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R Ziegler

Publications and source records attributed to R Ziegler.

At least 109 records · Page 6Linked to original sources
PubMed1998

Measurement of forearm bone mineral density: comparison of precision of five different instruments.

Measurement of bone mineral density (BMD) is used for clinical estimation of fracture risk in osteoporosis. The precision of the method is important for the evaluation of true and clinical relevant changes in BMD in patients with osteoporosis. We measured BMD of the forearm in 14 young, healthy probands (10 males, 4 females), aged 24. 6 +/- 1.5 years with five different instruments using dual-energy X-ray absorptiometry (DXA), single-photon absorptiometry (SPA), and peripheral quantitative computed tomography (pQCT). Precision was expressed as the percentage coefficient of variation (CV%). In addition, the standardized CV% (sCV%) and the root mean square standard deviation (rmsSD%) was calculated for long-term precision. CV% ranged from 1.04 (SPA, distal BMD) to 2.75% (pQCT, trabecular BMD) for short-term precision and from 1.49 (DXA, QDR 1000, 1/3-distal BMD) to 4.33% (SPA, ultradistal) for long-term precision, respectively. The results for the rmsSD% were higher but correlated well with the CV%. A change that exceeds 2 radical2 CV% has been considered as being significant. On this basis, 24.0 +/- 5.1% (mean +/- SEM) of the participants in our study would be expected to have a significant change in BMD without any correlation to the time-delay between the two measurements. Measurements of BMD were done at two locations with all five instruments: ultradistal and middistal BMD using DXA and SPA and total and trabecular BMD using pQCT, respectively. Coefficients of correlation for "between-instrumental" correlation were greater than 0.5 for almost all instruments. Distal and ultradistal BMD measured by SPA and trabecular and total BMD measured by pQCT correlated better with ultradistal BMD measured by DXA. Correspondingly, "within-instrumental" correlation was better for pQCT and SPA than for DXA. The coefficients of correlation between the different DXA methods were greater than 0.95 when corresponding locations were compared. We conclude that the clinical value of monitoring bone loss by measurement of forearm BMD is compromised by the low precision which was seen for DXA methods as well as for SPA and even pQCT in young healthy controls.

Absorptiometry, Photon↗
PubMed1998

Influence of inflammation-mediated osteopenia on the regional acceleratory phenomenon and the systemic acceleratory phenomenon during healing of a bone defect in the rat.

We have previously shown that restoration of a local bone defect in the rat not only leads to a regional acceleratory phenomenon (RAP), but also to a systemic acceleration of osteogenesis (SAP) at distant sites of the skeleton. In this study, we investigated whether specific inhibition of osteoblasts would affect the local RAP and the systemic acceleratory phenomenon (SAP) healing sites. Systemic inhibition of osteoblasts was induced by inflammation-mediated osteopenia (IMO), a nonspecific type of inflammation initiated by s.c. injections of sterile talc. A drill hole defect 1.2 mm in diameter was performed at the midshaft of the left tibia of female rats. On day 7, during the formation phase of the local healing process, IMO did not influence the number of osteoblasts or the bone volume in the marrow cavity of the local healing site, whereas it did lead to a significant reduction of osteoblast number and bone volume at the systemic site (subepiphyseal spongiosa of the tibia). By contrast, on days 14 and 21, during the resorption phase of bone healing. IMO led to a significant reduction in both osteoblast number and bone volume in the marrow cavity of the local healing site. At the same time, however, it did not influence the cortical area of the bone defect where newly formed bone is needed to ensure mechanical stability. In summary, our model of bone healing reveals that a humoral noxious osteoblast stimulus such as IMO is able to inhibit systemically osteoblasts stimulated by SAP, whereas it is not able to inhibit osteoblasts either from producing woven bone during a RAP or from producing bone that is needed to mechanically stabilize a defect.

Absorptiometry, Photon↗
PubMed1998

AGEs and their interaction with AGE-receptors in vascular disease and diabetes mellitus. I. The AGE concept.

