (-10% to -53%, p < 0.01) in women on alendronate. The changes in urinary cross-linked collagen at 6 months correlated with long-term bone density changes at the hip (r = -0.35, p < 0.01), trochanter (r = -0.36, p < 0.01), PA spine (r = -0.41, p < 0.01), and total body (r = -0.34, p < 0.05). At 6 months, patients with the greatest drop in urinary cross-linked collagen (65% or more) demonstrated the greatest gains in total hip, trochanteric, and vertebral bone density (all p < 0.05). A 30% decrease in urinary cross-linked collagen at 6 months predicted a bone density increase of 2.8-4.1% for the hip regions and 5.8-6.9% for the spine views at the 2.5-year time point (p < 0.05). There were no substantive associations between changes in biochemical markers and bone density in the placebo group. Alendronate therapy was associated with significant long-term gains in BMD at all clinically relevant sites, including the hip, in elderly women. Moreover, these improvements were associated with early decreases in biochemical markers of bone turnover. Early dynamic decreases in urinary cross-linked collagen can be used to monitor and predict long-term response to bisphosphonate therapy in elderly women. Future studies are needed to determine if early assessment improves long-term patient compliance or uncovers poor compliance, thereby aiding the physician in maximizing the benefits of therapy.     

Crevicular fluid osteocalcin and pyridinoline cross-linked carboxyterminal telopeptide of type I collagen (ICTP) as markers of rapid bone turnover in periodontitis. A pilot study in beagle dogs

The objective of this study was to correlate the levels of 2 putative markers of bone metabolism, namely osteocalcin and pyridinoline cross-linked carboxyterminal telopeptide of type I collagen (ICTP), to the progression of experimental alveolar bone loss in the beagle dog. 36 control sites and 36 experimental sites in 2 beagle dogs were assessed longitudinally at 2-week intervals for gingival crevicular fluid (GCF) osteocalcin and ICTP levels during a 6-month observation period. Analysis of osteocalcin and ICTP in GCF was performed by RIA. During the study, bone-seeking radiopharmaceutical uptake (BSRU) of 99mTc-MDP was assessed monthly; standardized radiographs were taken at 2-week intervals. The results showed osteocalcin and ICTP levels in GCF increased significantly (p < 0.05) by 2 weeks following initiation of disease. This increase preceded significant increases in BSRU by 2 weeks and radiographic evidence of bone loss by 4 weeks. BSRU was significantly elevated (p < 0.05) at experimental sites as compared to controls at 4 and 8 weeks post-disease initiation. Osteocalcin in GCF peaked 8 and 10 weeks after ligature placement in experimental sites at levels nearly 10-fold greater than contralateral paired control sites. ICTP levels in GCF remained elevated throughout the entire disease progression phase. Following the removal of ligatures, both GCF osteocalcin and ICTP levels dropped precipitously approaching control values. Osteocalcin revealed overall a positive predictive value (PPV) and negative predictive value (NPV) for future bone loss during disease progression of 0.87 and 0.34, respectively, while ICTP showed both high PPV and NPV of 0.87 and 0.91 respectively. Results from this study in the dog model indicate that osteocalcin and especially ICTP relate to indices of active periodontal bony destruction and suggest that these molecules may serve as predictive markers for future alveolar bone loss.     

Evaluation of osteocalcin and pyridinium crosslinks of bone collagen as markers of bone turnover in gingival crevicular fluid during different stages of orthodontic treatment

Treatment with serotonin reuptake inhibitors (SRIs) has been shown to cause reduced libido and anorgasmia in women. A large body of evidence suggests that serotonin may influence sexual behavior in estradiol + progesterone primed, gonadectomized female rats; however, the influence of selective SRIs on the estrous behavior of intact female rats has not been described previously. In the present study, the effect of 1 to 3 weeks of fluoxetine administration (10 mg/kg daily) on vaginal and behavioral estrus in intact female rats was studied; in addition, the effect of fluoxetine (same dose, 1-8 weeks) on copulatory behavior and on sexual motivation in hormone-primed gonadectomized rats was investigated. Subchronic administration of fluoxetine did not influence cyclicity as judged by the examination of vaginal smears but significantly reduced the percentage of rats displaying receptive behavior in the estrous phase. In addition, fluoxetine significantly reduced receptive behavior, including lordosis, in ovariectomized female rats primed with estradiol (6.25 micrograms/rat; -48 hr) plus progesterone (1.0 mg/rat, -4 hr); in contrast, sexual motivation--as reflected by the amount of time these rats elected to spend in the vicinity of a male rather than in the vicinity of a female or elsewhere--was little affected by the treatment.     

