Urinary Pyr Research Articles

Occupational and residential exposures to organophosphate and pyrethroid pesticides in a rural setting

Organophosphate (OP) and pyrethroid pesticides (PYR) are extensively used in agriculture, resulting in higher exposures among farmworkers. The present study reports the occurrence of 8 urinary OP and PYR metabolites in a sample of farmworkers and residents from Sucs (n = 87), a rural township in North West Catalonia (Spain). The aim of the present study was to examine differences in urinary pesticide metabolite concentrations between occupationally-exposed (farmworkers; n = 45) and environmentally-exposed subjects (n = 42) and to assess the relationship between pesticide's exposures and occupational activities in a real-case scenario.Six OP and two PYR metabolites have been investigated, urine samples were extracted using SPE extraction and analyzed by UPLC-MS/MS. Three OP metabolites were commonly detectable in urine, namely TCPY (metabolite of chlorpyrifos), PNP (parathion) and DEAMPY (pirimiphos). Regarding pyrethroids, the two analyzed metabolites, 3-PBA and 4F-3-PBA, were detected in a high proportion of urine samples. Differences in concentrations between both groups were statistically significant for TCPY and 4F-3-PBA (Mann-Whitney U Test for independent groups, p < 0.05). In the case of TCPY, the concentrations were higher among the farmworkers, which is consistent with their occupational activity. The small differences found in DEAMPY, PNP, 3-PBA or even the significant higher concentrations of 4F-3-PBA among rural population suggest a general exposure to these compounds, even in those who do not carry an occupational activity.Specific personal protective equipment (PPE) among farmworkers, such as the use of gloves and mask during mixing, showed a decrease in the exposure levels, although the differences were not statistically significant. However, a positive association was found between the use of a cap during mixing (for PNP and 3-PBA) and during application (only for 3-PBA). However, this piece of cloth is mainly used for sun protection, and when not cleaned after the handling of pesticides, it might represent a continuous source of exposure through dermal contact. Farmworkers using tractors with cabin had statistically significant lower concentrations of DEAMPY than those using a tractor without cabin. The previous results suggest that occupational protections should be encouraged among farmworkers and other potential workers handling with pesticides.

Urinary concentrations and determinants of pyrethroid metabolites in pregnant women from non-rural areas of Yunnan, China.

The study assesses the levels of urinary pyrethroid pesticide (PYR) in women during early pregnancy. The factors associated with exposure are also determined. A total of 480 pregnant women from non-rural areas visiting hospital for prenatal examination during early pregnancy were enrolled. A self-designed, structured questionnaire was used to collect data on potential factors of PYR exposure. Urinary PYR metabolite levels were quantified using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). The majority of urine samples (98.8%) contained one or more PYR metabolite, although only a few women self-reported pesticide exposure. Urinary 3-phenoxybenzoic acid (3PBA) levels were close to those reported in certain developed countries. However, the levels of 3-(2,2-dibromovinyl)-2,2-dimethylcyclopropane-1-carboxylic acid (DBCA) and 4-fluoro-3-phenoxybenzoic acid (4F3PBA) were higher than those reported in previous studies. Urinary PYR levels were positively associated with exposure to pesticides, consumption of bananas and oranges, the number of fruit types the women regularly ate, being multiparous, and cooked frequently. They were negatively associated with early pregnancy body mass index (BMI), unemployment, frequent intake of apples, and washing fruits and vegetables with soda or hot water. Pregnant women in non-rural areas were extensively exposed to low levels of PYRs. Dietary intake may be the primary pathway of exposure. The presented findings highlight the importance of using appropriate methods to reduce pesticide residues in food.

Pyrethroid pesticide exposure during early pregnancy and birth outcomes in southwest China: a birth cohort study.

