The greater pubertal increase in levels of bone specific alkaline phosphatase, osteocalcin and urinary deoxypyridinoline suggests that these markers may be relatively more sensitive as indicators of skeletal health during puberty. The differences between markers may reflect differences in the bone specificity of the analytes, or differing mechanisms of production and clearance. The negative correlation between oestradiol and markers of bone resorption and formation suggests that this hormone may be responsible for the reduction in bone turnover in late puberty.

The measurement of the 3-OH pyridinium compounds, pyridinoline (Pyr) and deoxypyridinoline (Dpyr), in urine by high performance liquid chromatography is potentially useful in clinical studies, since they are specific biochemical markers of bone resorption. The aims of the present study were to improve assay performance and optimize sample collection. An isocratic high performance liquid chromatogram (HPLC) separation with baseline resolution was accomplished within 4 min using heptafluorobutyric acid as an ion-pair. The sample preparation for HPLC, using CF1 cellulose, produced uncontaminated samples with a recovery higher than 90% for both crosslinks. An elastin-derived material, tentatively identified as isodesmosine (Ides), was also tested and proved to be a suitable internal standard. Use of this standard improved assay precision. The effect of an oral gelatin load on the excretion of Pyr and Dyr was investigated. The creatinine corrected excretion of Pyr and Dpyr was unchanged over a 6 h period, in contrast to the 10-fold increase in the excretion of urinary hydroxyproline with a peak 2-4 h after ingestion. In 20 postmenopausal women, 2 h fasting morning urine results correlated with results from 24-h urine collections Dpyr/Cr (r = 0.70, n = 20). There was a day-to-day variation of 26% in adults studied for 10 days.

Objectives-To determine whether there was a generalised increase in bone mineral density (BMD) in spinal osteoarthrosis (OA), and to determine the mechanism of this possible protection against osteoporosis as assessed by biochemical markers ofbone turnover. Methods-We studied 375 women (ages 50 to 85) from a population based group. Spinal OA was defined from radiographs as the presence of degenerative changes affecting intervertebral or facet joints. BMD of the lumbar spine (LS), femoral neck (FN) and total body (TB) was measured by dual energy x ray absorptiometry (Lunar DPX). Bone turnover rates were estimated from measurement of biochemical markers of bone formation and resorption (urine deoxypyridinoline (Dpyr) and serum bone specific alkaline phosphatase (BAP)). Results-BMD at each site was greater in the women with spinal OA (mean increase in LS-BMD 7 9%, 95%0 confidence interval (CI) 1-0 to 15-1; TB-BMD 8-4%, 95% CI 1P9 to 9 7; FN-BMD 6-4/o, 95% CI 0-3 to 12.6). (FN), although the increase at this site was smaller. Increased BMD in the presence of OA may, therefore, be greatest in the region affected by OA, but may also affect the skeleton generally.An increase in measured BMD in a region affected by OA may result from artefactual error caused by the presence of osteophytes, joint space narrowing and sclerosis within the region of interest. Alternatively, it may reflect a generalised effect of OA on the skeleton, or a combination of the two. If OA has a generalised effect on the skeleton, then study of bone metabolism in patients with OA may be important in understanding the pathophysiology of osteoporosis.Studies in patients with OA are complicated by the heterogeneous nature of the disease and by the poor correlation between symptoms and radiological signs.8 It is therefore necessary to determine the prevalence of OA from radiological surveys. It is also unknown whether all degenerative changes identified on radiographs are pathological, or whether minor changes may represent physiological changes of aging.There has been little study of the underlying mechanism of the interaction between bone mass and OA. The development of noninvasive biochemical assays for markers ofbone resorption and formation enable estimation of bone turnover in large cohorts of subjects. The urinary excretion of pyridinium crosslinks has been shown to be increased in patients with large joint OA,"'2 suggesting an increased rate of bone turnover in this condition; however, none of these studies allowed for the fact that there may have been an increased skeletal mass to account for the increase in crosslink excretion. There have been no reports of biochemical markers in subjects with spinal OA.It is now possible to make accurate and precise measurements of BMD using dual energy x ray absorptiometry (DXA). This technique enables measurement of the BMD of the whole skeleton, in addition to measurements at the IS and EN. It is also possible to make accurate measurements of the BMC of the whole skeleton which can be used to no...

