Disease relevance of (2R)-2-amino-6-[4-[(2S)-2-amino-2-carboxy-ethyl]-5-[(3S)-3-amino-3-carboxy-propyl]-3-hydroxy-pyridin-1-yl]hexanoic acid

• The free deoxypyridinoline level was increased in the amniotic fluid (urine) of CaSR-/- fetuses; this result suggests that fetal bone resorption is increased [1].
• Concentrations of the bone resorption markers pyridinoline and deoxypyridinoline and the bone formation marker osteocalcin were measured in 24-h urine collections from 30 subjects who underwent unilateral total hip replacements for monoarticular symptomatic osteoarthrosis and 10 controls [2].
• Other end points included changes in urinary deoxypyridinoline excretion, pain, functional impairment scores, and radiological osteolysis [3].
• Fifty-one HIV patients on HAART (aged 30-54 yr, 86% male) and 21 HIV-negative control subjects (aged 31-51 yr, 82% male) were examined with oral glucose tolerance testing, a fasting lipid profile, and dual x-ray absorptiometry, and markers of bone formation (serum osteocalcin) and resorption (urinary deoxypyridinoline) [4].
• Goiter volume; lumbar and femoral bone mineral density; serum osteocalcin; deoxypyridinoline; TSH; free T(4); total, high-density lipoprotein, and low-density lipoprotein cholesterol; and triglycerides were measured before and after the study period [5].

Psychiatry related information on (2R)-2-amino-6-[4-[(2S)-2-amino-2-carboxy-ethyl]-5-[(3S)-3-amino-3-carboxy-propyl]-3-hydroxy-pyridin-1-yl]hexanoic acid

• The most sensitive indices of the levels of physical activity proved to be the noncollagenous protein, OC, and the collagen crosslinker, DPD [6].
• Deoxypyridinoline levels decreased significantly in the HRT alone and HRT + T groups, - 14.4 +/- 6.8% and -26.9 +/- 7.6%, respectively [7].

High impact information on (2R)-2-amino-6-[4-[(2S)-2-amino-2-carboxy-ethyl]-5-[(3S)-3-amino-3-carboxy-propyl]-3-hydroxy-pyridin-1-yl]hexanoic acid

• Elevation of urinary deoxypyridinoline levels due to unloading was observed in wild-type but not in OPN(-/-) mice [8].
• However, KO animals were more responsive to exogenous human parathyroid hormone as evidenced by a greater increase of the serum calcium concentration and urine deoxypyridinoline crosslinks, an effect reversed by CT and mediated by a greater increase in bone resorption than in controls [9].
• Secondary outcome measures included changes in BMD of the hip and total body and biochemical markers of bone turnover (S-osteocalcin, urine pyridinoline, and urine deoxypyridinoline excretion) [10].
• Analyses of femoral bone sections from TRPV5 knockout (TRPV5(-/-)) mice revealed increased osteoclast numbers and osteoclast area, whereas the urinary bone resorption marker deoxypyridinoline was reduced compared with WT (TRPV5(+/+)) mice [11].
• Urine levels of deoxypyridinoline (DPyr), a specific marker of bone resorption, gradually elevated during the time course of G-CSF administration until day 7 after cessation of G-CSF, showing a simultaneous stimulation of bone degradation during G-CSF-induced HPC mobilization [12].

Chemical compound and disease context of (2R)-2-amino-6-[4-[(2S)-2-amino-2-carboxy-ethyl]-5-[(3S)-3-amino-3-carboxy-propyl]-3-hydroxy-pyridin-1-yl]hexanoic acid

• RESULTS: Pre- and postflight study results confirmed that, after landing, bone resorption was increased, as indicated by increases in urinary calcium (p < 0.05) and collagen cross-links (N-telopeptide, pyridinoline, and deoxypyridinoline were all increased >55% above preflight levels, p < 0.001) [13].
• The heritabilities (95% CIs) for markers of bone formation also were assessed; bone-specific alkaline phosphatase (BSAP), 74% (67-80%), and osteocalcin, 29% (14-44%); marker of bone resorption deoxypyridinoline (DPD), 58% (52-64%); and measure of calcium homeostasis 24 h urine calcium, creatinine (Cr), 52% (41-61%) [14].
• Urinary biochemical markers of bone resorption (hydroxyproline, deoxypyridinoline, and N-telopeptide of type I collagen) as well as a serum marker of bone resorption (type I collagen carboxytelopeptide) all demonstrated significant increases during bed rest which declined toward normal during reambulation [15].
• Urinary deoxypyridinoline excretion increased more in group 1 than in group 3 (P = 0.023), suggesting a significant effect of androgens on bone resorption, whereas serum N-telopeptide levels increased more in group 3 than in group 2 (P = 0.037), suggesting a significant effect of estrogen on bone resorption [16].
• The changes after ERT were: serum ionized calcium and ultrafiltrable calcium, no change; serum intact PTH, 38.2% increase (P < 0.0001); serum 1,25-dihydroxyvitamin D, 23.8% increase (P < 0.0001); urinary calcium excretion, 33.3% decrease (P < 0.001); and deoxypyridinoline (a marker for bone resorption), 19.5% decrease (P < 0.0001) [17].

