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Biomedical subjects

M Sowers

Publications and source records attributed to M Sowers.

At least 37 records · Page 2Linked to original sources

Role of calciotrophic hormones in calcium mobilization of lactation.

The postpartum period can be a time when profound changes in calcium metabolism and bone mineral density (BMD) occur, particularly in association with lactation. We investigated the hypothesis that calciotrophic hormones [1,25-dihydroxyvitamin D, 25-hydroxyvitamin D, and parathyroid hormone (PTH)] are different by lactation practice or hormone status [PTH-related peptide (PTHrP), estradiol, and prolactin] and have a potential role in the bone loss and recovery associated with lactation. 1,25-Dihydroxyvitamin D, 25-hydroxyvitamin D, PTH, femoral BMD, PTHrP, prolactin, estradiol, and bone turnover markers were measured at 2 wk and at 2, 4, 6, 12, and 18 mo postparturition in 115 postpartum women aged 20-40 y (parity: 0-1). Lumbar spine BMD was measured at 2 wk and at 6, 12, and 18 mo during the postpartum period. PTH, 1,25-dihydroxyvitamin D, and 25-hydroxyvitamin D concentrations were nonlinear across the 18-mo postpartum period. Between baseline and 18 mo postparturition, PTH and 1,25-dihydroxyvitamin D concentrations did not decline, while there was a substantial decline in 25-hydroxyvitamin D concentrations. PTH, 1,25-dihydroxyvitamin D, and 25-hydroxyvitamin D concentrations did not differ by lactation practice or by PTHrP, estradiol, or prolactin status. These classic calciotrophic hormones were not associated with concentrations of bone turnover markers or changes in BMD in lactating women. In summary, patterns of change in calciotrophic hormones (PTH, 1,25-dihydroxyvitamin D, and 25-hydroxyvitamin D) in the 18-mo postpartum period appeared to be independent of PTHrP, estradiol, prolactin, or lactation status and were not associated with bone turnover markers. These data do not support the hypothesis that these three calciotrophic hormones are a central part of the calcium mobilization associated with the bone loss of lactation.

Adult↗

The reproducibility of ultrasound bone measures in a triethnic population of pregnant adolescents and adult women.

We used bone ultrasound technology with its measurement of attenuation (broadband ultrasound attenuation [BUA] as dB/MHz) and sound velocity (speed of sound as m/s) for assessing the quantitative ultrasound index (QUI) summary measure in a triethnic population of 280 pregnant women. The study purpose was to describe the reproducibility of the ultrasound technology and determine if the correlations of age, weight, and ethnicity with the bone status measures in this population are consistent with the correlations of age, weight, and ethnicity that have been reported with other technologies that measure bone mass. We evaluated the first 280 women enrolled in our longitudinal study of lead turnover from maternal bone during pregnancy and lactation. Enrollees were pregnant, aged 12-29 years, and self-classified as black, white, or Hispanic. Bone ultrasound was measured twice at entry to prenatal care, which, on average, was at 14 weeks gestation. Reproducibility was described with intraclass correlations and the standard error of measurement. Age, weight, and ethnicity were associated with bone status measures using Spearman correlations and generalized linear models. The reproducibility of the summary bone measure, QUI, was high (96-97%). Variation in age and ethnicity did not alter reproducibility; however, the reproducibility of the attenuation measure (BUA as dB/MHz) lessened with increasing weight, declining from 95% to 89%. Since this attenuation is included in the summary QUI measure, there was a slight, and nonsignificant, decline in QUI reproducibility (from 97% to 96%) as women increased in size. There were no statistically significant differences in mean bone ultrasound measures according to age, where ages ranged from 12-29 years. Women who categorized themselves as black had, on average, an 8.5% greater QUI than did women who classified themselves as Hispanic or white. There were no significant pair-wise differences in mean ultrasound measures of bone between women classifying themselves as Hispanic or white. The use of ultrasound is a highly reproducible measure to assess bone characteristics in a population of pregnant adolescent and young adult women and its summary measure of bone mass is correlated with ethnic as well as body size characteristics.

