Deoxypyridinoline Research Articles

Association between collagen cross-links and trabecular microarchitecture properties of human vertebral bone

It has been suggested that age-related deterioration in trabecular microarchitecture and changes in collagen cross-link concentrations may contribute to skeletal fragility. To further explore this hypothesis, we determined the relationships among trabecular bone volume fraction (BV/TV), microarchitecture, collagen cross-link content, and bone turnover in human vertebral trabecular bone. Trabecular bone specimens from L2 vertebrae were collected from 51 recently deceased donors (54–95 years of age; 20 men and 30 women). Trabecular bone volume and microarchitecture was assessed by microCT and bone formation, reflected by osteoid surface (OS/BS, %), was measured by 2D histomorphometry. Pyridinoline (PYD), deoxypyridinoline (DPD), pentosidine (PEN) and collagen content in the cancellous bone were analysed by high-performance liquid chromatography. Associations between variables were investigated by Pearson correlations and multiple regression models, which were constructed with BV/TV and collagen cross-links as explanatory variables and microarchitecture parameters as the dependent variables. Results: Microarchitecture parameters were modestly to strongly correlated with BV/TV (r2=0.10–0.71). The amount of mature enzymatic PYD and DPD cross-links were not associated with the microarchitecture, either before or after adjustment for BV/TV. However, there was a positive correlation between PEN content and trabecular number (r=0.45, p=0.001) and connectivity density (r=0.40, p=0.004), and a negative correlation between PEN content and trabecular separation (r=−0.29, p=0.04). In the multiple regression models including BV/TV, age and PEN content was still significantly associated with several of the microarchitecture variables. In summary, this study suggests a link between trabecular microarchitecture and the collagen cross-link profile. As PEN reflects non-enzymatic glycation of collagen and generally increases with bone age, the association between PEN and trabecular architecture suggests that the preserved trabeculae may contain mainly old bone and have undergone little remodeling. Thus, vertebral fragility may not only be due to alterations in bone architecture but also to modification of collagen cross-link patterns thereby influencing bone's mechanical behavior.

Comparison in bone turnover markers during early healing of femoral neck fracture and trochanteric fracture in elderly patients

Healing of fractures is different for each bone and bone turnover markers may reflect the fracture healing process. The purpose of this study was to determine the characteristic changes in bone turnover markers during the fracture healing process. The subjects were consecutive patients with femoral neck or trochanteric fracture who underwent surgery and achieved bone union. There were a total of 39 patients, including 33 women and 6 men. There were 18 patients (16 women and 2 men) with femoral neck fracture and 21 patients (17 women and 4 men) with trochanteric fracture. Serum bone-specific alkaline phosphatase (BAP) was measured as a bone formation marker. Urine and serum levels of N-terminal telopeptide of type I collagen (NTX), as well as urine levels of C-terminal telopeptide of type I collagen (CTX) and deoxypyridinoline (DPD), were measured as markers of bone resorption. All bone turnover markers showed similar changes in patients with either type of fracture, but significantly higher levels of both bone formation and resorption markers were observed in trochanteric fracture patients than in neck fracture patients. BAP showed similar levels at one week after surgery and then increased. Bone resorption markers were increased after surgery in patients with either fracture. The markers reached their peak values at three weeks (BAP and urinary NTX), five weeks (serum NTX and DPD), and 2–3 weeks (CTX) after surgery. The increase in bone turnover markers after hip fracture surgery and the subsequent decrease may reflect increased bone formation and remodeling during the healing process. Both fractures had a similar bone turnover marker profile, but the extent of the changes differed between femoral neck and trochanteric fractures.

Homocysteine oxidative stress and relation to bone mineral density in post-menopausal osteoporosis

