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S R Cummings

Publications and source records attributed to S R Cummings.

At least 73 records · Page 4Linked to original sources
PubMed1999

Defining incident vertebral deformity: a prospective comparison of several approaches. The Study of Osteoporotic Fractures Research Group.

Vertebral deformities are common and important outcomes in clinical trials and epidemiologic studies of osteoporosis. While several different methods for defining new deformities have been proposed, it is not clear which is best. We used data from serial spine radiographs obtained an average of 3.7 years apart in 7238 women age >/=65 years from the Study of Osteoporotic Fractures to compare several approaches to defining new deformities by morphometry including a fixed percentage reduction in any vertebral height (FIXED%), a change in a summary spinal deformity index, a change in a vertebra from no prevalent deformity at baseline to a deformity at follow-up, as well as several variations of these methods. We compared results of each definition with several clinical correlates, including height loss, back pain, age, baseline bone mineral density, and the presence of a baseline deformity. We also estimated the sample size required for a clinical trial using various cut points. At a given level of incidence, all methods had similar relationships with each of the correlates. Given that similarity, the FIXED% method was simplest and needed no reference data. Using the FIXED% method, a 20-25% vertebral height reduction criterion for deformity maximized the power for a clinical trial. We conclude that all of the morphometric approaches to defining incident deformities have similar relationships to clinical correlates of vertebral deformity, but that use of a fixed percentage reduction in vertebral height is the simplest and most practical. For the FIXED% method, a 20-25% reduction in vertebral height minimizes the sample size required for clinical trials and epidemiologic studies.

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PubMed1999

Vitamin D receptor gene polymorphisms and the risk of fractures in older women. For the Study of Osteoporotic Fractures Research Group.

The association between vitamin D receptor gene polypmorphisms and bone mineral density is controversial. The relationship between vitamin D receptor genotype and risk of fracture is uncertain. To determine whether vitamin D receptor polymorphisms were associated with the risk of hip, vertebral, and other (nonhip, nonvertebral) fractures in elderly women, we conducted a case-cohort study within a prospective study of 9704 community-dwelling women aged 65 years and older. Vitamin D receptor allele and genotype frequencies in women who experienced first incident hip (n = 181), vertebral (n = 127), and other (n = 223) fractures were compared with those of control women selected randomly from the cohort. Average length of follow-up was 6.5, 3.7, and 5.4 years for women in hip, vertebral, and other fracture analyses, respectively. Vitamin D receptor polymorphisms were determined by polymerase chain reaction amplification of genomic DNA using TaqI and ApaI restriction site endonuclease digestion. All nonvertebral fractures were confirmed by X-ray reports; hip fractures were validated by review of X-ray films. Vertebral fractures were defined by morphometry using lateral spine radiography at baseline and an average of 3.7 years later. Allele or genotype frequencies did not differ between fracture cases and their respective controls. Vitamin D receptor genotype (defined by TaqI, ApaI, or the combination of TaqI and ApaI) was not significantly associated with the risk of hip, vertebral, or other fractures. For example, compared with the referent group of women with TT genotype, those with Tt and tt genotypes had similar age- and weight-adjusted risks of fracture at the hip (hazard ratios 0.9, 95% confidence interval [CI] 0.6-1.3, and 0.8, 95% CI 0.5-1.2, respectively), spine (odds ratios 1.1, 95% CI 0.7-1.8, and 0.7, 95% CI 0.4-1.3, respectively), or other skeletal site (hazard ratios 1.0, 95% CI 0. 7-1.4, and 1.0, 95% CI 0.7-1.5, respectively). These findings were not altered in additional analyses including those adjusted for and stratified by age, ethnic ancestry, calcaneal bone density, dietary calcium intake, use of calcium supplements, use of vitamin D supplements, and oral estrogen use. We conclude that Vitamin D receptor polymorphisms defined by TaqI and ApaI are not associated with the risk of fracture in older women. Our results suggest that determination of these vitamin D receptor polymorphisms is not a clinically useful test for the prediction of fracture risk in elderly women.

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PubMed1999

Prevalent vertebral deformities predict hip fractures and new vertebral deformities but not wrist fractures. Study of Osteoporotic Fractures Research Group.

