Free Deoxypyridinoline Research Articles

The Effect Of Prostaglandin E1 On Human Bone Metabolism: Evaluation By Biochemical Markers For Bone Turnover.

Prostaglandins (PGs) have complex and multiple effects on bone metabolism. Although the osteogenic effect of PGE in humans was initially found in an infant with a congenital heart disease, there have been few reports on the effect of PGE in human in vivo. The aim of this study was to investigate the effect of PGE1 on human bone metabolism, using biochemical bone markers. A total of 18 subjects were treated with PGE1 in lipid microspheres. Six subjects were given 10 μg of lipo-PGE1 intravenously daily for 14 days, and twelve subjects were given the same dose twice a week for 7 weeks. Before and after the administration of PGE1, blood and a spot urine was obtained in the morning. Bone formation markers (alkaline phosphatase, osteocalcin, procollagen I carboxy-terminal peptide) did not change. In the subjects with daily administration for 2 weeks, type I collagen pyridinolines crosslinked C-telopeptide (ICTP) increased significantly. In the subjects treated twice a week, free deoxypyridinoline (Dpd) increased significantly. When all subjects were analyzed, bone resorption markers (ICTP and Dpd) increased, but not significantly <p=0.055 for ICTP, p=0.055 for Dpd). Therefore, PGE1 at the dosage used in this study did not increase bone formation but increased bone resorption in humans.

Height, Bone Mineral Density and Bone Markers in Congenital Adrenal Hyperplasia

Aim: To evaluate height, bone growth, areal bone mineral density (aBMD), volumetric bone mineral density (vBMD) and markers of bone turnover in a group of patients affected by congenital adrenal hyperplasia (CAH). Patients: There were 50 patients (23 males, 27 females), aged 1–28 years, affected by CAH due to 21-hydroxylase deficiency: 27 with the salt-wasting (SW); 14 with the simple virilizing (SV), and 9 with the nonclassical (NC) forms. Methods: Bone morphometry was evaluated with the metacarpal index (MI) and lumbar aBMD and vBMD (L2–L4) by dual energy X-ray absorptiometry. Serum osteocalcin was used as a marker of bone formation, while urinary cross-linked N-telopeptides of type-I collagen and free deoxypyridinoline levels were evaluated as indexes of bone resorption. Results: The height standard deviation score (SDS) was –0.41 ± 1.4 in SW patients, –0.01 ± 1.9 in SV patients, and –0.01 ± 2.3 in NC patients. There was no significant difference among groups and against zero. The MI SDS was also not different between groups and against zero.aBMD was significantly lower in the pubertal patients compared with normal values, but only when patients with the SW and SV forms were considered together (p < 0.05). vBMD was significantly reduced in all patients with the classical form. Bone markers were not different in patients and controls. Conclusion: Our study shows that normal height can be attained in CAH patients; however, an impairment in bone growth and mineralization may be found in adolescents and young adults affected by the classical form.

Serum osteocalcin and urinary crosslaps are suitable markers of bone turnover in response to short-term hormone replacement therapy

In this study we evaluated the effect of short-term hormone replacement therapy (HRT) on bone formation (serum osteocalcin) and resorption markers (urinary type I collagen peptides (crosslaps), urinary total free pyridinoline (TPYRI) and urinary free deoxypyridinoline (DPYRI)) as well as female sex hormones (serum estradiol, follicle stimulating hormone (FSH) and luteinizing hormone (LH)) in a group of early postmenopausal women with severe estrogen deficiency. The 46 healthy postmenopausal women with serum estradiol levels < 10 ng/l were subsequently divided into two groups, according to their compliance with HRT.In the group taking HRT significant changes from baseline values could be observed in estradiol, FSH, urinary crosslaps and serum osteocalcin levels after 6 months, whereas no changes could be observed in LH, TPYRI and DPYRI from baseline values. In the group which refused HRT all values were increased relative to baseline values, indicating increased bone turnover.Serum osteocalcin and urinary crosslaps were significantly decreased in women taking HRT in comparison to the group refusing HRT. After 6 months the treated patients showed a decrease in urinary crosslaps of 42% (SD 12%) and in serum osteocalcin of 24% (SD 6%) in comparison with baseline values. In patients who refused HRT, urinary crosslaps were increased by 43% (SD 20%) and serum osteocalcin levels decreased by 2% (SD 9%) compared to baseline values.In postmenopausal women suffering from severe estrogen deficiency (estradiol < 10 ng/l) serum osteocalcin and urinary crosslaps are significantly increased, indicating a clear correlation between estrogen deficiency and an increase in bone resorption as well as bone formation. The recommended HRT dose was sufficient to reduce the rate of bone turnover to premenopausal values. Serum osteocalcin and urinary crosslaps are suitable candidates not only for the assessment of a high postmenopausal bone turnover, but also for monitoring the response to and for verifying the actual intake of HRT or other antiresorptive treatment.