Mildly elevated homocysteine (Hcy) and oxidative stress are novel and potentially modifiable risk factors for post-menopausal osteoporosis. We hypothesized that imbalance of oxidant/ antioxidant status and increased Hcy concentration stimulates osteoporotic activity, leading to increased collagen I breakdown in post-menopausal women. Patients were divided into 2 groups (NOP and OP). Group NOP had normal bone mineral density (BMD) and group OP low BMD. Thirty-four (69%) were in group OP and 15 (31%) in group NOP. Serum Total Antioxidant Status (TAS) and Total Peroxide (TPx) levels were determined with new automated methods. The study included measurement of Deoxypyridinoline (DPD). In OP patients plasma t-Hcy, urine deoxypyridinoline and plasma TPx were significantly higher than those in NOP controls. In addition, OP patients also had lower TAS levels than controls, which represent the oxidative imbalance. Pearson's correlation analysis revealed a negative correlation between t-Hcy and TAS (p<0.038). A significant negative correlation was also found between TAS level and BMD values for the spine in OP patients (p<0.035). In contrast, a positive correlation between t-Hcy and TPx in OP patients was demonstrated significantly, r=0.52, p<0.029. We show that the OP group had reduced TAS, whereas the elevated TPx was different from that in the NOP group. Slightly elevated homocysteinemia may contribute to increasing TPx and reducing TAS in the OP group. However, our results suggest a weak but negative relationship between TAS and BMD. Further investigations are needed to examine the relationship of oxidative stress as an endogenous bioactive agent to bone loss in post-menopausal women. Since oxidative stress is the imbalance between total oxidants and antioxidants in the body, any single oxidant/ antioxidant parameter may not reflect overall oxidative stress. Further studies are needed to understand the underlying mechanisms of these findings.

First line zidovudine/lamivudine/lopinavir/ritonavir leads to greater bone loss compared to nevirapine/lopinavir/ritonavir

We studied changes in bone mineral density (BMD) and bone turnover after initiation of combination antiretroviral therapy (cART) and the contribution of zidovudine/lamivudine (ZDV/3TC) in particular. Randomized clinical trial comparing lopinavir/ritonavir(LPV/r) + ZDV/3TC with LPV/r + nevirapine (NVP) in 50 cART-naive men. Dual energy X-ray absorptiometry (DXA) and quantitative computed tomography scans (QCT) were performed at baseline and 3, 12, and 24 months after cART initiation. Serum 25-hydroxy-vitamin D3, parathyroid hormone (PTH), osteocalcin, and urine deoxypyridinoline (DPD)/creatinine ratio were measured. BMD decreased rapidly in both femoral neck and lumbar spine after cART initiation. BMD loss during 24 months measured by DXA, but not by QCT, was greater in the ZDV/3TC/LPV/r group compared to the NVP/LPV/r group [femoral neck: -6.3% +/- 1.0% (P < 0.0001) compared to -2.3% +/- 0.9% (P = 0.01), between-group P = 0.0006); lumbar spine: -5.1% +/- 0.8% (P < 0.0001) compared to -2.6% +/- 0.7% (P = 0.0006), between-group P = 0.07]. Osteocalcin [+1.60 +/- 0.32 (P < 0.0001) and +1.81 +/- 0.29 (P < 0.0001) nmol/l] and the urine DPD/creatinine ratio [+1.35 +/- 0.44 (P = 0.0029) and +1.19 +/- 0.38 nmol/mmol (P = 0.0024)] increased in both groups over 24 months, with no significant difference between groups. PTH increased to a greater degree in the NVP/LPV/r group [+2.0 +/- 0.31 pmol/l (P < 0.0001)] compared to [+0.81 +/- 0.33 pmol/l (P = 0.021) in the ZDV/3TC/LPV/r group]. BMD in both femoral neck and lumbar spine decreased rapidly after initiation of cART, in parallel to an increase in bone turnover. The greater bone loss in the ZDV/3TC/LPV/r group compared to the NVP/LPV/r group suggests that ZDV/3TC contributes to this process. The PTH increase does not explain this greater bone loss.

Urinary excretion of hydroxy-pyridinium cross-links of collagen reflects skeletal growth velocity in normal children.

Two new markers of bone resorption, the collagen cross-linking amino acids pyridinoline (PYD) and deoxypyridinoline (DPD), were measured in 24-h urine collections from 88 healthy children (45 females, 43 males; age 4 to 18 years) and 17 adults. Normal values for pediatric use were established for these parameters. Related to daily excretion of creatinine PYD and DPD were about 3 to 6 fold higher in the pediatric groups than in adults. The collagen cross-links showed a highly significant correlation to the urinary excretion of hydroxyproline (OHP): r = 0.65 for PYD and r = 0.60 for DPD (p < 0.001). Both collagen cross-links and OHP excretion related to creatinine were significantly correlated to growth velocity (r = 0.67, 0.62 and 0.51 for PYD, DPD and OHP respectively; p < 0.001 in each case). PYD and DPD may be useful for the monitoring of growth in children.