Although vertebral deformities are known to predict future vertebral deformities, little is known about their ability to predict other osteoporotic fractures. We examined the association between prevalent vertebral deformities and incident osteoporotic fractures in the Study of Osteoporotic Fractures, a prospective study of 9704 women aged 65 years and older. Prevalent vertebral deformities were determined morphometrically from spinal radiographs at baseline and incident deformities from repeat spinal radiographs after a mean of 3.7 years. Appendicular fractures were collected by postcard every 4 months for a mean of 8.3 years. During follow-up, 389 women with new vertebral deformities, 464 with hip fractures, and 574 with wrist fractures were identified. Prevalent vertebral deformities were associated with a 5-fold increased risk (relative risk 5.4, 95% confidence interval [CI] 4.4, 6.6) of sustaining a further vertebral deformity; the risk increased dramatically with both the number and severity of the prevalent deformities. Similarly, the risks of hip and any nonvertebral fractures were increased with baseline prevalent deformity, with relative risks of 2.8 (95% CI 2.3, 3.4) and 1.9 (95% CI 1.7, 2.1), respectively. Risk increased with number and severity of deformities. These associations remained significant after adjustment for age and calcaneal bone mineral density (BMD). Although there was a small increased risk of wrist fracture, this was not significant after adjusting for age and BMD. In conclusion, the presence of prevalent morphometrically defined vertebral deformities predicts future vertebral and nonvertebral fractures, including hip but not wrist fractures. Spinal radiographs identifying prevalent vertebral deformities may be a useful additional measurement to classify further a woman's risk of future fracture.

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PubMed1999

Apolipoprotein E polymorphism: A new genetic marker of hip fracture risk--The Study of Osteoporotic Fractures.

Hip fractures are common and devastating events. The apolipoprotein E*4 (APOE) allele, associated with Alzheimer's disease, has also been associated with osteoporosis in hemodialysis patients. We prospectively studied 1750 women, age >/=65 years, who underwent measurements of hip and calcaneal bone mineral density (BMD), were typed for APOE and followed for approximately 7.0 years for the occurrence of fractures and falls. Women with at least one APOE*4 allele had an increased risk of hip fracture, relative hazard (RH) (95% confidence interval) = 1.90 (1.05-3.41) and wrist fracture, RH = 1.67 (1.01-2.77) compared with women without APOE*4, even after adjusting for age, cognitive function, falling, and BMD. The effect of APOE*4 on hip fracture was greatest among women with additional (>/=3) other risk factors. Women with an APOE*4 allele were also likely to report a maternal history of fracture. The average number of falls per year did not differ by APOE*4: 0.46 for APOE*4 women and 0.41 for women without an APOE*4 allele. Women with an APOE*4 allele experienced greater weight loss which contributed to faster rates of bone loss. We conclude that women with the APOE*4 polymorphism are at substantially increased risk of hip and wrist fracture that is not explained by bone density, impaired cognitive function, or falling. Possible alternate explanations include an effect of APOE on vitamin K, bone turnover, or weight loss. The APOE polymorphism may be a candidate gene for hip fractures among community dwelling nondemented women.

Accidental Falls↗
PubMed1999

Biochemical markers of bone turnover and prediction of hip bone loss in older women: the study of osteoporotic fractures.

To examine the ability of commercially available biochemical markers of bone formation and resorption to predict hip bone loss, we prospectively obtained serum and timed 2-h urine specimens from 295 women age 67 years or older who were not receiving estrogen replacement therapy. Serum was assayed for two markers of bone formation: osteocalcin (OC) and bone-specific alkaline phosphatase (BALP). Urine specimens were assayed for four markers of bone resorption: N-telopeptides (NTX), free pyridinolines (Pyr), free deoxypyridinoline (Dpyr), and C-telopeptides (CTX). Measurements of hip bone mineral density were made at the time the samples were collected and then repeated an average of 3.8 years later. Higher levels of all four resorption markers were, on average, significantly associated with faster rates of bone loss at the total hip, but not at the femoral neck. Women with OC levels above the median had a significantly faster rate of bone loss than women with levels below the median, but there was no significant association between levels of BALP and hip bone loss. The sensitivity and specificity of higher marker levels for predicting rapid hip bone loss was limited, and there was considerable overlap in bone loss rates between women with high and low marker levels. We conclude that higher levels of urine NTX, CTX, Pyr, Dpyr, and serum OC are associated with faster bone loss at the hip in this population of elderly women not receiving estrogen replacement therapy, but these biochemical markers have limited value for predicting rapid hip bone loss in individuals.