OBJECTIVE: This is the first part of a bipartite review that summarizes the rising knowledge on the molecular mechanisms underlying the action of advanced glycation endproducts (AGEs) and their contribution to diabetic complications and vascular disease. While the first part presented here focusses on AGE formation, the second part will describe the AGE-protein/receptor interactions and their role in mediating AGE-dependent intracellular signalling. RESULTS: Nonenzymatic glycation, in which reducing sugars are covalently attached to free amino groups and ultimately form AGEs, has been found to occur during normal aging and at accelerated rate in diabetes mellitus. Oxidation, accompanying glycation in vivo, further supports chemical modifications. AGE formation and protein crosslinking are irreversible processes that alter the structural and functional properties of proteins, lipid components and nucleic acids. AGE modifications do not only change the physicochemical properties of the afflicted molecules, but also induce cellular signalling, activation of transcription factors and subsequent gene expression in vitro and in vivo. CONCLUSIONS: AGEs elicit a wide range of cell-mediated responses that might contribute to the pathogenesis of diabetic complications, vascular and renal disease and Alzheimer's disease. Substances that inhibit AGE formation, reduce oxidative stress or destroy already formed crosslinks may limit the progression of disease and may offer new tools for therapeutic interventions in the therapy of AGEs mediated disease.

Diabetes Mellitus↗
PubMed1998

Molecular cloning of genes differentially regulated by TNF-alpha in bovine aortic endothelial cells, fibroblasts and smooth muscle cells.

OBJECTIVE: Tumor necrosis factor-alpha (TNF-alpha) is a pleiotropic-cytokine binding to and thereby stimulating vascular cells. TNF-alpha mediated intermediate stimulation of vascular cells is believed to play a pivotal role in the development of arteriosclerosis. While extensive information has recently become available on gene induction by TNF-alpha, less is known about gene suppression by TNF-alpha in vascular cells. Endothelial cells are the first cell layer within the vessel wall interacting with circulating, cytokine releasing cells. Therefore, they were selected as target for these study. METHODS: A differential screening approach has been used to isolate cDNAs whose abundance was suppressed by incubating bovine aortic endothelial cells (BAEC) for 6 h with 1 nM TNF-alpha. The gene expression of 6 isolated cDNAs after TNF-alpha was investigated by dot blots and nuclear run-on analysis in BAEC. The investigated genes were partially or completely sequenced. Differential expression after TNF-alpha stimulation of BAEC, bovine fibroblasts and vascular smooth muscle cells (SMC) was studied by Northern blots. RNA transcripts of the clone C7 in aortic aneurysms were examined by in situ hybridization. RESULTS: 49 independent cDNAs were isolated by the differential screening approach and 6 clones were further analyzed. These genes were downregulated in a time and dose dependent manner in BAEC. Sequence analysis revealed that 3 cDNAs encoded previously unidentified genes (C1, C5, C7), while 3 encoded known genes: connective tissue growth factor (CTGF; A1), fibronectin (A8) and the mitochondrial genome (B1). A1 and B1 were suppressed in BAEC, fibroblasts and SMC, whereas A8, C1, C5 and C7 were not uniformly downregulated in the investigated cells. C7 RNA transcripts were exclusively induced in the endothelium of an uninflamed aortic aneurysm. The transcripts were undetectable in an inflamed aortic aneurysm and control vessels. CONCLUSIONS: Gene suppression is a prominent feature of the intermediate effect of TNF-alpha on endothelial cells. Differences in the expression of the tested genes in endothelial cells, fibroblasts and vascular smooth muscle cells open possibilities for the study of cellular interactions in the vascular wall in disease situations with high local TNF-alpha concentrations.

Animals↗
PubMed1998

Analogs of Manduca adipokinetic hormone tested in a bioassay and in a receptor-binding assay.

Single amino acid replacement analogs of Manduca adipokinetic hormone (M-AKH) pGlu-Leu-Thr-Phe-Thr-Ser-Ser-Trp-GlyNH2 were tested for activity in bioassays as well as receptor binding assays. Amino acids were replaced by Ala and by D-analogs. In addition an extended M-AKH and analogs containing photo affinity labels were tested. All analogs had reduced activity. All the peptides which had enough activity to allow a full dose response curve reached the same maximal activity as native M-AKH. The use of analogs, in which L-Phe4 was replaced by Ala or by D-Phe and of L-Thr3 replaced by D-Thr, as competitors led to improved binding of M-AKH in our competitive receptor binding assay. In the bioassay an inactive concentration of Ala4 M-AKH increased the activity of a half optimal concentration of native M-AKH.