Despite the developmental toxicity reported in animals, few epidemiologic studies have investigated the potential effects of prenatal exposure to pyrethroid pesticides (PYRs) on fetal growth. A birth cohort study was conducted to examine the association between prenatal exposure to PYRs and birth outcomes, and a nested case-control study was conducted in this cohort to evaluate the effects of PYR on congenital defects. The assessment of PYR exposure was based on self-reported household pesticide use and urinary PYR metabolite levels. We found that pregnant women in this region were ubiquitously exposed to low-level PYRs, although few reported household pesticide use. Women who often ate bananas or cantaloupes had a higher level of urinary 3-(2,2-dibromovinyl)-2,2-dimethylcyclopropane-1-carboxylic acid (DBCA), and the number of fruit types consumed by pregnant women was positively related to the concentrations of 3-phenoxybenzoic acid (3PBA) and total PYR metabolites (P < 0.05). Increased urinary 4-fluoro-3-phenoxybenzoic acid (4F3PBA), DBCA, and total PYR metabolites were associated with increased birth weight, length, and gestational age, and with decreased risk of small for gestational age (SGA) and/or premature birth. However, maternal household pesticides use was related to congenital anomalies. Thus, although prenatal exposure to low-dose PYRs promoted the fetal growth, the beneficial effects of fruit intake may outweigh the adverse effects of pesticide exposure. This study provided us an insight into the biological mechanisms for the effect of prenatal PYR exposure on fetal development, and suggested that further investigations in a larger study population with low-dose PYR exposure is needed.

Urinary levels of pyridinoline and deoxypyridinoline and bone mineral density in children with type 1 diabetes mellitus

ABSTRACTObjective: There is still controversy over the impact of diabetes mellitus (DM) on bone mass in children. Pyridinoline (Pyr) and deoxypyridinoline (DPyr), which stabilize the collagen chains within the extracellular matrix, are known as specific bone turnover markers. The aim of this study was to investigate the relationship between urinary Pyr and DPyr excretions and bone mineral density (BMD) in children with type 1 DM. Methods: Serum levels of Ca, phosphorus (P), magnesium (Mg), and parathormone (PTH), alkaline phosphatase (ALP) activity, and urinary excretions of Pyr and DPyr were evaluated in 50 diabetic and 130 healthy control subjects aged between 7 and 15 years. The BMD was measured using DEXA at the lumbar vertebrae 2–4. Results: Serum levels of Ca, P and PTH, and BMD were similar between the two groups (p > 0.05). The serum ALP activity was significantly higher in diabetics than in healthy subjects (257.7 ± 86.5 vs. 188.2 ± 61.8, p < 0.05, respectively). Both urinary Pyr and DPyr excretions were significantly higher in diabetic subjects compared to control subjects (127.4 ± 95.5 vs. 88.7 ± 63.7, p < 0.05, respectively, and 23.6 ± 12.7 vs. 17.2 ± 9.6, p < 0.05, respectively). The urinary excretions of Pyr and DPyr were similar in male and female subjects within both groups. Conclusion: The urinary excretions of Pyr and DPyr are higher in diabetic subjects than in healthy controls, suggesting the presence of increased bone turnover in diabetic patients, but we could not observe any negative effect of childhood diabetes on BMD. These results may suggest that diabetic patients are at risk for a decreased peak bone mass.

Pyrethroid insecticide exposure in school-aged children living in rice and aquacultural farming regions of Thailand.

BackgroundPyrethroid insecticides (PYR) are commonly used in rice farms and household pest control in Thailand. No investigative study has yet been made regarding factors associated with PYR exposure among Thai children.ObjectiveThis study aimed to compare the levels of PYR exposure between children living in rice farms (high-intensity PYR used) and aquacultural areas (low-intensity PYR used) during the wet and dry seasons in Thailand, during which different amounts of PYR are applied. Environmental conditions and common activities of children were used to identify factors associated with PYR exposure.MethodsA cross-sectional study was done during the wet and dry seasons, respectively. A total of 53 participants aged between 6 and 8 years old were recruited from rice farms and aquacultural areas. A parental-structured interview was used to gather information about PYR use, household environments, and participants’ activities. First voided morning urine samples were collected for PYR urinary metabolites (ie, 3-phenoxybenzoic acid [3-PBA] and cis/trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid [DCCA]) measurements. Hand wipe samples were collected during home visits, to measure PYR residues on the hands.Results and discussionThe concentrations of urinary PYR metabolites were not significantly different between participants who lived in rice farming and those who lived in aquacultural areas, during both wet and dry seasons. Both participant groups had slightly increased urinary PYR metabolites during the wet season compared with the dry season. The results from linear regression analysis revealed that some environmental conditions and activities or practices may be used to predict trends of PYR exposure. Frequency of PYR use in farms (β=0.004) and households (β=0.07), proximity to rice farms (β=0.09), playing in rice farms (β=0.11), and oral exposure from objects exposed to PYR (β=0.08) were likely to be related to increased concentrations of PYR metabolites. These findings suggest that PYR use in rice farms and households may be significant sources of PYR exposure among children living in agricultural areas. However, a bigger sample size may be necessary in a subsequent study, to explore the association between long-term exposure to pesticide and its health effects on children.

