Urinary Pyridinium Crosslinks Research Articles

Bone Demineralization Following Urinary Intestinal Diversion Assessed by Urinary Pyridinium Cross-Links and Dual Energy X-Ray Absorptiometry

Purpose We investigated the acid-base balance and bone mineral status in patients with 3 types of urinary intestinal diversion. Materials and Methods Of 46 men with urinary intestinal diversions 20 had a Kock pouch, 15 had an Indiana pouch and 11 had an ileal conduit. Acid-base balance was assessed by arterial blood gas analysis. Bone mineral status was measured by urinary pyridinium cross-links and dual energy x-ray absorptiometry. In addition, urinary deoxypyridinoline was measured in 79 patients. Results Of the 46 patients 7 (15 percent) with the Kock pouch (1), Indiana pouch (5) and ileal conduit (1) had metabolic acidosis associated with significantly lower bone mineral densities (p less than 0.05) and higher urinary pyridinium cross-links (p less than 0.005) than did those with normal acid-base status. No difference was found in metabolic acidosis and bone demineralization among the 3 groups. Additionally, in 79 patients urinary deoxypyridinoline reached the highest level immediately postoperatively and then gradually decreased to the stable level within 1 or 2 years. Conclusions Metabolic acidosis following urinary intestinal diversion results in bone demineralization. The types of diversion did not cause differences in metabolic acidosis and bone resorption. Bone has a major role in buffering acid overload in the early postoperative period.

The effect of Cushing's disease on bone mineral density, body composition, growth, and puberty: a report of an identical adolescent twin pair.

As endogenous Cushing's syndrome (CS) in children occurs during a critical developmental period, when the majority of peak bone mass is acquired, we hypothesized that children with CS might be at an increased risk of osteoporosis. To determine the effects of CS on bone density, bone metabolism, and growth, we studied a 15-yr-old female identical twin pair, one of whom had CS (twin A), and the other of whom was healthy (twin B). Before therapy for CS, twin A showed a severe loss of bone mineral density [BMD; -3.2SD at the lumbar spine (LS)] compared to twin B (-0.1 SD), which in twin A was associated with low serum osteocalcin levels and urinary pyridinium cross-link excretion. Cure of CS in twin A led to a marked increase in these bone markers, suggesting a state of active bone remodeling. After 27 months of follow-up, even though twin A's BMD improved significantly, it still remained abnormal [-1.9 SD at LS compared with that of twin B (0 SD)], suggesting that twin A continued to be at increased long term risk of osteoporosis. In addition, as a consequence of CS, twin A's final height was 21 cm less than that of her identical twin. We recommend that all children with CS should have BMD monitored after treatment to determine the long term risk of osteoporosis.

Urinary excretion of pyridinoline and deoxypyridinoline measured by immunoassay in hypothyroidism.

We measured pyridinium cross-links, markers of bone resorption, by an enzyme-linked immunosorbent assay (ELISA) in hypothyroid patients to see whether bone resorption was reduced in hypothyroidism and whether it increased with T4 treatment. Eight hypothyroid patients, whose initial TSH levels were 268.1 +/- 87.7 mU/l (mean +/- SE), were treated with T4 (100 micrograms/day). Urinary excretion of pyridinium cross-links was assayed before and after T4 treatment. Pyrilinks and Pyrilinks-D kits were used. The Pyrilinks assay measures free forms of pyridinoline and deoxypyridinoline together (PYD), while the Pyrilinks-D assay measures deoxypyridinoline (DPD) alone. The Pyrilinks reference ranges for normal subjects are 8-24nmol/mmol creatinine in males and 10-28nmol/mmol creatinine in normal premenopausal females. The DPD reference ranges obtained from normal men and women aged 40-50 years were 3.20 +/- 0.75 (mean +/- SD) nmol/mmol creatinine and 4.55 +/- 1.22 nmol/mmol creatinine, respectively. The sensitivity of the assay was enhanced by simply using less diluted urine samples. Concentrations of both compounds of the urinary pyridinium cross-links were low in untreated hypothyroid patients and increased gradually as thyroid hormone status improved from hypothyroidism to euthyroidism. One month after treatment when the TSH levels in the patients were still as high as 74.4 +/- 44.5 mU/l, urinary PYD excretion has increased to 2.6 times the pretreatment level. When the TSH levels of the patients decreased below 10 mU/l, both PYD and DPD increased significantly to 3.8 and 3.3 times pretreatment values, respectively. Although hyperthyroidism or excess treatment with thyroid hormone has been known to induce bone resorption, this is the first report that urinary excretion of pyridinium cross-links is reduced in hypothyroidism and is normalized by physiological thyroid hormone replacement.