Biochemical markers of bone remodeling and bone sialoprotein in ankylosing spondylitis

The aim of this work was to determine bone mineral density (BMD) in a group of patients with ankylosing spondylitis (AS) and to study alterations in bone remodeling in these patients. Eighteen patients (16 males and two females) with AS, mean age 44.7, range 21–75, and 18 age- and sex-matched healthy controls were studied. BMD was evaluated by dual energy X-ray absorptiometry. The following biochemical markers of bone remodeling were studied: formation – serum amino and carboxyterminal propeptides of procollagen I (PINP and PICP); resorption – urinary total and free deoxypyridinoline and pyridinoline (TDpyr, FDpyr, TPyr and FPyr), crosslinked aminoterminal telopeptides of collagen I (NTX), carboxyterminal telopeptide of collagen I (CTX) and serum bone sialoprotein (BSP). Receiver operating characteristic (ROC) curves of markers were also performed. We found a decrease of bone mass and an increase in TPyr, FPyr, TDpyr, FDpyr, NTX and BSP in AS, but no significant differences were found in PICP, PINP and CTX. FDpyr, FPyr and TPyr showed the highest discrimination between patients and controls according to the results of the ROC curves. TPyr/TDpyr was higher in AS than in controls. We found osteopenia, with a normal formation and a significant increase in bone resorption in AS. FDpyr, FPyr and TPyr seem to present the best sensitivity for the study of alterations of bone resorption in this pathology, although NTX, TDpyr and BSP also show significant differences. The elevation in the ratio TPyr/TDpyr in AS compared to controls indicates that in AS there is a type I-collagen degradation in tissues different from bone.

Dietary sodium, an independent determinant for urinary deoxypyridinoline in elderly women. A cross-sectional study on the effect of dietary factors on deoxypyridinoline excretion in 24-h urine specimens from 763 free-living healthy Japanese.

To investigate the effect of sodium, protein and calcium in habitual diets on bone resorption. A cross-sectional study. A community-based study. Healthy free-living male (n=342) and female (n=421) volunteers aged 20-79 y recruited for a health and nutrition examination survey conducted by a local government. Bone resorption was assessed by the measurement of free deoxypyridinoline in 24 h urine. Dietary assessment was by one-day dietary record method. Sodium and urea in 24 h urine were also measured for assessment of sodium and protein intake. The relationships between deoxypyridinoline excretion and the dietary factors were examined using correlation and multiple regression statistics. In women aged 50-79 y, protein intake was positively associated with deoxypyridinoline excretion (P<0.05); and the urinary deoxypyridinoline/creatinine ratio was positively associated with both the urinary calcium/creatinine ratio (P<0.01) and sodium/creatinine ratio (P<0.05). In the multiple regression model, the association of the deoxypyridinoline/creatinine ratio and sodium/creatinine ratio was still significant (P<0.05) after adjustment for possible confounders, in this sex and age group. In elderly women, habitual excess sodium in diets may result in bone loss through accelerated bone resorption.

Changes in bone mass and bone turnover following distal forearm fracture.