Effect of graded levels of niacin supplementation of a semipurified diet on energy and nitrogen balance, growth performance, diarrhea occurrence, and niacin metabolite excretion by growing swine1

Thirty-six crossbred barrows with an average initial age of 42 d and BW of 13.8 kg were placed in individual metabolism crates in a 35-d experiment to evaluate the supplementation of a semipurified diet with graded levels of crystalline niacin. Response criteria were energy and N balance, growth performance, occurrence of niacin deficiency diarrhea, and urinary excretion of the niacin metabolite N(1)-methyl-2-pyridone-5-carboxylamide (PYR). The basal diet met the true ileal Trp requirement of growing swine, and supplementation with 6, 10, 14, 18, 22, or 44 mg of niacin/kg made 6 treatments. Pigs were observed for scours twice daily, and pig BW and feed consumption were determined weekly. Total urine collections and fecal grab samples were made twice daily from each pig from d 28 to 35. Pigs fed the diet containing 14 mg of niacin/kg absorbed and retained more (P < 0.05) grams of N/d, had a greater N digestibility (%, P < 0.05), a greater ADFI and ADG (P < 0.10), and no diarrhea (P < 0.05) compared with pigs fed the diet containing 6 mg of niacin/kg, and pigs fed the diet containing 10 mg of niacin/kg were intermediate in ADG. There were no additional improvements in the response criteria with niacin supplementation greater than 14 mg/kg. Urinary PYR criteria (mg/L and mg/d) were greater (P < 0.001) for pigs fed the diet containing 44 mg of niacin/kg than for pigs fed the diets containing 6 to 22 mg of niacin/kg. However, urinary PYR criteria for pigs fed the diets containing 6 to 22 mg of niacin/kg did not differ from each other, indicating that PYR was not a sensitive indicator of niacin status for growing swine. Niacin treatment did not affect the percentages of N retained/N absorbed, N retained/N intake, DE, or ME. In conclusion, 14 mg of crystalline niacin/kg of semipurified diet adequate in Trp was the minimum concentration of niacin that maximized N utilization and growth performance, and prevented niacin deficiency diarrhea of growing swine in the current experiment. Because practical feed ingredients may be sources of available endogenous niacin, supplementation of practical diets with 100% of the current NRC requirement for niacin should provide adequate niacin for growing swine.

Effect of DDVP on urinary excretion levels of pyrethroid metabolite 3-phenoxybenzoic acid in rats

Pyrethroid insecticide (PYR) is used worldwide in agriculture and for indoor extermination of harmful insects. Urinary PYR metabolites (e.g. 3-phenoxybenzoic acid, 3PBA) have been used as the most sensitive biomarker for environmental PYR exposure since the late 1990s. In this study, we examined the effect of organophosphorus insecticide (OP) dichlorvos (DDVP) on excretion levels of urinary cis-permethrin-derived 3PBA in rats. Concentration of urinary 3PBA and cis-permethrin in plasma was monitored using gas chromatography–mass spectrometry and high-performance liquid chromatography after cis-permethrin injection (20 mg/kg) via the tail vein of rats pretreated intraperitoneally with DDVP (low dose, 0.3 mg/kg; high dose, 1.5 mg/kg). The amount of urinary 3PBA excretion over 48 h after cis-permethrin administration in control was 21.5 ± 5.1 μg (mean ± S.D.). In the low- and high-dose DDVP groups, the amounts of urinary 3PBA excretion were decreased to 81.1% (17.4 ± 2.7 μg) and 70.3% (15.1 ± 2.6 μg) of control, respectively. The plasma concentrations of cis-permethrin-derived 3-phenoxybenzyl alcohol (3PBAlc), which is a metabolite derived following hydrolysis of cis-permethrin, in high-dose DDVP group (0.18 ± 0.01 μg) were significantly lower than in control (0.23 ± 0.03 μg) 1 h after cis-permethrin injection. Both in the control and high-dose DDVP group, no differences were observed in the excretion levels of urinary 3PBA after injection of 3PBAlc (25 mg/kg, i.v.). These results suggested that the effect of DDVP on the amount of urinary 3PBA excretion was caused by the DDVP-induced modification of the cis-permethrin metabolic pathway. In conclusion, the possible decrease in urinary excretion level of 3PBA due to co-exposure to OPs should be considered in the biological monitoring of PYR exposure.