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PubMed1998

Endogenous hormones and the risk of hip and vertebral fractures among older women. Study of Osteoporotic Fractures Research Group.

BACKGROUND AND METHODS: In postmenopausal women, the serum concentrations of endogenous sex hormones and vitamin D might influence the risk of hip and vertebral fractures. In a study of a cohort of women 65 years of age or older, we compared the serum hormone concentrations at base line in 133 women who subsequently had hip fractures and 138 women who subsequently had vertebral fractures with those in randomly selected control women from the same cohort. Women who were taking estrogen were excluded. The results were adjusted for age and weight. RESULTS: The women with undetectable serum estradiol concentrations (<5 pg per milliliter [18 pmol per liter]) had a relative risk of 2.5 for subsequent hip fracture (95 percent confidence interval, 1.4 to 4.6) and subsequent vertebral fracture (95 percent confidence interval, 1.4 to 4.2), as compared with the women with detectable serum estradiol concentrations. Serum concentrations of sex hormone-binding globulin that were 1.0 microg per deciliter (34.7 nmol per liter) or higher were associated with a relative risk of 2.0 for hip fracture (95 percent confidence interval, 1.1 to 3.9) and 2.3 for vertebral fracture (95 percent confidence interval, 1.2 to 4.4). Women with both undetectable serum estradiol concentrations and serum sex hormone-binding globulin concentrations of 1 microg per deciliter or more had a relative risk of 6.9 for hip fracture (95 percent confidence interval, 1.5 to 32.0) and 7.9 for vertebral fracture (95 percent confidence interval, 2.2 to 28.0). For those with low serum 1,25-dihydroxyvitamin D concentrations (< or =23 pg per milliliter [55 pmol per liter]), the risk of hip fracture increased by a factor of 2.1 (95 percent confidence interval, 1.2 to 3.5). CONCLUSIONS: Postmenopausal women with undetectable serum estradiol concentrations and high serum concentrations of sex hormone-binding globulin have an increased risk of hip and vertebral fracture.

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PubMed1998

Bone mineral density and risk of breast cancer: differences by family history of breast cancer. Study of Osteoporotic Fractures Research Group.

Recent studies have suggested that bone mineral density (BMD) is related to risk of breast cancer in elderly women. This study investigated whether the level of breast cancer risk associated with BMD in women with a positive family history of breast cancer is different from that in women without a family history of breast cancer. Radial and calcaneus BMD were measured at baseline (1986-1988) in 7,250 elderly white women enrolled in the Study of Osteoporotic Fractures, and initial breast cancer status was ascertained at year 1 of follow-up. After a mean of 3.2 years of additional follow-up, 104 incident breast cancer cases, 20 of which appeared in women with a family history of breast cancer, were identified and confirmed by medical record review. Modification of the BMD effect by family history status was assessed by inclusion of interaction terms in proportional hazards regression models. Among women without a family history of breast cancer, those with a proximal radius BMD in the highest tertile were at a 1.48-fold increased risk compared with women in the lowest tertile; among women with a positive family history of breast cancer, those with highest tertile BMD were at a 3.41-fold increased risk compared with women in the lowest tertile. These results suggest that the association between BMD and breast cancer may be different in subgroups of women defined by family history.

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PubMed1998

The association of radiographically detected vertebral fractures with back pain and function: a prospective study.

