Urinary Nâ Telopeptide as Predictor of Onset of Menopauseâ Related Bone Loss in Preâ and Perimenopausal Women

The menopause transition (MT) is a period of rapid bone loss and has been proposed to be a timeâ limited window for early intervention to prevent permanent microarchitectural damage and reduce the risk of subsequent fracture. To intervene early, however, we first need to be able to determine whether menopauseâ related bone loss is about to begin, in advance of substantial bone loss. The objective of this study was, therefore, to assess whether urinary Nâ telopeptide (Uâ NTX) in preâ or early perimenopause can predict the onset of menopauseâ related bone loss. Repeated Uâ NTX measurements were obtained during preâ and early perimenopause in 1243 participants from the Study of Women’s Health Across the Nation (SWAN). We examined the ability of Uâ NTX to predict the onset of significant menopauseâ related bone loss (categorical outcome, yes versus no) at the lumbar spine (LS) and femoral neck (FN), defined as annualized bone mineral density (BMD) decline at a rate faster than the smallest detectable change in BMD over the 3 to 4 years from the time of Uâ NTX measurement. Adjusting for age, race/ethnicity, body mass index, urine collection time, starting BMD, and study site in multivariable, modified Poisson regression, every standard deviation increment in Uâ NTX, measured at baseline in early perimenopausal women, was associated with an 18% and 22% greater risk of significant bone loss at the LS (pâ =â 0.003) and FN (pâ =â 0.003), respectively. The area under the receiverâ operator curve for predicting LS and FN bone loss was 0.72 and 0.72, respectively. In mixedâ effects analysis of all repeated measures of early perimenopausal Uâ NTX over followâ up, Uâ NTX predicted onset of bone loss at the LS (pâ =â 0.002) but not at the FN. We conclude that Uâ NTX can be used early in the MT to determine if a woman is about to experience significant LS bone loss before there has been substantial skeletal deterioration. © 2018 The Authors. JBMR Plus is published by Wiley Periodicals, Inc. on behalf of the American Society for Bone and Mineral Research.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/149249/1/jbm410116_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/149249/2/jbm410116.pd

Perceived stress across the midlife: longitudinal changes among a diverse sample of women, the Study of Women’s health Across the Nation (SWAN)

Abstract Background In women, midlife is a period of social and physiological change. Ostensibly stressful, cross-sectional studies suggest women experience decreasing stress perceptions and increasing positive outlook during this life stage. The aim of this paper was to describe the longitudinal changes in perceived stress as women transitioned through the midlife. Methods Premenopausal women (n = 3044) ages 42–52 years at baseline, were recruited from seven sites in the Study of Women’s Health Across the Nation, and followed approximately annually over 13 visits with assessment of perceived stress and change in menopausal status. Longitudinal regression models were used to assess the effects of age, menopausal status and baseline sociodemographic variables on the trajectory of perceived stress over time. Results At baseline, mean age was 46.4 ± 2.7 years; participants were white (47%), black (29%), Hispanic (7%), Japanese (9%), or Chinese (8%). Hispanic women, women with lesser educational attainment, and women reporting financial hardship were each more likely to report high perceived stress levels at baseline (all p < 0.0001). After adjustment for baseline sociodemographic factors, perceived stress decreased over time for most women (p < 0.0001), but increased for both Hispanic and white participants at the New Jersey site (p < 0.0001). Changing menopausal status was not a significant predictor of perceived stress. Conclusions Self-reported stress decreased for most women as they transitioned across the midlife; changing menopausal status did not play a significant role after adjustment for age and sociodemographic factors. Future studies should explore the stress experience for women by racial / ethnic identity and demographics.https://deepblue.lib.umich.edu/bitstream/2027.42/142790/1/40695_2018_Article_32.pd

Estradiol and Follicleâ Stimulating Hormone as Predictors of Onset of Menopause Transitionâ Related Bone Loss in Preâ and Perimenopausal Women

