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Biomedical subjects

S R Cummings

Publications and source records attributed to S R Cummings.

At least 37 records · Page 2Linked to original sources
PubMed2001

A high ratio of dietary animal to vegetable protein increases the rate of bone loss and the risk of fracture in postmenopausal women. Study of Osteoporotic Fractures Research Group.

BACKGROUND: Different sources of dietary protein may have different effects on bone metabolism. Animal foods provide predominantly acid precursors, whereas protein in vegetable foods is accompanied by base precursors not found in animal foods. Imbalance between dietary acid and base precursors leads to a chronic net dietary acid load that may have adverse consequences on bone. OBJECTIVE: We wanted to test the hypothesis that a high dietary ratio of animal to vegetable foods, quantified by protein content, increases bone loss and the risk of fracture. DESIGN: This was a prospective cohort study with a mean (+/-SD) of 7.0+/-1.5 y of follow-up of 1035 community-dwelling white women aged >65 y. Protein intake was measured by using a food-frequency questionnaire and bone mineral density was measured by dual-energy X-ray absorptiometry. RESULTS: Bone mineral density was not significantly associated with the ratio of animal to vegetable protein intake. Women with a high ratio had a higher rate of bone loss at the femoral neck than did those with a low ratio (P = 0.02) and a greater risk of hip fracture (relative risk = 3.7, P = 0.04). These associations were unaffected by adjustment for age, weight, estrogen use, tobacco use, exercise, total calcium intake, and total protein intake. CONCLUSIONS: Elderly women with a high dietary ratio of animal to vegetable protein intake have more rapid femoral neck bone loss and a greater risk of hip fracture than do those with a low ratio. This suggests that an increase in vegetable protein intake and a decrease in animal protein intake may decrease bone loss and the risk of hip fracture. This possibility should be confirmed in other prospective studies and tested in a randomized trial.

Absorptiometry, Photon↗
PubMed2001

Older women with diabetes have an increased risk of fracture: a prospective study.

To determine whether type 2 diabetes is associated with fracture in older women, we analyzed data from 9654 women, age 65 yr or older, in the Study of Osteoporotic Fractures. Diabetes with age at onset 40 yr or older was reported by 657 women, of whom 106 used insulin. A total of 2624 women experienced at least one nonvertebral fracture during an average follow-up of 9.4 yr, and 388 had at least one vertebral fracture during an average interval of 3.7 yr. Although diabetes was associated with higher bone mineral density, it was also associated with a higher risk of specific fractures. Compared with nondiabetics, women with diabetes who were not using insulin had an increased risk of hip [relative risk (RR), 1.82; 95% confidence interval (CI), 1.24-2.69] and proximal humerus (RR, 1.94; 95% CI, 1.24-3.02) fractures in multivariate models controlling for age, body mass index, bone density, and other factors associated with fractures and diabetes. Insulin-treated diabetics had more than double the risk of foot (multivariate adjusted RR, 2.66; 95% CI, 1.18-6.02) fractures compared with nondiabetics. This study indicates that diabetes is a risk factor for hip, proximal humerus, and foot fractures among older women, suggesting that fracture prevention efforts should be a consideration in the treatment of diabetes.

Aged↗
PubMed2001

Associations of serum osteoprotegerin levels with diabetes, stroke, bone density, fractures, and mortality in elderly women.

Osteoprotegerin (OPG) and its ligand are cytokines that regulate osteoclastogenesis and that may be involved in the regulation of vascular calcification. We examined whether serum OPG levels were associated with stroke, mortality, and cardiovascular risk factors, including diabetes, as well as with bone mineral density and fractures in a sample of 490 participants in a prospective cohort of white women, at least 65 yr of age. We found that OPG levels, assayed blinded from serum obtained at baseline, were about 30% greater in women with diabetes (mean +/- SD, 0.30 +/- 0.17 ng/mL) than in those without diabetes (0.23 +/- 0.10 ng/mL; P = 0.0001). OPG levels were associated with all-cause mortality [age-adjusted odds ratio, 1.4/SD (0.11 ng/mL) increase in serum OPG level; 95% confidence interval, 1.2--1.8] and cardiovascular mortality (odds ratio, 1.4; 95% confidence interval, 1.1--1.8); these effects were not confounded by diabetes. OPG levels were not associated with baseline bone mineral density or with subsequent strokes or fractures. The association of serum OPG levels with diabetes and with cardiovascular mortality raises the possibility that OPG may be a cause of or a marker for vascular calcification.