BACKGROUND: Vertebral fractures are a hallmark of postmenopausal osteoporosis and an important end point in trials of osteoporosis treatment, but the clinical significance of these fractures remains uncertain. OBJECTIVE: To determine the association of new vertebral fractures with back pain and back-related functional limitation in older women. DESIGN: Prospective observational study. SETTING: Multicenter Study of Osteoporotic Fractures. PARTICIPANTS: 7223 white women aged 65 years and older. MEASUREMENTS: Lateral spine radiographs were obtained at baseline and at a follow-up examination an average of 3.7 years later. Prevalent and incident radiographic vertebral fractures were assessed by quantitative morphometry. Frequency and severity of back pain, disability in doing six activities involving the back, and days of bed rest and days of limited activity due to back pain were assessed annually by questionnaire during follow-up. RESULTS: Among women without a vertebral fracture at baseline, those with at least one incident vertebral fracture were more likely to have increased back pain (odds ratio [OR], 2.4 [95% CI, 1.7 to 3.3]) and back disability (OR, 2.6 [CI, 1.9 to 3.7]) and at least 1 day of bed rest due to back pain (OR, 6.7 [CI, 4.4 to 10.2]) and 7 days of limited activity due to back pain per year (OR, 3.8 [CI, 2.7 to 5.0]). Among women with a fracture at baseline, those with an incident vertebral fracture also had a greater risk for increased back pain (OR, 2.0 [CI, 1.4 to 2.8]) and back disability (OR, 2.2 [CI, 1.5 to 3.1]) and at least 1 day of bed rest (OR, 7.9 [CI, 4.9 to 12.9]) and 7 days of limited activity per year (OR, 3.5 [CI, 2.4 to 5.0]). Women with incident fracture had about 10 additional limited-activity days and 1 to 2 days of bed rest per year. New vertebral fractures that did not come to medical attention were associated with increased back pain and functional limitation. CONCLUSION: New vertebral fractures, even those not recognized clinically, are associated with substantial increases in back pain and functional limitation due to back pain in older white women. Prevention of new vertebral fractures should reduce the burden of back pain and functional limitation in women with vertebral osteoporosis.

Activities of Daily Living↗
PubMed1998

Warfarin use and risk for osteoporosis in elderly women. Study of Osteoporotic Fractures Research Group.

BACKGROUND: Vitamin K deficiency may be associated with osteoporosis. OBJECTIVE: To assess the effects of warfarin on bone. DESIGN: Prospective observational study. SETTING: Four centers in the United States. PARTICIPANTS: 6201 elderly, postmenopausal women. MEASUREMENTS: Self-reported warfarin use, bone mineral density at the hip and the heel, hip bone loss over 2 years, and fractures during 3.5 years of follow-up. Analyses were adjusted for baseline differences, age, weight, and estrogen use. RESULTS: Compared with warfarin nonusers (n = 6052), warfarin users (n = 149) more frequently had poor health, involuntary weight loss, nonthiazide diuretic use, and frailty but had similar bone mineral density at the hip (difference, 1.6% [95% CI, -0.7% to 4.1%]) and heel (difference, 2.1% [CI, -1.6% to 5.6%]). Users and nonusers had similar rates of bone loss (1.1% and 0.8%; P = 0.18) and fractures (relative hazard, 1.0 [CI, 0.60 to 1.71). CONCLUSION: In this population, warfarin use did not decrease bone mineral density or increase fracture rates.

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PubMed1998

Family history and risk of osteoporotic fracture. Study of Osteoporotic Fractures Research Group.

The importance of family history of fractures as a risk factor for fractures is unclear. The aim of this study was to test the hypothesis that family history of fracture increased a woman's risk of hip, wrist and other osteoporotic fracture and determine whether the influence of family history is independent of low bone density. We tested this hypothesis in a prospective study of 9704 Caucasian women, age 65 years or older, by assessing family history and bone density of the radius and calcaneus at baseline; 7963 women had femoral bone density measurements two years later. Fractures occurring during an average of 7.1 years of follow-up since baseline and 5.2 years since the second examination were confirmed by radiographic report. After adjusting for age, risk of hip fracture was increased in those with a maternal (1.48; 95% CI = 1.03-2.11); sister's (1.83; 1.20-2.80) or brother's history of hip fracture (2.26; 1.16-4.42). Risk of wrist fracture was increased by maternal (1.52; 1.10-2.11) and paternal (2.41; 1.14-5.07) history of wrist fracture. Adjustment for bone density did not consistently and substantially affect the strength of the associations. Family history of hip fracture was not associated with an increased risk of wrist fracture and family history of wrist fracture did not increase the risk of hip fracture. We conclude that family history is an important risk factor for fracture that may act, at least in part, through means besides bone density. Furthermore, the effect of family history is not a general but site-specific predisposition to fracture.

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PubMed1998

Serum fructosamine level and the risk of hip fracture in elderly women: a case-cohort study within the study of osteoporotic fractures.

