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Biomedical subjects

P Garnero

Publications and source records attributed to P Garnero.

At least 109 records · Page 6Linked to original sources
PubMed1996

Healthy elderly French women living at home have secondary hyperparathyroidism and high bone turnover in winter. EPIDOS Study Group.

It was recently demonstrated that calcium and vitamin D supplements were capable of decreasing the incidence of hip fractures in institutionalized elderly subjects through a reduction of senile secondary hyperparathyroidism. As there are no appropriate data to recommend such a supplement to the elderly living at home, the aim of this study was to determine the incidence of senile secondary hyperparathyroidism in old French women from the general community, its relation to vitamin D status, and its contribution to bone turnover. Four hundred and forty women, aged 75-90 yr, were randomly selected from the general community by mailing from electoral listing in 5 French cities whose latitude varies from 49 degrees 9N to 43 degrees 6N. At the end of the winter, with previous hip fractures or those who were institutionalized were excluded. The results obtained in these women were compared to those obtained in 59 institutionalized old women and 54 younger healthy women. In the five cities for the women living at home, we found a mean PTH value greater than that obtained in young women (63 +/- 28 vs. 43 +/- 15 pg/ml; P = 0.001), but lower that that found in institutionalized women (76 +/- 49 pg/mL; P = 0.05). The mean 25-hydroxyvitamin D (25OHD) level was not different in subjects from the 5 cities, but in all of them it was significantly greater than that found in 59 institutionalized women (42.5 +/- 25.0 vs. 15.5 +/- 6.5 nmol/L; P = 0.0001) but lower than that in young adults (P < 0.001). The main determinants of PTH were in equal ratio, i.e. age (r = 0.19; P < 0.001), 25OHD, and, to a lesser degree, creatinine clearance (r = 0.10; P = 0.03). For 25OHD, the main determinant was the personal outdoor score and, to a lesser extent, the amount of daily sunlight in the city. The mean values of biochemical markers of bone turnover, bone alkaline phosphatase, osteocalcin, and Crosslaps, were significantly increased compared with the results obtained in young women, and significant negative correlations were found between these markers and hip bone mineral density. These results show that vitamin D status of a French aged population in good health and living at home depends mainly on lifestyle. Like institutionalized women, old women living at home exhibit clear evidence of senile hyperparathyroidism in the winter, secondary in part to a reduced 25OHD level and associated with biological signs of increased bone turnover. The maintenance of PTH within the normal range for healthy adults by vitamin D and calcium treatment might constitute an approach for the prevention of bone loss in the entire aged population.

Aged↗
PubMed1995

Different effects of bisphosphonate and estrogen therapy on free and peptide-bound bone cross-links excretion.

We have measured the free and peptide-bound type I collagen cross-link excretions in normal women and in patients with metabolic bone disease using the HPLC technique and immunoassays recognizing specifically the free or peptide-bound forms of pyridinoline (Pyr). After menopause, free deoxypyridinoline (free D-Pyr) excretion measured by HPLC without urine hydrolysis and expressed as a fraction of the total excretion was lower than in premenopausal women (45 +/- 15% vs. 59 +/- 12%, p < 0.005), whereas the fraction of free Pyr was not changed. In normal pre- and postmenopausal women (n = 43), the fraction of free D-Pyr was negatively correlated with bone turnover rate as assessed by the total urinary excretion of Pyr (r = -0.64, p < 0.001). In patients with a variety of metabolic bone diseases characterized by increased bone turnover (osteoporosis, Paget's disease, and hyperthyroidism), the fractions of free Pyr and free D-Pyr were significantly lower than in premenopausal controls (p < 0.001 for all diseases). After 3 days of intravenous (iv) treatment with the bisphosphonate pamidronate in patients with Paget's disease and osteoporosis, the urinary excretion of cross-linked peptides measured by high performance liquid chromatography (HPLC) or enzyme-linked immunoassay (ELISA) (NTX and CrossLaps) was markedly decreased (-52% and -85% for NTX, -71% and -93% for CrossLaps in Paget's disease and osteoporosis, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Vitamin D receptor gene polymorphisms do not predict bone turnover and bone mass in healthy premenopausal women.

