25-hydroxyvitamin D, biomarkers of endothelial dysfunction and subclinical organ damage in adults with hypertension.

BACKGROUND: The mechanism that underlies the association between low 25-hydroxyvitamin D [25(OH)D] and hypertension is not well understood; it seems to involve regulation of the renin-angiotensin-aldosterone system and the impact on endothelial function, cardiac remodeling, and subclinical organ damage. Vitamin D supplementation presents an ambiguous effect on endothelial function and arterial stiffness. We assess serum 25(OH)D3, biomarkers of endothelial dysfunction (soluble intercellular adhesion molecule [sICAM], C-reactive protein [CRP], homocysteine [Hcy]) and subclinical organ damage in adults with newly diagnosed untreated hypertension. METHODS: Patients were classified based on ambulatory blood pressure monitoring: 98 had hypertension, whereas in 60 persons BP was normal. Laboratory assays including serum 25(OH)D3, hsCRP, Hcy, sICAM, glucose, insulin, lipids, echocardiography, pulse wave velocity (PWV), intima-media thickness (IMT), and left-ventricular mass (LVM) measurements were performed. RESULTS: 25(OH)D3 was significantly lower in hypertensive patients. The logistic regression analysis indicated that 25(OH)D3 reduced the probability of hypertension occurrence after adjusting for body mass index (BMI). 25(OH)D3 in those with hypertension correlated significantly with systolic BP (SBP; r = -0.39), PWV, IMT (r = -0.33), and diastolic BP (r = -0.26). Multiple regression analysis in patients with hypertension revealed that 25(OH)D3 and sICAM accounted for up to 27% of SBP variation after adjusting for age, BMI, and smoking. 25(OH)D3 and either PWV or IMT accounted for 23% of SBP variation. The impact of 25(OH)D3 was 10%. CONCLUSION: The impact of 25(OH)D3 on SBP variation, mediated by its effect on endothelial dysfunction and subclinical organ damage, is modest but significant.

[Bone turnover in children and adolescents with diabetes mellitus type 1]. / Przebudowa tkanki kostnej u dzieci i mlodziezy z cukrzyca typu 1.

Biochemical bone turnover markers are fragments of protein structural elements of the bone created during the synthesis or degradation and enzymes specific for bone cells, released into the circulation during the metabolic activity of osteoblasts and osteoclasts. Bone turnover markers are used as indicators to evaluate the activity of modeling and remodeling processes. They are the result of the activity of all remodeling processes taking place at the moment in the whole skeleton. The assay allows quick assessment of the rate of bone formation and resorption processes. Among many complications in children with type 1 diabetes increased bone turnover leading to a reduction in bone mass may increase the risk of osteopenia or osteoporosis in adulthood. The aim of this manuscript is to review recent papers about bone turnover in children and adolescents with diabetes mellitus type 1.

[Alterations of bone metabolism in children and adolescents with diabetes mellitus type 1]. / Zaburzenia metabolizmu kostnego u dzieci i mlodziezy z cukrzyca typu 1.

Diabetes mellitus type 1 is one of the most common chronic diseases in children and adolescents. The incidence of diabetes mellitus type 1 is increasing rapidly worldwide. Recently, the largest rate of increase is observed in children aged 0-4 years. Chronic hyperglycemia leads to microvascular and macrovascular complications including retinopathy, nephropathy, neuropathy and cardiomyopathy. Pathological changes occur in the bone structure. The lack of diagnosis and treatment of alterations of the bone tIssue metabolism may lead to osteoporosis, which is characterized by much reduced bone mineral density and changes in the microarchitecture of the bone tIssue, which in consequence results in increased susceptibility to fractures. Diabetes mellitus type 1 most often starts before achieving peak bone mass, which constitutes a point of reference for predicting risk of fractures in a later period of life. Mechanisms responsible for loss of the bone tIssue in diabetes of type 1 still remain unexplained. Many research findings indicate the anabolic role of insulin and insulin-like growth factors, mainly IGF-1. The aim of this manuscript is to review recent papers about alterations of bone metabolism in children and adolescents with diabetes mellitus type 1.

Thyroid-Stimulating Hormone Within Normal Range Does Not Affect Bone Turnover in Euthyroid Postmenopausal Women with Osteoporotic Fracture - A Preliminary Report.

BACKGROUND: Pathogenic role of TSH suppression in the damaged bone tissue, in contrast to increased concentrations of thyroid hormones is still unknown. The aim of study was to evaluate the relationship between serum TSH and biochemical bone turnover markers in postmenopausal women with normal thyroid function and to answer whether the differences in TSH concentration within reference range may affect bone metabolism. MATERIAL AND METHODS: 34 women (60-93 years old) admitted to the hospital after osteoporotic fracture participated in the study. Serum propeptide of type 1 procollagen (P1NP) as a bone formation marker and crosslinked C-terminal telopeptides (CTX-I), as a bone resorption marker and TSH were assayed. RESULTS: Median P1NP (p=0,05) was significantly higher in the 1st tertile of TSH values (0,35-1,88 mlU/mL). In the 3rd tertile of TSH concentrations (3,42-4,94 mlU/mL), the highest CTX-I value was found that exceed the reference range for age. No differences were found in bone markers between a group of euthyroid and a group of subjects with TSH<0,35 mlU/mL. No relationship was observed between TSH and bone formation and resorption markers in the whole group of euthyroid postmenopausal women, however bone formation was found to be in the lower reference range for age in the euthyroid subjects as well as in these with decreased TSH. Weight and BMI correlated negatively with CTX (r=-0,68 p<0,03) in fractured women in the 1st tertile of TSH. CONCLUSION: We found no consistent evidence that TSH concentrations within reference range was associated with changes in bone turnover markers.