Case-control analysis of bone resorption markers, disability, and hip fracture risk: the Rotterdam study.

Several factors besides bone mineral mass have been related to the risk of hip fracture. Bone quality, the rate of bone loss, and non-skeletal factors have been identified as important.1 2 High rates of bone resorption may be associated with disruption of the trabecular network as well as with an increased rate of bone loss. Furthermore, immobility associated with disability induces bone resorption not followed by increased bone formation.3 Urinary pyridinium crosslinks are markers of bone resorption. We investigated whether these were associated with the risk of hip fracture and also whether such an association was attributable to disability. This nested case-control analysis was conducted as part of the Rotterdam study, a prospective cohort study of the incidence of and risk factors for chronic disabling diseases.4 Briefly, all 10275 residents of a district of Rotterdam aged 55 or over were invited to participate. The study consisted of an initial home interview followed by a series …

Circadian rhythm of in vitro bone-resorbing activity in human serum.

Calciotropic hormones as well as biochemical parameters of bone formation and resorption show circadian rhythms. In a previous study in the rat, we observed a circadian rhythm in serum bone-resorbing activity (SBRA). In the present study, we investigated whether there was a circadian rhythm of SBRA in human serum. For this purpose, we studied 10 healthy premenopausal women and 5 healthy men. Blood was collected every 2 h, and urine samples were collected during 4-h periods for 24 h. For the determination of SBRA, media were prepared by reconstituting serum samples with Dulbecco's Modified Eagle's Medium at a ratio of 20% serum and 80% Dulbecco's Modified Eagle's Medium. Limb bones were dissected from 19-day old fetal rats prelabelled with 45Ca and were cultured for 72 h in the presence of the sera. Bone resorption was assessed from the 45Ca released into the culture medium and from that retained in the bone and was expressed as percentage 45Ca release. Serum calcium, phosphorus, PTH, cortisol, and urinary pyridinium cross-links were also determined. SBRA in human serum followed a circadian rhythm with a peak at about 0300 h and a nadir at 0700 h. There was no significant difference between the rhythm of SBRA of women and men. At concurrent time points, SBRA and serum PTH were positively correlated (r = 0.629; P < 0.01), and SBRA and serum cortisol were negatively correlated (r = 0.797; P < 0.01). To further investigate the possible contribution of these hormones to SBRA, either neutralizing anti-PTH antibody or RU-486 (mifepristone), a glucocorticoid receptor antagonist, was added to the serum samples of 6 subjects. Neutralizing the effect of PTH did not change the pattern of SBRA rhythm. The addition of RU-486 had a significant effect on the rhythm of SBRA, reducing the peak and nadir amplitudes. Thus we conclude that cortisol plays a major role in the rhythm of SBRA present in human serum; however, the influence of other factors cannot be excluded. Cortisol may be an important determinant of the circadian rhythm of bone resorption in vivo.

Dose-related decrease in bone density among asthmatic patients treated with inhaled corticosteroids

