Vitamin D status, parathyroid function, bone turnover, and BMD in postmenopausal women with osteoporosis: global perspective

Poor vitamin D status is common in the elderly and is associated with bone loss and fractures. The aim was to assess worldwide vitamin D status in postmenopausal women with osteoporosis according to latitude and economic status, in relation to parathyrold function, bone turnover markers, and BMD. The study was performed in 7441 postmenopausal women from 29 countries participating in a clinical trial on bazedoxifene (selective estrogen receptor modulator), with BMD T-score at the femoral neck or lumbar spine 75 nM was 5.9%, 29.4%, 43.5%, and 21.2%, respectively, in winter and 3.0%, 22.2%, 47.2%, and 27.5% in summer. Worldwide, a negative correlation between 25(OH)D and latitude was observed. With increasing 25(OH)D categories of 75 nM, mean PTH, OC, and CTX were decreasing (p<0.001), whereas BMD of all sites was increasing (p<0.001). A threshold in the positive relationship between 25(OH)D and different BMD parameters was visible at a 25(OH)D level of 50 nM. Our study showed a high prevalence of low 25(OH)D in postmenopausal women with osteoporosis worldwide. Along with latitude, affluence seems to be an important factor for serum 25(OH)D level, especially in Europe, where it is strongly correlated with latitude

Vitamin D deficiency as a risk factor for osteoporotic fractures

The evidence on the association between vitamin D deficiency and fracture incidence is contradictory. Therefore, the objective of this study was to examine whether low serum 25-hydroxyvitamin D (25(OH)D) levels are associated with osteoporotic fractures. The study was conducted among 1311 community-dwelling older men and women of the Longitudinal Aging Study Amsterdam (LASA), an ongoing multidisciplinary cohort study. Serum 25(OH)D was determined using a competitive protein binding assay. Fractures were assessed during six years of follow-up. The data were analyzed using Cox proportional hazards model. In total, 11.3% of the persons had a serum 25(OH)D below 10 ng/ml, 48.4% had a value below 20 ng/ml, and 82.4% had a value below 30 ng/ml. Furthermore, 115 persons (8.5%) had one or more osteoporotic fractures. Different cut points of serum 25(OH)D were examined with a cut point of 12 ng/ml giving the best discrimination between persons with and without fractures (17.5% of the persons fell below this cut point). The lowest percentage of fractures (5.6%) was found above 30 ng/ml. Because an interaction effect with age was found (p = 0.04), further analyses were conducted separately for persons aged 65-75 years (n = 656) and for persons aged 75-89 years (n = 664) at baseline. After adjustment for age, sex, season of blood collection, body mass index, number of chronic diseases, serum creatinine, cognition, smoking and alcohol use, serum 25(OH)D below or equal to 12 ng/ml was associated with an increased fracture risk in the youngest age group (HR = 3.1; 95% CI: 1.4-6.9), but not in the oldest age group (HR = 1.3; 95% CI: 0.7-2.2). For commonly used cut points of serum 25(OH)D (< 10 ng/ml, 10-19.9 ng/ml, 20-29.9 ng/ml, ≥ 30 ng/ml), no statistically significant associations were found after adjustment for confounding. Serum 25(OH)D levels below or equal to 12 ng/ml were associated with an increased fracture risk in persons aged 65-75 years. The relatively low cut point of serum 25(OH)D in our population is possibly caused by high calcium intake in the Netherlands. © 2007 Elsevier Inc. All rights reserved

Relationships of serum 25-hydroxyvitamin D to bone mineral density and serum parathyroid hormone and markers of bone turnover in older persons