Bone mineral density (BMD) is under strong genetic control. Polymorphisms at the vitamin D receptor (VDR) gene have been recently suggested to account for up to 75% of this genetic effect. We analyzed these polymorphisms, i.e., that of BsmI, TaqI, and ApaI restriction enzymes by PCR of the DNA in 189 healthy premenopausal women aged 31 to 57 years. For the BsmI polymorphism they were 17% BB homozygotes, 51% Bb heterozygotes, and 32% bb homozygotes, genotype frequencies that are very similar to those previously reported in other Caucasian populations of north European ancestry. Women in the three genotypes for any of the three polymorphisms were matched for age and did not differ in body weight, height, physical activity, nor smoking habits. We found no relationship between the genotype for any of the three polymorphisms nor bone formation and resorption rate assessed by five specific biochemical markers of bone turnover nor with BMD measured at the spine, proximal femur, forearm, and whole body by dual-energy X-ray absorptiometry (DXA). We concluded that these polymorphisms are not predictive of bone turnover nor BMD in a sample of healthy premenopausal women drawn from the French population.

Adult↗
PubMed1995

Age-related changes in Os calcis ultrasonic indices: a 2-year prospective study.

We performed repeated ultrasound measurements approximately 2 years apart (average 23 months +/- 3 months) on the os calcis of 113 healthy postmenopausal women recruited from two large prospective cohort studies named OFELY and EPIDOS. Group A (from OFELY) consisted of 88 women aged 52-72 (63 +/- 5) years, randomly selected from a large insurance company, and group B (from EPIDOS) consisted of 25 women aged 75-88 (80 +/- 4) years, randomly selected from the voting lists. We obtained broadband ultrasonic attenuation (BUA) and speed of sound (SOS) measurements, as well as the Stiffness index, with a Lunar Achilles ultrasound machine. We performed dual energy X-ray absorptiometry (DXA) measurements of femoral neck bone mineral density (neck BMD) with a Hologic QDR 2000 for group A and with a Lunar DPX Plus for group B. The decrease that we observed over 2 years was on average +/- 1 SD: -1.01 +/- 4.6 dB/MHz (p = 0.02) for BUA (which is approximately equal to the long-term precision error in vitro), -11.3 +/- 9.2 m/s (p = 0.0001) for SOS (approximately 5 times the precision error), -3.8 +/- 4.2% YA (p = 0.0001) for Stiffness (2.5 times the precision error) and -0.01 +/- 0.03 g/cm2 (p = 0.0001) for neck BMD (approximately equal to the precision error). In terms of percentage change this represents: -1.0% +/- 4.3% for BUA, -0.8% +/- 0.6% for SOS and -1.85% +/- 4.4% for neck BMD. At the individual level, most SOS and Stiffness values were consistent with a decrease, whereas BUA and neck BMD values were spread out above and below the zero line of no change. The decreases in SOS and Stiffness were significantly larger in the early postmenopause (< or = 20 years since menopause [YSM]) than in the late postmenopause (> 20 YSM). We observed a similar trend for BUA and BMD but this did not reach statistical significance. We found a weak but significant correlation between changes in ultrasound variables and changes in neck BMD. However, the 2-year changes observed in SOS were not significantly correlated with changes in BUA. This study suggests that the heel ultrasound measurements of SOS and Stiffness are valuable indices of postmenopausal bone loss, and could be used for follow-up in therapeutic trials.

Absorptiometry, Photon↗
PubMed1995

Decreased bone turnover in oral contraceptive users.