Adipose Tissue↗
PubMed1998

Benefits of growth hormone treatment on bone metabolism, bone density and bone strength in growth hormone deficiency and osteoporosis.

Bone mass is reduced in patients with GH deficiency (GHD) leading to an increased vertebral fracture rate and clinically significant osteoporosis. Patients with GHD of juvenile onset have reduced skeletal mineralization. When substituting GH in patients with GHD, bone turnover is increased and bone mineral density initially decreases during the first year due to the increase in remodelling space. From the experience in patients with acromegaly, cortical bone mass is increased and trabecular bone mass is normal in eugonadal or decreased in the hypogonadal patients. However, bone mineral content and bone area are increased leading to a higher biomechanical competence of bone as shown in rats. In patients with GHD of juvenile onset, mineralization and bone maturation are achieved during treatment with GH in adult life after having reached final body height leading to an increase in bone mass. The GH/ IGF-I system is dysregulated in patients with post-menopausal osteoporosis. This is shown by reduced systemic IGF and IGFBP-3-levels in osteoporosis suggesting a decrease of endogenous GH-secretion or a dysregulation of the GH receptor system which is beyond the normal ageing process of the GH/IGF system, the "somatopause". A premature somatopause may be responsible for the dysregulation in some patients with osteoporosis. However, 24-h GH profiles do not differ between patients suffering from osteoporosis or osteoarthritis. Treatment of osteoporosis with GH might be beneficial due to the increased bone metabolism and improved bone geometry which occurs with GH. The substantial increase of bone remodelling achieved with GH may be helpful during late post-menopause with decreased bone turnover and impaired osteoblastic function. Using GH to prevent physiological bone loss that occurs with age seems possible, but has to be discussed on an ethical and economic basis.

Acromegaly↗
PubMed1998

Effects of estrogen on the concentration of insulin-like growth factor-I in rat bone matrix.

Insulin-like growth factor-I (IGF-I) plays an important role in bone metabolism, but data on the regulation of IGF-I in bone tissue in vivo are still limited. In the present study, we examined the effects of ovariectomy (ovx) and estrogen replacement on the skeletal concentration of IGF-I in the femur shaft of 6-10 week-old female rats. Ovx had no consistent effect on bone matrix IGF-I concentration regardless of animal age at ovx. In contrast, administration of estradiol in doses that exceeded physiological replacement (50 and 150 nmol/kg per day, subcutaneously) significantly increased the bone matrix IGF-I concentration. These are the first in vivo data which demonstrate that estrogens are capable of increasing the concentration of IGF-I in bone tissue. However, this stimulatory effect appears to be limited to supraphysiological estrogen concentrations.

Animals↗
PubMed1998

Positive association between circulating free thyroxine and insulin-like growth factor l concentrations in euthyroid elderly individuals.

OBJECTIVE: Previous studies have shown marked changes in circulating insulin-like growth factor-l (IGF-l) levels in hypo- and hyperthyroid patients. In this study we examined whether the circulating concentration of IGF-l may also be affected by normal thyroid hormone levels. DESIGN: A cross-sectional study of thyroid hormones and plasma IGF components in a population-based sample. PATIENTS: 50-80 year-old men (n = 262) and women (n = 218) with normal concentrations of serum free thyroxine (fT4), free triiodothyronine (fT3) and thyrotrophin (TSH). MEASUREMENTS: Plasma concentrations of IGF-l, IGF-ll and IGFBP-3, and serum concentrations of TSH, fT3 and fT4. RESULTS: Serum fT4 values were weakly positively correlated and serum TSH levels were inversely correlated with circulating IGF-l concentrations. The associations persisted after adjustment for age and ideal body weight. CONCLUSIONS: Our data demonstrate that thyroid hormones are positively correlated to IGF-l plasma levels even under physiological conditions. However, thyroid hormones explain only 1-2% of the normal variability of circulating IGF-1.

Aged↗
PubMed1998

Automated and manual assays for urinary crosslinks of collagen: which assay to use?