Aged↗
PubMed2001

Influence of smoking on the antiosteoporotic efficacy of raloxifene.

The efficacy of estrogen therapy may be modified in women who smoke because of increased catabolism of estrogen and the interaction of tobacco products with the estradiol receptor. We examined whether the efficacy of raloxifene differed in smoking vs. nonsmoking women. We compared change in bone mineral density and biochemical markers of bone turnover, and incidence of new vertebral fracture in postmenopausal women of the Multiple Outcomes on Raloxifene Efficacy trial, who were randomized to either raloxifene (60 or 120 mg/d) or placebo. In the 17% of women who were current smokers, we found, compared with nonsmokers, lowered baseline trochanter bone mineral density (0.540 vs. 0.557 g/cm(2); P < 0.001) and serum osteocalcin (24.8 vs. 26.6 ng/liter; P < 0.001). Baseline urinary type I collagen breakdown products was increased among smokers (291.8 vs. 276.9 micromol/liter; P = 0.04). Body mass index was also lower in smokers (24.3 vs. 25.4; P < 0.001). After 6 months of treatment, there was no significant difference in reduction of bone turnover between smokers and nonsmokers. After 4 yr of treatment, the smoking-treatment interaction was not significant between smokers and nonsmokers for the percent increase in femoral neck bone mineral density (P = 0.25), trochanter bone mineral density (P = 0.24), and spine bone mineral density (P = 0.37). The smoking-treatment interaction for reduction in vertebral fracture risk was not significant either [odds ratio for fracture, 0.67 (0.45-0.98) for smokers and 0.56 (0.47-0.68) for nonsmokers; P = 0.44]. These results were not modified after stratification by tertiles of body mass index or when comparing heavy smokers vs. light smokers. We conclude that smoking does not influence the antiosteoporotic effect of raloxifene. This may represent an advantage over estrogen replacement therapy.

Biomarkers↗
PubMed2001

Effects of current and discontinued estrogen replacement therapy on hip structural geometry: the study of osteoporotic fractures.

It is assumed that estrogen influences bone strength and risk of fractures by affecting bone mineral density (BMD). However, estrogen may influence the mechanical strength of bones by altering the structural geometry in ways that may not be apparent in the density. Repeated dual energy X-ray absorptiometry (DXA) hip scan data were analyzed for bone density and structural geometry in elderly women participating in the Study of Osteoporotic Fractures (SOF). Scans were studied with a hip structural analysis program for the effects of estrogen replacement therapy (ERT) on BMD and structural geometry. Of the 3,964 women with ERT-use data, 588 used ERT at both the start and end of the approximately 3.5-year study, 1,203 had past use which was discontinued by clinic visit 4, and 2,163 women had never used ERT. All groups lost BMD at the femoral neck, but the reduced BMD among users of ERT was entirely due to subperiosteal expansion and not bone loss, whereas both bone loss and expansion occurred in past or nonusers. BMD increased 0.8%/year at the femoral shaft among ERT users but decreased 0.8%/year among nonusers. Section moduli increased at both the neck and shaft among ERT users but remained unchanged in past and nonusers. Current, but not past, use of estrogen therapy in elderly women seems to increase mechanical strength of the proximal femur by improving its geometric properties. These effects are not evident from changes in femoral neck BMD.

Aged↗
PubMed2001

Classification of osteoporosis based on bone mineral densities.