Collagen-related markers of bone turnover reflect the severity of liver fibrosis in patients with primary biliary cirrhosis

In vitro studies have connected immune cell function to Peptide F. The primary purpose of this investigation was to examine the responses of plasma Peptide F and epinephrine along with the changes in B cell antibody production in vivo in physically fit and unfit women in response to physical exercise on a cycle ergometer at 60% and 80% of peak oxygen consumption. Seven aerobically fit and eight untrained (i.e., unfit) women between the ages of 18 and 30 volunteered to participate in this investigation. Blood samples (analyzed for plasma Peptide F and epinephrine along with the number of antibody-producing B cells) were obtained 24 hours prior to the exercise session, pre-exercise, during each exercise intensity, and five minutes post-exercise. The fit group had a significantly higher plasma Peptide F concentration after the 80% exercise intensity along with significantly higher numbers of antibody producing B cells compared to the unfit group. The results of this investigation show that physically fit women have an enhanced secondary response of B cells to a specific antigen under conditions where Peptide F is increased. Such data demonstrate that physical fitness as promoted by the Public Health Service (e.g., Healthy People 2000) influences the underlying hormonal and immune cell responses when challenged by physical exercise stress.     

Evaluation of markers of bone and collagen turnover in patients with active and preclinical Cushing''s syndrome and in patients with adrenal incidentaloma

OBJECTIVE: The purpose of this study was to evaluate whether the changes in plasma cytokine levels including interleukin-6 (IL-6) interleukin-1 beta (IL-1 beta), and tumor necrosis factor-alpha (TNF-alpha) are involved in postoperative fever following oral and maxillofacial surgery. STUDY DESIGN: Ten patients undergoing elective oral and maxillofacial surgery were studied. We investigated the plasma cytokine levels by using an enzyme-linked immunosorbent assay and measured the core temperature and degree of postoperative shivering and peripheral vasoconstriction after surgery. The relationships between the changes in plasma cytokine levels and postoperative fever were statistically evaluated using Spearman's rank correlation coefficients. RESULTS: The elevation of plasma IL-6 level was significantly correlated with the increase in core temperature after surgery and with the degree of postoperative shivering and vasoconstriction, whereas the changes in plasma II-1 beta or TNF-alpha levels were not. CONCLUSIONS: Elevation of plasma IL-6 level is probably involved in postoperative fever following oral and maxillofacial surgery.     

Symptomatic hypocalcemia in a patient with latent hypoparathyroidism and breast carcinoma with bone metastasis following administration of pamidronate

Pamidronate is an effective drug used not only in patients with tumor-associated hypercalcemia, but also in normocalcemic patients with metastatic bone disease to relieve pains. We describe a 39-year-old normocalcemic patient with subclinical hypoparathyroidism and bone metastasis due to breast carcinoma. Following parenteral administration of 60 mg pamidronate, the corrected serum level of calcium decreased from 2.12 mmol/l (=8.9 mg/dl) to 1.42 mmol/l (5.7 mg/dl), accompanied with carpal pedal spasm. The present case indicates that the hypocalcemia due to latent hypoparathyroidism was compensated by extensive osteolysis due to bone metastasis, and that overt hypocalcemia may develop after intravenous administration of pamidronate in such a patient.     