Bone loss occurs close to a fracture and is associated with increased bone turnover. Fracture healing itself results in increased markers of bone turnover. But the exact patterns of these changes after different fractures are unclear. We aimed to investigate the changes in bone density and biochemical markers following distal forearm fracture. Twenty women (mean age 63 years) were recruited following fracture of the distal radius and ulna. Bone mineral density (BMD) of the hand and forearm were measured by dual-energy X-ray absorptiometry (DXA) and quantitative ultrasound (QUS) of the fingers was measured at 0, 6, 12, 26 and 52 weeks after fracture. Serum and urine samples were collected at 0, 3 and 7 days and at 2, 4, 6, 12, 26 and 52 weeks after fracture to measure markers of bone turnover. For bone formation we measured: bone alkaline phosphatase (iBAP), osteocalcin (Oc), procollagen type I N-terminal propeptide (PINP); and for bone resorption: tartrate-resistant acid phosphatase (TRAcP), free deoxypyridinoline (iFDpd), N-telopeptides of type I collagen (NTx). We used the nonfractured limb to calculate values for baseline BMD and amplitude-dependent speed of sound (AD-SoS). There was a decrease in BMD at the hand and in AD-SoS of the fingers after forearm fracture (p<0.001). This bone loss was maximal for BMD by 6 weeks at 9% (p<0. 001) and remained decreased at 52 weeks. AD-SoS decreased at 12 weeks by 3% (p<0.01) and recovered completely by 52 weeks. Bone formation markers increased between 2 and 4 weeks by 13-52% (p<0. 001), and were still elevated at 52 weeks. Bone resorption markers increased between 2 and 6 weeks by 18-35% and returned to baseline at 52 weeks (TRAcP remained elevated). We conclude that BMD decreased distal and immediately proximal to the fracture line when measured with DXA and QUS. Bone loss after distal forearm fracture did not recover by 52 weeks and most bone turnover markers did not return to baseline.

Total and Free Deoxypyridinoline after Acute Osteoclast Activity Inhibition

Deoxypyridinoline (Dpd) is one of the two pyridinium cross-links that provide structural rigidity to type I collagen in bone. During osteoclastic resorption, Dpd is released into circulation and is excreted in the urine in free and peptide-bound forms. Free and total Dpd are highly correlated, but whether the free-to-total cross-link ratio is constant in both normal and high bone turnover states remains controversial. To compare free and total Dpd performance in a physiological condition, urinary free and total Dpd were measured after a short-term inhibition of osteoclast activity such as that induced by an oral calcium load. Total and free Dpd were measured by HPLC and by immunosorbent assay, respectively, in two groups of subjects, one (calcium-treated; n = 16) taking calcium and the other not (control; n = 9). The urinary excretion of total Dpd at 2 and 4 h after oral calcium loading was decreased compared with controls. By contrast, changes in free Dpd were similar in the calcium-treated and control groups, reflecting only circadian rhythm. Total and free Dpd do not show comparable sensitivity in detecting short-term inhibition of osteoclast activity. The degradation process of peptide-bound to free Dpd could render free Dpd insensitive to acute changes of osteoclast activity.

Lack of effect of short-term micronized progesterone on bone turnover in postmenopausal women.

A number of studies suggest that progestogens have beneficial effects on bone in postmenopausal women, particularly in combination with estrogen, although these studies have used derivatives that may have estrogenic and androgenic properties in addition to effects mediated by progesterone receptors. Progesterone itself affects only progesterone and glucocorticoid receptors. However, until the development of micronized progesterone (MP), absorption of progesterone preparations was too low to be clinically useful. MP has similar protective effects on the uterus and fewer effects on the lipid profile than other preparations, but its effects on bone are unknown. We tested the hypothesis that MP would alter bone turnover, as measured by serum and urine biochemical markers, in postmenopausal women. Fourteen women aged 65 or over who were not on estrogen replacement received a 6-week course of daily MP (200 mg). Markers of bone turnover were measured in serum and urine collected at baseline, at 6 weeks on MP, and 6 weeks after termination of MP. We also measured total and high-density lipoprotein (HDL) cholesterol and progesterone levels during the study. Markers of bone resorption were urinary free deoxypyridinoline cross-linked N-telopeptides and C-telopeptides of type I collagen. Markers of bone formation were serum osteocalcin, bone alkaline phosphatase, and type I C-terminal and N-terminal procollagen peptides. Using repeated measures analysis of variance, markers of bone formation and resorption did not change with MP treatment in spite of an increase in progesterone levels in all women. We conclude that 6-week treatment with MP alone does not have an effect on bone turnover in postmenopausal women in spite of high physiological levels. These data suggest that effects on bone demonstrated using other progestogen preparations might be due to androgenic or estrogenic effects or that progesterone may not affect bone in estrogen-deficient women.

