Bone turnover rate in postmenopausal women: bimodal distribution?

There is considerable evidence that elevated bone turnover is an independent form of low bone mineral density (BMD) risk factor of osteoporotic fractures. The aim of our study was to test whether a group of postmenopausal women could be divided into subgroups of high and low bone turnover rate using different pairs of bone turnover markers (one resorption, one formation). Cluster analysis was used to obtain high and low bone turnover subgroups within the study group. A magnitude of difference in lumbar spine BMD (expressed as Z-score) between high- and low-turnover groups was used as a criterion of division success. According to this criterion, the division obtained with a urinary type I collagen crosslinked N-telopeptide/bone alkaline phosphatase pair of markers appeared to be the most significant. This method of separation of two subgroups was highly concordant with the division based on the upper thresholds of the normal values for those markers found for the premenopausal women. It seems that the observed existence of high-and low-turnover subject clusters is not an incidental phenomenon, because the effects obtained for the whole study group were further confirmed by the consistent results of cluster analysis, performed separately for two randomly selected subgroups (A and B) from the study group. The results obtained appear to support the view that bone turnover rate in postmenopausal women is distributed in the bimodal fashion. This finding seems to justify further investigations of more elaborated models, enabling clinicians to individually classify their patients as low- or high-turnover cases with higher efficiency, as in the case of cutoff values for single markers.

Treatment of cholestatic children with water-soluble vitamin E (alpha-tocopheryl polyethylene glycol succinate): effects on serum vitamin E, lipid peroxides, and polyunsaturated fatty acids.

BACKGROUND: Treatment of vitamin E-deficient cholestatic children with water-soluble alpha-tocopherol polyethylene glycol succinate (TPGS) was previously shown to normalize vitamin E status and to improve neurological outcome. METHODS: Because vitamin E plays an important role as a free-radical scavenger, we studied the effects of long-term TPGS supplementation on lipid peroxidation and polyunsaturated fatty acid status in 15 children ages 9 months-3.4 years (median, 1.3 years) with chronic cholestasis with low serum vitamin E concentrations [1.95 (0.8-3.7) mg/L; median (1st-3rd quartile)]. The previous supplementation of alpha-tocopherol was replaced by a 20% solution of TPGS in one daily dose of 20 IU/kg. Serum alpha-tocopherol, plasma lipid peroxides expressed as thiobarbiturate reactive substance concentration (TBARS) and plasma phospholipid fatty acid profile were estimated at baseline and again after 1 month in all 15 patients, and after 1 year of TPGS therapy in 11 patients. RESULTS: alpha-Tocopherol was significantly increased after 1 month [6.9 (4.4-8.4) mg/L; p = 0.008] and rose further after 1 year [9.7 (7.2-14.9) mg/L]; similar results were obtained for the ratio vitamin E/total lipids. TBARS concentrations were significantly higher in cholestatic children at baseline [2.9 (1.5-3.32) nmol/ml] than in a control group [1.2 (1.1-1.3) nmol/ml; p = 0.0006], but were not changed significantly during TPGS therapy [after 1 year 2.34 (1.9-3.0) nmol/ml]. Compared with controls, the contributions of polyunsaturated fatty acids to total phospholipid fatty acids were markedly decreased in cholestatic patients at baseline [27.7 (22.4-31.5)% versus 36.9 (34.5-39.0)%; p = 0.001] and did not show major changes after 1 year of TPGS supplementation. CONCLUSIONS: We conclude that oral TPGS supplementation of cholestatic children can quickly normalize serum vitamin E levels but does not improve the increased lipid peroxidation and poor polyunsaturated fatty acid status.

Collagen peptides in osteogenesis imperfecta, idiopathic juvenile osteoporosis and Ehlers--Danlos syndrome.

We evaluated the potential of the carboxy-terminal propeptide of type I procollagen (PICP), the carboxy-terminal telopeptide of collagen I (ICTP), and the amino-terminal propeptide of type III procollagen (PIIINP) to differentiate osteogenesis imperfecta (OI) from Ehlers-Danlos syndrome (EDS) and idiopathic juvenile osteoporosis (IJO) in paediatric patients. Markedly decreased serum concentrations of PICP were found in type I OI, while in IJO they were much less diminished, and in EDS they were near to normal. In type III and IV OI, the serum PICP level was lowered in prepubertal patients, whereas at puberty it was comparable to that in controls. Serum ICTP and PIIINP levels in patients with OI did not differ significantly from the levels in EDS and IJO. Measurements of serum PICP levels seem to be useful in discriminating OI from EDS and IJO in prepubertal children. In pubertal children, however, they lose their diagnostic power.

Rapid method for measuring physiological concentrations of 25-hydroxyvitamin D levels in blood serum.

A new single-step Extrelut column procedure for obtaining the 25-hydroxyvitamin D extract, suitable for a direct radiocompetitive test, is described. Separation of 0.1 ml of serum, on a small Extrelut column and radioassay allows a rapid, sensitive and accurate determination of 25-hydroxyvitamin D concentration. The detection limit of the determination was 2 nmol/l (0.8 microgram/l) of serum. The recovery of 250HD3 added to serum was 99-108%. Intra-assay and interassay CV values were 10 and 14%, respectively. Although the method does not permit separation of dihydroxylated metabolites of vitamin D from 25-hydroxyvitamin D, it is useful in clinical practice.

Comparison of angiotensin I and angiotensin II antibody trapping methods for determination of plasma renin concentration and activity.

Comparative determinations were made of the renin activity of human blood plasma by applying a radioimmunoassay of angiotensin I and angiotensin II, and also by parallel determinations of PRA I and PRA II. To protect the angiotensin generated in plasma, the antibody trapping method was used. The concentration of renin was also determined. It was found that, under the experimental conditions applied, when determining PRA II the renin was gradually inactivated in plasma; when determining PRA I it was protected by EDTA added to plasma. Thus PRA II is present to a lesser degree than PRA I. The experiemnts performed have confirmed the advantages of determining PRA I by the antibody trapping method.