Decreased Bone Mineral Density in Adults Born with Very Low Birth Weight: A Cohort Study

Background

Very-low-birth-weight (VLBW, <1,500 g) infants have compromised bone mass accrual during childhood, but it is unclear whether this results in subnormal peak bone mass and increased risk of impaired skeletal health in adulthood. We hypothesized that VLBW is associated with reduced bone mineral density (BMD) in adulthood.

Methods and Findings

The Helsinki Study of Very Low Birth Weight Adults is a multidisciplinary cohort study representative of all VLBW births within the larger Helsinki area from 1978 to 1985. This study evaluated skeletal health in 144 such participants (all born preterm, mean gestational age 29.3 wk, birth weight 1,127 g, birth weight Z score 1.3), and in 139 comparison participants born at term, matched for sex, age, and birth hospital. BMD was measured by dual energy X-ray absorptiometry at age 18.5 to 27.1 y. Adults born with VLBW had, in comparison to participants born at term, a 0.51-unit (95% confidence interval [CI] 0.28–0.75) lower lumbar spine Z score and a 0.56-unit (95% CI 0.34–0.78) lower femoral neck Z score for areal BMD. These differences remained statistically significant after adjustment for the VLBW adults'' shorter height and lower self-reported exercise intensity.

Conclusions

Young adults born with VLBW, when studied close to the age of peak bone mass, have significantly lower BMD than do their term-born peers. This suggests that compromised childhood bone mass accrual in preterm VLBW children translates into increased risk for osteoporosis in adulthood, warranting vigilance in osteoporosis prevention. Please see later in the article for the Editors'' Summary     

Detection, analysis and interactions of plasma ghrelin, leptin and growth hormone in the mink (Mustela vison)

The aim of this study was to obtain basic knowledge of the plasma concentrations and interactions of weight regulatory hormones in juvenile minks (Mustela vison). Ghrelin, leptin, and growth hormone (GH) levels were validated and determined by radioimmunoassay methods from the plasma of 30 female and 30 male minks. The female minks had higher plasma ghrelin and GH levels than the males. The plasma ghrelin concentrations of the females correlated positively with their body masses (BMs). The plasma leptin levels did not differ between sexes, but there was a positive correlation between the plasma leptin concentrations and BMs in the male minks. When the data from the male and female minks were combined, the correlation between the leptin levels and the BMs was still clear, but this was not observed in the females alone. In the male minks, the plasma GH levels correlated positively with the BMs and with the plasma leptin concentrations. However, there was no correlation between the plasma ghrelin and GH or leptin concentrations. The hormone concentrations were quite similar to earlier measurements in other carnivores.     

Phytosterols affect endocrinology and metabolism of the field vole (Microtus agrestis)

Phytosterols or plant sterols (PS) enter the ecosystem via pulp mill effluents. They are also consumed by the general population of developed countries in natural remedies and margarines to lower elevated serum cholesterol levels. This study screened the endocrine and enzymatic parameters of the field vole (Microtus agrestis) for the effects of subchronic PS exposure at three doses (0, 5, or 50 mg of PS kg(-1) day(-1)). PS at 5 or 50 mg kg(-1) day(-1) decreased the relative liver weight of the voles. The kidney glycogen phosphorylase activity decreased at 5 or 50 mg kg(-1) day(-1), but the liver glycogen phosphorylase activity increased at 5 mg kg(-1) day(-1). The plasma estradiol and testosterone concentrations of males were higher due to PS supplement at 5 mg kg(-1) day(-1). This can be due to increased sex steroid synthesis from PS precursors. Biotransformation enzyme activities were not affected. PS caused multiple, previously unreported effects that were more pronounced at a low dose. As 5 mg PS kg(-1) day(-1) is the recommended dose for various health products, a thorough risk assessment of the effects and interactions of PS is warranted.     

Effects of fasting and exogenous melatonin on annual rhythms in the blue fox (Alopex lagopus)

The arctic fox (Alopex lagopus) is a winter-active inhabitant of the high arctic with extreme fluctuations in photoperiod and food availability. The blue fox is a semi-domesticated variant of the wild arctic fox reared for the fur industry. In this study, 48 blue foxes were followed for a year in order to determine the effects of exogenous melatonin and wintertime food deprivation on their reproductive and thyroid axes. Half of the animals were treated with continuous-release melatonin capsules in July 2002, and in November-January, the animals were divided into three groups and either fed continuously or fasted for one or two 22-day periods. Food deprivation decreased the plasma triiodothyronine and thyroxine concentrations probably in order to preserve energy due to a decreased metabolic rate. The same was observed in the plasma testosterone levels of the males but not in the plasma estradiol concentrations of the females. Exogenous melatonin advanced the autumn moult and seasonal changes in the voluntary food intake. It also advanced the onset of the testosterone peak in the males. The plasma estradiol levels of the females were unaffected, but the progesterone levels peaked more steeply in the sham-operated females. Melatonin exerted a strong influence not only on the reproductive axis of the males but also on the seasonal food intake. The species seemed quite resistant to periodic involuntary food deprivation.     

Enzymatic/biochemical analysis of Actinomyces with commercial test kits with an emphasis on newly described species

In clinical microbiology laboratories, the identification of Actinomyces-like bacteria can be very laborious and problematic. In the present study, we focused on reactivity patterns of 4 commercial test kits, RapID ANA II, RapID 32A, RapID CB Plus, and BBL Crystal ANR ID, that could be used for rapid preliminary identification of Actinomyces isolates belonging to newly described Actinomyces and closely related species. Out of the 54 strains tested, 25 strains (46%) were correctly identified to the genus/group level by BBL Crystal ANR ID system, 16 strains (30%) by RapID 32 A, 11 strains (20%) by RapID CB Plus, and 7 strains (13%) by RapID ANA II. The main problems with these kits were due to occasional weak enzymatic and sugar fermentation reactions. In conclusion, chromogenic substrate sensitivity and specificity need to be enhanced in order to improve the reliability of the test results of these kits, and the present database updated in order to more precisely identify newly described Actinomyces and closely related species.     