1. To investigate whether there is a nyctohemeral rhythm in bone turnover, we measured serum bone Gla-protein (osteocalcin, an index of osteoblast activity) concentration every 2h and urinary deoxypyridinoline (a marker of bone collagen resorption) excretion for 8h periods in 10 pubertal girls (aged 10-14 years), 15 premenopausal women (aged 20-49 years) and 17 postmenopausal women (aged 50-75 years). 2. The serum concentration of bone Gla-protein and the urinary excretion of deoxypyridinoline were five times higher in the pubertal girls than in the premenopausal women. The urinary excretion of deoxypyridinoline in the postmenopausal women was twice that in the premenopausal women. 3. There was a nyctohemeral pattern in all age groups with mean night-time increases of 28% (P < 0.001) in the urinary excretion of deoxypyridinoline and of 5% (P < 0.001) in the serum bone Gla-protein concentration. 4. There also were nyctohemeral patterns in the urinary excretion of calcium (P < 0.02), sodium (P < 0.001) and potassium (P < 0.001), with decreases at night. There was a negative correlation between the night-time changes in the urinary excretion of deoxypyridinoline and calcium, especially in adult women (P < 0.01). 5. The serum level of parathyroid hormone increased with age, but this effect was only observed at night (01.00 to 07.00 hours). There was a nyctohemeral rhythm of the serum intact parathyroid hormone level at all ages, with a peak in the afternoon and night. 6. Thus, at night, there is a large increase in bone resorption and a small increase in osteoblastic activity, representing a nyctohemeral rhythm of bone turnover.(ABSTRACT TRUNCATED AT 250 WORDS)

The pyridinium cross-links of collagen pyridinoline (Pyd) and deoxypyridinoline (Dpd) are released during bone resorption and are neither metabolized nor absorbed from the diet. The aim of this study was to validate their use in osteoporosis. We studied 19 women with osteoporosis and estimated the bone resorption rate from a combined calcium balance/kinetics technique without (R) and with partial (R H ) and "complete" (Res) correction for long-term exchange. The strongest correlation was observed between the bone-specific marker (Dpd) and with complete correction for long-term exchange (Res) (r ‫؍‬ 0.71, p < 0.001). The intercept was not different from zero, suggesting that bone was the major source for Dpd.

Urinary pyridinoline and deoxypyridinoline, new markers of bone resorption, remain fairly constant in the years before the menopause and start to increase about 6 months after the last menstrual bleeding. This increase is reversed by hormone replacement therapy.

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The aims of the study were to characterize the denaturation of urinary free and conjugated pyridinoline (Pyr) and deoxypyridinoline (Dpyr) on exposure to ultraviolet (UV) and natural light at different pH levels and to study the effects of X- and gamma-irradiation on Pyr and Dpyr in urine and in the mineralized and non-mineralized compartments of human bone. Urine samples from six normal subjects, adjusted to pH 3.0, 7.0 and 9.0 were exposed to UV light for up to 3 days. Urine collections (2 mL and 24 h) from three subjects, pH adjusted to 1.0, 2.0, 3.0, 4.0 and 5.0, were exposed to natural light for up to 1 day. Urine samples and bone slices from seven human cadaveric femurs were irradiated with increasing doses of X-rays (0-100 Gy) and high-dose gamma-radiation (28 kGy). Mineralized and non-mineralized bone were separated using a modification of a published method employing heat denaturation followed by trypsin hydrolysis and analysed for Pyr, Dpyr and hydroxyproline (Hypro). The rate of UV photolysis of urinary Pyr and Dpyr increased with pH and was faster in the free fraction (after 3 days' exposure: free Pyr and Dpyr at pH 7.0 vs. 9.0, P < 0.05, conjugated pH 3.0 vs. 9.0, P < 0.05). Exposure to natural light for 3 h did not significantly decrease urinary Pyr and Dpyr in either sample collections, but levels were reduced in the 2-mL aliquots after exposure for 1 day (P < 0.05). X-irradiation of urine and bone did not affect Pyr and Dpyr. Pyr content was similar in both bone compartments (Pyr/ Hypro = 0.12 +/- 0.004), but Dpyr was higher in the non-mineralized compartment (Dpyr/Hypro = 0.047 +/- 0.002 vs. 0.038 +/- 0.002, P < 0.001). UV light and gamma-irradiation result in denaturation of pyridinium cross-links in urine. These cross-links are present in both the mineralized and non-mineralized bone compartments but are not affected by the doses of gamma-irradiation that denature these cross-links in urine.