During growth, bones change their dimensions rapidly with the changes involving both formation and resorption processes. Small cross-linked peptides coming from type I collagen molecules are excreted in urine when bone is resorbed. To date, conflicting results have been presented concerning the age- and puberty-related changes of urinary markers. The purpose of the present study was to verify the effect of age, gender, and puberty on the urinary excretion of type I collagen degradation products in healthy children and adolescents. Timed spot urines from 176 children (4-20 years old) and 50 young adults were analyzed. The concentrations of N-telopeptides of type I collagen (NTx), pyridinolines (Pyr), and deoxypyridinolines (Dpyr) were measured, and the results were normalized to creatinine. Age-related changes in cross-links excretion were observed. The levels decreased with age, and a peak of excretion was shown at the beginning of adolescence. Prepubertal levels of all the markers were four- to five-fold higher than in adults, and they decreased towards adult levels in late puberty. Girls had significantly higher levels of all biochemical markers than boys at pubertal stage 2. We also observed a remarkable effect of puberty on the levels of bone degradation products that was independent of age and gender. Our results indicate that bone resorption is high in children relative to that in adults, and that urinary levels of NTx, Pyr, and Dpyr change as a function of age, gender, and puberty.
Calcium supplementation is widely used in deficiency status and as an adjuvant in the treatment of osteoporosis. As usual with endogenous substances, the calcium absorption, distribution and elimination processes are strictly controlled by homeostatic equilibria. Free calcium ion is the most representative active fraction of the circulating ion. Ion excretion is controlled by a saturable tubular reabsorption process which leads to a renal threshold. Cumulative urinary excretion of calcium is the end-point of absorption, distribution and elimination processes, and is thus a good indicator of bioavailability. In order to increase the oral bioavailability of calcium, the ion is administered in association with vitamin D, which is known to enhance intestinal calcium absorption. The aim of this study was to evaluate the absorption of calcium administered alone and in fixed combination with cholecalciferol (vitamin D3, CAS 67-97-0). In accordance with the study protocol, calcium carbonate (CAS 471-34-1; 1500 mg = 600 mg as calcium ion) was administered as such (reference) and associated with cholecalciferol (400 IU) (test) for four days (2 doses/day) to 18 healthy male volunteers in a sequential pattern, namely reference followed by test. Urinary excretion of total calcium, and serum concentration of free and total calcium, 25-OH-vitamin D3 and parathyroid hormone were carefully analysed the day before (baseline) and on the 4th day of dosing, with validated methods. The effect of cholecalciferol in promoting calcium absorption was clearly observed from urinary excretion of total calcium, which with the test treatment showed a 16.6% increase in excretion (p = 0.025) compared with the reference treatment. The mean excretion values on the 4th day, expressed in mg, were 238.85 and 204.83 with test and reference respectively. Moreover, the results demonstrated an increased serum concentration of both free and total calcium after dosing with test and reference by comparison with the baseline situation. The area under the serum concentration-time curve of total calcium increased from day -1 to day 4 from 550.98 to 575.90 mg l-1 h with test and from 543.03 to 568.16 mg l-1 h with reference. Similarly, ionised calcium increased on day 4 with both the treatments. Parathyroid hormone showed the expected typical decreasing behaviour after dosing with the test and reference drugs. The results of this study suggest that calcium carbonate is absorbed through the intestine when administered either alone or in association with cholecalciferol. Cholecalciferol, however, showed the typical expected activity in promoting calcium absorption, which was evident from the cumulative urinary excretion of the ion. To the authors' knowledge, this study is the first published paper demonstrating the absorption and pharmacodynamic effect of short-term administration of vitamin D associated with calcium at the doses recommended for supplementation in a fixed-combination pharmaceutical product.
The kinetics and metabolism of L-alpha-glycerylphosphoryl-choline (alpha-GPC) were investigated in male and female rats after i.v. (10 mg/kg) and oral doses (100-300 mg/kg). alpha-GPC was labelled with [14C]-glycerol ([14G]-GPC) or [14C]-choline ([14C]-GPC). Different kinetic and metabolic profiles were observed after i.v. and oral administration. It is assumed that alpha-GPC is hydrolyzed by phosphodiesterases in the gut mucosa. The different labelled metabolites have different kinetic properties of absorption, distribution and clearance, leading to different blood concentration-time curves of total radioactivity. Both labelled compounds gave a wide distribution of radioactivity, particularly concentrated in the liver, kidney, lung and spleen compared to blood. Brain concentrations of [14C]-GPC were comparable to ([14G]-GPC) or lower than ([14C]-GPC) total blood radioactivity. The metabolite profile in the perfused brain showed a small amount of choline and two unknown metabolites, probably the same as in blood. In addition, choline was incorporated into brain phospholipids in increasing amounts within 24 h of dosing. In all cases renal and fecal excretion of radioactivity was low and comparable for [14G]-GPC and [14C]-GPC. Mostly the administered radioactivity was exhaled as 14CO2, this degradation being faster and more pronounced for the glycerol-labelled metabolites than for the choline-labelled metabolites for both routes of administration. In all cases the results were the same for male and female rats.
Objectives-To assess urinary and synovial concentrations of hydroxypyridinium crosslinks of collagen in patients with rheumatoid arthritis (RA) and osteoarthritis (OA) and to evaluate whether a combined measurement in the two compartments could give additional information about the origin of these compounds in joint diseases. Methods-Concentrations of hydroxypyridinoline (HP) and lysylpyridinoline (LP) were measured by high pressure liquid chromatography in urinary and synovial samples collected from 20 patients with RA and 20 patients with knee OA. Full laboratory and clinical assessments were performed. Results-Urinary concentrations of both HP and LP were significantly greater in RA than in OA. Urinary HP in RA correlated with the number of swollen joints corrected for Lansbury index and with erythrocyte sedimentation rate and C reactive protein. In synovial fluid from both groups, only relatively small amounts of HP were measured, while bone type I collagen specific LP was below the limit of detection in all samples. In RA patients, but not in OA patients, there was a strong correlation between urinary and synovial concentrations of HP (r = 0.75).Conclusions-The results underline the relationship between urinary HP and disease extent and activity in RA. The findings in synovial fluid support the hypothesis of an extraskeletal origin ofHP in chronic joint diseases in which cartilage and synovial turnover may be increased. (Ann Rheum Dis 1995; 54: 144-147) The pyridinium derivatives hydroxylysylpyridinoline (HP) and lysylpyridinoline (LP) are intermolecular crosslinks present in the mature form of collagen. During the process of collagen breakdown, the two crosslinks are released into blood and are subsequently excreted in urine.' While LP is considered a specific marker of bone and dentine type I collagen degradation, HP is more widely distributed and has been shown to be retained in considerable amounts also in all three cartilage specific collagens: types II, IX and XI.2 Several studies reported that urinary excretion of pyridinium crosslinks provides a reliable clinical index of bone turnover in patients with metabolic bone disorders.3 4 Increased amounts of urinary pyridinolines in patients with joint diseases such as rheumatoid arthritis (RA)5-8 or osteoarthritis (OA)9`have been reported, but definitive information about their potential source is lacking. Furthermore, no data exist concerning their concentration in synovial fluid. The purpose of this study was to evaluate the relationship between urinary excretion of pyridinium crosslinks and clinical variables in arthritic diseases, and to measure crosslinks concentrations in the synovial compartment in order to test the hypothesis that a combined measurement could give additional information about the origin of these compounds in arthritic diseases. Patients and methodsSamples of urine, serum and synovial fluid were collected from a total of 40 in-and outpatients attending the Department of Rheumatology at the University of Milan.The first g...
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