The relationship between body composition and the urinary excretion of deoxypyridinoline and galactosyl-hydroxylysine in children and adolescents

The study intends to investigate the relationship of body composition (%fat, percent body fat; FM, fat mass; FFM, fat free mass; FA and MA cross-sectional fat and muscle area) to the urinary excretion of deoxypyridinoline (DPD) and galactosyl-hydroxylysine (Gal-Hyl). 231 healthy children and adolescents (age 5-19 years; 112 males) of the DONALD study were analyzed for FM and FFM by measuring 4 skinfold thicknesses, for DPD and Gal-Hyl in urine samples and for bone parameters, FA and MA at the forearm by peripheral quantitative computed tomography. In contrast to adrenarchal females, adrenarchal males with low %fat had low levels of DPD and Gal-Hyl. %fat was correlated with DPD in pre-adrenarchal males (r = 0.290) and females (r = 0.298). Cortical bone mineral density (BMDcort) was correlated with DPD (r = -0.351) in adrenarchal males. Controlled for BMDcort, FM was correlated with DPD in pre-adrenarchal males (r = 0.348), and FA was correlated with DPD in pre-adrenarchal females (r = 0.294). FFM was negatively correlated with Gal-Hyl in adrenarchal males (r = -0.436) and females (r = -0.338). Less than 40% of variance of excreted DPD and Gal-Hyl was explained by regression models based on parameters of body composition. The effect of body composition explains the minor part of variance of the urinary excretion of DPD and Gal-Hyl. The association of body composition to excreted DPD and Gal-Hyl was not explained by the effect of adipose tissue on bone formation and bone resorption.

Influence of exercise mode and osteogenic index on bone biomarker responses during short-term physical training

Prescribing exercise based on intensity, frequency, and duration of loading may maximize osteogenic responses in bone, but a model of the osteogenic potential of exercise has not been established in humans. In rodents, an osteogenic index (OI) has been used to predict the osteogenic potential of exercise. The current study sought to determine whether aerobic, resistance, or combined aerobic and resistance exercise programs conducted over eight weeks and compared to a control group could produce changes in biochemical markers of bone turnover indicative of bone formation. We further sought to determine whether an OI could be calculated for each of these programs that would reflect observed biochemical changes. We collected serum biomarkers [bone-specific alkaline phosphatase (BAP), osteocalcin, tartrate-resistant acid phosphatase (TRAP), C-terminal telopeptide fragment of type I collagen (CTx), deoxypyridinoline (DPD), 25-hydroxy vitamin D (25(OH)D), and parathyroid hormone (PTH)] in 56 women (20.3 ± 1.8 years) before, during and after eight weeks of training. We also measured bone mineral density (BMD) at regional areas of interest using DXA and pQCT. Biomarkers of bone formation (BAP and osteocalcin) increased in the Resistance and Combined groups ( p < 0.05), while biomarkers of bone resorption (TRAP and DPD) decreased and increased, respectively, after training ( p < 0.05) in all groups. Small changes in volumetric and areal BMD ( p < 0.05) were observed in the distal tibia in the Aerobic and Combined groups, respectively. Mean weekly OIs were 16.0 ± 1.9, 20.6 ± 2.2, and 36.9 ± 5.2 for the Resistance, Aerobic, and Combined groups, respectively. The calculated osteogenic potential of our programs did not correlate with the observed changes in biomarkers of bone turnover. The results of the present study demonstrate that participation in an eight week physical training program that incorporates a resistance component by previously inactive young women results in alterations in biomarkers of bone remodeling indicative of increased formation without substantial alterations in markers of resorption.