With the increasing demand for clinically useful biomarkers of bone turnover, a number of assays for the measurement of bone resorption markers have been developed. In the present study, automated (ACS: 180 DPD, Chiron Diagnostics, USA) and manual (DPD-ELISA, Pyrilinks-D, Metra Biosystems, USA) immunoassays for free DPD, and a manual immunoassay for the aminoterminal telopeptide of type I collagen (NTX, Osteomark, Ostex International, USA) were compared to the automated HPLC method for free DPD. Urine samples from a total of 538 healthy and diseased subjects aged 20 to 80 years were analyzed. The age and sex stratified reference ranges were essentially identical for the HPLC, ACS: 180 and the DPD-ELISA, but differed from the NTX assay. Individual values for free DPD as generated by HPLC and immunoassay techniques were highly correlated with each other, whereas correlations between assays measuring free and peptide-bound crosslink components were less pronounced. Precision of the automated techniques (HPLC and ACS: 180) was superior to that of the manual immunoassays. Disease-specific changes in crosslink excretion were similar for all assays and most pronounced in metastatic osteopathy, primary hyperparathyroidism and untreated Paget's disease of bone. We conclude that the automated assays for free DPD in urine, i.e. the HPLC and the ACS: 180 assay, show better analytical performance than the manual immunoassays studied. All techniques used in the present study appear to provide similar or identical clinical information. Therefore, the decision which assay to use largely depends on the laboratory set-up, the number of samples to be analysed, the turn-around time required, and the application for which the test should be used.

Adult↗
PubMed1998

Regulation of interleukin-6 expression in human osteoblastic cells in vitro.

Interleukin-6 (IL-6) is a potent stimulator of bone resorption which has been demonstrated in a variety of in vivo and in vitro models. We investigated the regulation of IL-6 secretion in primary human osteoblastic cells (HOC) in vitro by cytokines known to play an important role in coupling bone formation to bone resorption. HOC were isolated from healthy adults who underwent selective orthopedic surgery and treated with cytokines released in the bone microenvironment during coupling i.e Interleukin-1beta (IL-1beta), Tumor Necrosis Factor alpha (TNFalpha), Transforming Growth Factor beta1 and 2 (TGFbeta 1 and 2) and Endothelin-1 (ET-1). Furthermore, we determined whether systemically-acting steroid hormones of gonadal and adrenal origin as well as glucocorticoids affect the local regulation of IL-6 secretion in primary HOC. To examine the effects of different steroid hormones on IL-6 production, HOC were exposed to estradiol (E2), dihydrotestosterone (DHT), dehydroepiandrosterone (DHEA) and dexamethasone (Dexa) with and without a subsequent treatment of the HOC populations with cytokines. We observed that (1) IL-1beta and TNFalpha induced IL-6 in a dose and time-dependent fashion, (2) TGFbeta 1 and 2 enhanced basal and IL-1beta and TNFalpha induced IL-6 expression, (3) ET-1 elicited a dose-dependent stimulatory effect on IL-6 expression. (4) E2, DHT and DHEA alone and in combination with IL-1beta and TNFalpha elicited no reproducible dose-dependent effect on IL-6 production, whereas Dexa inhibited basal and IL-1beta and TNFalpha induced IL-6 expression dose dependently. In conclusion, IL-1beta, TNFalpha, TGFbeta 1 and 2 and ET-1 may participate in the regulation of bone resorption by stimulating IL-6 expression in HOC. Dexa inhibits the constitutive and cytokine stimulated IL-6 expression, whereas there is no in vitro evidence that sex steroids exert a major inhibitory effect on the osteoblastic secretion of IL-6 as demonstrated in a primary human bone cell model.

Aged↗
PubMed1998

Clinical usefulness of a new chemiluminescent two-site immunoassay for human calcitonin.