A longitudinal analysis of urinary biochemical markers and bone mineral density in STR/Ort mice as a model of spontaneous osteoarthritis

To investigate the longitudinal changes both in the urinary concentrations of biochemical markers and in bone mineral density (BMD) during disease progression in the STR/Ort mouse model of osteoarthritis (OA). Male STR/Ort mice were studied, with CBA mice used as nonarthritic controls. Radiographic evaluation and grading of the knee and measurements of urinary C-terminal crosslinking telopeptide of type II collagen (CTX-II), pyridinoline (Pyr), and deoxypyridinoline were performed between 8 weeks and 40 weeks of age. The BMD of the femoral shaft was measured from 20 weeks to 40 weeks of age and adjusted for body weight. Histologic evaluation and grading were performed at 40 weeks of age. STR/Ort mice were divided into 2 subgroups (STR OA and STR non-OA) based on histologic grading. No significant differences between STR/Ort and CBA mice were observed for any biochemical marker or BMD at any time point. Urinary CTX-II levels and BMD in the STR OA subgroup were higher than those in the STR non-OA subgroup before radiographic changes of OA were apparent. Higher urinary Pyr levels in the STR OA subgroup were observed at the advanced stage of OA. Urinary CTX-II could be a useful marker in the early diagnosis and predicting the progression of OA, and urinary Pyr may be a potential marker to assess the severity of OA at an advanced stage. An increase in BMD prior to the establishment of radiographic OA may be related to the induction of OA.

Longitudinal changes of biochemical markers and bone mineral density in hyperthyroid patients during antithyroid drug therapy

Objective: The aim of the present study was to clarify whether patients with Graves' disease who have lost bone mass can restore bone mass to age-matched control levels by antithyroid drug therapy.Patient/Materials and Methods: One male and 16 female patients (aged 21-71 years, mean±SE 39.9±16.5) with untreated Graves' disease were included in the study. Methimazole or propylthiouracil was given to all of the patients. Biochemical markers (serum N-mid osteocalcin (OCN-mid), alkaline phosphatase (ALP), type I collagen C-terminal telopeptide (sCTx), urinary pyridinoline (Pyr), deoxypyridinoline (Dpyr) and type I collagen C-terminal telopeptide (uCTx) and bone mineral density at the distal one third of the radius were assessed prior to treatment, and in the first, third, sixth and twelfth months of treatment.Results: All biochemical markers had increased significantly 12 months after treatment compared with the baseline values (OCN-mid, p<0.05; ALP, p<0.01; sCTx, p<0.05; Pyr, Dpyr, uCTx, p<0.01). Among the biochemical markers, urinary Pyr and Dpyr had decreased the most prominently 12 months after treatment. However, BMD at the distal one third of the radius did not improve after 12 months of treatment.Conclusion: Based on assessments of BMD at the distal one third of the radius, one year is not enough to restore bone mass using antithyroid drug therapy in patients with Graves' disease.

Bone Involvement in Multiple Myeloma Patients Carrying the T (4;14) Chromosomal Translocation.