Oxidative Criteria And Somebone Turnover Markers In Beta-Thalassemic Patients

Bone disease in beta-thalassemic patients has multifactorial etiology;increased iron stores and per-oxidative stress are involved factors.This study aimed to investigate the relationship between some boneturnover markers and some oxidants, antioxidants parameters of betathalassemicpatients. The study included 50 patients were diagnosedas beta-thalassemia major aged between 3 and 40 years, 30 males and20 females compared to 34 normal controls of same age and sex ratio.The patients and the controls were divided into 2 groups: group A1&le;18 years compared to their controls group B1 and group A2 > 18years compared to their controls group B2. All were subjected to fullclinical examination and laboratory analysis of their blood and urinefor bone turnover markers; osteocalcin (OC), bone specific alkalinephosphatase (BAP) and urinary deoxypyridinoline (DPD).Alsoparathormone (PTH), serum calcium (Ca) and phosphorus (Ph).Oxidants and antioxidants determined were; plasma malondialdehyde(MDA), nitric oxide (NO), blood reduced glutathione (GSH),erythrocyte Cu- Zn Superoxide dismutase (SOD). Serum levels ofcopper (Cu), zinc (Zn), selenium (Se), vitamin E and total antioxidantcapacity (TAOC) were also determined. The results showedsignificant increase in urinary DPD and decrease in serum OC, BAPand PTH in thalassemic groups compared to controls. Also, the resultsrevealed significant elevation in plasma MDA, NO, SOD and serumCu and TAOC especially in group A1. While there was significant decrease in GSH, serum Zn, Se, and vitamin E. Plasma OC waspositively correlated with serum iron and NO and negativelycorrelated with plasma TAOC in thalassemic patients within agegroup 3 &le;18 years. On other hand, plasma BAP level was positivelycorrelated with the frequency of transfusion. Moreover, a significantinverse correlation of plasma PTH with blood GSH and plasma Vit.Ewere observed in thalassemic patients within age group 18 &le; 40.Furthermore, a significant positive correlation of plasma OC withheight, DPD with age and Ph. were seen too in the same group. Also,plasma DPD was negatively correlated with NO in thalassemicpatients within age group 18 &le; 40. In Conclusion, there aredisturbance in bone turnover markers in beta-thalassemic patientswhich favor increased bone resorption and decreased bone formation.These markers have to some extent correlations with oxidantantioxidantparameters in those patients.Key Words : Oxidative stress markers , MDA , antioxidant , osteocalcin, PTH

Ameliorative effects of Vaccaria segetalis extract on osteopenia in ovariectomized rats

The purpose of this study was to determine the ameliorative effects of a crude extract of Vaccaria segetalis (Neck.) Garcke (Caryophyllaceae) (VSE) on osteopenia in ovariectomized (OVX) rats over 12 weeks. Rats were divided into the sham and OVX groups. The OVX rats were allowed to lose bone for 6 weeks. At 6 weeks post-OVX, the OVX rats were divided into four groups treated with water, 17beta-estradiol (30 microg/kg, daily subcutaneous injection), or VSE (0.5 or 1.0 g/kg, daily, orally) for 6 weeks. In OVX rats, the increases of serum total cholesterol were significantly decreased by VSE or 17beta-estradiol treatment. There were decreases in bone density and calcium content, including the left femur and the fourth lumbar vertebra, when compared with the sham control rats. Treatment with 17beta-estradiol or VSE ameliorated these changes induced by OVX. In addition, ovariectomy increased urinary deoxypyridinoline (DPD) amounts (P < 0.001). The increases were suppressed by 17beta-estradiol and 0.5 or 1.0 g/kg VSE (P < 0.01, P < 0.05, P < 0.01, respectively). Our results demonstrated that VSE ameliorates ovariectomy-induced osteopenia by inhibition of bone resorption.

Bone Resorption in Kidney Transplant Recipients

Early diagnosis of persistent hyperparathyroidism (HP) following kidney transplantation may prevent worsening of osteodystrophy and potential damage to the graft. We evaluated the utility of collagen pyridinoline (PYD) and deoxypyridinoline (DPD) urinary cross-links beyond the common HP markers to evaluate 70 selected stable recipients between 1997 and 2006 who were divided into 2 group depending on the immunosuppressive protocol. All patients showed elevated levels of urinary cross-links even though calcemia and phosphoremia values were normal. Their mean creatinine level was slightly increased. Data were assessed as mean values ± SD. All variables underwent a correlation matrix analysis and a stepwise regression, with posttransplant intact parathyroid hormone (iPTH) as the dependent variable and other variables as regressors. A statistically significant correlation was observed between PYD and alkaline phosphatase (ALP; P = .0026, r = .41); PYD and DPD ( P = .015, r = .34); pre- and posttransplant iPTH ( P = .024, r = .31); and creatinine and ALP ( P = .024, r = .31). Taking the groups separately, there were significant correlations between PYD and ALP ( P = .0076, r = .42); PYD and DPD ( P = .017, r = .38); ALP and posttransplant iPTH ( P = .038, r = .33); osteocalcin (OC) and posttransplant iPTH ( P = .048, r = .32); and pre- and posttransplant iPTH ( P = .019, r = .37) among subjects in the first group, whereas subjects in the second group showed a correlation between posttransplant iPTH and age at transplantation ( P = .032, r = .61). In conclusion, we showed that urinary cross-links may be helpful to reveal bone resorption in kidney recipients when usual bone metabolism parameters do not demonstrate hyperparathyroidism.