The objective of this study was to determine the effect of oral contraceptive pills on bone turnover. The design consisted of a cross-sectional analysis of a prospective cohort. There were 52 women taking oral contraceptives and 156 nonuser controls from a large cohort of 1039 healthy women, aged 31-89 years (OFELY study). Most users were taking combined oral contraceptives containing 30 micrograms ethinyl estradiol and the mean duration of pill use was 6.7 +/- 6.4 years. Users and nonusers were matched for age [mean age (years): 39.3 +/- 3.5 vs. 40.5 +/- 4.3, range 35-49 years for both]. Main outcome measures included three markers of bone formation (serum osteocalcin, bone-specific alkaline phosphatase, and C-terminal propeptide of type I collagen) and two markers of bone resorption that are pyridinoline crosslinked peptides (Crosslaps and NTX). Users and nonusers did not differ for weight, height, alcohol and tobacco use, dietary calcium intake, parity, exercise activity, body fat and lean composition, and calcium chemistry tests. In pill users all bone formation and resorption markers were decreased compared with controls: osteocalcin, 7.7 +/- 2.7 vs. 10.1 +/- 3.1 ng/mL (-24%, p < 0.001); bone-specific alkaline phosphatase, 7.5 +/- 2.3 vs. 8.8 +/- 2.7 ng/mL (-15%, p < 0.003); C-terminal propeptide of type I collagen, 77.2 +/- 93.1 vs. 93.1 +/- 31.9 ng/mL (-17%, p = 0.001); Crosslaps: 175 +/- 91 vs. 211 +/- 105 micrograms/mmol Cr (-17%, p = 0.03); and NTX, 16.2 +/- 5.9 vs. 22.5 +/- 9.4 nmol of bone collagen equivalent/mmol Cr (-28%, p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Absorptiometry, Photon↗
PubMed1994

Characterization of immunoreactive forms of human osteocalcin generated in vivo and in vitro.

Three monoclonal antibodies recognizing the 5-13, 25-37, and 43-49 sequence of the human osteocalcin were used in competitive and two-site radioimmunoassays (RIA) to characterize specifically various immunoreactive forms of circulating human osteocalcin. The intact molecule accounts for 36% of total in normals (2.6 nM), 46% in patients with osteoporosis (3.1 nM), and 26% in chronic renal failure (6.9 nM). Four fragment were detected in addition to the intact molecule in the serum of healthy adults and patients with metabolic bone disease. N-terminal, mid, and mid C-terminal fragments were present in minute amounts (each accounting for 5-14% of the total circulating osteocalcin immunoreactivity). In contrast, the N-terminal midfragment, probably resulting from the cleavage around amino acids 43-44, represents about 30% (2 nM) of the total osteocalcin immunoreactive level in normals and patients with osteoporosis and up to 50% (13 nM) in patients with chronic renal failure. This large N-terminal midfragment, representing 75-80% of the intact osteocalcin level, is not lower when the plasma assay is performed immediately after sampling (within 20 minutes at 4 degrees C with proteinase inhibitors), indicating that it circulates in vivo. In addition, this fragment was detected in the supernatant of osteoblastic cells, representing about 28% of the intact peptide. Levels of N-terminal midfragment were not changed after treatment of patients with metabolic bone disease (Paget's disease, reflex sympathetic dystrophy, fibrous dysplasia, and osteoporosis) by bisphosphonate, suggesting that it is not released during bone resorption. The osteocalcin level measured with the two-site immunoradiometric assay specific for the intact molecule or with a conventional bovine RIA was rapidly decreased after incubation of serum at room temperature (-20 and -15%, respectively, after 3 h), whereas the total level of intact osteocalcin plus N-terminal midfragment was not changed. Intact osteocalcin loss can be partially avoided by proteinase inhibitors and by incubating serum at 4 degrees C. In conclusion, we characterized multiple immunoreactive forms of osteocalcin that circulate in addition to the intact molecule, none of them being specifically altered in osteoporosis. The N-terminal midfragment circulates in a large amount, probably resulting from cleavage of the intact molecule in the circulation and/or at peripheral sites. These fragments can also be generated in vitro by proteolytic degradation of the intact molecule. To obtain reliable intact osteocalcin values but also reliable levels measured with conventional competitive RIA, careful control of the sampling conditions is warranted.

Adult↗
PubMed1994

Markers of bone turnover in hyperthyroidism and the effects of treatment.