Chromosomal translocations involving the immunoglobulin heavy chain switch region (IgH) are quite common in multiple myeloma (MM), and some of them can reliably predict disease outcome. In particular, t(4;14) chromosomal abnormality is one of the most adverse prognostic factors for response duration and survival after high dose therapy and autologous stem cell transplantation. Despite the dismal prognosis, however, in this subset of patients, bone involvement, as evaluated by spine MRI, is relatively infrequent, at variance to what has been observed in other MM subtypes according to TC classification. In the present study we aimed at further testing this hypothesis by analyzing the extent of whole bone involvement in patients showing t(4;14) chromosomal translocation as compared to negative patients. For this purpose, 50 newly diagnosed MM patients (32M, 18F, median age = 54 yrs) underwent evaluation of total skeletal X-ray, whole spine MRI and, at the same time, quantification of markers of bone resorption (urinary NTX, PYR and DPYR and serum crosslaps) and bone formation (bone alkaline phosphatase-BAP and osteocalcin) was performed. Using a real-time PCR assay to detect the presence of IgH/MMSET fusion gene as a surrogate marker for t(4;14), we found 15 patients carrying this chromosomal abnormality, 7 of whom (46%) were also positive for the deletion of chromosome 13, this abnormality was detected in 11/35 (31%) patients who proved negative for IgH/MMSET hybrid transcript. The two groups of patients did not differ significantly in terms of median age, distribution of M protein isotype and light chain, beta-2 microglobulin, bone marrow plasma cell infiltration and disease stage. Spinal MRI was negative in 3/15 (20%) t(4;14) positive patients as compared to 12% t(4;14) negative patients; skeletal involvement, however, was more pronounced in t(4;14) positive patients (median skeletal score = 6.24, as compared to 3.58 in t(4;14) negative cases, p= 0.00). These data were confirmed by the evaluation of bone resorption markers; specifically, serum crosslaps were significantly increased in patients with t(4;14) abnormality compared to negative individuals (7984 pmol/L±1682SE vs 5123pmol/L±783SE p=0.04). Conversely, no difference in bone formation markers was found in the two groups of patients. Our results indicate that, despite a spinal involvement at MRI that is comparable to what is observed in negative patients, individuals who are t(4;14) positive show a more pronounced bone resorption pattern, this in contrast to what has been reported so far, but in line with the aggressive features of the disease in these patients.

The relationship between the zinc nutritive status and biochemical markers of bone turnover in older European adults: the ZENITH study

To investigate the relationship between indices of zinc nutritive status and biochemical markers of bone turnover in older adult European subjects. Use of baseline data from a multicentre prospective zinc intervention (ZENITH) study. Centres in France, Italy and Northern Ireland. A total of 387 healthy adults, aged 55-87 y. Zinc intake was assessed by 4-day recall records. Circulating and urinary biochemical zinc status measures were assessed by atomic absorption spectrophometry. Serum bone-specific alkaline phosphatase and osteocalcin were assessed by ELISA and urinary pyridinoline (Pyr) and deoxypyridinoline (Dpyr) by HPLC. Zinc intake was negatively correlated with urinary Pyr and Dpyr (r = -0.298 and -0.304, respectively; P < 0.0001), but was not correlated with bone formation markers. There was a tendency for serum zinc to be negatively correlated with urinary Dpyr (r = -0.211; P = 0.080). Erythrocyte zinc was negatively correlated with serum osteocalcin (r = -0.090; P < 0.0001). None of the other correlations were significant. After adjustment for confounder (age, gender and research centre) the only significant association that remained was between serum osteocalcin and erythrocyte zinc (beta = -0.124; P = 0.011). There was some, albeit inconsistent, evidence of a relationship between zinc nutritive status and bone turnover in the older adult participants of the ZENITH study.