Background: Inhaled corticosteroids are being prescribed more commonly and in higher doses than previously in the management of asthma. Although these topically active compounds have less potential for systemic impact than oral steroids, biochemical markers suggest that they are not devoid of systemic side effects. We conducted this study to investigate the effect of commonly prescribed doses of inhaled steroids on bone density. Methods: We studied 36 patients with asthma. Those in group A ( n = 18) had been taking inhaled beclomethasone dipropionate or budesonide in a dosage of 800 μg or more per day for at least 1 year. Those in group B ( n = 18) had used only bronchodilator therapy. Adrenal function was assessed by morning serum cortisol level and by short adrenocorticotropic hormone stimulation test. Bone turnover was assessed by measurement of serum osteocalcin, alkaline phosphatase, and urinary pyridinium cross-links. Bone mineral density was measured by dual-energy x-ray absorptiometry with a Hologic QDR-1000 densitometer (Holologic Inc., Waltham, Mass.). Results: Group A, mean age (SD) = 36.6 (8.4) years, had used inhaled corticosteroids at a mean dose of 1323 μg/day (range, 800 to 2000 μg/day) for a median duration of 24 months. Group B, mean age (SD) = 33.4 (8.1) years, had not been taking any form of steroid. Four patients from group A had suppressed morning serum cortisol; three of these had abnormal adrenocorticotropic hormone stimulation test results. All patients in group B had normal baseline adrenal function and an appropriate response to adrenocorticotropic hormone. Mean serum osteocalcin level in group A was significantly lower than that in group B (8.8 vs 14.2 ng/ml, p = 0.0003). Bone density measurements showed parallel changes: in group A the mean Z score (SD) of the femoral neck was -0.78 (1.02), significantly below predicted normal values ( p = 0.0025). Mean Z scores of the lumbar spine and of femoral Ward's triangle were not significantly reduced. In group B the mean Z scores of the lumbar spine, femoral neck, and femoral Ward's triangle were all within normal limits. In group A the dose duration of inhaled corticosteroid therapy corrected for body mass index correlated negatively with bone density and adrenal function measurements. Conclusion: We conclude that the regular use of conventional doses of inhaled corticosteroids by patients with asthma can suppress adrenal function and decrease bone density in a dose-related fashion. (J A LLERGY C LIN I MMUNOL 1995;96:571-9.) J A LLERGY C LIN I MMUNOL 1995;96:571-9.

Carboxy-terminal propeptide of human type I collagen and pyridinium cross-links as markers of bone growth in infants 1 to 18 months of age

Serum carboxy-terminal propeptide of human type I collagen (PICP) concentrations, as a marker for bone formation, and urinary pyridinium (Pyd) cross-link concentrations, as a marker of bone resorption, were determined in 66 healthy infants aged 1-18 months who are being studied longitudinally. We hypothesized that there would be a positive correlation of growth velocity, increase in bone area, and bone mass accretion rates with PICP and Pyd cross-link concentrations. Since osteocalcin is currently used as a marker of bone formation, serum osteocalcin concentrations were also measured. Mean serum PICP and urinary Pyd cross-link concentrations were significantly greater than adult concentrations. Future growth velocity, increase in bone area, and bone mass accretion rates were not associated with PICP, Pyd cross-link, or osteocalcin concentrations. Growth velocity during the 3 months preceding sample collection correlated with serum PICP, Pyd/kg, and osteocalcin concentrations (r = 0.474, p < 0.001; r = 0.379, p < 0.001; and r = 0.516, p < 0.001, respectively). Previous increase in bone area correlated with serum PICP concentrations (r = 0.359, p = 0.01). The relationship between the infant's previous bone mass accretion rate and PICP was of borderline significance (r = 0.281, p = 0.055). In summary, normative data for PICP, Pyd cross-link concentrations, and parameters of bone growth are provided for infants 1-18 months of age and indicate that these markers reflect past and current bone metabolism and may be helpful in monitoring bone disorders in infants.

Changes in bone mass and metabolism after surgery for primary hyperparathyroidism