In this article we examine the role of bone mineral density (BMD) in the diagnosis of osteoporosis. Using information from 7671 women in the Study of Osteoporotic Fractures (SOF) with BMD measurements at the proximal femur, lumbar spine, forearm, and calcaneus, we examine three models with differing criteria for the diagnosis of osteoporosis. Model 1 is based on the World Health Organization (WHO) criteria using a T score of -2.5 relative to the manufacturers' young normative data aged 20-29 years, with modifications using information from the Third National Health and Nutrition Examination Survey (NHANES). Model 2 uses a T score of -1 relative to women aged 65 years at the baseline of the SOF population. Model 3 classifies women as osteoporotic if their estimated osteoporotic fracture risk (spine and/or hip) based on age and BMD is above 14.6%. We compare the agreement in osteoporosis classification according to the different BMD measurements for the three models. We also consider whether reporting additional BMD parameters at the femur or forearm improves risk assessment for osteoporotic fractures. We observe that using the WHO criteria with the manufacturers' normative data results in very inconsistent diagnoses. Only 25% of subjects are consistently diagnosed by all of the eight BMD variables. Such inconsistency is reduced by using a common elderly normative population as in model 2, in which case 50% of the subjects are consistently diagnosed as osteoporotic by all of the eight diagnostic methods. Risk-based diagnostic criteria as in model 3 improve consistency substantially to 68%. Combining the results of BMD assessments at more than one region of interest (ROI) from a single scan significantly increases prediction of hip and/or spine fracture risk and elevates the relative risk with increasing number of low BMD subregions. We conclude that standardization of normative data, perhaps referenced to an older population, may be necessary when applying T scores as diagnostic criteria in patient management. A risk-based osteoporosis classification does not depend on the manufacturers' reference data and may be more consistent and efficient for patient diagnosis.

Adult↗
PubMed2001

Structural adaptation to changing skeletal load in the progression toward hip fragility: the study of osteoporotic fractures.

Longitudinal, dual-energy X-ray absorptiometry (DXA) hip data from 4187 mostly white, elderly women from the Study of Osteoporotic Fractures were studied with a structural analysis program. Cross-sectional geometry and bone mineral density (BMD) were measured in narrow regions across the femoral neck and proximal shaft We hypothesized that altered skeletal load should stimulate adaptive increases or decreases in the section modulus (bending strength index) and that dimensional details would provide insight into hip fragility. Weight change in the approximately 35 years between scan time points was used as the primary indicator of altered skeletal load. "Static" weight was defined as within 5% of baseline weight, whereas "gain" and 'loss" were those who gained or lost >5%, respectively. In addition, we used a frailty index to better identify those subjects undergoing changing in skeletal loading. Subjects were classified as frail if unable to rise from a chair five times without using arm support. Subjects who were both frail and lost weight (reduced loading) were compared with those who were not frail and either maintained weight (unchanged loading) or gained weight (increased loading). Sixty percent of subjects (n = 2,559) with unchanged loads lost BMD at the neck but not at the shaft, while section moduli increased slightly at both regions. Subjects with increasing load (n = 580) lost neck BMD but gained shaft BMD; section moduli increased markedly at both locations. Those with declining skeletal loads (n = 105) showed the greatest loss of BMD at both neck and shaft; loss at the neck was caused by both increased loss of bone mass and greater subperiosteal expansion; loss in shaft BMD decline was only caused by greater loss of bone mass. This group also showed significant declines in section modulus at both sites. These results support the contention that mechanical homeostasis in the hip is evident in section moduli but not in bone mass or density. The adaptive response to declining skeletal loads, with greater rates of subperiosteal expansion and cortical thinning, may increase fragility beyond that expected from the reduction in section modulus or bone mass alone.

Absorptiometry, Photon↗
PubMed2001

A normative reference database study for Pronosco X-posure System.

Cortical width from radiographs has been used for more than 40 yr as a means of estimating bone strength. In the last 5-10 yr, increased availability of computers and the development of automated algorithms for image assessment have led to an increased interest in radiogrammetry. In this study, we examined a new radiogrammetry device, the Pronosco X-posure System, which estimates bone mineral density (BMD) from forearm/hand radiographs. We obtained hand and forearm radiographs and performed dual X-ray absorptiometry (DXA) at the wrist and hip on 832 women ages 20-79 at four clinical centers across the United States. We then used the X-posure System to estimate BMD (DXR-BMD). The goal of the study was to establish reference ranges for the method and to compare the measurement to DXA measurements of BMD at the wrist and hip. Using statistical models, we estimated that the peak value for DXR-BMD occurred at age 38 (mean = 0.598 g/cm2, standard deviation = 0.034 g/cm2). The correlation between DXR-BMD and DXA was 0.90 at the wrist and 0.61 at the hip. The relationship of DXR-BMD to reported history of fracture was of similar magnitude to that for DXA at the wrist and hip. The strong correlation of DXR-BMD from the X-posure System with DXA at the wrist from the Hologic machine suggests that the X-posure System may be an alternative to DXA at the wrist for the assessment of osteoporosis.