Accelerated Bone Turnover in Pregnant Women with McCune-Albright Syndrome

Bone turnover in pregnant women with McCune-Albright syndrome may be affected by both the syndrome and pregnancy. This study evaluated changes in biochemical bone turnover markers in pregnant women with the syndrome. Serum calcium, phosphorus, 1,25-dihydroxyvitamin D (1,25-(OH)₂D), intact osteocalcin (I-OC) and alkaline phosphatase (ALP), and urinary pyridinoline (Pyr), deoxypyridinoline (D-Pyr) and hydroxyproline (HPR) were measured during pregnancy and postpartum in 2 women with McCune-Albright syndrome. Serum calcitonin (CT), and plasma intact parathyroid hormone (I-PTH) and parathyroid hormone-related protein (PTHrP) were also measured in 1 patient. Serum corrected Ca levels were normal or low-normal; phosphorus levels were normal, and 1,25-(OH)₂D levels increased toward term and decreased thereafter, similar to normal pregnant women. Urinary Pyr, D-Pyr and HPR were elevated during pregnancy compared to normal pregnant women, peaked just after delivery, and decreased thereafter. Serum I-OC and ALP levels were high during pregnancy and postpartum. Intact PTH levels were increased during pregnancy and postpartum compared to normal pregnant women, whereas serum CT and PTHrP levels were not elevated. Both bone formation and absorption appear to be more enhanced during pregnancy and postpartum in women with McCune-Albright syndrome than in normal pregnant women. Additional or amplified cyclic AMP synthesis in bone cells through activation of the α subunit of G protein, independent of hormonal control, may explain the high local bone turnover.

The effect of conjugated linoleic acid on calcium absorption and bone metabolism and composition in adult ovariectomised rats

The effect of conjugated linoleic acid (CLA) on postmenopausal bone metabolism has not been investigated. Therefore, forty-three adult ovariectomised (OVX) rats (8–9 rats per group) were fed either a control diet containing 40g/kg soyabean oil (SBO diet) or the SBO diet with 0 (control OVX), 2.5, 5 or 10g/kg of CLA (replacing soybean oil) for 9 weeks. A group of sham-operated (SH) rats were fed the SBO diet. OVX rats had significantly (P<0.05) lower femoral bone mineral density and macromineral concentration, and intestinal Ca absorption compared to SH rats. CLA supplementation had no effect on these parameters. Ex vivo PGE2 biosynthesis by bone and urinary Pyr and Dpyr (markers of bone resorption) were significantly higher (P<0.001) in control OVX rats compared with SH rats, and were significantly (P<0.001) lowered by CLA supplementation with 5 and 10, but not 2.5g/kg diet in OVX rats. In conclusion, CLA supplementation appeared to reduce the rate of bone resorption in adult OVX rats.

Association between craniofacial growth and urinary bone metabolic markers (pyridinoline, deoxypyridinoline) in growing rats.

Pyridinoline (Pyr) and deoxypyridinoline (Dpyr) are intermolecular cross-links of mature collagen and reflect the bone turnover. The purpose of this study was to elucidate the association between craniofacial growth and urinary Pyr and Dpyr levels. Lateral cephalograms and 24-hour urine were taken for 7 male rats from 5 to 20 wks old. The urinary Pyr and Dpyr were quantified by high-performance liquid chromatography. The neurocranium and upper viscerocranium exhibited significant increases in size, with the maximum rate at around 6 wks old. The mandible presented more substantial growth, with the maximum change at 8 wks old. The urinary Pyr and Dpyr levels gradually increased and reached the maximum at 8 wks old. No prominent association was found between neurocranial growth and urinary levels of pyridinium cross-links, whereas Pyr and Dpyr levels exhibited similar time-dependent metabolic changes to mandibular growth. In conclusion, it is shown that urinary pyridinium cross-links may be useful for the prediction of mandibular growth.

The effects of nandrolone decanoate on bone mass and metabolism in ovariectomized rats with osteopenia.