Preliminary Clinical Study to Evaluate the Relationship between Systemic Bone Turnover and the Microstructure of the Alveolar Bone

The objective of this study was to assess the possibility of developing a clinical minimally invasive and standardized method to evaluate the relationship between the microstructure of the jaw bone and systemic bone turnover. For this purpose, we performed standardized bone biopsy of the alveolar bone, and compared the 3D bone microstructure using micro-computed tomography (micro-CT) with bone mineral density (BMD) of the lumbar spine and biochemical markers of bone turnover. We evaluated a total of 9 samples taken from 6 patients by standardized biopsy using a trephine bur. BMD was evaluated using dual energy X-ray absorptiometry (DXA). Regarding the biochemical markers of bone turnover, serum bone-specific alkaline phosphatase (BAP) and serum osteocalcin (OC) were used as bone formation markers, and urinary cross-linked N-telopeptides of type I collagen (NTx) and urinary deoxypyridinoline (DPD) were selected as bone resorption markers. We scanned micro-CT images of these samples. Bone volume fraction (BV/TV), trabecular thickness (Tb.Th), trabecular number (Tb.N), trabecular spacing (Tb.Spac), fractal dimension, trabecular bone pattern factor (TBPf) and node-strut (Nd.Nd/TV, TSL/TV) were measured. Regarding the correlations between the parameters of bone microstructures, TB/TV, Tb.N, fractal dimension, and node-strut seemed to be positively correlated and Tb.Spac and TBPf seemed to be negatively correlated with each other, but Tb.Th seemed to have a low correlation with other parameters. OC and/or BAP showed a significantly high correlation with many structural parameters (p < 0.05%). In conclusion, some microstructural parameters may change according to the systemic bone turnover.

Feeding Orange Pulp Improved Bone Quality in a Rat Model of Male Osteoporosis

Oxidative stress and inflammation have been linked to bone loss. We evaluated the effects of feeding orange pulp (OP), a source of vitamin C and flavonoids, on bone quality in a rat model of male osteoporosis. One-year-old retired breeder rats (n = 43) were orchidectomized (ORX) or sham-operated (SHAM). Three days postsurgery, ORX rats were randomly assigned to treatments: ORX or ORX with 2.5% OP, 5% OP, or 10% OP. Diets were isonitrogenous, isocaloric, modified AIN-93M diets with equal fiber content. All ORX rats were fed for 4 months to the mean food intake of the SHAM group. At the end of the study blood, urine and bone samples were collected. Plasma antioxidant capacity and urinary deoxypyridinoline (DPD) were determined. Bone density, structure, and strength were assessed using dual energy X-ray absorptiometry, microcomputed tomography, and finite element analyses. ORX decreased (P < .05) antioxidant status, while OP as low as 2.5% maintained the antioxidant capacity of ORX rats comparable to that of the SHAM group. Cortical thickness at the tibial midshaft was significantly decreased by ORX and increased by OP, and urinary DPD was significantly increased by ORX and decreased by OP. In fourth lumbar trabecular cores, ORX rats had significantly reduced bone volume fraction, connectivity density, and trabecular number and increased trabecular separation. OP significantly increased bone volume fraction and trabecular number and decreased trabecular separation in ORX rats. Improvements due to OP in microarchitectural properties of vertebral bones and in cortical thickness of long bones were subtle but significant. The consistently negative impacts of ORX on bone density, structure, and strength parameters confirm the previously reported importance of testosterone for bone.

