Application of the Population Health Approach to Drinking Water System Surveillance

A drinking water supply is a complicated system in its construction,operation,maintenance and need for public health surveillance.     

Thyroid-stimulating hormone restores bone volume, microarchitecture, and strength in aged ovariectomized rats.

We show the systemic administration of low levels of TSH increases bone volume and improves bone microarchitecture and strength in aged OVX rats. TSH's actions are mediated by its inhibitory effects on RANKL-induced osteoclast formation and bone resorption coupled with stimulatory effects on osteoblast differentiation and bone formation, suggesting TSH directly affects bone remodeling in vivo. INTRODUCTION: Thyroid-stimulating hormone (TSH) receptor haploinsufficient mice with normal circulating thyroid hormone levels have reduced bone mass, suggesting that TSH directly affects bone remodeling. We examined whether systemic TSH administration restored bone volume in aged ovariectomized (OVX) rats and influenced osteoclast formation and osteoblast differentiation in vitro. MATERIALS AND METHODS: Sprague-Dawley rats were OVX at 6 months, and TSH therapy was started immediately after surgery (prevention mode; n = 80) or 7 mo later (restoration mode; n = 152). Hind limbs and lumbar spine BMD was measured at 2- or 4-wk intervals in vivo and ex vivo on termination at 8-16 wk. Long bones were subjected to microCT, histomorphometric, and biomechanical analyses. The direct effect of TSH was examined in osteoclast and osteoblast progenitor cultures and established rat osteosarcoma-derived osteoblastic cells. Data were analyzed by ANOVA Dunnett test. RESULTS: In the prevention mode, low doses (0.1 and 0.3 microg) of native rat TSH prevented the progressive bone loss, and importantly, did not increase serum triiodothyroxine (T3) and thyroxine (T4) levels in aged OVX rats. In restoration mode, animals receiving 0.1 and 0.3 microg TSH had increased BMD (10-11%), trabecular bone volume (100-130%), trabecular number (25-40%), trabecular thickness (45-60%), cortical thickness (5-16%), mineral apposition and bone formation rate (200-300%), and enhanced mechanical strength of the femur (51-60%) compared with control OVX rats. In vitro studies suggest that TSH's action is mediated by its inhibitory effects on RANKL-induced osteoclast formation, as shown in hematopoietic stem cells cultivated from TSH-treated OVX rats. TSH also stimulates osteoblast differentiation, as shown by effects on alkaline phosphatase activity, osteocalcin expression, and mineralization rate. CONCLUSIONS: These results show for the first time that systemically administered TSH prevents bone loss and restores bone mass in aged OVX rats through both antiresorptive and anabolic effects on bone remodeling.     

Effects of sex and age on bone microstructure at the ultradistal radius: a population-based noninvasive in vivo assessment.

In a population-based cross-sectional study, we examined effects of sex and age on bone microstructure at the wrist using high-resolution 3-D pQCT. Compared with women, men had thicker trabeculae in young adulthood and had less microstructural damage with aging. These findings may contribute to the virtual immunity of men to age-related increases in wrist fractures. INTRODUCTION: Although changes in bone microstructure contribute to fracture risk independently of BMD, it has not heretofore been possible to assess this noninvasively in population-based studies. MATERIALS AND METHODS: We used high-resolution 3-D pQCT imaging (voxel size, 89 mum) to define, in a random sample of women (n = 324) and men (n = 278) 21-97 years of age, sex and age effects on bone microstructure at the wrist. RESULTS: Relative to young women (age, 20-29 years), young men had greater trabecular bone volume/tissue volume (BV/TV; by 26%, p = 0.001) and trabecular thickness (TbTh; by 28%, p < 0.001) but similar values for trabecular number (TbN) and trabecular separation (TbSp). Between ages 20 and 90 years, cross-sectional decreases in BV/TV were similar in women (-27%) and in men (-26%), but whereas women had significant decreases in TbN (-13%) and increases in TbSp (+24%), these parameters had little net change over life in men (+7% and -2% for TbN and TbSp, respectively; p < 0.001 versus women). However, TbTh decreased to a greater extent in men (-24%) than in women (-18%; p = 0.010 versus men). CONCLUSIONS: Whereas decreases with age in trabecular BV/TV are similar in men and women, the structural basis for the decrease in trabecular volume is quite different between the sexes. Thus, over life, women undergo loss of trabeculae with an increase in TbSp, whereas men begin young adult life with thicker trabeculae and primarily sustain trabecular thinning with no net change in TbN or TbSp. Because decreases in TbN have been shown to have a much greater impact on bone strength compared with decreases in TbTh, these findings may help explain the lower life-long risk of fractures in men, and specifically, their virtual immunity to age-related increases in distal forearm fractures.     