Serum osteocalcin (OC) and bone-specific alkaline phosphatase (B-ALP), reflecting bone formation, and urinary pyridinoline cross-link (Pyr) excretion, reflecting bone resorption, have been measured in 27 patients with hyperthyroidism and 30 age-matched controls using direct and novel immunoassays. Hyperthyroid patients had higher (P < 0.001) levels of all 3 markers compared with control values: Pyr, 246 +/- 181 nmol/mmol creatinine vs. 40 +/- 12 (+515%); OC, 55 +/- 23 vs. 23 +/- 7.4 micrograms/L (+139%); and B-ALP, 22 +/- 17 vs. 10.0 +/- 5.0 micrograms/L (+120%). OC and Pyr levels were elevated above the normal range in most patients and were significantly correlated with serum free T3 concentrations (r = 0.53; P < 0.01 and r = 0.76; P < 0.001; for OC and Pyr, respectively). B-ALP levels were elevated in 11 of the 27 patients and did not correlate with serum thyroid hormone concentrations. After therapy for hyperthyroidism, Pyr and OC levels returned to normal within 1 month, whereas B-ALP transiently increased after 1 month before falling to baseline levels. The relapse of hyperthyroidism observed in 1 patient was associated with a steep increase in bone markers. These results indicate that Pyr, measured using a new and convenient immunoassay, is a highly sensitive marker for altered bone metabolism in hyperthyroidism. The increases in OC and B-ALP were less impressive, suggesting an imbalance between resorption and formation with subsequent rapid bone loss in untreated hyperthyroidism. OC and B-ALP also appear to reflect different aspects of osteoblast metabolism during the treatment of hyperthyroid patients.

Adult↗
PubMed1994

Assessment of bone resorption with a new marker of collagen degradation in patients with metabolic bone disease.

We have used a new enzyme-linked immunoassay (ELISA) to measure the urinary excretion of type I collagen peptides (CrossLaps) released during bone matrix degradation in a sample of healthy adults comprising 146 women and 60 men, aged 31-89 yr, and in patients with metabolic bone disease. The intra- and interassay coefficients of variation were less than 10% and 13%, respectively. The recovery of CrossLaps antigen from urine samples ranged from 92-115%, and the ELISA was linear for serial sample dilutions. The CrossLaps assay does not cross-react with either free pyridinoline (Pyr) or free deoxypyridinoline (D-Pyr). CrossLaps measured by ELISA and the total excretion of Pyr measured by high performance liquid chromatography were highly correlated in normal women (n = 91; r = 0.73; P < 0.001). Urinary CrossLaps excretion increased with age in women, but not in men. In women, the menopause was reflected by a mean 141% increase in CrossLaps excretion [from an average 217 to 524 micrograms/mmol creatinine (Cr)] that was higher than the mean increase in total D-Pyr (+91%) and total Pyr (+47%) measured by HPLC and the mean increase in bone alkaline phophatase (+48%) and osteocalcin (+41%). Urinary CrossLaps excretion was increased from control values in Paget's disease (n = 32; mean, 1810 +/- 2300 micrograms/mmol Cr; P < 0.001), in patients with primary hyperparathyroidism (n = 10; mean, 780 +/- 380 micrograms/mmol Cr; P < 0.001), and in patients with hyperthyroidism (n = 27; mean, 1280 +/- 970 micrograms/mmol Cr; P < 0.001), with Z-scores (number of SD from the mean of sex- and age-matched controls) of 4.4 +/- 6.6, 1.5 +/- 1.2, and 6.7 +/- 6.5, respectively. In patients with Paget's disease, CrossLaps values were highly correlated with urinary hydroxyproline levels (r = 0.91; P < 0.001), and the decrease in urinary CrossLaps excretion was greater than that in urinary hydroxyproline (-71% vs. -17%; P < 0.001) after 3 days of i.v. treatment with the bisphosphonate pamidronate. In patients with hyperthyroidism, CrossLaps excretion was elevated above the normal range in most patients (78%) and returned to normal within 1 month of treatment for hyperthyroidism. It is concluded that this new convenient assay represents a sensitive and specific index of the bone resorption rate, and that it should be useful for the clinical investigation and therapeutic monitoring of patients with osteoporosis and other metabolic bone diseases.

Adult↗
PubMed1994

Comparison of new biochemical markers of bone turnover in late postmenopausal osteoporotic women in response to alendronate treatment.