The effects of nandrolone decanoate (ND) treatment on bone mass and metabolism were studied in ovariectomized (OVX) rats with osteopenia. The 6-month-old rats were divided into Sham (n = 12) and OVX (n = 24). The OVX rats were allowed to lose bone for 6 weeks. At 6 weeks post ovariectomy, the OVX rats were divided into two groups: (1) OVX + Vehicle and (2) OVX + ND. The effects of ND on bone mineral density (BMD), bone mineral content (BMC), and bone metabolism were studied by dual-energy X-ray absorptiometry (DXA) and biochemical markers including urinary pyridinoline (Pyr), deoxypyridinoline (Dpyr), and serum osteocalcin. After 24 weeks of treatment, histomorphometry of the right tibiae and the wet weight of the gastrocnemius and soleus skeletal muscles were also examined. Ovariectomy resulted in a significant increase in biochemical markers and a significant decrease in spine BMD (0.221+/-0.016g/cm2 in OVX group vs 0.239+/-0.008g/cm2 in Sham group) and BMC (0.550+/-0.055g in OVX group vs 0.605+/-0.042g in Sham group) at 6 weeks post ovariectomy. Spine BMD (0.227+/-0.017g/cm2), femoral BMD (0.263+/-0.012g/ cm2), and bone density of femur (1.035+/-0.036g/cm3) in the OVX + ND group were significantly greater than those in the OVX + Vehicle group (0.204+/-0.013g/cm2 for spine BMD, 0.243+/-0.009g/cm2 for femoral BMD, 0.938+/-0.06g/cm3 for bone density of femur) after 24 weeks of treatment. ND treatment decreased urinary Pyr and Dpyr significantly in OVX rats. Histomorphometric findings indicated that ND-treated rats had greater cancellous bone volume, greater trabecular number, greater trabecular thickness, and less trabecular separation than vehicle-treated OVX rats. OVX rats had greater wet weight of the gastrocnemius and soleus muscles than rats treated with ND. The data suggest that the effect of ND on bone mass is not influenced by the condition of the muscles in OVX rats. Our findings indicate that ND blocks further bone loss by inhibition of bone resorption in OVX rats with osteopenia.

Effect of hormone replacement therapy on the bone mass and urinary excretion of pyridinium cross-links.

The menopause accelerates bone loss and is associated with an increased bone turnover. Bone formation may be evaluated by several biochemical markers. However, the establishment of an accurate marker for bone resorption has been more difficult to achieve. To study the effect of hormone replacement therapy (HRT) on bone mass and on the markers of bone resorption: urinary excretion of pyridinoline and deoxypyridinoline. Cohort correlational study. Academic referral center. 53 post-menopausal women, aged 48-58 years. Urinary pyr and d-pyr were measured in fasting urine samples by spectrofluorometry after high performance liquid chromatography and corrected for creatinine excretion measured before treatment and after 1, 2, 4 and 12 months. Bone mineral density (BMD) was measured by dual energy X-ray absorptiometry (DEXA) before treatment and after 12 months of HRT. The BMD after HRT was about 4.7% (P < 0.0004); 2% (P < 0.002); and 3% (P < 0. 01) higher than the basal values in lumbar spine, neck and trochanter respectively. There were no significant correlations between pyridinium cross-links and age, weight, menopause duration and BMD. The decrease in pyr and d-pyr was progressive after HRT, reaching 28.9% (P < 0.0002), and 42% (P < 0.0002) respectively after 1 year. Urinary pyridinoline and deoxypyridinoline excretion decreases early in hormone replacement therapy, reflecting a decrease in the bone resorption rate, and no correlation was observed with the bone mass evaluated by densitometry.

Biochemical Markers and Bone Mineral Density in Patients with Hip Fractures in Men

The purpose of this study was to determine whether males with hip fractures have associated decreased gonadal function. Second void urine and serum samples were obtained from 25 male hip fracture patients (mean age±SD, 78.5±5.9 years) and 19 age- and gender-matched controls (77.6±6.2 years). Serum levels of luteinizing hormone (LH), total testosterone (Te), total estradiol (E2), dehydroepiandrosterone sulfate (DHEAS), 1,25(OH)2D3, N-mid osteocalcin (OCN-mid). type I collagen degradation products (S-CTx) and urinary levels of pyridinoline (Pyr), deoxypyridinoline (Dpyr) and type I collagen degradation products (U-CTx) were measured. Bone mineral density (BMD) of the L2-4 spine, femoral neck, trochanter. Ward's triangle, distal one third portion of the radius and ultradistal radius were also measured in the fracture group. Serum levels of LH, E2, Te, DHEAS, 1,25(OH)2D3 and OCN-mid in the fracture group were not statistically different from those in the control group. Levels of urinary Pyr, CTx and S-CTx in the fracture group increased significantly compared with those in the control group. In the fracture group, serum levels of Te correlated positively with distal one third portion of the radius BMD and ultradistal radius BMD. U-CTx and S-CTx correlated negatively with all the BMD measurement sites in the hip region and with the radius BMD. An imbalance between bone resorption and bone formation was evident in male hip fracture patients. However, male patients with hip fractures did not show associated decreased gonadal function in this study.