Bone metabolism and bone mineral density in childhood hypophosphatasia

Childhood hypophosphatasia (HP) is an inborn error of bone metabolism, characterized by a reduced tissue-nonspecific isoenzyme of alkaline phosphatase (TNSALP). Bone mineral density (BMD) in childhood HP has not been reported so far. We measured BMD, in addition to markers of bone metabolism, in 6 boys with childhood HP (age 2–13 years) and in 10 parents and one sibling, each carrying the autosomal-recessive trait. BMD, measured by peripheral quantitative computed tomography (pQCT) and by dual-energy X-ray absorptiometry (DXA), was expressed as standard deviation from the normal mean ( Z scores) and compared with bone mineralization by standard X-rays of the same locations. HP was confirmed by low TNSALP and its elevated substrates. In patients, BMD of the total body or spine, measured by DXA, was in the lower normal range. Total BMD of the distal metaphyses of the radius, measured by pQCT, was normal ( Z score: mean +1.5). However, trabecular BMD of both radius ( Z score: mean +4) and femur was grossly elevated. In parallel, X-rays showed reduced transradiancy of the radial and femoral metaphyses in all patients. In parents of patients with HP, BMD was in the lower normal range. Only one father had a decreased lumbar BMD. The discrepancy in BMD between cortical and trabecular bone of the metaphyses in patients was not present in their relatives. TNSALP levels in all first degree relatives were just below or in the lower normal range. The markers of bone turnover hydroxyproline and free deoxypyridinoline in urine were normal in patients and relatives. Hypermineralization/sclerosis of trabecular bone might serve as a compensation for a mechanically incompetent bony structure due to an impaired mineralization of cartilage caused by the genetic deficiency of alkaline phosphatase.

The degree of osteoporosis in patients with vertebral fracture and patients with hip fracture: relationship to incidence of vertebral fracture.

The most typical fracture that occurs in osteoporotic patients is a vertebral fracture, whereas hip fractures are thought to occur in the most severe osteoporotic patients. The purpose of this study was to compare the degree of osteoporosis between patients with vertebral fractures and patients with hip fracture by examining bone mineral density, biochemical markers of bone metabolism, and the incidence of vertebral fractures. Subjects were 50 female patients with vertebral fractures (VX) and 60 female patients with hip fracture (HX). Bone mineral densities (BMD) of the lumbar spine, femoral neck (Neck), and one-third of the radius were determined by DXA. Total and bone alkaline phosphatase, osteocalcin, N-MID osteocalcin, PICP, free deoxypyridinoline, and CTx were measured. All z-scores of BMD in the three areas of VX and HX patients were negative, meaning those BMDs were lower in VX and HX than a decade-matched normal reference. The z-score of Neck BMD was significantly lower in HX than in VX. Deoxypyridinoline and CTx were significantly higher in HX than in VX. N-MID osteocalcin was significantly lower in HX than in VX. VX and HX patients were divided into four subgroups according to the number of their vertebral fractures: VX, with a single fracture; VX, with multiple fractures; HX, without vertebral fractures: and HX, with vertebral fractures. VX with multiple fractures and HX with vertebral fractures had lower z-scores at all skeletal sites. HX with vertebral fractures had the lowest median z-score at spine and Neck, whereas HX without vertebral fractures had a low z-score only at Neck compared to VX with a single fracture. There was no significant difference in markers among the subgroups. The number of vertebral fractures was negatively correlated with z-scores of BMD at all three sites. We concluded that uncoupling between bone formation and resorption is greater in hip fractures than in vertebral fractures. Vertebral fractures are associated with general osteopenia of the total skeleton. We suggest that there are two types of osteoporosis in patients with hip fractures: one is that the bone mass of the femoral neck is specifically reduced, and the other is a terminal stage of osteoporosis which follows osteoporosis with vertebral fractures.

Vitamin D insufficiency increases bone turnover markers and enhances bone loss at the hip in patients with established vertebral osteoporosis.