Biochemical markers of bone cell activity in children with type 1 diabetes mellitus.

AIMS: To evaluate bone turnover in children with type 1 diabetes mellitus (DM1) at onset, after 3 and 12 months of treatment, and in children with longer duration of disease, and its association with glycemic control. PATIENTS AND METHODS: 17 children with DM1 at onset, 30 with DM1 of longer duration and 45 controls participated in the study. Tartrate-resistant acid phosphatase 5b (TRACP5b), crosslinked C-terminal telopeptides of type I collagen (CTX) and osteocalcin (OC) were assessed. RESULTS: At onset of DM1 osteocalcin (p < 0.0003) and log CTX (p < 0.003) were lower than in controls but returned to reference levels after 3 months of therapy. TRACP5b in children with DM1 increased gradually and after 12 months was higher than at onset (p < 0.03). OC at onset inversely correlated with HbA1c (r = -0.40, p = 0.03). In children with DM1 of longer duration and HbA1c > 6.5%, sex-dependent differences were found in OC and CTX. Girls with HbA1 > 6.5% had lower OC and CTX than controls (p < 0.005, p < 0.003). Inverse correlations were found between HbA1c and OC and CTX (r = -0.50, p = 0.04; r = -0.49, p = 0.03). CONCLUSIONS: Proper glycemic control has a beneficial influence on bone turnover, which may prevent low bone mass in adulthood.

Does serum osteoprotegerin level relate to fragility fracture in elderly women with low vitamin D status?

BACKGROUND: Increased osteoprotegerin (OPG) with elevated bone turnover is supposed to be a homeostatic mechanism limiting bone loss. MATERIAL/METHODS: Whether osteoprotegerin relates to low-energy fracture in elderly women was investigated by analyzing the relationship between OPG and bone turnover. Sixty-nine women with a first fragility hip fracture participated. The reference group consisted of 23 age-matched women. Serum calcium, 25-OHD3, parathormone, osteocalcin (OC), cross-linked C-terminal telopeptides (CTX-I), tartrate-resistant acid phosphatase (TRAP5b), and osteoprotegerin were assayed immediately post-fracture. RESULTS: In both groups, median vitamin D and calcium concentrations were in the low reference range, CTX-I were moderately elevated, and TRAP5b activity and parathormone were within the reference range. Significantly lower osteocalcin, a trend to higher OPG, and an inverse correlation between OPG and osteocalcin was found in the fracture group. The distribution of fracture was related to osteocalcin and OPG concentrations: the lower the OC level, the higher the number of women with fracture at increasing OPG concentrations. A relative imbalance between bone formation and resorption was found in the fracture group. The lowest osteocalcin level (Q1) was observed only and vitamin 25-OHD3 insufficiency predominantly in the fracture group and higher OPG, TRAP5b, and elevated CTX-I concentrations (Q3) were found more often or predominantly in this group. CONCLUSIONS: The data demonstrate a relative imbalance between bone formation and resorption associated with fragility fracture in elderly women with low vitamin D status. The authors suggest that compensatory elevation of serum OPG, particularly with reduced bone formation, is insufficient to limit bone loss leading to fracture.

Bone Turnover Markers and Osteoprotegerin in Uncomplicated Pregnancy.

Although calcium metabolism during pregnancy is well described the mechanisms involved in bone metabolism are not quite clear. Increase of osteoprotegerin (OPG) with elevated bone turnover is supposed to be a homeostatic mechanism limiting bone loss. The aim of the study was to assess bone turnover in pregnancy in relation to serum osteoprotegerin level. Osteocalcin (OC), beta-crosslaps (CTx), OPG, vitamin 25 OH D3, parathormone (PTH), and calcium (Ca) were determined in 30 healthy women at 1(st) and at 3(rd) trimester of pregnancy and 27 healthy age-matched non pregnant women. In pregnant women average OPG, CTx and serum calcium concentrations were found to be highly elevated. During pregnancy OPG and bone resorption significantly rised whereas only slight increase in OC level was found with concomitant decrease in serum calcium. OPG correlated positively with OC and Ca only at 1(st) trimester. Serum CTx and OPG at 1(st) trimester seemed to be the only parameters to differentiate between elevated and normal bone turnover among pregnant women. In pregnancy bone turnover increases mainly due to enhanced bone resorption. The determination of osteocalcin at the beginning of pregnancy seems to be of limited clinical use, whereas measuring bone resorption markers such as CTx and/or osteoprotegerin may have a good predictive value for later pregnancy-associated bone loss.

New Biochemical Serum Markers of Boneturnover in Renal Osteodystrophy.

Renal osteodystrophy is a multifactorial disorder of bone remodelling that develops in patients with chronic renal failure. During the last few years numerous biochemical markers of bone turnover have been proposed for the non-invasive diagnosis of renal osteodystrophy. Several enzymes and matrix proteins produced by osteoblasts and osteoclasts, including collagen type I degradation products, have been recognized as circulating biochemical markers of both bone formation and bone resorption process. The aim of this article was to present and estimate the clinical utility of new serum markers of bone metabolism like bone specific alkaline phosphatase (bAP), procollagen type I extension peptides (PICP/PINP), osteocalcin (Oc), tartrate-resistant acid phosphatase (TRAP), procollagen type I crosslinked carboxyterminal telopeptide (ICTP), pyridinoline (PYR), deoxypyridinoline (DPD), C- or N-terminal telopeptides of type I collagen (CTx, NTx) and other potential markers in diagnosis of renal osteodystrophy in patients with chronic renal failure.