Endocrinologic adaptations to wintertime fasting in the male American mink (Mustela vison)

The aim of this study was to investigate the endocrine response to wintertime starvation in the male American mink (Mustela vison) fasted for 16 hrs, 2 days, 3 days, 5 days, or 7 days (n =10 per group). After 2 days of fasting, the plasma leptin concentrations decreased, along with the triiodothyronine, testosterone, and progesterone levels, and the blood monocyte counts. Leptin also seems to trigger the response to fasting in mustelids by inducing immunosuppression and downregulation of the reproductive and thyroid axes. The dramatic increase in the peptide YY concentrations after 3 days of fasting may be required to suppress gastrointestinal processes during food scarcity. The plasma insulin levels decreased, and those of glucagon increased after 5 days of fasting in association with efficient glucose sparing and lipid mobilization. Body energy stores cannot be wasted for growth during nutritional scarcity and, thus, the growth hormone levels of the minks decreased after 5 days of fasting. The plasma noradrenaline and cortisol concentrations also decreased after 3 and 7 days without food, respectively. The plasma ghrelin, adiponectin, resistin, thyroxine, adrenaline, or estradiol levels did not respond to fasting. The endocrine response to food deprivation is remarkably similar in divergent mammalian orders, indicating that the hormonal signals enhancing survival during nutritional scarcity must be evolutionarily old and well conserved.     

Adaptations of the raccoon dog (Nyctereutes procyonoides) to wintering--effects of restricted feeding or periodic fasting on lipids, sex steroids and reproduction

The raccoon dog (Nyctereutes procyonoides) is an omnivorous canid with autumnal hyperphagia and fattening followed by mid-winter passivity and fasting in boreal latitudes with seasonal snow cover. The effects of two different feeding levels (400 or 200 kcal/animal/d) or fasting (5-week fasting+1-week feeding+3-week fasting) on plasma lipids, sex steroids and reproductive success of farm-bred raccoon dogs (n=60 females and 24 males) were studied in winter. The body masses, body mass indices (BMIs) and levels of plasma triacylglycerols (TG), total cholesterol and low- and high-density lipoprotein cholesterol did not differ between the fed and the restrictively fed animals. During fasting, the plasma TG concentrations increased and the BMIs decreased, indicating the release of fatty acids from adipose tissue. After the fasting periods, the levels of plasma cholesterol and high-density lipoprotein cholesterol increased, whereas the TG levels decreased indicating the rebuilding of energy reserves. The fact that the different wintertime feeding regimes had no impact on the plasma glucose, total protein, cortisol, estradiol, progesterone or testosterone levels, or on the reproductive success, indicates versatile adaptive capacity in the species.     

Thermoregulatory adaptations of the overwintering captive raccoon dog (Nyctereutes procyonoides) in boreal climate

The raccoon dog (Nyctereutes procyonoides) is a nocturnal canid thought to utilise passive wintering strategy in the boreal climate. To record the deep body temperature (T(b)), 12 farmed raccoon dogs were implanted with intra-abdominal T(b) loggers on November 26, 2003. Between December 3, 2003 and January 27, 2004 half of the animals were fasted for 8 weeks. The amplitude of the diurnal T(b) oscillations increased due to fasting. However, the mean diurnal T(b) was lower in the fasted animals only during two occasions. Unlike observed previously in other species, not only did the raccoon dogs experience hypothermia between 0600 and 1000 hr but also hyperthermia between noon and 1800 hr. The fasted animals were as active as the fed animals measured after 42-43 days of fasting and there was a significant cross-correlation between physical activity and T(b). The nocturnal period of hypothermia is probably an adaptation to save energy during food deprivation. The diurnal hyperthermia could be explained by the opportunistic foraging behaviour of the species. Opposite to the established assumptions, the raccoon dog does not seem to enter winter sleep on fur farms. In the future it is important to determine if true winter sleep occurs in nature in the species.     

Stress,immunocompetence and leukocyte profiles of pied flycatchers in relation to brood size manipulation

The two main trade-offs considered determining reproductive patterns in iteroparous organisms are the one between current and future reproduction, and the one between the number and quality of offspring. Recently, it has been suggested that these trade-offs may be mediated by stress-induced reduction in immunocompetence. To test the hypothesis that stress reduces immune function, we investigated the effects of brood size manipulation on stress hormone levels, leukocyte profiles and immune responses against challenge with novel antigens in nestling and parent male pied flycatchers ( Ficedula hypoleuca). In male parents, heterophil (H) and lymphocyte (L) numbers, as well as H/L ratio increased with experimentally enlarged brood size, and corticosterone levels tended to do so, indicating that high parental work load altered their stress level and physiological state. Despite this, we found no effects on humoral immune responsiveness, measured as antibody production against diphtheria-tetanus vaccine. In nestlings, heterophil numbers and H/L ratio increased in enlarged broods, whereas T-cell-mediated immune responsiveness, measured against phytohemagglutinin (PHA), decreased in enlarged broods. The results support the view that growth-stress-induced immunosuppression may be an important physiological pathway mediating the trade-off between the number and viability of offspring. The difference in the observed immune-related responses between nestlings and males may be because we measured different aspects of the immune system (cellular vs humoral). However, it may also be a result of males lowering their own costs by feeding less, (and their mate possibly compensate by feeding more), whereas nestlings cannot escape the costs of increased intra-brood competition.