Absorptiometry, Photon↗
PubMed2000

Cognitive decline in women in relation to non-protein-bound oestradiol concentrations.

BACKGROUND: Previous studies have found no association between serum concentrations of total oestradiol and cognitive function, but these measurements may not reflect concentrations of hormone available to the brain. We tested the hypothesis that concentrations of non-protein-bound (free) and loosely bound (bioavailable) sex hormones are associated with cognitive function in older women. METHODS: We measured cognitive performance with a modified mini mental status examination (mMMSE) at baseline (1986-88) and 6 years later in 425 women (65 years or older). Concentrations of non-protein-bound and bioavailable oestradiol and total and non-protein-bound testosterone were measured by RIA in serum samples taken at baseline. FINDINGS: Initial cognitive scores did not differ by tertile of non-protein-bound oestradiol, bioavailable oestradiol, or testosterone. Cognitive impairment (a decrease of 3 points or more in mMMSE score) occurred in five (5%) of 94 women in the high tertile for non-protein-bound oestradiol and in 17 (16%) of 106 in the low tertile (odds ratio 0.3 [95% CI 0.1-0.8]). After adjustment for age, years of education, body-mass index, current oestrogen use, history of surgical menopause, and baseline mMMSE score, the odds ratio was 0.3 (0.1-0.9). The results were similar for bioavailable oestradiol (five [5%] vs 15 [15%]; adjusted odds ratio 0.3 [0.1-1.0]). There was no association between risk of cognitive impairment and serum testosterone. INTERPRETATION: Women with high serum concentrations of non-protein-bound and bioavailable oestradiol, but not testosterone, were less likely to develop cognitive impairment than women with low concentrations. This finding supports the hypothesis that higher concentrations of endogenous oestrogens prevent cognitive decline.

Aged↗
PubMed2000

Monitoring osteoporosis therapy with bone densitometry: misleading changes and regression to the mean. Fracture Intervention Trial Research Group.

CONTEXT: The principle of "regression to the mean" predicts that patients with unusual responses to treatment might represent outliers who are likely to have more typical responses if treatment is continued without change. OBJECTIVE: To test whether women who lose bone mineral density (BMD) during the first year of treatment for osteoporosis continue to lose BMD if the same treatment is continued beyond 1 year. DESIGN AND SETTING: Two randomized, double-blind, placebo-controlled trials in 11 US clinical research centers for the Fracture Intervention Trial and 180 centers in the United States and other countries for the Multiple Outcomes of Raloxifene Evaluation Trial. PARTICIPANTS AND INTERVENTIONS: Postmenopausal women with low BMD assigned to treatment with 5 mg/d of alendronate sodium in the Fracture intervention Trial who completed 2 years of BMD monitoring and adhered to study medication (n = 2634), and postmenopausal women with osteoporosis assigned to treatment with 60 or 120 mg/d of raloxifene hydrochloride in the Multiple Outcomes of Raloxifene Evaluation trial who similarly completed 2 years of monitoring while adhering to study medication (n = 3954). MAIN OUTCOME MEASURES: Baseline, 12-, and 24-month hip and spine BMD. RESULTS: Women with the greatest loss of BMD during the first year of treatment were the most likely to gain BMD during continued treatment. Specifically, among women taking alendronate whose hip BMD decreased by more than 4% during the first year, 83% (95% confidence interval [CI], 82%-84%)had increases in hip BMD during the second year, with an overall mean increase of 4.7%. In contrast, those who seemed to gain at least 8% during the first year lost an average of 1% (95% CI, 0.1%-1.9%) during the next year. Similar results were observed among women taking raloxifene for 2 years. CONCLUSIONS: Our data suggest that most women who lose BMD during the first year of treatment with alendronate or raloxifene will gain BMD if the same treatment is continued for a second year. These results illustrate the principle of regression to the mean and suggest that effective treatments for osteoporosis should not be changed because of loss of BMD during the first year of use.