Biological context of (2R)-2-amino-6-[4-[(2S)-2-amino-2-carboxy-ethyl]-5-[(3S)-3-amino-3-carboxy-propyl]-3-hydroxy-pyridin-1-yl]hexanoic acid

• In patients, urine deoxypyridinoline (D-Pyr) as a marker of bone resorption and serum bone alkaline phosphatase (b-AP) as a marker of bone formation were significantly higher than in control subjects (P < .001 and P < .01, respectively) [18].
• Biochemical bone markers (pyridinoline [PYR], deoxypyridinoline [DPYR], procollagen type I carboxy-terminal peptide [PICP]) and bone mineral density (BMD) were measured at baseline and at 6, 12, and 24 months [19].
• With subgroups matched for age and years from menopause, only DPD discriminated between POST and UTO [20].
• BAP was positively correlated with concurrent serum Dpyr (p = 0.015) during the menstrual cycle [21].
• Serum Dpyr was higher during the follicular phase (FP) than in the luteal phase (p = 0.027) [21].

Anatomical context of (2R)-2-amino-6-[4-[(2S)-2-amino-2-carboxy-ethyl]-5-[(3S)-3-amino-3-carboxy-propyl]-3-hydroxy-pyridin-1-yl]hexanoic acid

• Pyridinoline (Pyd), an indicator of connective tissue disease, and deoxypyridinoline (Dpyd), an indicator of bone degradation, both of which represent products of lysyl oxidase-mediated crosslinking in collagen, were analyzed by ion-paired and gradient high-performance liquid chromatography (HPLC) methods with fluorescence detection [22].
• Two recently discovered markers, urinary pyridinoline (PYD) and deoxypyridinoline (DPD), are apparently directly related to bone matrix degradation and may be more accurate markers of bone resorption than OHP or TRAP [20].
• In rat ovariectomized model of estrogen deficiency, continuous administration of NFkappaB decoy ODN attenuated the increase of TRAP activity, accompanied by a significant increase in calcium concentration in tibia and femur and decrease in urinary deoxypyridinoline [23].
• Long-term cultures of control fibroblasts produced both Pyr and Dpyr, with a pattern resembling that of normal skin [24].
• In wild-type (WT) mice, osteoclast formation in vertebrae and tibiae increased 5 days after systemic LPS injection, and urinary excretion of deoxypyridinoline, a sensitive marker for bone resorption, statistically increased 10 days after injection [25].

Associations of (2R)-2-amino-6-[4-[(2S)-2-amino-2-carboxy-ethyl]-5-[(3S)-3-amino-3-carboxy-propyl]-3-hydroxy-pyridin-1-yl]hexanoic acid with other chemical compounds

• Unloading-induced increase in the levels of osteoclastic activities such as osteoclast number and surface as well as urinary deoxypyridinoline was all suppressed by the treatment with propranolol [26].
• Plasma Hcy was measured with IMx, serum vitamin B12 with competitive immunoassay (IA) luminescence, serum osteocalcin (OC) with immunoradiometric assay (IRMA), and urinary excretion of deoxypyridinoline (DPD) with competitive IA and corrected for creatinine (Cr) concentration [27].
• Prompt increases in markers of resorption--pyridinoline (PD), deoxypyridinoline (DPD), and hydroxyproline (Hyp)/g creatinine--during the first few days of inactivity were paralleled by tartrate-resistant acid phosphatase (TRAP) with significant increases in all these markers by day 4 of bed rest [6].
• We conclude that higher levels of urine NTX, CTX, Pyr, Dpyr, and serum OC are associated with faster bone loss at the hip in this population of elderly women not receiving estrogen replacement therapy, but these biochemical markers have limited value for predicting rapid hip bone loss in individuals [28].
• Samples were collected at 0, 3, and 6 months to measure serum calcium, 25-hydroxyvitamin D [25(OH)D], parathyroid hormone (PTH), osteocalcin, and urinary deoxypyridinoline (DPD) [29].

Gene context of (2R)-2-amino-6-[4-[(2S)-2-amino-2-carboxy-ethyl]-5-[(3S)-3-amino-3-carboxy-propyl]-3-hydroxy-pyridin-1-yl]hexanoic acid

• On this low calcium diet, both groups of mice had the same serum 1alpha,25D3, with similar increments in intestinal calcium absorption, serum AP, OC, and urinary DPD [30].
• Analysis of a second urine specimen obtained from 19 of the subjects 1 to 7 months after the first also revealed a significant correlation between thrombin generation and IL-6, DpD, and VEGF excretion [31].
• METHODS: Using ELISA and radioimmunoassay methods, we estimated serum concentrations of IL-6, osteocalcin, ICTP, intact PTH, and spot urine concentrations of NTx and Dpd in 25 female patients with active RA, 25 female patients with suppressed disease, and 25 age matched healthy female controls [32].
• CRP in RA patients correlated with DPD and inversely with PTH [33].
• The principal outcomes associated with the presence of a low BMD were high OPG and lysylpyridinoline/creatinine ratio (Dpd) values [34].

Analytical, diagnostic and therapeutic context of (2R)-2-amino-6-[4-[(2S)-2-amino-2-carboxy-ethyl]-5-[(3S)-3-amino-3-carboxy-propyl]-3-hydroxy-pyridin-1-yl]hexanoic acid

• We measured free and total deoxypyridinoline (DPD) in serum (S) and urine (U) by high-performance liquid chromatography (HPLC) [35].
• One week after surgery, free deoxypyridinoline levels in 24-h urine samples, which were collected from 6 h after administration of FR167356, were measured by ELISA [36].
• Direct, enzyme-linked immunoassay for urinary deoxypyridinoline as a specific marker for measuring bone resorption [37].
• The longitudinal effects of LY on bone were studied by dual-energy X-ray absorptiometry and biochemical markers including urinary pyridinoline (Pyr), deoxypyridinoline (Dpyr), and serum osteocalcin [38].
• Similarly, DPD increased significantly at the onset of bed rest, remained elevated for the duration of bed rest, and returned to pre-bed rest levels upon reambulation [6].

References