The menopause transition (MT) may be an opportunity for early intervention to prevent rapid bone loss. To intervene early, we need to be able to prospectively identify preâ and perimenopausal women who are beginning to lose bone. This study examined whether estradiol (E2), or follicleâ stimulating hormone (FSH), measured in preâ and perimenopausal women, can predict significant bone loss by the next year. Bone loss was considered significant if bone mineral density (BMD) decline at the lumbar spine (LS) or femoral neck (FN) from a preâ or early perimenopausal baseline to 1â year after the E2 or FSH measurement was greater than the least detectable change. We used data from 1559 participants in the Study of Women’s Health Across the Nation and tested E2 and FSH as separate predictors using repeated measures modified Poisson regression. Adjusted for MT stage, age, race/ethnicity, and body mass index, women with lower E2 (and higher FSH) were more likely to lose BMD: At the LS, each halving of E2 and each doubling of FSH were associated with 10% and 39% greater risk of significant bone loss, respectively (pâ <â 0.0001 for each). At the FN, each halving of E2 and each doubling of FSH were associated with 12% (p = 0.01) and 27% (pâ <â 0.001) greater risk of significant bone loss. FSH was more informative than E2 (assessed by the area under the receiverâ operator curve) at identifying women who were more versus less likely to begin losing bone, especially at the LS. Prediction was better when hormones were measured in preâ or early perimenopause than in late perimenopause. Tracking withinâ individual change in either hormone did not predict onset of bone loss better than a single measure. We conclude that measuring FSH in the MT can help prospectively identify women with imminent or ongoing bone loss at the LS. © 2019 American Society for Bone and Mineral Research.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/153118/1/jbmr3856_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/153118/2/jbmr3856.pd

Moving toward a prevention strategy for osteoporosis by giving a voice to a silent disease

Abstract A major unmet challenge in developing preventative treatment programs for osteoporosis is that the optimal timing of treatment remains unknown. In this commentary we make the argument that the menopausal transition (MT) is a critical period in a woman’s life for bone health, and that efforts aimed at reducing fracture risk later in life may benefit greatly from strategies that treat women earlier with the intent of keeping bones strong as long as possible. Bone strength is an important parameter to monitor during the MT because engineering principles can be applied to differentiate those women that maintain bone strength from those women that lose bone strength and are in need of early treatment. It is critical to understand the underlying mechanistic causes for reduced strength to inform treatment strategies. Combining measures of strength with data on how bone structure changes during the MT may help differentiate whether a woman is losing strength because of excessive bone resorption, insufficient compensatory bone formation, trabeculae loss, or some combination of these factors. Each of these biomechanical mechanisms may require a different treatment strategy to keep bones strong. The technologies that enable physicians to differentially diagnose and treat women in a preventive manner, however, have lagged behind the development of prophylactic treatments for osteoporosis. To take advantage of these treatment options, advances in preventive treatment strategies for osteoporosis may require developing new technologies with imaging resolutions that match the pace by which bone changes during the MT and supplementing a woman's bone mineral density (BMD)-status with information from engineering-based analyses that reveal the structural and material changes responsible for the decline in bone strength during the menopausal transition.http://deepblue.lib.umich.edu/bitstream/2027.42/134529/1/40695_2016_Article_16.pd

Variance as a predictor of health outcomes: Subject-level trajectories and variability of sex hormones to predict body fat changes in peri- and post-menopausal women

Longitudinal biomarker data and cross-sectional outcomes are routinely collected in modern epidemiology studies, often with the goal of informing tailored early intervention decisions. For example, hormones such as estradiol and follicle-stimulating hormone may predict changes in womens' health during the midlife. Most existing methods focus on constructing predictors from mean marker trajectories. However, subject-level biomarker variability may also provide critical information about disease risks and health outcomes. In this paper, we develop a joint model that estimates subject-level means and variances of longitudinal biomarkers to predict a cross-sectional health outcome. Simulations demonstrate excellent recovery of true model parameters. The proposed method provides less biased and more efficient estimates, relative to alternative approaches that either ignore subject-level differences in variances or perform two-stage estimation where estimated marker variances are treated as observed. Analyses of women's health data reveal larger variability of E2 or larger variability of FSH were associated with higher levels of fat mass change and higher levels of lean mass change across the menopausal transition