To evaluate the clinical utility of recently developed biochemical markers of bone turnover to monitor the response of osteoporotic patients to antiresorptive therapy, we compared the results of three advanced assays for markers of bone resorption and four of bone formation to high pressure liquid chromatography (HPLC)-fluorometric assays for urinary pyridinoline and deoxypyridinoline. These assays were also used to resolve the uncertainties concerning the rate of bone turnover in late postmenopausal (late-PMP) osteoporotic women. The rate of bone turnover in 85 women (mean +/- SD age, 63 +/- 6 yr) with low bone mass and all more than 5 yr postmenopausal (mean +/- SD yr PMP, 16 +/- 7 yr) was compared to that in 46 premenopausal women (mean +/- SD age, 40 +/- 5 yr) randomly selected from a large cohort and all having a normal spine bone mineral density (BMD). The late-PMP osteoporotic patients were a subset of patients enrolled in a double blind, placebo-controlled, randomized study comparing the effects of several doses of oral alendronate, a potent and specific inhibitor of bone resorption. Periodically during the 2-yr study, the women's spinal BMD and the level of several markers of bone turnover were measured. Serum total and intact osteocalcin, bone-specific alkaline phosphatase, and carboxy-terminal propeptide of type I collagen measured by RIA were used to assess bone formation. To assess bone resorption, we measured the urinary excretion of total pyridinoline (HPLC Pyr) and deoxypyridinoline (HPLC D-Pyr) by HPLC, type I collagen cross-linked N-telopeptide and urinary free PYR (F-Pyr) by enzyme-linked immunosorbent assay, and the serum concentration of type I collagen cross-linked C-telopeptide (ICTP) by RIA. All bone formation markers, except carboxy-terminal propeptide of type I collagen, and all bone resorption markers, except ICTP, were significantly increased above normal (33-171%; P < 0.001) in late-PMP osteoporotic women. The long term within-patient variability assessed over a 15-month period in the placebo group was low and was somewhat lower for serum markers (12.5-17.4%) than for urinary markers (24-29%). Under treatment with alendronate, resorption markers decreased earlier than markers of bone formation, consistent with a direct action of the drug to inhibit osteoclastic bone resorption. With the exception of F-Pyr and ICTP, the levels of bone markers were reduced to the normal premenopausal range, and this steady state was maintained from 6-15 months.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1994

[Measurement of bone density in the wrist using X-ray absorptiometry: comparison with measurements of other sites].

In order to validate a new technique to measure bone mineral density (BMD) of the forearm with a single X-ray absorptiometry device (DTX 100), we have measured the BMD of 195 women, aged 32 to 83 years, free of metabolic bone disease, simultaneously on two devices: 1. BMD of the ultradistal radius and of the distal radius and ulna on DTX 100, Osteometer, 2. BMD of the lumbar spine, of the proximal femur, of the whole body and of the distal and ultradistal radius by dual X-ray absorptiometry (DXA) on an Hologic 2000 device. The precision of DTX, assessed by 5 repeated measurements on 9 volunteers, was 1% for the distal site and 2% for the ultradistal site. There was a high correlation (r = 0.93) between radial BMD measurement by DTX and Hologic 2000. Correlations between forearm BMDs measured by DTX and whole body BMD were as high (r = 0.80-0.82) as between whole body BMD and lumbar spine (r = 0.82), femoral neck (r = 0.77) and femoral trochanter (r = 0.76). Age-related bone loss measured by DTX was 27% and 31% at the distal and ultra distal radius respectively, as compared to 17% for the lumbar spine, 21% for the femoral neck and 16% for the whole body BMD. In a group of 20 untreated osteoporotic women with vertebral fractures, forearm BMD was as sensitive (T score of -3.1 and -2.9 for distal and ultra distal) as was lumbar spine (T = -2.9) and femoral neck (T = -2.5).(ABSTRACT TRUNCATED AT 250 WORDS)

Absorptiometry, Photon↗
PubMed1993

Immunoassay of pyridinoline crosslink excretion in normal adults and in Paget's disease.

A new immunoassay (ELISA) based on an antiserum that preferentially recognizes the free form of the pyridinoline (Pyr) crosslink was used to assess the urinary excretion of Pyr in a large normal sample of the population comprising 236 men and 193 women 30-90 years of age. Urinary Pyr increased significantly with age in both sexes. In women Pyr was higher than in men (57 +/- 21 versus 46 +/- 17 nmol/mmol creatinine, p < 0.001), and the menopause was reflected by a mean 37% increase, from an average 43 to 59 nmol/mm creatinine (p < 0.001). In 52 patients with active Paget's disease of bone, Pyr excretion was markedly increased (206 +/- 160 nmol/mmol creatinine, p < 0.001 versus controls) and decreased by 71% after 3 days of IV treatment with the bisphosphonate pamidronate. Free Pyr measured by the ELISA and the total urinary excretion measured by HPLC were highly correlated both in normals (n = 74, r = 0.83, p < 0.001) and in Pagetic patients (n = 20, r = 0.93, p < 0.001). The mean intra- and interassay coefficients of variation of the ELISA were below 9 and 15%, respectively. It is concluded that this new convenient immunoassay of Pyr should be valuable for the clinical investigation of patients with osteoporosis and other metabolic bone diseases.