Absorptiometry, Photon↗
PubMed2000

Low fractional calcium absorption increases the risk for hip fracture in women with low calcium intake. Study of Osteoporotic Fractures Research Group.

BACKGROUND: Decreased ability to absorb calcium with age limits adaptation to low calcium intake and is thought to lead to secondary hyperparathyroidism and increased risk for hip and other fractures. However, the associations between fractional calcium absorption, dietary calcium intake, and risk for fracture have never been studied. OBJECTIVE: To determine whether low fractional calcium absorption in women with low calcium intake increases the risk for subsequent hip and other nonspine fractures. DESIGN: Prospective cohort study. SETTING: Four clinical centers in Baltimore County, Maryland; Portland, Oregon; Minneapolis, Minnesota; and the Monongahela Valley, Pennsylvania. PARTICIPANTS: 5452 nonblack women 69 years of age or older participating in the fourth examination of the Study of Osteoporotic Fractures. MEASUREMENTS: Fractional calcium absorption was measured by using a 3-hour single isotope (45Ca) technique. Incident fractures were identified prospectively and were confirmed by radiographic report. RESULTS: During an average of 4.8 years, 729 women (13%) experienced at least one nonspine fracture; 153 of these women had hip fractures. After adjustment for age, women with lower fractional calcium absorption were at increased risk for hip fracture (relative risk per 1-SD [7.7%] decrease in fractional calcium absorption, 1.24 [95% CI, 1.05 to 1.48]). Women with low fractional calcium absorption and low calcium intake were at greatest risk for subsequent hip fracture; among women whose dietary calcium intake was less than 400 mg/d, those who had fractional calcium absorption at or below the median value of 32.3% had a 2.5-fold (CI, 1.29-fold to 4.69-fold) increase in risk for hip fracture compared with those who had greater absorption efficiency. Fractional calcium absorption was not related to risk for other nonspine fractures (relative risk per 1-SD [7.7%] decrease in fractional calcium absorption, 1.05 [CI, 0.96 to 1.14]). CONCLUSIONS: In elderly women, low fractional calcium absorption in the setting of low calcium intake increases the risk for hip fracture. Our findings support the hypothesis of type II osteoporosis, which postulates that decreased calcium absorption is an important risk factor for hip fracture in older persons.

Aged↗
PubMed2000

Is diabetes associated with cognitive impairment and cognitive decline among older women? Study of Osteoporotic Fractures Research Group.

BACKGROUND: The long-term effect of type 2 diabetes on cognitive function is uncertain. OBJECTIVE: To determine whether older women with diabetes have an increased risk of cognitive impairment and cognitive decline. DESIGN: Prospective cohort study. SETTING: Four research centers in the United States (Baltimore, Md; Portland, Ore; Minneapolis, Minn; and the Monongahela Valley, Pennsylvania). PARTICIPANTS: Community-dwelling white women 65 years and older (n = 9679). MEASUREMENTS: Physician-diagnosed diabetes and other aspects of health history were assessed by interview. Three tests of cognitive function, the Digit Symbol test, the Trails B test, and a modified version of the Mini-Mental State Examination (m-MMSE), were administered at baseline and 3 to 6 years later. Change in cognitive function was defined by the change in the score for each test. Major cognitive decline was defined as the worst 10th percentile change in the score for each test. RESULTS: Women with diabetes (n = 682 [7.0%]) had lower baseline scores than those without diabetes on all 3 tests of cognitive function (Digit Symbol and Trials B tests, P<.01; m-MMSE, P = .03) and experienced an accelerated cognitive decline as measured by the Digit Symbol test (P<.01) and m-MMSE (P = .03). Diabetes was also associated with increased odds of major cognitive decline as determined by scores on the Digit Symbol (odds ratio = 1.63; 95% confidence interval, 1.20-2.23) and Trails B (odds ratio, 1.74; 95% confidence interval, 1.27-2.39) tests when controlled for age, education, depression, stroke, visual impairment, heart disease, hypertension, physical activity, estrogen use, and smoking. Women who had diabetes for more than 15 years had a 57% to 114% greater risk of major cognitive decline than women without diabetes. CONCLUSION: Diabetes is associated with lower levels of cognitive function and greater cognitive decline among older women.