Increased serum OPG in atrophic nonunion shaft fractures

BackgroundBone repair alteration is hypothesized for nonunion fracture pathogenesis. Since it is involved in osteoclast regulation, the RANK/RANKL/OPG system (receptor activator of nuclear factor kB/its ligand/osteoprotegerin) may play a role.Materials and methodsSerum OPG, free RANKL, bone alkaline phosphatase (BAP), osteocalcin (OC), and urinary deoxypyridinoline (DPD) were determined in 16 male patients (20–39 years) with long bone atrophic nonunion fractures. Serum markers were also measured in 18 age-matched male controls who healed from the same type of fractures within six months, and in 14 age-matched male controls who were healing from the same fractures one month after injury. One-way ANOVA and Bonferroni’s test were used for statistical analysis.ResultsOnly OPG was significantly higher (0.56 sd 0.11 ng/ml) in the patients compared to healed (0.26 sd 0.04 ng/ml; P < 0.001) and healing (0.29 sd 0.09 ng/ml; P < 0.001) controls. The patients’ DPD levels were normal. No correlations were found between bone markers and the characteristics of the subjects in all groups.ConclusionsA normal steady state of bone metabolism seems to be present in patients with atrophic nonunion fractures, despite the high serum OPG. The reason for the inability of the patients’ OPG to inhibit osteoclastic activity is unknown. Osteoblast activity also appears normal, so another cellular source of OPG can be hypothesized.

Risk factors for hip fracture in Japanese elderly women with osteoporosis: Applicability of biochemical markers in bone turnover

The purpose of this study was to investigate risk factors for hip fracture in 169 Japanese elderly women. Patients were divided into three groups: 53 patients had osteoporosis with hip fractures (FX-G), 59 patients had osteoporosis without hip fractures (NFX-G) and 57 patients had low back pain with neither osteoporosis nor hip fracture (NOP-G). Bone mineral density (BMD) of lumbar spine, bone-specific alkaline phosphatase (BAP) and deoxypyridinoline (DPD) were compared among the three groups. The mean BMD of FX-G and NFX-G was lower than that of NOP-G, but there was no significant difference between FX-G and NFX-G. Although the mean BAP of FX-G was similar to that of NOP-G, both were lower than NFX-G (P < 0.05). However, the mean DPD of FX-G was higher than the other groups (P < 0.05, vs NFX-G, P < 0.001, vs NOP-G). The percentage of patients who showed BAP levels less than 35 IU/L and DPD levels of 7.5 nmoL/mmol-Cr or more, was highest in FX-G (72.7%). This percentage was lower for NFX-G (30.9%) and NOP-G (16.4%). The odds ratio of hip fracture occurring was 5.77 (95% confidence interval, 2.25-14.66). Bone turnover consisting of increase in bone resorption and decrease in bone formation apart from BMD of lumbar spine resulted in a higher incidence of hip fracture for Japanese elderly women with osteoporosis.

Combining bone resorption markers and heel quantitative ultrasound to discriminate between fracture cases and controls

This nested case-control analysis of a Swiss ambulatory cohort of elderly women assessed the discriminatory power of urinary markers of bone resorption and heel quantitative ultrasound for non-vertebral fractures. The tests all discriminated between cases and controls, but combining the two strategies yielded no additional relevant information. Data are limited regarding the combination of bone resorption markers and heel quantitative bone ultrasound (QUS) in the detection of women at risk for fracture. In a nested case-control analysis, we studied 368 women (mean age 76.2 +/- 3.2 years), 195 with low-trauma non-vertebral fractures and 173 without, matched for age, BMI, medical center, and follow-up duration, from a prospective study designed to predict fractures. Urinary total pyridinolines (PYD) and deoxypyridinolines (DPD) were measured by high performance liquid chromatography. All women underwent bone evaluations using Achilles+ and Sahara heel QUS. Areas under the receiver operating-characteristic curve (AUC) for discriminative models of the fracture group, with 95% confidence intervals, were 0.62 (0.56-0.68) and 0.59 (0.53-0.65) for PYD and DPD, and 0.64 (0.58-0.69) and 0.65 (0.59-0.71) for Achilles+ and Sahara QUS, respectively. The combination of resorption markers and QUS added no significant discriminatory information to either measurement alone with an AUC of 0.66 (0.60-0.71) for Achilles+ with PYD and 0.68 (0.62-0.73) for Sahara with PYD. Urinary bone resorption markers and QUS are equally discriminatory between non-vertebral fracture patients and controls. However, the combination of bone resorption markers and QUS is not better than either test used alone.