Adolescent↗

Bone mineral density and its change in white women: estrogen and vitamin D receptor genotypes and their interaction.

Low bone mineral density (BMD) is a major risk factor for development of osteoporosis; increasing evidence suggests that attainment and maintenance of peak bone mass as well as bone turnover and bone loss have strong genetic determinants. We examined the association of BMD levels and their change over a 3-year period, and polymorphisms of the estrogen receptor (ER), vitamin D receptor (VDR), type I collagen, osteonectin, osteopontin, and osteocalcin genes in pre- and perimenopausal women who were part of the Michigan Bone Health Study, a population-based longitudinal study of BMD. Body composition measurements, reproductive hormone profiles, bone-related serum protein measurements, and life-style characteristics were also available on each woman. Based on evaluation of women, ER genotypes (identified by PvuII [n = 253] and XbaI [n = 248]) were significantly predictive of both lumbar spine (p < 0.05) and total body BMD level, but not their change over the 3-year period examined. The VDR BsmI restriction fragment length polymorphism was not associated with baseline BMD, change in BMD over time, or any of the bone-related serum and body composition measurements in the 372 women in whom it was evaluated. Likewise, none of the other polymorphic markers was associated with BMD measurements. However, we identified a significant gene x gene interaction effect (p < 0.05) for the VDR locus and PvuII (p < 0.005) and XbaI (p < 0.05) polymorphisms, which impacted BMD levels. Women who had the (-/-) PvuII ER and bb VDR genotype combination had a very high average BMD, while individuals with the (-/-) PvuII ER and BB VDR genotype had significantly lower BMD levels. This contrast was not explained by differences in serum levels of osteocalcin, parathyroid hormone, 1,25-dihydroxyvitamin D, or 25-dihydroxyvitamin D. These data suggest that genetic variation at the ER locus, singly and in relation to the vitamin D receptor gene, influences attainment and maintenance of peak bone mass in younger women, which in turn may render some individuals more susceptible to osteoporosis than others.

Absorptiometry, Photon↗

Bone mineral density and its change in pre-and perimenopausal white women: the Michigan Bone Health Study.

There is a need to better understand potential bone mineral density (BMD) loss during the menopausal transition since this period may include the initiation of interventions. The study purpose was to determine if there was BMD loss at the femoral neck, lumbar spine, or total body bone sites in a population-based study of women approaching or transitioning the midlife. The 583 enrollees were 25-45 years of age at the first of four annual measurements from 1992 through 1996. Bone mineral content and bone width were measured using dual-energy X-ray absorptiometry. Considering all enrollees collectively, there was a significant 3-year decline (1%) in BMD at the femoral neck over the 3-year period (p = 0.076). There was no significant annual change in the lumbar spine (p = 0.11), and a significant annual increase in the total body BMD (p = 0.0003). Within subgroups and cross-sectionally, BMD values of the femoral neck were 5% lower in women classified as perimenopausal compared with premenopausal enrollees; BMD was 3% and 1% lower at the lumbar spine and total body site, respectively. Longitudinally, among perimenopausal women, a double oophorectomy was associated with BMD loss in the spine (p = 0.0003), even though 75-85% of these women had a hormone replacement prescription at some time during the study period. In summary, the site with evidence of loss was the femoral neck, specifically among perimenopausal women. There was little evidence of substantial total body or lumbar spine BMD loss in premenopausal women with ovaries who maintained follicle-stimulating hormone levels < 20 mIU/l in the early follicular period. Double oophorectomy, even with hormone replacement, was associated with bone loss.

Absorptiometry, Photon↗

Urinary ovarian and gonadotropin hormone levels in premenopausal women with low bone mass.