The introduction of two-site immunoassays has greatly improved the measurement of human calcitonin (CT). But even within the two-site assays differences in sensitivity and ease of performance are noted. We evaluated the clinical usefulness of a new sensitive chemiluminescence two-site immunoassay for CT (Nichols) in comparison to an established two-site elisa (Medgenix). The range of measurement spans from 0.7 to 2500 pg/ml after 4h incubation for the chemiluminescent assay, compared to 2.0 to 1000 pg/ml after overnight incubation for the elisa. We investigated 179 healthy subjects (55 males, 124 females) to assess the upper limit of normal for CT values obtained by the chemiluminescence assay, which was defined as the 95th percentile of the distribution. The values obtained were 6.55 pg/ml for males and 4.13 pg/ml for females (p < 0.0005, Mann Whitney test). After pentagastrin-stimulation of 19 healthy volunteers (9 male, 10 female), the upper limit of normal for pentagastrin-stimulated CT was found at 43.0 pg/ml for males and 36.8 pg/ml for females (p < 0.05, Mann Whitney test). CT values obtained in patients with proven medullary thyroid carcinoma (MTC) or in subjects with suspected familial disease were positively correlated between both two-site assays (rho 0.961, p < 0.0001, Spearman rank correlation). More importantly the results led to the same clinical decision (normal vs. elevated) in 92.5% (37 of 40) patients. In all three patients with discordant results, clinical follow up supported the decision based on the chemiluminescence assay. Pentagastrin stimulation tests in MTC patients and localization studies of occult MTC tissue by selective venous catheterization led to concordant results in both assays. The new Nichols chemiluminescence assay demonstrated advantages in handling, a lower detection limit and a slightly higher sensitivity than the Medgenix elisa. CT values obtained by the chemiluminescence assay were on average 1.4-fold lower, which may be due to a slightly superior specificity of the assay, although this problem was not specifically addressed in this study. The clinical usefulness of both assays is highly satisfactory. In all cases, however, where clinically meaningful differences occurred, follow up proved the results obtained with the chemiluminescence assay to be correct.

Adolescent↗
PubMed1998

Ultrasound transmission speed and ultrasound bone profile score (UBPS) of the phalanges in normal women and women with osteoporosis.

The distal metaphysis of the first phalanx of the fingers II-V is, like the vertebral body, a useful site for the measurement of mineralisation and structure of the bone because of the simultaneous presence of compact and trabecular bone. With an ultrasound device (DBM sonic 1200, IGEA, Italy), we measured the adSOS (the amplitude dependent speed of sound) and the UBPS (ultrasound bone profile score), a score which is calculated from the graphic traces of the receiving probe with an expert system which uses fuzzy-logic at phalanges II-IV, as well as bone mineral density (BMD) at lumbar spine using dual X-ray absorptiometry (DXA). Precision of the measurements was as follows: adSOS: short-time-CV% = 0.576, long-time-CV% = 1.1, SCV% = 5.9, RMSSD% = 1.825. UBPS: short-time CV% = 5.95. There was no correlation between adSOS or UBPS and lumbar BMD (DXA). There was a significant positive correlation between adSOS and UBPS, r = 0.804 (p<0.00001). The validity of adSOS and UBPS was examined in 25 young and healthy women (mean age: 33.4 year), 15 postmenopausal healthy women (mean age: 58.5 years), 17 women with osteopenia, (mean age: 52.4 years), as defined by a t-score between -1 to -2.5 SD as lumbar BMD (DXA), and 20 women with osteoporosis and vertebral fractures (mean age: 61.4 years). We compared the healthy postmenopausal women and the women with osteoporotic vertebral fractures, the z-score of the adSOS was below minus 1.5 SD and UBPS was below 40, sensitivity was 0.7 for adSOS, and 0.85 for UBPS, with a specificity 0.97 for adSOS, and of 0.93 for UBPS; positive predictive value: adSOS: 0.93, UBPS: 0.85. AdSOS declined with age (r= 0.694, p=0.021); the UBPS was not age dependent (r=-0.15, p = n.s.). The ROC-curve shows a value of 0.96 for adSOS and 0.94 for UBPS. AdSOS and UBPS could discriminate well between the healthy controls and the women with osteopenia or vertebral fractures (p<0.00001). These results show that adSOS and UBPS are precise parameters to be measured at the phalanges. The detection level of pathological changes in osteoporosis are similar between adSOS and lumbar BMD (DXA) and improved by using the UBPS. This might be explained by the influence of structural changes in bone on UBPS, rather than change in bone mineral alone. Prospective studies have to clarify the role of adSOS and UBPS in fracture prediction.