Bone mass is often reduced in patients with primary hyperparathyroidism (pHPT) and is usually partially reversible after parathyroidectomy. However, site specific and overall skeletal benefits of surgery in mild asymptomatic pHPT remain uncertain. Cross-sectional and longitudinal studies. Fourteen patients (12 women and 2 men) with pHPT. Baseline bone mass was assessed at the lumbar spine, left hip and whole body using dual-energy X-ray absorptiometry, and at the left os calcis using broad-band ultrasound attenuation. Changes in bone mass, serum intact PTH and osteocalcin, and urinary pyridinium cross-link excretion were recorded in 10 patients followed for 6 months after surgery. (1) Cross-sectional study: Baseline measurements at the lumbar spine and hip were inversely related to both the serum PTH concentration and the weight of the parathyroid gland removed at surgery. (2) Longitudinal study: Six months after adenectomy, bone mass had increased significantly at the femoral neck, greater trochanter, whole body and os calcis, but not at the lumbar spine or Ward's area. Serum PTH, osteocalcin and pyridinium cross-link excretion all fell significantly after surgery. The percentage increment in whole body bone mineral content at 6 months was proportional to the baseline PTH. In primary hyperparathyroidism, preoperative reductions and post-operative gains in bone mass are proportional to the initial serum PTH concentration. Mild primary hyperparathyroidism probably does not cause appreciable bone loss at clinically relevant fracture sites such as the spine and hip, and in such cases the overall skeletal benefits of surgery are likely to be negligible.

Supplemented gamma-linolenic acid and eicosapentaenoic acid influence bone status in young male rats: Effects on free urinary collagen crosslinks, total urinary hydroxyproline, and bone calcium content

The effect of different ratios of the prostaglandin precursors gamma-linolenic (GLA) and eicosapentaenoic (EPA) acids on bone status in growing rats measured as a function of free urinary pyridinium crosslinks and hydroxyproline levels was investigated. Male Sprague-Dawley rats were weaned onto an essential fatty acid deficient diet and from their fifth week, different groups of rats received a balanced, semisynthetic diet, supplemented with different ratios of GLA:EPA supplied as a mixture of evening primrose oil (EPO) and fish oil (FO). Controls were supplemented with linoleic (LA; sunflower oil) and alpha-linolenic (ALA; linseed oil) acids (3:1) or a commercially available rat chow. Animals were terminated at 84 days and femur length, ash weight, calcium content, free urinary pyridinium crosslinks (Pyd and Dpyd), total hydroxyproline (Hyp), and creatinine levels measured. Free urinary Pyd and Dpyd are good indicators of bone status and they correlated well with Hyp. Pyd and Dpyd excretion were significantly decreased in the higher GLA:EPA dietary groups and correlated well (r = 0.7) with Hyp levels. Concomitantly, bone calcium content increased significantly in the same dietary groups. These results suggest that diet supplementation with relatively high GLA:EPA ratios are more effective in inhibiting bone resorption than LA:ALA.

Post-pregnancy osteoporosis and urinary pyridinium crosslinks: A case report

Post-pregnancy osteoporosis and urinary pyridinium crosslinks: A case report

Effect of Urinary Intestinal Diversion on Urinary Risk Factors for Urolithiasis

We investigated the effect of urinary intestinal diversion on risk factors for calcium urolithiasis, such as calcium, phosphate, magnesium, uric acid, oxalate and citrate, in 3 groups of patients (Kock pouch, Indiana pouch and ileal conduit). Mean urinary volume was not significantly different among the 3 groups. Mean serum creatinine and 24-hour creatinine clearance in the continent reservoir group were better than in the ileal conduit group. Mean urinary excretion of calcium, phosphate and magnesium was significantly greater in the continent reservoir group than in the ileal conduit group. Although calcium excretion had a positive correlation with 24-hour creatinine clearance, calcium excretion per ml. per minute creatinine clearance still showed a significant difference. Increased calcium excretion is considered to reflect metabolic disturbances resulting from reabsorption of urinary solutes through the intestinal segments. Overall, there was no significant difference in the urinary parameters between the Kock and Indiana pouch groups. While mean urinary oxalate and citrate were within the normal range in all 3 groups, more than a third of the patients in each group were hypocitraturic (less than 100 mg. per day). In none of the 3 groups did the levels of urinary calcium, phosphate and magnesium, as well as other urinary risk parameters show any correlation with the duration of diversion. In summary, our study indicated that the continent urinary reservoir causes a long-term increase in urinary excretion of calcium, phosphate and magnesium. These urinary metabolic alterations might promote the formation of calcium urolithiasis as well as infectious stones. The degree of metabolic alterations may be greater with a continent reservoir than with an ileal conduit.