We hypothesized that lower ovarian and gonadotropin hormone concentrations would be associated with lower levels of peak bone mineral density (BMD) in apparently normally menstruating women who did not exercise intensively and did not report anorexia or bulimia. This hypothesis was evaluated using a case-with-control study design (n = 65) which was nested within a population-based longitudinal study of peak bone mass (Michigan Bone Health Study) with annual assessment in women aged 25-45 years (n = 582). Cases were 31 premenopausal women with BMD of the lumbar spine, femoral neck, and total body less than the 10th percentile of the distribution, where controls were 34 premenopausal women with BMD between the 50th and 75th percentile. BMD was measured by dual-energy X-ray absorptiometry. In addition to their annual measurement, these 65 participants collected first-voided morning urine specimens daily through two consecutive menstrual cycles. The urine from alternating days of this collection was analyzed for estrone-3-glucuronide (E1G), pregnanediol glucuronide (PdG), testosterone, and follicle-stimulating hormone by radioimmunoassay and these values adjusted for daily creatinine excretion levels. Additionally, analyses of daily urine specimens for luteinizing hormone (uLH) was undertaken to better characterize the possible uLH surge. Cases had significantly lower amounts of E1G (p = 0.009) and PdG (p = 0.002) than did controls, whether amounts were characterized by a mean value, the highest value, or the area under the curve, and after statistically controlling for body size. Further, when B-splines were used to fit lines to the E1G and PdG data across the menstrual cycle, the 95% confidence intervals (CIs) about the line for the controls consistently excluded and excluded and exceeded the 95% confidence bands for the cases in the time frame associated with the luteal phase in ovulatory cycles. Likewise, 95% CIs for the LH surge in controls exceeded the fitted line for cases around the time associates with the LH surge. The cases and controls were not different according to dietary intake (energy, protein, calcium), family history of osteoporosis, reproductive characteristics (parity, age at menarche, age of first pregnancy), follicular phase serum hormone levels, calciotropic hormone levels, or by evidence of perimenopause. We conclude that these healthy, menstruating women with BMD at the lowest 10th percentile from a population-based study had significantly lower urinary sex steroid hormone levels during the luteal phase of menstrual cycles as compared with hormone levels in premenopausal women with BMD between the 50th and 75th percentile of the same population-based study, even after considering the role of body size. These data suggest that subclinical decreases in circulating gonadal steroids may impair the attainment and/or maintenance of bone mass in otherwise reproductively normal women.

Absorptiometry, Photon↗

Clinical epidemiology and osteoporosis. Measures and their interpretation.

Identifying patients with a high risk of fracture and monitoring a patient's therapeutic response are important. Current methods to evaluate the risk of fracture include the measurement of bone mineral density as well as other risk factors, including those associated with the risk of falling. Several considerations are important in defining the risk for fracture. There is currently no level of bone mineral density at which the risk of fracture is zero, that is, some high-risk women will not have a fracture and some low-risk women will. The monitoring of high-risk individuals for subtle changes in their bone status is not economically feasible at this time. Given the precision of current measurement technology, it is more reasonable to expect to monitor individuals on a 3- to 5-year basis rather than every 6 months to 1 year. There is no single optimal site at which measurement is highly precise and predictive of bone mineral density measurement at other skeletal locations. Currently, measurement of the femoral neck seems to have the most universal applicability. Measurement of bone turnover markers remains more effective as a research tool and is less effective as a method to diagnose or monitor the bone status of individual patients.

Biomarkers↗

The menopause transition.

New paradigms for the study of menopause will increase our understanding of whether symptoms, syndromes, and chronic diseases are associated with menopause. Rather than considering menopause as a discrete event, it has become clear that the menopause transition takes place over many years. Although this realization is central to our understanding of menopause, it is difficult to measure the temporal pattern of changes in hormones and their relation to concurrent or subsequent health-related events. The model of hormonal changes at the time of the transition has been expanded to include not only declines in estrogen but changes in a broader range of hormones, including the potential role of androgens. New models are attempting to account for the pattern and frequency of changes in hormone levels. Another level of complexity is contributed by the expansion of the menopause model to include comorbid medical and psychiatric conditions, environmental influences, and behaviors as covariates that influence the expression of menopause-related events. Although this more complicated paradigm makes the conduct of menopause research more challenging, it is also likely to elucidate previously confusing data, as the proper understanding of potentially complex exposures, effect modifiers, and confounders is more likely to provide clearer answers to critical research questions.