Urinary Bone Resorption Markers (Deoxypyridinoline and C-Terminal Telopeptide of Type I Collagen) in Healthy Persons, Postmenopausal Osteoporosis and Patients with Type I Diabetes

Deoxypyridinoline (DPD) is a derivative of hydroxypyridinium, which is released during bone resorption into the blood stream and is eliminated unmodified with urine. A further collagen-derived marker of bone resorption is the C-terminal telopeptide of type I collagen (beta-CTX-I, here abbreviated as CTX), which is released in bone resorption and almost entirely excreted by the kidneys. The aim of our study was to investigate different well-described patient groups as well as normal probands in view of differences and expected correlations of these two parameters: patients with insulin-dependent diabetes mellitus, postmenopausal women with osteoporosis and healthy control persons. We used a solid-phase chemiluminescence enzyme immunoassay (Pyrilinks D-IMMULITE) for urinary DPD measurement and for the assessment of urinary CTX we used a quantitative ELISA (Osteometer Biotec A-S, CrossLaps ELISA). We found a highly significant correlation between both parameters in the group of healthy persons (r = 0.75, p < 0.05, n = 28) as well as in the group of patients with diabetes mellitus type I (r = 0.79, p < 0.05, n = 65). Also, a significant correlation was observed between DPD and CTX (r = 0.583, p < 0.05, n = 88) in the group of female osteoporotic patients. Despite good correlations between DPD and CTX in all of the investigated groups, these urinary markers were of limited diagnostic significance in the group of postmenopausal osteoporosis due to a wide spread (few patients showed concentrations above the range of healthy persons) in this newly diagnosed drug-naïve patient collective.

Peptide Bound Hypohydroxyprolinuria in Handigodu Disease: A Familial Syndrome of Spondylo Epi(meta)physeal Dysplasia

Handigodu Disease (HD) is disorder of the osteoarticular system prevalent in few villages of two districts of the state Karnataka in southern India. 24 hrs urinary excretions of proline (Pro) and 4-hydroxyproline (Hyp) were analyzed by HPLC. Decreased peptide bound Hyp excretions (μmole/24 hrs) were found in patient group when compared with controls (Nonaffected; 113.02 ± 67.96, Type-I; 36.22 ± 20.76, Type-II; 45.74 ± 14.95, Type-III; 40.46 ± 22.68) and without significant difference in Pro excretions. Significant increased peptide bound Pro to Hyp ratio were found in patient group compared to control (Nonaffectedn= 63: 2.02 ± 1.65, Type-In= 18: 3.144 ± 1.42, Type-IIn= 28: 4.21 ± 1.95, Type-IIIn= 8: 8.60 ± 6.55). 24 hrs urinary excretions of deoxypyridinoline (DPD) crosslinks were found without significant difference among affected and control, hence HD ruled out from general bone reduction. These results suggest hypohydroxyprolinuria may be because of reduced bone turnover or defective hydroxylation of prolyl residues during post translational modification of collagen biosynthesis.

Effects of taurine supplementation on bone mineral density in ovariectomized rats fed calcium deficient diet

Taurine supplementation has been shown to have a beneficial effect on femur bone mineral content in ovariectomized rats. It therefore seemed desirable to find out whether the beneficial effect of taurine on ovariectomized rats fed calcium deficient diet could also be reproduced. Forty female Sprague-Dawley rats were divided into two groups. One group was OVX and the other group received sham operation (SHAM), and received either control diet or a taurine supplemented diet for 6 weeks. All rats were fed on calcium deficient diet (AIN-93: 50% level of calcium) and deionized water. Bone mineral density (BMD) and bone mineral content (BMC) were measured in spine and femur. The serum and urine concentrations of calcium and phosphorus were determined. Bone formation was measured by serum osteocalcin and alkaline phosphatase (ALP) concentrations. Bone resorption rate was measured by deoxypyridinoline (DPD) crosslinks immunoassay and corrected for creatinine. Urinary calcium and phosphorus excretion, osteocalcin in blood and cross link value were not significantly different among the groups. Within the OVX group, the taurine supplemented group had not higher femur bone mineral content than the control group. This study established the need for a study on the taurine effect on bone with different calcium levels.