Correlation of quantitative ultrasound of bone with biochemical markers of bone resorption in women with osteoporotic fractures.

The purpose of this study was to examine the correlation of parameters of bone quality assessed by quantitative ultrasound (QUS) with biochemical indexes of bone resorption. QUS of the calcaneus and the hand phalanges, and biochemical parameters (urinary excretion of pyridinoline [Pyr] and deoxypyridinoline [D-Pyr]) were measured in a group of 30 well-characterized postmenopausal women with established osteoporosis and fragility fractures. All patients were treatment free. QUS data significantly correlated with both urinary Pyr and D-Pyr (p < 0.001 for speed of sound [SOS], broadband ultrasound attenuation [BUA], and stiffness at the heel; p < 0.001 for amplitude-dependent SOS at the proximal phalanges of the nondominant hand). No significant correlation was observed between spine and femoral bone mineral density and the urinary excretion of Pyr and D-Pyr. Results of this study suggest that QUS of bone evaluates characteristics of bone influenced by the bone resorption rate.

The effect of moderately and severely restricted dietary magnesium intakes on bone composition and bone metabolism in the rat.

Forty 3-week-old male rats, Wistar strain, average weight 59 g, were randomized by weight into five groups of eight rats each. Three groups were fed ad libitum on a semi-purified diet containing (per kg) 400 (adequate), 200 (moderately Mg-restricted) or 20 (severely Mg-restricted) mg Mg for 3 weeks while two groups were pair-fed with the Mg-adequate diet in the same quantities as those consumed by the two Mg-restricted groups respectively. While weight gains and food conversion efficiency values for the Mg-restricted groups were similar to those of the corresponding pair-fed control groups, serum and kidney Mg, and femoral dry weight were reduced by 70, 7 and 9% respectively in the severely Mg-restricted group and were unaffected in the moderately Mg-restricted group. Significant reductions were observed in urinary pyridinoline (Pyr) (by 44 and 34%) and deoxypyridinoline (Dpyr) levels (by 40 and 33%) (markers of bone resorption), serum osteocalcin levels (by 46 and 28%) (marker of bone formation), femoral Mg levels (by 52 and 14%) and osteocalcin mRNA levels (by 46 and 22%) compared with the corresponding pair-fed controls, in the severely and moderately Mg-restricted groups respectively, and these reductions, except for those in urinary Pyr and Dpyr, were more marked in the severely Mg-restricted group. Femoral Ca and P concentrations were unaffected by dietary Mg restriction. These results show that not only severe but also moderate dietary restriction of Mg over 21 d results in qualitative changes in bone (i.e. reduced Mg concentration) as well as in aberrant bone turnover in young growing rats (i.e. severely depressed rates of bone formation and bone resorption), which may impair bone development and bone strength.

Estimation of the effects of prednisolone on bone metabolism in rats by biochemical markers

The effects of prednisolone treatment on bone turnover in rats were studied by biochemical markers. Female Wistar rats were randomized into three groups: (1) control; (2) prednisolone 25 mg/kg body weight (BW) (lower dose), twice a week subcutaneously; and (3) prednisolone 50 mg/kg BW (higher dose). Serum calcium, phosphorus, alkaline phosphatase (Alp), and urinary pyridinoline (Pyr) and deoxypyridinoline (Dpyr) were measured once a week for 4 weeks. Bone mineral density (BMD) of excised femur, tibia, and lumbar vertebrae were measured by dual energy X-ray absorptiometry (DXA). Dry and ash weights of excised femur were measured by conventional methods, and the content of pyridinium cross-links in tibias was measured. Higher prednisolone treatment produced a significant increase of urinary Pyr and Dpyr at weeks 3 and 4. Although serum osteocalcin was not found to be reduced in prednisolone treatment except at week 4 in the higher prednisolone treatment group, BMD and dry and ash weights of excised bones was reduced by prednisolone administration. Further, the content of Pyr and Dpyr in bone was reduced by prednisolone administration. Our findings confirm that prednisolone induced osteoporosis in rats, mainly because of the increase of bone resorption activity..