The diagnostic value of urinary pyridinium cross-links of collagen, serum total alkaline phosphatase, and urinary calcium excretion in neoplastic bone disease

The diagnostic value of urinary pyridinium cross-links of collagen, serum total alkaline phosphatase, and urinary calcium excretion in neoplastic bone disease

The diagnostic value of urinary pyridinium cross-links of collagen, serum total alkaline phosphatase, and urinary calcium excretion in neoplastic bone disease.

Bone metastases strongly affect skeletal metabolism by both their growth and their paracrine activities. However, so far no specific laboratory marker has been found to signal the spread of neoplastic disease to bone. We performed a cross-sectional study of 153 cancer patients and an equal number of healthy controls matched for sex and age, in which we determined serum levels of calcium and total alkaline phosphatase (TAP) as well as the fasting urinary excretion of calcium (uCa) and of the collagen cross-links pyridinoline (uPYD) and deoxypyridinoline (uDPD). The aim of the study was to analyze the diagnostic validity of the biochemical parameters measured with regard to neoplastic bone involvement. In the cancer group, 98 patients had overt bone metastases, as judged from radiographic and radioisotopic bone imaging. The remaining 55 patients were also in an advanced stage of disease, but there was no evidence of malignant bone involvement. In comparison to healthy controls, patients both with and without metastatic bone disease had significantly higher levels of TAP, uPYD, and uDPD (P < 0.0001). Only in cancer patients with bone metastases was the median serum calcium level higher than in the healthy controls (P < 0.02). uCa was the same in cancer patients and the control group. Within the collective of cancer patients, individuals with skeletal metastases had higher levels of serum calcium (P < 0.05), TAP (P < 0.01), and uPYD and uDPD (both P < 0.0001), than patients without evidence of malignant bone disease. uCa did not differ between the 2 groups of cancer patients. The cancer patients were then stratified into 4 subgroups according to the serum calcium level (< or = 2.6 mmol/L >) and the absence or evidence of bone metastases. This stratification revealed that in patients with bone metastases, uPYD and uDPD levels were similar in normocalcemic and hypercalcemic subjects, whereas in hypercalcemic patients, uCa levels significantly exceeded those in normocalcemic patients. When the efficacy of TAP, uCa, uPYD, and uDPD in discriminating between patients with and without bone metastases was evaluated by use of receiver-operating characteristic curves and stepwise multivariate regression analysis, uPYD was found to have the highest diagnostic validity. Using 50 mumol PYD/mol creatinine (i.e. the upper limit of normal range) as the cut-off level, the sensitivity of uPYD was 88.7%, whereas the specificity was only 41.8% (odds ratio, 5.598; 95% confidence interval, 2.547-12.306).(ABSTRACT TRUNCATED AT 400 WORDS)

Posture, age, menopause, and osteopenia do not influence the circadian variation in the urinary excretion of pyridinium crosslinks.

This study was performed to investigate whether the circadian variation in urinary pyridinium crosslinks is related to physical activity, age, the menopause, and asymptomatic osteopenia. We measured urinary pyridinoline/creatinine (Pyr/Cr) and deoxypyridinoline/creatinine (D-Pyr/Cr) in 9 healthy premenopausal women in two 27 h studies, before and at the end of 5 days of total bed rest. Both Pyr/Cr and D-Pyr/Cr showed highly significant circadian variations, with the peak at night and the nadir during the day (p < 0.001). The 5 days of complete bed rest produced no changes in the circadian pattern, but a general increase of 28% was observed in pyridinium crosslinks. A group of 12 healthy, early postmenopausal women (aged 55 +/- 2 years), 12 healthy, elderly postmenopausal women (aged 73 +/- 1 years), and 12 elderly osteopenic but otherwise healthy women (aged 73 +/- 1 years) were also studied for 27 h. All three groups showed highly significant (p < or = 0.001) circadian variations in the urinary excretion of pyridinium crosslinks. As expected, both Pyr/Cr (p < 0.05) and D-Pyr/Cr (p < 0.001) increased at the time of menopause, but the circadian variations in Pyr/Cr and D-Pyr/Cr were similar in all groups studied. We conclude that the circadian variation in the urinary excretion of pyridinium crosslinks is independent of physical factors. Furthermore, the circadian variation in pyridinium crosslinks was not related to age, menopausal status, or asymptomatic osteopenia.