Aged↗
PubMed2000

Effect of alendronate on limited-activity days and bed-disability days caused by back pain in postmenopausal women with existing vertebral fractures. Fracture Intervention Trial Research Group.

BACKGROUND: Women with new vertebral fractures have an increased risk of back pain and functional limitation because of back pain. Alendronate sodium treatment reduces the risk of new vertebral fracture by 50% in postmenopausal women with osteoporosis. OBJECTIVE: To determine the effect of alendronate therapy on days affected by back pain in postmenopausal women with existing vertebral fractures. DESIGN: Three-year, placebo-controlled, randomized, double-blind study. SETTING: Fifteen university-based research clinics in the United States. PARTICIPANTS: A total of 2027 postmenopausal women aged 55 to 81 years with low femoral neck bone density and a preexisting vertebral fracture. INTERVENTION: Alendronate sodium (5 mg/d for 2 years and 10 mg/d for the third year) or placebo. MAIN OUTCOME MEASURES: Occurrence and severity of back pain, number of days with back pain, and number of days of bed rest or limited activity because of back pain during 3 years of follow-up. RESULTS: Irrespective of treatment assignment, women with new, clinically recognized vertebral fractures during follow-up had an increased risk of days of bed disability and days of limited activity because of back pain after the fracture. Women receiving alendronate reported an average of 3.2 fewer days of bed rest (P = .001) and 11.4 fewer days of limited activity (not including days of bed rest) because of back pain (P = .04) during follow-up than those receiving placebo. In the alendronate group, relative to the placebo group, there was a reduced risk of 1 or more bed-rest days (relative risk, 0.68; 95% confidence interval, 0.53-0.87), of 7 or more bed-rest days (0.44; 0.30-0.64), and of 7 or more limited-activity days (0.87; 0.76-0.99). There were no statistically significant differences between treatment groups in the frequency of days of back pain or increases in back-related disability between baseline and study end. CONCLUSION: In postmenopausal women with preexisting vertebral fracture, alendronate therapy for 3 years reduced the number of days of bed disability and days of limited activity caused by back pain.

Activities of Daily Living↗
PubMed2000

Femoral neck and intertrochanteric fractures have different risk factors: a prospective study.

The aim of this study was to determine whether both types of hip fracture, femoral neck and intertrochanteric, have similar risk factors. A prospective cohort study was carried out on community-dwelling elderly women in four areas of the United States: Baltimore, MD; Pittsburgh, PA; Minneapolis, MN and Portland, OR. The participants were 9704 Caucasian women, 65 years and older, of whom 279 had fractured their femoral neck and 222 had fractured their trochanteric region of the proximal femur. The predictors used were the bone mass of the calcaneus and proximal femur, anthropometry, history of fracture (family and personal), medication use, functional status, physical activity and visual function. The main outcome measures were femoral neck and intertrochanteric fractures occurring during an average of 8 years of follow-up. In multivariate proportional hazards models, several risk factors increased the risk of both types of hip fracture; including femoral neck bone density and increased functional difficulty. In hazard regression models that directly compared risk factors for the two types of hip fracture, calcaneal bone mineral density (BMD) predicted femoral neck fractures more strongly than intertrochanteric fractures (OR = 1.16; 95% CI = 1.02-1.31). Steroid use and impaired functional status also predicted femoral neck fractures instead of intertrochanteric fractures. Poor health status (OR = 0.74; 95% CI = 0.55-1.00) predicted intertrochanteric fractures more strongly than femoral neck fractures. We conclude that femoral neck fractures are largely predicted by BMD and poor functional ability while aging and poor health status predispose to intertrochanteric fractures.

Age Factors↗