Assessment of urinary pyridinoline excretion with a specific enzyme-linked immunosorbent assay in normal adults and in metabolic bone diseases

Pyridinoline (Pyr), a specific bone resorption marker, is usually assessed in urine by high-performance liquid chromatography (HPLC) after acid hydrolysis and a prepurification step. Immunoassays have been developed to measure urinary Pyr directly. Here we developed and evaluated an enzyme-linked immunosorbent assay (ELISA), specific for the urinary free Pyr form, in normal adults and in patients with metabolic bone diseases. Urinary Pyr excretion increased significantly with age for men (r = 0.288; p < 0.001) and for women (r = 0.362; p < 0.001). An average 55% increase was noted between premenopausal (n = 41) and early postmenopausal (n = 42) women (mean +/- 1 SD; 22.4 +/- 6.3 nmol Pyr/mmol creatinine and 34.7 +/- 16.8 nmol Pyr/mmol creatinine, respectively; p < 0.001). High Pyr levels were found in patients with hyperthyroidism (n = 29; 126.5 +/- 84.2 nmol Pyr/mmol creatinine), Paget's disease of bone (n = 30; 61.8 +/- 45.8 nmol Pyr/mmol creatinine), and primary hyperparathyroidism (n = 10; 57.4 +/- 23.9 nmol Pyr/mmol creatinine). In patients with Paget's disease, urinary free Pyr excretion was correlated with urinary hydroxyproline, the conventional bone resorption marker (r = 0.87; p < 0.001), and with total alkaline phosphatase, a marker of bone formation (r = 0.55; p < 0.005). Free Pyr measured by ELISA was highly correlated with total Pyr and with total deoxypyridinoline HPLC measurements in postmenopausal women (n = 35; r = 0.94 and 0.91, respectively) and in patients with metabolic bone diseases (n = 22; r = 0.91 and 0.88, respectively; p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparison of ribotyping and arbitrarily primed PCR for molecular typing of Salmonella enterica and relationships between strains on the basis of these molecular markers

Arbitrarily primed PCR (AP-PCR) using a discriminatory 10-mer primer and an automated EcoRI ribotyping technique (Riboprinter) were compared for their ability to discriminate between 100 serovars of Salmonella, including multiple isolates representing Salm. Enteritidis PT4 and Salm. Typhimurium DT104. Profiles generated by each method were subjected to numerical analysis using GelCompar software, resulting in the construction of phylogenetic trees and calculation of Simpson's numerical index of diversity (DI). Both methods were highly discriminatory for isolates of Salmonella (Ribotype DI = 0.990, AP-PCR DI = 0.997) with EcoRI ribotyping proving more discriminatory than AP-PCR for isolates of Typhimurium DT104. The population structure was found to be clonal by numerical analysis of markers generated by both methods with serovars being polyphyletic in some cases and grouped in a single cluster in others. No absolute correlation was observed in the relationships between strains formed on the basis of ribo- and AP-PCR markers and serological characteristics.     

Evaluation of bone mineral turnover in children with nephrotic syndrome--the implications of original disease and the effects of corticosteroids on bone metabolism

A long term corticosteroids (CS) treatment is often required for children with nephrotic syndrome (NS), which may affect their bone metabolism. In this study we evaluate the effects of CS, and also the implication of the character of NS itself on bones. We divided sixteen cases of idiopathic NS in children into two groups, such as CS responder group (R; male/female = 8/4, mean age 10.9 years old), and CS non-responder group (NR; male/female = 4/0, mean age 10.2 years old). We measured the bone mineral density of lumber vertebrae by quantitative computed tomography (QCT), some biochemical and endocrinological markers for about half a year. The bone mineral density was significantly decreased soon after the beginning of CS therapy. A significant decrease in the serum osteocalcin level and a slight tendency for an increase in urinary excretion of the free hydroxyproline in the both R and NR groups. In addition, NR group showed hypocalcemia, a decrease in the serum 25-hydroxyvitamin D3 and 1,25-dihydroxyvitamin D3, and a slight tendency for an increase in the C-parathyroid hormone and highly sensitive parathyroid hormone levels. In conclusion, the results suggested that the effects of CS on bone metabolism were mainly the suppression of bone formation. In addition, the effects of CS and the character of NS itself should be evaluated separately when we consider about bone metabolism in children with NS and in greater detail.