Adult↗
PubMed1993

Assessment of the serum levels of bone alkaline phosphatase with a new immunoradiometric assay in patients with metabolic bone disease.

We measured serum bone alkaline phosphatase (B-ALP) with a new immunoradiometric assay (IRMA) in a large sample of healthy controls comprising 173 women and 180 men, 20-88 yr of age, and in patients with metabolic bone disease. Using serum samples from patients with liver disease and patients with Paget's disease with elevated total alkaline phosphatase (T-ALP) as a source of, respectively, liver and bone isoenzymes, we determined a liver cross-reactivity of the IRMA of 16% that was confirmed by electrophoresis of the circulating alkaline phosphatase isoenzymes. The IRMA was linear for serial sample dilutions, the recovery ranged from 89-110%, and the intra- and interassay variations were below 7% and 9%, respectively. B-ALP increased linearly with age in both sexes, and the mean B-ALP serum levels were not significantly different for women and men (11.3 +/- 4.8 ng/mL for women; 11.0 +/- 4.0 ng/mL for men). The increase in B-ALP after the menopause was significantly higher than that in T-ALP (+77% vs. +24%; P < 0.001). When the values of postmenopausal women were expressed as the SD from the mean of premenopausal women, the mean Z scores were 2.2 +/- 1.8 for B-ALP and 0.9 +/- 1.3 for T-ALP (P < 0.001 between the two). Serum B-ALP was increased from control values in patients with Paget's disease (n = 57; mean, 171.8 +/- 135.6 ng/mL; P < 0.001), in patients with primary hyperparathyroidism (n = 18; mean, 17.2 +/- 5.9 ng/mL; P < 0.001), and in patients with chronic renal failure on hemodialysis (n = 83; mean, 36.6 +/- 35.7 ng/mL; P < 0.001). In patients with Paget's disease, B-ALP was highly correlated with T-ALP (r2 = 0.94; P < 0.001), and the decrease in its serum level was larger than that in T-ALP after treatment with the bisphosphonate pamidronate (-58% vs. -43%; P < 0.03). In patients with various liver diseases, B-ALP was slightly increased, but stayed within the normal range (mean +/- 2 SD) until T-ALP did not exceed 4.5 mu katal/L. We conclude that this new IRMA for B-ALP is reliable, has a low cross-reactivity with the liver isoenzyme, and appears to be more sensitive than T-ALP for the clinical investigation of patients with osteoporosis and other metabolic bone diseases.

Adult↗
PubMed1992

Measurement of serum osteocalcin with a human-specific two-site immunoradiometric assay.

We developed a sensitive and specific two-site radioimmunoassay (IRMA) for human osteocalcin using human osteocalcin as a standard and two monoclonal antibodies raised against human osteocalcin purified from human cortical bone, a solid-phase anti-25-37 region and a tracer anti-5-13 sequence of the molecule. A wide range of osteocalcin levels (up to 300 ng/ml) can be measured with a sensitivity of 0.4 ng/ml. The intra- and interassay coefficients of variation are less than 4 and 6%, respectively. The recovery of human osteocalcin from serum samples ranges from 96 to 103%. IRMA was linear for serial sample dilutions in a wide range of serum osteocalcin levels, even in patients with chronic renal failure on hemodialysis. Depletion of serum in intact osteocalcin demonstrated that IRMA detects, in addition to the intact peptide, a large N-terminal midregion fragment that represents about 50% of total osteocalcin levels in normals and patients with Paget's disease and up to 75% in patients with chronic renal failure. This large fragment, previously unrecognized because it cannot be distinguished from intact osteocalcin with gel filtration chromatography, is not generated in vitro by incubation of the serum up to 26 h. We measured osteocalcin in the serum of 309 healthy adults (180 men and 129 women, age range 20-95 years), 36 patients with Paget's disease, 12 patients with primary hyperparathyroidism, 70 patients with chronic renal failure on hemodialysis, and 10 patients on corticosteroid therapy, simultaneously with human IRMA and with a conventional radioimmunoassay (RIA) based on bovine reagents. A tight correlation (r = 0.889) was observed between the two assays in the normal population, but the values obtained with IRMA were about threefold higher (mean 23.3 +/- 10.5 versus 7.5 +/- 3.4 ng/ml) than those obtained with RIA. Reported as Z scores, that is, number of standard deviations from the predicted normal mean adjusted for sex and age, these two assays (IRMA and RIA) gave concordant results in patients with Paget's disease (4.05 +/- 6.21 versus 2.41 +/- 2.53), primary hyperparathyroidism (4.14 +/- 7.17 versus 2.13 +/- 2.28), chronic renal failure (25.32 +/- 24.49 versus 6.93 +/- 5.48), and glucocorticoid treatment (-1.48 +/- 0.78 versus -1.11 +/- 0.57). However, IRMA was more discriminant from controls for all these metabolic bone diseases because the absolute values of mean Z scores with IRMA were significantly higher than those obtained with the RIA (p < 0.05-0.0001).(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMedDate not supplied