Adult↗

Lactation and weight retention.

The effect of lactation on weight retention was investigated longitudinally, with data collected at 0.5, 2, 4, 6, 12, and 18 mo after parturition in 110 women aged 20-40 y who had been nulliparous or primiparous. At each evaluation women were categorized as fully breast-feeding, partly breast-feeding, or bottle-feeding including infants weaned to a bottle (bottle feeding/weaned). Postpartum weight retention was calculated by subtracting weight before pregnancy from weight at each evaluation. Lactation practices were found to be significantly associated (P < 0.05) with postpartum weight retention by longitudinal regression analysis. Women who bottle-fed their infants retained more weight over time than women who breast-fed their infants. Significantly slower rates of weight loss were observed when women ceased breast-feeding or switched from fully to partly breast-feeding. Weight retention over time was greater in women who were older, unmarried, or had greater weight gain during pregnancy (P < 0.05). A pattern of weight gain rather than weight loss was observed in unmarried women. Our findings suggest that lactation influences the pattern of postpartum weight retention; however, the effect of lactation on weight retention was sufficiently limited to warrant minimal emphasis on lactation as a means of minimizing postpartum weight retention.

Adult↗

Parenteral zinc supplementation in adult humans during the acute phase response increases the febrile response.

The acute phase response (APR) that follows injury or infection is characterized by a decrease in serum zinc concentrations, which we hypothesized benefits the host. Additionally, we proposed that preventing this decline by supplementing zinc would result in an exaggerated APR as indicated by elevated temperatures, increased serum cytokine concentrations, interleukin 6 and the acute phase protein (ceruloplasmin). A prospective, randomized, double-blinded, clinical trial was conducted. Patients on home parenteral nutrition with a diagnosis of catheter sepsis and patients with a diagnosis of pancreatitis, also on total parenteral nutrition (TPN), were recruited for the study. Following enrollment, block randomization was used to assign patients to receive 0 mg (n = 23) or 30 mg (n = 21) of zinc per day for the first 3 d of TPN. Blood samples for measurement of serum zinc, copper, ceruloplasmin and interleukin-6 were obtained upon enrollment and on d 1 through 3 of TPN. The highest temperatures reported on these days in the medical record were also recorded. Repeated measures ANOVA was used to determine differences in the primary outcome variables over time. No significant differences between groups were observed in serum interleukin-6 or ceruloplasmin concentrations. A significantly higher (P = 0.035) temperature was observed in the zinc-supplemented group compared with the control group on d 3 of parenteral nutrition. We conclude that parenteral zinc supplementation in patients experiencing a mild APR resulted in an exaggerated APR as evidenced by a significantly higher febrile response.

Acute-Phase Reaction↗

Pelvic fractures following irradiation for endometrial carcinoma.

PURPOSE: To investigate the incidence and etiologic factors of pelvic fractures following radiation therapy for endometrial carcinoma. METHODS AND MATERIALS: Tumor registry and radiation oncology records of patients treated for endometrial carcinoma at The Toledo Hospital between April 1989, and December 1992, were reviewed. Patients identified as having pelvic fractures without the presence of metastatic disease underwent total body mineral density measurement with dual x-ray densitometry. RESULTS: Two of 75 patients (2.7%) were found to have pelvic fractures an average of 29 months from the completion of postoperative irradiation. One patient, who received preoperative irradiation, was also identified as having developed a fracture of the pelvis and was included in the analysis. All patients were treated prone with 10-15 MV photons in four fields daily. All three fracture patients received 45 Gy external beam radiation therapy. The two postoperative patients each received a single vaginal brachytherapy application delivering 20 Gy to 0.5 cm deep to the vaginal mucosa with a vaginal cylinder containing 30 mgRaeq 137Cs. The preoperative patient received a single brachytherapy application with tandem and colpostats delivering 20 Gy to point A. Only one of the three fracture patients had the entire pubis included in the field of external beam treatment. One patient was taking nonsteroidal anti-inflammatory medication, one patient thyroid hormone replacement, and one patient was taking both types of medication. CONCLUSION: The etiology of pelvic fractures after irradiation is multifactorial. A complete medication history should be obtained, and care should be exercised in positioning the radiation fields to avoid inclusion of the entire pubis prior to the initiation of the radiation treatment.