Absorptiometry, Photon↗
PubMed1998

Controlled clinical laboratory comparison of two supplemented aerobic and anaerobic media used in automated blood culture systems to detect bloodstream infections.

A 20-ml blood sample was collected from adult patients with suspected bloodstream infections and distributed equally into the four volume-controlled bottles of a blood culture set consisting of aerobic and anaerobic BACTEC Plus/F bottles and aerobic and anaerobic BacT/Alert FAN bottles. All bottles were incubated in their respective instruments for a standard 5-day protocol or until the instruments signalled positivity. Samples in all bottles with negative results by these instruments were terminally subcultured. A total of 8,390 blood culture sets were obtained during the study period, of which 4,402 (52.5%) met the study criteria. Of these, 946 (21.5%) were positive either by instrument signal or by additional terminal subculture of all negative bottles and yielded growth of microorganisms. Five hundred eighty-nine (13.4%) blood culture sets were considered to have recovered 663 clinically significant organisms. When both the BACTEC and the BacT/Alert systems were used, 465 positive sets were detected; BACTEC alone detected 52 positive sets and BacT/Alert alone detected 72 (P = 0.09). No differences were found between the two systems in microbial recovery rate from blood cultures obtained from patients on antibiotic therapy. Significantly more members of the family Enterobacteriaceae (P < 0.01) were detected from patients without antimicrobial therapy by BacT/Alert than by BACTEC. The false-negative rates were 0.20% for BACTEC and 0.32% for BacT/Alert. A significantly higher false-positive rate was found for BACTEC (P < 0.0001). Both systems were comparable for the time to detection of microorganisms. However, gram-positive bacteria were detected faster by BACTEC and Enterobacteriaceae were detected faster on average by BacT/Alert. We concluded that both systems are comparable in their abilities to recover aerobic and anaerobic organisms from blood cultures and a terminal subculture might not be necessary for either of the two systems. The increased positivity rate when using an anaerobic bottle in a two-bottle blood culture set is due to the additional blood volume rather than to the use of an anaerobic medium.

Adult↗
PubMed1998

Molecular mechanisms of diabetic angiopathy--clues for innovative therapeutic interventions.

Advanced glycation end products (AGEs), known to accumulate during aging and at accelerated rate during the course of diabetes, have been demonstrated to induce changes in endothelial properties that might contribute to the pathogenesis of micro- and macroangiopathy. Since AGE-formation not only changes the physicochemical properties of proteins, but also induces cellular signalling, activation of transcription factors and subsequent gene expression, AGEs are now regarded as important mediators of diabetic vascular disease. The growing knowledge on the molecular mechanisms underlying the AGE-dependent activation of vascular endothelial cells implicates possible new therapeutic interventions in the therapy of diabetic angiopathy.

Diabetic Angiopathies↗
PubMed1998

Seasonal variation of biochemical indexes of bone turnover: results of a population-based study.

Biochemical markers of bone turnover have been shown to provide valuable information for the diagnosis and monitoring of metabolic bone disease. However, these dynamic indexes are influenced by a number of factors that need to be clearly identified to improve their clinical usefulness. To evaluate the contributions of anthropometric, life style, and environmental variables on bone turnover, biochemical markers of bone metabolism were determined in a population-based sample of 580 adults, aged 50-81 yr (297 men and 283 women). Subjects were recruited during 14 consecutive months within the framework of the European Vertebral Osteoporosis Study. Serum total and bone-specific alkaline phosphatase (S-BAP), serum C-terminal propeptide of type I collagen, and serum osteocalcin (S-OC) were measured as bone formation markers. Urinary total pyridinoline and deoxypyridinoline were included as bone resorption indexes. In females, serum levels of 25-hydroxyvitamin D3 were significantly higher (P < 0.01) in summer (May-September) than in winter (October-April), whereas no significant differences were found in males. In both sexes, no seasonal changes were seen in serum PTH. In males, serum total alkaline phosphatase (P < 0.01), S-BAP (P < 0.001), and S-OC (P < 0.05) were significantly higher in winter than in summer. During the same period, females had higher values of S-BAP (P < 0.05), S-OC (P < 0.01), and urinary pyridinoline and deoxypyridinoline (P < 0.001, respectively). Univariate analyses of the effects of life style habits on markers of bone metabolism revealed that in females, regular alcohol consumption and current smoking led to a suppression of markers of bone turnover, whereas in males, only alcohol intake was associated with such changes. In contrast, physical activity was associated with higher levels of bone formation markers and reduced levels of bone resorption indexes in both sexes. As shown by multivariate regression analyses, seasonal variations accounted for more of the variability in most biomarkers (up to 12%) than any of the other anthropometric or life style factors except age. This effect may be attributed to subclinical vitamin D deficiency during the winter period, which is common in countries of the northern hemisphere. We conclude that seasonal variation contributes significantly to the biological variability of bone turnover and needs consideration when interpreting the results of bone marker measurements.