Knee osteoarthritis in obese women with cardiometabolic clustering

Objective To assess the role of obesity and metabolic dysfunctionality with knee osteoarthritis (OA), knee joint pain, and physical functioning performance, adjusted for joint space width (JSW) asymmetry. Methods Knee OA was defined as a Kellgren/Lawrence score ≥2 on weight-bearing radiographs. Obesity was defined as a body mass index ≥30 kg/m 2 . Cardiometabolic clustering classification was based on having ≥2 of the following factors: low levels of high-density lipoprotein cholesterol; elevated levels of low-density lipoprotein cholesterol, triglycerides, blood pressure, C-reactive protein, waist:hip ratio, or glucose; or diabetes mellitus. The difference between lateral and medial knee JSW was used to determine joint space asymmetry. Results In a sample of women (n = 482, mean age 47 years), prevalences of knee OA and persistent knee pain were 11% and 30%, respectively. The knee OA prevalence in nonobese women without cardiometabolic clustering was 4.7%, compared with 12.8% in obese women without cardiometabolic clustering and 23.2% in obese women with cardiometabolic clustering. Nonobese women without cardiometabolic clustering were less likely to perceive themselves as limited compared with women in all other obesity/cardiometabolic groups ( P < 0.05). Similar associations were seen with knee pain and physical functioning measures. The inclusion of a joint space asymmetry measure was associated with knee OA but not with knee pain or physical functioning. Conclusion Knee OA was twice as frequent in obese women with cardiometabolic clustering compared with those without, even when considering age and joint asymmetry. Obesity/cardiometabolic clustering was also associated with persistent knee pain and impaired physical functioning.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/64312/1/24739_ftp.pd

Femoral Neck External Size but not aBMD Predicts Structural and Mass Changes for Women Transitioning Through Menopause

The impact of adult bone traits on changes in bone structure and mass during aging is not well understood. Having shown that intracortical remodeling correlates with external size of adult long bones led us to hypothesize that ageâ related changes in bone traits also depend on external bone size. We analyzed hip dualâ energy Xâ ray absorptiometry images acquired longitudinally over 14 years for 198 midlife women transitioning through menopause. The 14â year change in bone mineral content (BMC, R2â =â 0.03, pâ =â 0.015) and bone area (R2â =â 0.13, pâ =â 0.001), but not areal bone mineral density (aBMD, R2â =â 0.00, pâ =â 0.931) correlated negatively with baseline femoral neck external size, adjusted for body size using the residuals from a linear regression between baseline bone area and height. The dependence of the 14â year changes in BMC and bone area on baseline bone area remained significant after adjusting for race/ethnicity, postmenopausal hormone use, the 14â year change in weight, and baseline aBMD, weight, height, and age. Women were sorted into tertiles using the baseline bone areaâ height residuals. The 14â year change in BMC (pâ =â 0.009) and bone area (pâ =â 0.001) but not aBMD (pâ =â 0.788) differed across the tertiles. This suggested that women showed similar changes in aBMD for different structural and biological reasons: women with narrow femoral necks showed smaller changes in BMC but greater increases in bone area compared to women with wide femoral necks who showed greater losses in BMC but without large compensatory increases in bone area. This finding is opposite to expectations that periosteal expansion acts to mechanically offset bone loss. Thus, changes in femoral neck structure and mass during menopause vary widely among women and are predicted by baseline external bone size but not aBMD. How these different structural and mass changes affect individual strengthâ decline trajectories remains to be determined. © 2017 American Society for Bone and Mineral Research.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/137625/1/jbmr3082.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/137625/2/jbmr3082_am.pd

Effectiveness of the Tobacco Tactics program in the Department of Veterans Affairs

http://deepblue.lib.umich.edu/bitstream/2027.42/109488/1/12971_2014_Article_190.pd

The urgent need for disability studies among midlife adults

Abstract Issues of poor physical functioning and disability are burdensome for midlife adults and evidence suggests that the prevalence of these conditions is increasing temporally. Physical functioning during the midlife period, however, may be highly amendable to intervention given the highly dynamic nature of functioning during this life stage. Thus, efforts to improve or forestall poor physical functioning and/or disability during midlife may not only improve the health status and quality of life for midlife adults but may have important ramifications on the health of these individuals who will become older adults in the future. This thematic series on women and disability includes contributions addressing issues of person, place and time with respect to disability in midlife and into late adulthood. The purpose of this commentary is to provide a summary overview of the major themes of the series and to offer insight into areas of most promise for intervention among midlife populations to improve physical functioning and prevent disability.http://deepblue.lib.umich.edu/bitstream/2027.42/174023/1/40695_2020_Article_57.pd

Nurses' delivery of the Tobacco Tactics intervention at a Veterans Affairs Medical Center

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/108030/1/jocn12460.pd