Aged↗

A prospective study of bone density and pregnancy after an extended period of lactation with bone loss.

OBJECTIVES: To determine if pregnancy after an extended period of lactation curtails the recovery of maternal bone mineral density. METHODS: Twenty-five women who fully breast-fed their infants for at least 6 months and had a subsequent pregnancy within 18 months of initiating lactation were studied longitudinally. Twenty controls breast-fed similarly, but had no subsequent pregnancy. The women were healthy, well-nourished, and between 20-40 years old. Bone mineral density was measured by dual x-ray energy absorptiometry at the spine and hip. RESULTS: Both cases and controls lost bone mineral density with extended lactation. The case group had a bone mineral density recovery comparable to the controls. CONCLUSION: Women with the dual calcium demands of extended lactation and a subsequent pregnancy are not at risk for failure of bone recovery to pre-lactation levels.

Absorptiometry, Photon↗

Biochemical markers of bone turnover in lactating and nonlactating postpartum women.

We measured two bone-formation markers, osteocalcin and bone-specific alkaline phosphatase, and one bone-resorption marker, N-telopeptide, in a longitudinal study in order to describe levels of these markers in lactating and nonlactating women after parturition. This 18-month postpartum period included an initial 6 months in which a 5% short-term bone loss occurred at both spine and femoral neck among breast-feeding women. The second part of the 18-month period was characterized by bone recovery among women who had lost bone. These bone-change characteristics provided an opportunity to evaluate the performance of biochemical markers during both bone loss and recovery and to identify environmental exposures during lactation associated with bone turnover. The eligible population comprised 115 women whose bone-turnover markers were measured at 2 weeks (baseline) and at 2, 4, 6, 12, and 18 months after parturition. Participants reported reproductive characteristics, diet, physical activity, use of medications, and infant-feeding practices at each contact. Women were grouped according to lactation duration: 0-1 months, 2-5 months, and 6 months or more. Women who breast-fed for at least 6 months had significantly different levels of all three bone-turnover markers compared with the levels in bottle-feeding controls, which were indicative of substantially increased bone turnover. Factors that predicted the difference in biochemical markers from baseline to 6-month values by regression analysis were lactation of 2-6 months duration and lactation for 6 months or more. Dietary calcium intake, physical activity level, and body size did not explain the differences in the change from the baseline level to the 6-month level, a period of time that corresponded with bone loss in the lactating women. Factors that predicted the differences in bone-turnover markers between 6 and 18 months (the time of bone-mass recovery) were lactation status and number of months to resumption of menses. By the 18-month observation, there was no difference in the mean values for the measured bone-turnover markers among the three lactation groups. This suggests that menstrual activity, rather than diet or physical activity, is the primary factor in bone-mass recovery after the bone loss of lactation.

Adult↗

Relationships between physical activity, insulin levels and lipids in non-diabetic low income residents of Mexico City: the Mexico City Diabetes Study.

The epidemiologic data supporting an association between physical activity and lipoprotein profile is controversial. We hypothesized that physical activity is positively associated with triglyceride levels and negatively associated with high density lipoprotein (HDL) cholesterol levels, and that these associations are mediated by insulin activity. We tested these hypotheses in 819 male and 1159 female healthy non-diabetic Mexicans, aged 35-64 years, residing in Mexico City. Physical activity was assessed using a modified Stanford 7-day Physical Activity Recall. Serum glucose and insulin were evaluated in the fasting state and 2 h following a glucose challenge. Crude analysis indicated that physical activity was not associated with HDL cholesterol in males, but was associated with HDL cholesterol in females (r = 0.06; p = 0.025). Physical activity was not associated with triglyceride concentration in males or females. Multivariate results showed that the positive association between HDL cholesterol and physical activity in women remained after controlling for age, estrogen status, body mass index, and smoking. Furthermore, there was a significant interaction between physical activity, HDL cholesterol and an index of insulin sensitivity. Women with higher levels of insulin sensitivity had higher levels of HDL cholesterol. However, among women at lower levels of insulin sensitivity, those with greater physical activity were significantly more likely to have higher HDL cholesterol values.

