Vitamin D action and regulation in bone cells

It is well known that the biologically most active metabolite of vitamin D, I ,25-(0H)2DJ, is an essential hormone in the regulation of calcium homeostasis. Furthermore, evidence has accumulated to suggest that I ,25-(0H)2D3 regulates bone metabolism not only indirectly via its effect on intestinal absorption of calcium and phosphorus, but also directly through actions on bone remodelling cells and their progenitors. The aim of the present thesis has been to contribute to a better understanding of the effects of I,25-(0H)2D3 on the osteoblastic population and to investigate the cellular mechanisms in.volved in the regulation of the biological response to the hormon

Osteoporosis in the Netherlands; A burden of illness study commissioned by Merck Sharp & Dohme

This report provides an overview of the available quantitative information about osteoporosis in the Netherlands, and of the costs associated with it. We present information relevant for this country, making as few assumptions as possible. Although the main subject is osteoporosis, the focus in this report is on fractures, as these are the most relevant outcome events of this condition. Data were collected from publicly available data sources and from international literature and information is mostly about the year 1993. The reader finds detailed information about the occurrence of osteoporosis and fractures, the utilization of health care, mortality, and the costs in the results section of this report. In the conclusions, we present a synthesis of the most important findings. Osteoporosis is, by consensus, defined as a systemic skeletal disease, characterized by low bone mass and microarchitectural deterioration of bone tissue with a consequent increase in bone fragility and susceptibility to fracture. There is an important age-related decrease in bone mass and bone strength. Osteoporosis is primarily described in post-menopausal women but men are not free from it; they also reach high fracture incidence rates at an older age. Combined with the longer survival of women, this leads to the observation that most osteoporotic fractures are encountered in females. Osteoporosis and fractures are a major source of illness and healthcare costs in the Netherlands, both today as in the foreseeable future. Especially the most serious consequence, hip fracture, is frequent and the incidence is increasing. The total number of hip fractures will inevitable rise if no serious prevention efforts are undertaken. For the prevention of osteoporotic fractures it is important to know who are at risk as well as which preventive strategy is effective for the different risk categories. The parameter that is most commonly used nowadays to determine fracture risk is bone mineral density (BMD), but also other factors are important contributors to the fracture risk, namely the previously mentioned bone quality and the propensity to fall. Prevention only focussed on bone mineral density will thus do nothing to prevent the hip fractures caused by the above mentioned factors. An additional effect of therapy on bone quality can be important and the intervention should certainly not have adverse effects on bone quality. Reducing the frequency and severity of falls, and the use of external protective devices, together with physical exercise and other lifestyle interventions, have been looked at as additional intervention possibilities. Patients with a hip fracture more often have concomitant illnesses and a poor general condition. This condition in itself can increase the risk of falling and the perioperative risk. This situation can also impair the rehabilitation after treatment and hamper mobilization. Osteoporosis and fractures are found to be an important cause of health care consumption. Hip fractures lead to long hospita

A prospective study on circulating insulin-like growth factor I (IGF-I), IGF-binding proteins, and cognitive function in the elderly

The objective of this study was to investigate the longitudinal relation between the insulin-like growth factor I (IGF-I)/IGF-binding protein (IGFBP) system and cognitive function. The study population consisted of a sample of 186 healthy participants from the population-based Rotterdam Study, aged 55-80 yr. At baseline, we determined fasting blood levels of free and total IGF-I, IGFBP-1, and IGFBP-3. The 30-point Mini-Mental State Examination (MMSE) was used to assess cognitive impairment at baseline (MMSE score of <26; 6% of the sample) and cognitive decline after, on the average, 1.9 yr of follow-up (drop in MMSE score of >1 point/year; 22% of the sample). Odds ratios (OR) and 95% confidence intervals (95% CI) were estimated using logistic regression, with adjustment for age, sex, education, body mass index, and fasting insulin levels. Total IGF-I appeared to be inversely related to cognitive impairment, although not significantly. Higher total IGF-I and the total IGF-I/IGFBP-3 ratio were associated with less cognitive decline (OR per SD increase = 0.65; 95% CI = 0.44-0.95 and OR = 0.59; 95% CI = 0.39-0.87, respectively). No relation was observed between free IGF-I and cognitive decline (OR = 0.99; 95% CI = 0.68-1.44). In conclusion, in this prospective study higher serum total IGF-I levels and higher total IGF-I/IGFBP-3 ratios, but not higher free IGF-I levels, were associated with less cognitive decline over the following 2 yr. Circulating total IGF-I levels may reflect an underlying biological process that influences cognitive decline

Vitamin D: A modulator of cell proliferation and differentiation

Abstract 1,25-Dihydroxyvitamin D3, [1,25(OH)2D3], the biologically most active metabolite of vitamin D3, is involved in the regulation of calcium homeostasis and bone metabolism. Recently, receptors for 1,25(OH)2D3 have also been shown in cells and tissues not directly related to calcium homeostasis. Experimental data obtained with leukemic and cancer cell lines, both in vitro and in vivo, showed the effects of 1,25(OH)2D3 on cell differentiation and proliferation. However, high doses of the sterol have to be used to observe these effects. Additional studies are needed to establish whether 1,25(OH)2D3 or suitable analogues have a therapeutic potential in malignant diseases without unacceptable toxicity like the development of hypercalcemia