Bone resorption in healthy and osteoporotic postmenopausal women: comparison markers for serum carboxy-terminal telopeptide of type I collagen and urinary pyridinium cross-links

We compared two highly specific markers for bone resorption-pyridinium cross-links (pyridinoline (PYR) and deoxypyridinoline (DPR)) in urine and carboxy-terminal telopeptide of type I collagen (ICTP) in serum-in 63 healthy postmenopausal women and 63 women with osteoporosis characterized by more bone resorption than bone formation. The ICTP, PYR and DPR levels were all higher, by 24% (p = 0.001), 16% (p = 0.05) and 25% (p = 0.004), respectively, in the osteoporotic women. For the merged groups, there were significant correlations between serum ICTP concentration and urinary PYR (r = 0.667, p < 0.0001) and DPR (r = 0.452, p < 0.0001) excretion; for the osteoporotic and normal women separately, the r values were 0.73 (p < 0.01) and 0.45 (p < 0.01) for PYR and 0.51 (p < 0.01) and 0.22 (p = 0.08) for DPR versus ICTP respectively. Weak correlations in linear regression between ICTP and various indices of bone formation (osteocalcin, bone-specific alkaline phosphatase and carboxy-terminal propeptide of type I procollagen) disappeared when the correlation between ICTP and pyridinolines was accounted for by calculation of partial correlation coefficients in multiple regression analysis. Serum ICTP concentration appears to discriminate between groups of normal and osteoporotic women as well as urinary pyridinium cross-links, which is thus far the most sensitive method for assessing bone resorption.

Urinary hydroxypyridinium crosslinks of collagen in population-based screening for overt vertebral osteoporosis: Results of a pilot study

The urinary pyridinium crosslinks pyridinoline (PYD) and deoxypyridinoline (DPD) have been shown to provide valid indices of bone resorption. At present, both crosslink components are determined by reversed-phase HPLC, a time-consuming method precluding the use of these markers for routine purposes. Therefore, efforts have been made to develop simple immunoassays for the rapid measurement of urinary crosslinks, and their application to large-scale osteoporosis screening has been proposed. To evaluate the applicability and diagnostic validity of pyridinium crosslink measurements for screening purposes, urinary concentrations of total and free PYD and DPD were determined by HPLC and immunoassay technique (ELISA) in a sample of 269 individuals (male to female ratio = 130:139; age 50-81 years) recruited at random within a population survey of vertebral osteoporosis. On a molar basis, ELISA measures of crosslink-related epitopes were highly correlated with both total and free PYD and DPD as determined by HPLC (r > 0.82, p < 0.001). Age-specific means for creatinine-corrected total and free pyridinium crosslinks were significantly higher in females than in males (p < 0.001). In both sexes, neither age nor anthropometric variables (weight, height, and body mass index) showed a linear effect on the urinary crosslink/creatinine ratio. On average, 50% of the total amount of urinary crosslinks were present in free form. For both PYD and DPD, this proportion was significantly higher in women than in men (p < 0.05), but no change was observed with age or anthropometric measures. The excretion of pyridinium crosslinks was higher in osteoporotic (n = 18) than in nonosteoporotic individuals (n = 208) from the same population.(ABSTRACT TRUNCATED AT 250 WORDS)

Sulfasalazine may interfere with HPLC assay of urinary pyridinium crosslinks

Journal Article Sulfasalazine may interfere with HPLC assay of urinary pyridinium crosslinks Get access N Peel, N Peel Search for other works by this author on: Oxford Academic Google Scholar A al-Dehaimi, A al-Dehaimi Search for other works by this author on: Oxford Academic Google Scholar A Colwell, A Colwell Search for other works by this author on: Oxford Academic Google Scholar G Russell, G Russell Search for other works by this author on: Oxford Academic Google Scholar R Eastell R Eastell Search for other works by this author on: Oxford Academic Google Scholar Clinical Chemistry, Volume 40, Issue 1, 1 January 1994, Pages 167–168, https://doi.org/10.1093/clinchem/40.1.167 Published: 01 January 1994