Aged↗
PubMed1998

Concentration of insulin-like growth factor (IGF)-I and -II in iliac crest bone matrix from pre- and postmenopausal women: relationship to age, menopause, bone turnover, bone volume, and circulating IGFs.

Insulin-like growth factor-I (IGF-I) and -II are important local regulators of bone metabolism, but their role as determinants of human bone mass is still unclear. In the present study, we analyzed the concentration of IGF-I and -II in the bone matrix of 533 human biopsies from the iliac crest that were obtained during surgery for early breast cancer. There was an inverse association of bone matrix IGF-I concentration with age that was unaffected by menopause. Bone matrix IGF-I was positively associated with histomorphometric and biochemical parameters of bone formation and bone resorption and with cancellous bone volume. Based on the estimates of the linear regression analysis, women with a bone matrix IGF-I concentration 2 SD above the mean had a 20% higher bone volume than women with a bone matrix IGF-I concentration 2 SD below the mean. In contrast, serum IGF-I was neither correlated with bone turnover nor with bone volume and was only weakly associated with bone matrix IGF-I when adjusted for the serum concentration of IGF binding protein-3. Bone matrix IGF-II was positively associated with the osteoblast surface, but in contrast to IGF-I, tended to be positively associated with age and was unrelated to cancellous bone volume. In summary, our study suggests the following. 1) The concentration of IGF-I in cancellous bone undergoes age-related decreases that are similar to those of circulating IGF-I. 2) Menopause has no effect on this age-related decline. 3) Physiological differences in bone matrix IGF-I are associated with differences in iliac crest cancellous bone volume. 4) Bone matrix IGF-I is a better predictor of cancellous bone volume than circulating IGF-I. 5) The role of IGF-II in human bone tissue is clearly distinct from that of IGF-I.

Adult↗
PubMed1998

Changes in bone turnover induced by aerobic and anaerobic exercise in young males.

Physical activity is considered an important factor in attaining bone mass. However, the mechanisms by which exercise affects bone metabolism are not completely understood. The present study was performed to investigate the effects of aerobic and anaerobic exercise on bone turnover. Twenty healthy young males (aged 20-29 years) were followed through an 8-week program of aerobic (n = 10) and anaerobic training (n = 10). Ten age-matched individuals served as controls. Serum bone-specific alkaline phosphatase (BAP), serum osteocalcin (OC), and urinary pyridinoline (Pyd) and deoxypyridinoline (Dpd) were determined as indices of bone metabolism. After 4 weeks of aerobic training, serum BAP and OC (p < 0.01), and urinary Pyd (p < 0.001) and Dpd (p < 0.01) were significantly reduced. After 8 weeks, BAP and OC levels had returned to baseline values, whereas the urinary cross-link excretion remained low. In the anaerobic training group, elevated levels of BAP (p < 0.05 vs. week 4), OC (p < 0.05 vs. week 4), and Pyd (p < 0. 01 vs. week 0) were observed after 8 weeks of exercise. Changes in urinary Pyd and Dpd (week 0 vs. week 8) were positively correlated with changes in the mean power level in the Wingate test, a parameter of the anaerobic performance capacity (r = 0.50 and r = 0. 55, p < 0.01, respectively). In the controls, no significant changes in biochemical markers were observed. We conclude that aerobic and anaerobic training excert different effects on bone metabolism. While aerobic training led to changes compatible with reduced bone resorption activity, anaerobic training seems to result in an overall accelerated bone turnover. Therefore, the impact of physical activity on bone turnover may depend on the kind of exercise performed.

Adult↗