Toward a VA women’s health research agenda: Setting evidence-based priorities to improve the health and health care of women veterans

The expansion of women in the military is reshaping the veteran population, with women now constituting the fastest growing segment of eligible VA health care users. In recognition of the changing demographics and special health care needs of women, the VA Office of Research & Development recently sponsored the first national VA Women’s Health Research Agenda-setting conference to map research priorities to the needs of women veterans and position VA as a national leader in Women’s Health Research. This paper summarizes the process and outcomes of this effort, outlining VA’s research priorities for biomedical, clinical, rehabilitation, and health services research.     

A potentially deleterious role of IGFBP-2 on bone density in aging men and women.

The role of the IGFs and IGFBPs on age-related changes in BMD in adult men and women is not well understood. Studying an age-stratified community based sample of 344 men and 276 women, we found higher IGFBP-2 levels to be associated with lower BMD. IGFBP-2, which increases with age in both men and women, was the strongest, most consistent predictor of BMD among the IGF/IGFBPs studied. INTRODUCTION: Insulin-like growth factors (IGFs) and their binding proteins (IGFBPs) are important regulators of tissue growth and metabolism, but their association with BMD in adult men and women is controversial. MATERIALS AND METHODS: In an age-stratified, random sample of the community population, we examined the role of serum levels of IGF-I, IGF-II, and IGFBP-1, -2, and -3 on BMD of the proximal femur (total hip), lateral spine, midshaft, and ultradistal radius as measured by DXA. We explored the association before and after adjustment for potential confounders, including age, bioavailable estradiol and testosterone, sex hormone binding globulin (SHBG), and measures of total fat and skeletal muscle mass. RESULTS: We studied 344 men (age, 23-90 years) and 276 women (age, 21-93 years; 166 postmenopausal) not on hormone replacement or oral contraceptives. In both men and women, IGF-I and IGFBP-3 levels fell with advancing age, whereas IGFBP-2 levels tended to rise with age. There was an inverse association of IGFBP-2 with BMD at most skeletal sites in men and both premenopausal and postmenopausal women, whereas lower IGF-I and IGFBP-3 were associated with lower BMD in men and postmenopausal women only. Lower IGF-II was associated with lower BMD in men only. There were no associations between IGFBP-1 and BMD in either sex. After adjustment for age, in most cases, we found no further associations between IGF-I, IGF-II, or IGFBP-3 and BMD. In contrast, after age adjustment, higher IGFBP-2 remained a predictor of lower BMD in men and postmenopausal women at all sites except for the lateral spine (for men: r = -0.21, -0.20, and -0.19, all p < 0.001; and for postmenopausal women: r = -0.34, -0.24, and -0.25, all p < 0.01, for the total hip, midshaft, and ultradistal radius, respectively). IGFBP-2 remained an independent negative predictor of BMD in men, postmenopausal women, and all women combined after additional adjustment for bioavailable sex steroids, but not at all sites after adjustment for SHBG and muscle mass. In premenopausal women, IGFBP-2 had similar associations as seen in postmenopausal women, but they were weaker and not statistically robust. CONCLUSIONS: Among the IGF/IGFBPs in our study, IGFBP-2 was a key negative predictor of BMD among men and women, particularly postmenopausal women. Our findings suggest a potential role of the IGF/IGFBP system in regulating bone loss in aging men and women and identify a previously under-recognized, potentially deleterious role for IGFBP-2, a known inhibitor of IGF action that increases with age in both sexes. Whether the action of the IGF/IGFBP system on bone metabolism is mediated partly through its effects on muscle mass or SHBG deserves further study.     

GnRH receptor signalling to ERK: kinetics and compartmentalization.

Many hormones, neurotransmitters and growth factors influence their target cells by activation of mitogen-activated protein kinase cascades. The consequences of such activation reflect not only the magnitude, but also the kinetics and cellular compartmentalization of kinase activity. Gonadotropin-releasing hormone (GnRH) receptors are seven-transmembrane receptors that have undergone a period of rapidly accelerated molecular evolution in which the advent of type I mammalian GnRH receptors has been associated with the loss of the carboxyl-terminal tail, a structure present in all other seven-transmembrane receptors. Here, we review spatiotemporal aspects of extracellular-signal-regulated kinase activation by gonadotropin-releasing hormone receptors, emphasizing how the absence or presence of the carboxyl-terminal tail dictates the receptors' ability to engage and signal via arrestins.