The aim of this study was to determine whether the presence of vitamin D insufficiency increases bone turnover and enhances bone loss by examining the relationship between bone turnover markers and Bone mineral density (BMD) in vitamin D insufficient and vitamin D sufficient patients, with established vertebral osteoporosis. 119 consecutive, active, community dwelling, elderly women were assessed over a 7-month period between the months of March to October. There was a significant correlation between parathyroid hormone (PTH) and 25 hydroxyvitamin D (25(OH)D), r = - 0. 42 (P < 0.01). The prevalence of vitamin D insufficiency was 26.9% (defined by a 25(OH)D >/= 6.1 microg/l and </= 12 microg/l). This resulted in a statistically significant increase in bone turnover markers compared to the vitamin D sufficient group: bone alkaline phosphatase (P < 0.05), osteocalcin (P < 0.01), hydroxyproline (P < 0.05), free deoxypyridinoline (P < 0.05) and lower bone mineral density at the total hip (P < 0.01). These results show that there is a high prevalence of vitamin D insufficiency in the active community dwelling elderly with established vertebral osteoporosis presenting to clinical attention, which leads to increased bone turnover, decreased BMD at the hip and thus enhanced risk of further osteoporotic fractures in comparison with vitamin D sufficient subjects.

Age-related changes in bone turnover in men.

Biochemical markers of bone turnover can be used to study the pathophysiology of osteoporosis. So far there have been few such studies in men. The aims of this study were to determine the effect of aging on bone turnover and to identify which hormones might regulate bone turnover in men. We studied 178 healthy Caucasian men, ages 20-79 years (30 per decade). The data for the effect of age on bone turnover was best fit by a quadratic function (nadirs at age 56, 57, 53, 39, and 58 years for intact propeptide of type I procollagen, osteocalcin, bone alkaline phosphatase, free deoxypyridinoline, and cross-linked N-telopeptides of type I collagen, respectively). For most markers, bone turnover tended to be highest in the third decade, lowest in the fifth and sixth decade, with a small increase in some markers in the eighth decade. Insulin-like growth factor-I (IGF-I), insulin-like growth factor binding protein-3, dehydroepiandrosterone sulfate, testosterone, estradiol, and free androgen index all decreased significantly with age (54, 17, 76, 26, 33, and 57%, respectively), while sex hormone binding globulin and parathyroid hormone increased significantly with age (62% and 43%). IGF-I and sex hormones were positively correlated with bone turnover, and this association was stronger in young men than older men. In conclusion, increased IGF-I and sex hormones may be associated with increased bone turnover in young men, with less influence on bone turnover in older men.

Clinical usefulness of biochemical resorption markers in osteoporosis.

We have evaluated three commercial assays for collagen cross-links, two urine assays and a recently developed serum assay, as markers of bone turnover in 30 postmenopausal women with osteoporosis during their first year of treatment with the anti-resorptive drug alendronate. Before treatment, urine free deoxypyridinoline crosslinks (Dpd), urine N-telopeptide crosslinks (NTx) and serum C-telopeptide (CTx) values were within postmenopausal reference ranges. After 3 months' treatment the decrease in NTx and CTx was greater than that of Dpd (-50%, P < 0.0001 and -48%, P < 0.0001, compared with -11%, NS), as it was after 6 months (-51%, P < 0.0001, and -57%, P < 0.0001, compared with -19%, P < 0.01). The decrease in resorption markers after 6 months was significant in 23% (Dpd), 66% (NTx) and 66% (CTx) of individuals. Neither baseline resorption marker values nor the per cent change after 6 months' therapy correlated with bone mineral density change (BMD) at either lumbar spine or femoral neck after one year's therapy, except baseline Dpd and lumbar spine BMD (P < 0.01). We conclude that NTx and serum CTx were more sensitive markers of bone turnover suppression by alendronate, but only baseline Dpd was useful in the prediction of individual bone density response after one year.

Low Dose Estrogen and Calcium Have an Additive Effect on Bone Resorption in Older Women