Adult↗

Obesity as a risk factor for osteoarthritis of the hand and wrist: a prospective study.

The Tecumseh Community Health Study provides an opportunity to investigate the role of obesity in the etiology of osteoarthritis. This longitudinal study, conducted in Tecumseh, Michigan, began in 1962 with baseline examinations of clinical, biochemical, and radiologic characteristics. A 1985 reexamination of the cohort characterized osteoarthritis status in 1,276 participants, 588 males and 688 females, who were aged 50-74 years at this follow-up. Baseline obesity, as measured by an index of relative weight, was found to be significantly associated with the 23-year incidence of osteoarthritis of the hands among subjects disease free at baseline. Greater baseline relative weight was also associated with greater subsequent severity of osteoarthritis of the hands. The difference between baseline and follow-up weight values was not significantly associated with the incidence of osteoarthritis of the hands. Furthermore, there was no evidence that development of osteoarthritis subsequently led to increased incidence of obesity.

Adult↗

A comparison of periodontal disease among rural Amish and non-Amish adults.

Periodontal disease can be more efficiently studied within a homogeneous population where genetic influences and lifestyles are similar enough to negative their effect on the disease process. This study focuses on an Amish population in southern Michigan who isolate themselves from outside influences and their non-Amish neighbors. A total of 425 Amish and 290 non-Amish were contacted resulting in 330 Amish and 215 non-Amish who were examined in their homes giving a participation rate of 76.2%. Ages ranged from 18 to 82 years. Prevalence of periodontal disease tended to be higher among males and increased with age. There were slightly more Amish females (52%) than non-Amish (49%). Means of periodontal conditions for Amish were 1.35 mm for attachment loss, 2.59 mm for pocket depth, 0.24 for calculus, 0.77 for plaque and 0.74 for gingivitis. For non-Amish, the means were 1.03 mm for attachment loss, 2.38 mm for pocket depth, 0.40 for calculus, 0.95 for plaque and 0.87 for gingivitis. It is of interest that the Amish do not practice routine oral hygiene. Only 36.8% of Amish reported brushing at least 1 x a day compared to 84.6% of non-Amish. Similarly, only 8.2% of Amish reported flossing at least 1 x a week compared to 40.8% of non-Amish.

Adolescent↗

Higher risk of cardiovascular mortality among lean hypertensive individuals in Tecumseh, Michigan.

BACKGROUND: A cohort of 2181 men and women, aged 40 to 79 years, without evidence of coronary heart disease or cancer at entry to the Tecumseh Study was evaluated. METHODS AND RESULTS: Subjects were defined as lean if their Metropolitan Life Insurance table relative weight was < 110 (n = 584) and as obese if their relative weight was > or = 120 (n = 1024). There were 688 subjects with hypertension at study entry (systolic blood pressure > or = 160, diastolic blood pressure > or = 95, or treated). The 29-year relative risk (RR) of mortality from ischemic heart disease (IHD) or cardiovascular disease (CVD) associated with systolic blood pressure level was significant for both lean and obese subjects. Among hypertensive subjects, the RR of fatal IHD for lean versus obese hypertensive subjects was 1.87 (95% confidence interval, 1.21 to 2.88) and the RR of fatal CVD was 1.56 (95% confidence interval, 1.10 to 2.20) using a Cox proportional-hazards model to adjust for the independent effects of age and traditional CVD risk factors. The findings are consistent with other studies in men showing lean hypertensive subjects to be at greater risk of IHD or CVD mortality than obese hypertensive subjects. A similar finding is now observed in women. CONCLUSIONS: Associations do not prove causality or dictate management. Nevertheless, the unexplained higher mortality in lean versus obese hypertensive subjects has now been reported with sufficient frequency to suggest that the association is real (if unexplained). Determining the reasons for this association may improve targeted prevention and treatment strategies.

Adult↗