Context: Serum 25-hydroxyvitamin D[25(OH)D] may influence serum PTH and other parameters of bone health up to a threshold concentration, which may be between 25 and 80 nmol/liter. Objective: The aim of the study was to assess the threshold serum 25(OH)D with regard to PTH, bone turnover markers, and bone mineral density (BMD). Design and Setting: This was part of the Longitudinal Aging Study Amsterdam, an ongoing cohort study. Participants: A total of 1319 subjects (643 men and 676 women) between the ages of 65 and 88 yr participated in the study. Main Outcome Measures: Serum 25(OH)D, PTH, osteocalcin, urinary deoxypyridinoline/creatinine, quantitative ultrasound of the heel, BMD of lumbar spine and hip, total body bone mineral content, and physical performance. The relationship between the variables was explored by analysis of covariance and the locally weighted regression (LOESS) plots. Results: Serum 25(OH)D was below 25 nmol/liter in 11.5%, below 50 nmol/liter in 48.4%, below 75 nmol/liter in 82.4%, and above 75 nmol/liter in 17.6% of the respondents. Mean serum PTH decreased gradually from 5.1 pmol/liter when serum 25(OH)D was below 25 nmol/liter to 3.1 pmol/liter when serum 25(OH)D was above 75 nmol/liter (P < 0.001) without reaching a plateau. All BMD values were higher in the higher serum 25(OH)D groups, although only significantly for total hip (P = 0.01), trochanter (P = 0.001), and total body bone mineral content (P = 0.005). A threshold of about 40 nmol/liter existed for osteocalcin and deoxypyridinoline/creatinine, 50 nmol/liter for BMD, and 60 nmol/liter for physical performance. Conclusions: Low serum 25(OH)D concentrations are common in the elderly. Bone health and physical performance in older persons are likely to improve when serum 25(OH)D is raised above 50-60 nmol/liter. (J Clin Endocrinol Metab 94: 1244-1250, 2009

The effect of iron loading and iron chelation on the innate immune response and subclinical organ injury during human endotoxemia: a randomized trial

In this double-blind randomized placebo-controlled trial involving 30 healthy male volunteers we investigated the acute effects of iron loading (single dose of 1.25 mg/kg iron sucrose) and iron chelation therapy (single dose of 30 mg/kg deferasirox) on iron parameters, oxidative stress, the innate immune response, and subclinical organ injury during experimental human endotoxemia. The administration of iron sucrose induced a profound increase in plasma malondialdehyde 1 h after administration (433+/-37% of baseline; P<0.0001), but did not potentiate the endotoxemia-induced increase in malondialdehyde, as was seen 3 h after endotoxin administration in the placebo group (P=0.34) and the iron chelation group (P=0.008). Endotoxemia resulted in an initial increase in serum iron levels and transferrin saturation that was accompanied by an increase in labile plasma iron, especially when transferrin saturation reached levels above 90%. Thereafter, serum iron decreased to 51.6+/-9.7% of baseline at T=8 h in the placebo group versus 84+/-15% and 60.4+/-8.9% of baseline at 24 h in the groups treated with iron sucrose and deferasirox, respectively. No significant differences in the endotoxemia-induced cytokine response (TNF-alpha, IL-6, IL-10 and IL-1RA), subclinical vascular injury and kidney injury were observed between groups. However, vascular reactivity to noradrenalin was impaired in the 6 subjects in whom labile plasma iron was elevated during endotoxemia as opposed to those in whom no labile plasma iron was detected (P=0.029). In conclusion, a single dose of iron sucrose does not affect the innate immune response in a model of experimental human endotoxemia, but may impair vascular reactivity when labile plasma iron is formed. (Clinicaltrials.gov identifier:01349699)

Ultrasonografia ossea del calcagno

Nel 1984 sono stati pubblicati i risultati di uno studio che, per la prima volta, utilizzava gli ultrasuoni per la misura dell’osso, in particolare del calcagno

Predictive validity and cut-off scores in four diagnostic tests for falls – a study in frail older people at home

Artikkelen rapporterer en studie hvor hensikten var å undersøke validiteten og treffsikkerheten for instrumentene Downton Fall Risk Index, Timed Up and Go og Romberg test, når det gjelder prediksjon av fall hos hjemmeboende eldre.No study has investigated the predictive validity and cut-off scores in diagnostic tests for falls used in in-home assessment in frail older people. The objective was to investigate the predictive validity for falls in the Downton Fall Risk Index (DFRI), Timed Up and Go (TUG) and Romberg test (RT) used in in-home assessment of frail older people (65+ years). Data on the diagnostic tests were collected at baseline (N = 153) and fall frequency were collected at six- and twelve-month follow-ups. The optimal cut-offs were 3 p in DFRI and 12 s in TUG. However, the validity indexes were generally low and only 40–50% were correctly classified. The RT showed low sensitivity. To increase the predictive validity for falls in this context, the use of DFRI and/or TUG as a part of a comprehensive fall-risk assessment tool, should be investigated in future studies