Previous studies have shown that treatment with estrogen or calcium decreases bone turnover in older women. The mechanisms by which estrogen and calcium exert their effects are probably different. We therefore examined the possibility of an additive or synergistic effect of combined treatment with calcium and low dose estrogen on bone turnover in older women, using biochemical markers. Thirty-one healthy women over 70 yr of age were randomized to 12 weeks of treatment with either micronized 17beta-estradiol [0.5 mg/day Estrace (E2)] or 1500 mg/day elemental calcium, given as carbonate plus vitamin D (800 IU/day; Ca+D). At the end of the initial 12-week treatment period, both groups received both Ca+D and E2 for an additional 12 weeks. Eleven older women were followed for 36 weeks without any treatment and served as a control group. Serum and urine were collected at baseline, at 12 and 24 weeks on treatment, and at 12 weeks after treatment was terminated for measurement of biochemical markers of bone turnover. Markers of bone formation were bone alkaline phosphatase, osteocalcin, and type I procollagen peptide; markers of bone resorption were urinary cross-linked C-telopeptides and N-telopeptides of type I collagen, serum cross-linked N-telopeptides of type I collagen, urinary free deoxypyridinoline cross-links, and serum bone sialoprotein. Repeated measures ANOVA was used to determine changes in bone turnover measures over time by group. All markers of bone resorption decreased with initial treatment and decreased further with combination therapy (P < 0.001). Markers of bone formation decreased with Ca+D treatment, but not with E2 alone; there was no additional effect of combination therapy on formation markers compared to Ca+D alone. Neither markers of formation nor resorption changed in the control group. These results suggest that there is an additive effect of low dose estrogen and calcium on bone resorption, but not on bone formation, in older women. Thus, the combination of low dose estrogen plus calcium is likely to be more effective in older women than either treatment alone.

Biochemical markers of bone turnover do not decline after menopause in healthy women.

To investigate the duration of high bone turnover after menopause in normal healthy women. Study recruited from three screening studies for health care in the elderly held in the area of Hamamatsu city. Department of Orthopaedic Surgery, Hospital at Hamamatsu University School of Medicine, Hamamatsu. Ninety-two healthy postmenopausal women aged 47-81 years and 18 premenopausal women. Bone mass was determined by densitometry of the spine and the os calcis, or by ultrasound of the os calcis. Biochemical markers of bone turnover were measured including total and bone-specific alkaline phosphatase, osteocalcin, C-terminal propeptide of type I procollagen, free deoxypyridinoline and urinary degredation products of type I collagen. All markers except the C-terminal propeptide of type I procollagen were significantly higher in early postmenopausal women than in premenopausal women. Postmenopausal women were divided into four groups according to years since menopause. There was no difference in biochemical markers among those women in whom years since menopause were 1 to 5, 6 to 15, 16 to 25 and >26. There were no correlations between biochemical markers and age in postmenopausal women. When the postmenopausal women were divided into three groups according to t-scores of bone mass, there was no significant difference in the biochemical markers among the groups. High bone turnover occuring after menopause lasts for >25 years during the postmenopausal period.

Effects of age, menopause and osteoporosis on free, peptide-bound and total pyridinium crosslink excretion.

We evaluated urinary excretion of free pyridinoline (PYD)-deoxypyridinoline (DPD) by an enzymelinked immunosorbent assay (ELISA) method, free and total PYD by high-performance liquid chromatography (HPLC), free DPD by ELISA, chemiluminiscent immunoassay (CLEIA) and HPLC, total DPD by HPLC, and N-telopeptides (NTX) and C-telopeptides (CTX) by ELISA in 234 women distributed into three groups: 43 healthy young women (aged 26.2 +/- 2.5 years), 56 control postmenopausal women (aged 55.9 +/- 4.5 years) and 133 untreated osteoporotic women (aged 55.1 +/- 4.0 years). The control postmenopausal women had increased values of all markers considered, except NTX, compared with healthy young women. The osteoporotic postmenopausal women had significantly increased values compared with control postmenopausal women for free DPD by HPLC and free DPD by ELISA or CLEIA. HPLC, ELISA and CLEIA showed adequate correlation to measure free PYD and DPD. Control postmenopausal women had significantly decreased values of the fraction of free PYD and DPD (48.4% and 32.0%, respectively), as did the osteoporotic postmenopausal women (48.0% and 46.1%), compared with healthy young women (55.3% and 57.0%). We found a significant negative correlation comparing age with fraction of free PYD and DPD, but a positive correlation with total PYD and DPD, considering or not the osteoporotic postmenopausal women. T-score and Z-score values derived from healthy young women and control postmenopausal women for PYD, DPD, NTX and CTX measured by immunoassays were calculated to detect changes in bone turnover, DPD by ELISA or CLEIA showing the highest Z-score. The sensitivity and specificity of the different assays were evaluated using a receiver operating characteristic (ROC) curve. With a specificity of 90% the sensitivity of the markers considered was low (from 33% for DPD by CLEIA to 11% for PYD-DPD by ELISA), but increased considerably with a specificity of 75%. In conclusion, urinary pyridinium crosslink derivatives increase with age and after the menopause, and rise slightly in women with osteoporosis, there being a negative correlation among age and the fraction of free PYD and DPD of the total urinary excretion. Among the resorption markers most often available in clinical laboratories, free DPD by ELISA or CLEIA was the best at discriminating osteoporotic postmenopausal women from aged-matched control postmenopausal women.