Evaluation and comparison of urinary pyridinium crosslinks in two rat models of bone loss — ovariectomy and adjuvant polyarthritis — using a new automated HPLC method

A specific HPLC system was developed to assess urinary excretion of collagen crosslinks (pyridinoline (Pyr) and deoxypyridinoline (D.Pyr)) in two models of osteopenia in rats, ovariectomy and adjuvant polyarthritis. The sensitivity of this method was in the picomolar range. In ovariectomized rats, a specific model of bone resorption, Pyr and D.Pyr levels rose early, reaching a peak 2 weeks after surgery. Both levels remained raised during the whole observation period (6 weeks) with no change in the Pyr/D.Pyr ratio. So, in this high bone turnover model, hyperresorption is reflected by the parallel increase of both crosslinks resulting in a significant decrease of bone mineral density (BMD) at 6 weeks (−7.3% vs. control). In polyar-thritic rats, in the 2 post-adjuvant weeks, Pyr levels increased in parallel with inflammatory parameters, whereas D.Pyr levels remained unchanged. This is in agreement with our previous report that at the end of the 2nd week after adjuvant there is no change in bone resorption. From the 3rd week, both Pyr and D.Pyr increased. The Pyr/D.Pyr ratio was always significantly higher in polyarthritic rats. These results suggest that the early increase of Pyr level reflects non-osseous collagen breakdown and that bone resorption occurs at a later stage when D.Pyr rises, leading to a dramatic decrease of BMD at 4 weeks (−17.7% vs. control). Taken together, our results suggest that in rat as in human, urinary Pyr is a marker of bone and cartilage breakdown, whereas D.Pyr is a specific marker of bone loss. This automated method described may constitute a very useful tool to evaluate bone and/or cartilage breakdown in rats and for the assessment of protective treatments.

Low bone mass and high bone turnover in male long distance runners.

Running is a popular sport, but in some studies long distance running in women has been related to reduced bone mass and a potential risk of osteoporosis. To investigate the impact of running on bone mass in men, 120 healthy, physically active men (19-56 yr old; running 0-160 km/week) were studied. Bone mineral content was measured in the lumbar spine, total body, and proximal femurs by dual energy x-ray absorptiometry and in the forearm by single photon absorptiometry. Bone turnover was assessed by urinary pyridinium cross-links, plasma osteocalcin, and serum alkaline phosphatase. Lumbar bone mineral content was negatively correlated to the weekly distance run (r = -0.37; P < 0.0001), with a difference of 19 +/- 5% (mean +/- SEM) between controls and elite runners. A similar relation was found for all measurement sites. After adjustment for possible confounders, the correlations remained statistically significant in areas with a high proportion of trabecular bone. Bone turnover parameters were 20-30% higher in the elite runners, whereas sex hormone status was unrelated to running activity. We conclude that male long distance runners had reduced bone mass and increased bone turnover compared to controls, which suggests accelerated bone loss. The pathophysiological explanation was not clear, but sex hormones did not seem to play a key role.

Can urinary pyridinium crosslinks and urinary oestrogens predict bone mass and rate of bone loss after the menopause?

We measured urinary pyridinoline and deoxy-pyridinoline by high performance liquid chromatography, and urinary oestrogens by radioimmunoassay, in 68 healthy postmenopausal women to evaluate these assays for the prediction soon after the menopause of the risk of developing osteoporotic fractures in later life. Change in forearm bone mineral content was assessed by single photon absorptiometry over 4 years. Although there was no significant correlation between the pyridinium crosslinks and urinary oestrogens, we found that up to 58% of the variation in the rate of loss of bone mineral content in women soon after the menopause could be explained by pyridinoline and oestradiol glucuronide assays together with body mass index. Measurement of the urinary pyridinium crosslinks and oestradiol glucuronide may make a significant contribution to a biochemical screening procedure for future osteoporotic fracture.