[Biochemical markers of bone turnover : clinical usefulness in osteoporosis].

The recent development of specific and sensitive biochemical markers reflecting the overall rate of bone formation and bone resorption, has markedly improved the non invasive assessment of bone turnover in various metabolic bone diseases, especially for osteoporosis. The immunoassay of human osteocalcin recognizing the intact molecule and its major proteolytic fragment, assays for bone alkaline phosphatase and the intact form of the N-terminal extension propeptide of type I collagen are currently the most sensitive markers to assess bone formation. The best indices of bone resorption are the new immunoassays for the pyridinoline crosslinks and type I collagen related peptides in urine, but also very recently available in serum. Using these new markers, several studies have shown that bone turnover increases markedly after the menopause and remains elevated in late postmenopausal and elderly women. An increased bone turnover rate is related to a fast rate of bone loss in postmenopausal women and to a decreased bone mass in elderly women. Recent data suggest that some of the new immunoassays for pyridinoline crosslinks and related peptides could predict the subsequent risk of hip fracture in elderly women. Thus, bone markers might be used in combination with bone mass measurement to improve the prognostic assessment of postmenopausal women, i.e. their risk of developing osteoporosis and ultimately fractures. Treatment of postmenopausal women with antiresorptive drugs such as estrogens, bisphosphonates and calcitonin is followed by rapid decrease of the levels of bone markers that is correlated with the long term increase of bone mass as assessed by dual-energy X ray absorptiometry measurement. Thus, bone markers should be useful in monitoring treatment efficacy in patients with osteoporosis. Appropriate combination of the most efficient markers of bone formation and resorption will probably provide a powerful tool in the clinical investigation of osteoporosis.

Absorptiometry, Photon↗
PubMedDate not supplied

[Biochemical markers of bone remodeling: pre-analytical variations and guidelines for their use. SFBC (Société Française de Biologie Clinique) Work Group. Biochemical markers of bone remodeling].

Biochemical markers of bone turnover have been developed over the past 20 years that are more specific for bone tissue than conventional ones such as total alkaline phosphatase and urinary hydroxyproline. They have been widely used in clinical research and in clinical trials of new therapies as secondary end points of treatment efficacy. Most of the interest has been devoted to their use in postmenopausal osteoporosis, a condition characterized by subtle modifications of bone metabolism that cannot be detected readily by conventional markers of bone turnover. Although several recent studies have suggested that biochemical markers may be used for the management of the individual patient in routine clinical practice, this has not been clearly defined and is a matter of debate. Because of the crucial importance to clarify this issue, the Société Francaise de Biologie Clinique prompted an expert committee to summarize the available data and to make recommendations. The following paper includes a review on the biochemical and analytical aspects of the markers of bone formation and resorption and on the sources of variability such as sex, age, menstrual cycle, pregnancy and lactation, physical activity, seasonal variation and effects of diseases and treatments. We will also describe the effects of pre-analytical factors on the measurements of the different markers. Finally based on that review, we will make practical recommendations for the use of these markers in order to minimize the variability of the measurements and improve the clinical interpretation of the data.

Adolescent↗