Urinary excretion of pyridinium crosslinks in healthy 4-10 year olds.

Urinary pyridinoline and deoxypyridinoline, pyridinium crosslinks released during breakdown of mature collagen, might serve as useful markers of bone resorption. Before their role can be identified, reference values must be established. In this study, free pyridinoline (f-Pyr), free deoxypyridinoline (f-DPyr), and creatinine (Cr) were measured in first morning void urine samples from 250 girls and 265 boys between the ages of 4 and 10 years. Overall, there was a decrease in f-Pyr:Cr and f-DPyr:Cr ratios with increasing age in both sexes, but there was a wide range of values for individuals of similar ages. Further studies are required to assess whether urinary pyridinium crosslink excretion is sufficiently deranged in conditions affecting bone metabolism for the measurement of these compounds to be of clinical value.

One year prospective open study of the effect of high dose inhaled steroids, fluticasone propionate, and budesonide on bone markers and bone mineral density

BACKGROUNDInhaled corticosteroids are recognised as the most effective agents in the treatment of asthma. However, concerns have been expressed about the effects of high doses of inhaled corticosteroids on safety...

Monitoring antiosteoporotic treatment of postmenopausal women using biochemical markers of bone turnover.

Postmenopausal osteoporosis is preventable. An increasing number of antiresorptive therapies including estrogen, selective estrogen receptor modulators (the so-called designer estrogens), bisphosphonates and calcitonins are now available as treatment options for osteoporosis. These agents reduce the level of bone turnover and consequently slow or arrest bone loss and decrease the risk of fracture. However, these therapies are only effective if they are taken as prescribed. Unfortunately, most women who initiate antiresorptive therapy are unwilling or unable to make a long-term commitment to maintain such therapy. The test for biochemical markers of bone turnover can be used to confirm a biochemical response of bone within 3-6 months of initiating therapy, far sooner than the 2 years required for bone density testing. Such information incorporates a timely assessment of the woman's physiologic response with therapeutic compliance. A test result indicating the expected response to treatment may motivate some patients to remain compliant and maintain the therapy for an extended period of time. Bone turnover markers with demonstrated efficacy in monitoring the reduction of bone turnover induced by antiresorptive therapies include bone-specific alkaline phosphatase and osteocalcin (bone formation markers), and free deoxypyridinoline, N-telopeptide and C-telopeptide (bone resorption markers).

Bone Loss in Patients with Inflammatory Bowel Disease Is Less Than Expected: A Follow-up Study

In spite of the accumulating evidence of an increased prevalence of osteopenia and osteoporosis in patients with inflammatory bowel diseases (IBD), the time course of bone loss is not well described, and there is little knowledge about factors indicating an increased risk of rapid bone loss. We conducted a follow-up study in 80 IBD patients (45 men and 25 premenopausal and 10 postmenopausal women), 19 with ulcerative colitis and 61 with Crohn disease, with a mean follow-up time of 568 +/- 60 days, to assess bone loss, risk factors of rapid bone loss, and value of bone markers to predict bone loss. Bone mineral density was measured by dual-energy X-ray absorptiometry, bone formation by bone alkaline phosphatase (BAP), and bone resorption by N-terminal telopeptide of type-I collagen (NTX) and free deoxypyridinoline (DPD). Bone density changes per year were 0.46% +/- 3% at the spine, 0.06% +/- 5.1% at the femoral neck, -1.1% +/- 7.7% at the triangle of Ward, and -0.52% +/- 1.86% at total body level. Type and duration of disease, sex, age, and level of NTX, DPD, and BAP at base line did not show significant differences between patients who lost and those who did not lose bone mass. Bone loss was significantly higher in patients with (n = 28) than in those without steroids (n = 52) at the femoral neck and Ward triangle but not at the spine and total body. Change in bone mass in IBD patients during short-term follow-up is low on average, but there is great heterogeneity within the population, which cannot be explained by the use of steroids alone. Bone loss cannot be predicted by analysis of bone markers.