Dietary calcium has little effect on mineral balance and bone mineral metabolism through twenty weeks of lactation in Holstein cows

Calcium and P balance and mobilization from bone were evaluated through 20 wk of lactation to determine the timing and extent of net resorption of bone mineral and mineral balance in lactating dairy cows. Eighteen Holstein cows were blocked by parity and calving date and randomly assigned to 1 of 3 dietary treatments: high (1.03%, HI), medium (0.78%, MED), or low (0.52%, LOW) dietary Ca. Dietary P was 0.34% in all diets. Cows consumed treatment diets from calving to 140 DIM. Total collection of milk, urine, and feces was conducted 2 wk before expected calving and in wk 2, 5, 8, 11, and 20 of lactation. Blood samples were collected at 14 and 10 d before expected calving and 0, 1, 3, 5, 10, 14, 21, 28, 35, 56, 70, 84, 98, and 140 d after calving. Blood samples were analyzed for Ca, P, and parathyroid hormone concentration. Serum concentrations of osteocalcin (OC), a marker of bone formation, and deoxypyridinoline (DPD), a marker of bone resorption, were measured to assess bone mobilization. Rib bone biopsies were conducted within 10 d postcalving and during wk 11 and 20 of lactation. Dietary Ca concentration affected Ca balance, with cows consuming the HI Ca diet in positive Ca balance for all weeks with the exception of wk 11. Interestingly, all cows across all treatments had a negative Ca balance at wk 11, possibly the result of timed estrous synchronization that occurred during wk 11. At wk 20, Ca balances were 61.2, 29.9, and 8.1g/d for the HI, MED, and LOW diets, respectively. Phosphorus balances across all treatments and weeks were negative. Bone Ca content on a fat-free ash weight basis was least in cows consuming the MED diet, but bone P was not different. Serum Ca and P were not affected by treatment. Dietary Ca concentration did not affect P balance in the weeks examined, but there was a clear effect of parity on balance, markers of bone metabolism, and bone P. Primiparous cows had greater serum OC and DPD concentrations than multiparous cows. Regardless of dietary treatment, serum OC concentration peaked around d 35 of lactation. Simultaneously, DPD concentration began to decrease, which may indicate a switch from net bone resorption to formation after d 35. However, this was not reflected in balance measures. This information may help refine dietary mineral recommendations for lactating dairy cows and suggests that dietary P requirements are independent of dietary Ca.

Effects of Arginine Supplementation on Bone Mineral Density and Bone Markers in OVX Rats

As far as we know, there were no studies of the effect of L-arginine on bone metabolism in post-menopausal women or ovariectomized rats. The primary objective of the current study was to determine whether arginine supplementation was associated with alterations in femoral and spinal bone mineral density (BMD) and bone markers in ovariectomized (Ovx) rats. Forty female Sprague-Dawley rats were divided into two groups, Ovx and sham groups, which were each randomly divided into two subgroups that were fed control and arginine supplemented diet. All rats were fed on experi- mental diet and deionized water ad libitum for 9 weeks. Bone formation was measured by serum osteocalcin and alka- line phosphatase (ALP) concentrations. Bone resorption was measured by deoxypyridinoline (DPD) crosslinks immu- noassay and corrected for creatinine. Serum osteocalcin, growth hormone, insulin-like growth factor-1 (IGF-1), para- thyroid hormone (PTH) and calcitonin were analyzed using radioimmunoassay kits. Bone mineral density (BMD) and bone mineral content (BMC) were measured using PIXImus (GE Lunar Co, Wisconsin, USA) in spine and femur. The serum and urine concentrations of Ca and P were determined. The plasma was analyzed for arginine. Diet did not affect weight gain, mean food intake, and plasma arginine concentration. Urinary Ca excretion was decreased by arginine supplementation in Ovx rats, but statistically not significant. The Ovx rats fed arginine-supplemented diet were not sig- nificantly different in ALP, osteocalcin, crosslinks value, PTH, calcitonin and IGF-1 compared to those fed control diet. The arginine-supplemented group had significantly higher serum Ca and growth hormone than control group. Spine and femur BMD were significantly increased by arginine supplementation on 5th and 9th weeks after feeding. Our findings indicate that dietary L-arginine supplementation decreased bone mineral density loss in Ovx rats. Therefore, dietary arginine supplementation may represent a potentially useful strategy for the management of osteoporosis. (Korean J Nutr 2009; 42(4): 309 ~ 317)