PURPOSE: While a high serum fructosamine level may be an indicator of undiagnosed diabetes, a low level may be indicative of poor nutrition or frailty. As malnutrition is a risk factor for osteoporosis, low serum fructosamine levels may be associated with an increased risk of osteoporotic fracture. We examined the association between serum fructosamine levels and the risk of subsequent hip and vertebral fracture. SUBJECTS AND METHODS: We performed a case-cohort study within the Study of Osteoporotic Fractures. Subjects were elderly, ambulatory, community-dwelling, Caucasian, women. Fructosamine levels were measured in baseline serum. Incident vertebral fractures were identified by comparing baseline spinal radiographs to those obtained an average of 3.5 years later. Hip fractures were confirmed by radiograph. We randomly selected 101 women who suffered a hip fracture, 100 women who developed a vertebral fracture, and 276 controls. We compared fructosamine levels in women with subsequent osteoporotic fractures to controls. All analyses were adjusted for age, weight, and use of estrogens. RESULTS: Women with fructosamine levels in the lowest decile (< or = 223 micromol/L) had a three-fold increase in the risk of hip fracture (95% confidence interval 1.4-6.4), compared with all other women. Adjustment for markers of frailty, including smoking, functional status, and serum albumin levels, reduced the strength of this association. No clear association was observed between serum fructosamine level and the risk of vertebral fracture. CONCLUSION: Low serum fructosamine levels, which likely reflect frailty or malnutrition, may be a useful clinical tool to identify women at risk for hip fracture.

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PubMed1998

Associations between low levels of serum estradiol, bone density, and fractures among elderly women: the study of osteoporotic fractures.

To evaluate the skeletal effects of endogenous serum estradiol, we measured bone mineral density (BMD) at the calcaneus and radius (single photon absorptiometry) and at the hip and spine (dual x-ray absorptiometry) in 274 women aged 65 yr or more who participated in the Study of Osteoporotic Fractures. Lateral radiographs of the thoracic and lumbar spine were also taken, and serum was assayed for estradiol. Those who had estradiol levels from 10-25 pg/mL had 4.9%, 9.6%, 7.3%, and 6.8% greater BMD at total hip, calcaneus, proximal radius, and spine than those with levels below 5 pg/mL. After multiple adjustments, BMD differences remained statistically significant and corresponded to about 0.4 SD. Vertebral deformities were less prevalent among women whose estradiol level exceeded 5 pg/mL; the multiple adjusted odds ratio was 0.4 (95% confidence interval, 0.2-0.8). We conclude that physiologically low estradiol has a salutary effect on the skeleton in elderly women, possibly by reducing skeletal remodeling.

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PubMed1998

Intermittent use of nitrates increases bone mineral density: the study of osteoporotic fractures.

Nitric oxide slows bone remodeling and bone loss in animals. Because nitroglycerin and other nitrates increase nitric oxide levels, we hypothesized that nitrate use may be associated with greater bone mineral density (BMD) and decreased risk of fracture in humans. Further, intermittent nitrate use may be associated with greater benefits than daily nitrate use, which results in tachyphylaxis. We tested this hypothesis using data from the Study of Osteoporotic Fractures. We prospectively studied 6201 elderly women of whom 317 took nitrates on a daily basis and 74 used them intermittently. We measured BMD at the hip and the heel and adjusted all comparisons for multiple potential confounders. We found that women taking daily nitrates had slightly greater hip BMD (difference, 13%; 95% confidence interval [CI], 0.14-4.1%) but the same heel BMD (difference, 0%; 95% CI -2.6-2.6%) as nonusers. By contrast, women using nitrates intermittently had substantially greater hip (difference, 2.6%; 95% CI, 0.4-6.8%) and heel BMD (difference, 53%; 95% CI, 2.6-11%) than nonusers. This study suggests that the intermittent administration of nitrates may enhance BMD.

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PubMed1998

Hormonal predictors of bone loss in elderly women: a prospective study. The Study of Osteoporotic Fractures Research Group.

To test the hypotheses that baseline concentrations of sex steroids, sex hormone binding globulin (SHBG), and calciotropic hormones predict rates of bone loss in elderly women, sera were stored at -190 degrees, and calcaneal bone mineral density (BMD) was measured in 9704 community-dwelling white women aged 65 and over (1986-1988). Hip BMD was measured 2 years later (1900). Repeat measurements of a calcaneal and hip BMD were obtained in 1993-1994, after 5.7 and 3.5 years of follow-up, respectively. In 1994, sera were assayed for circulating hormone levels in random subcohorts of 231 and 218 women who did not report current use of hormone replacement therapy at baseline. Lower levels of endogenous estrogens and higher SHBG concentrations were associated with more rapid subsequent bone loss from both the calcaneus and hip. After adjusting for age and weight, women with high SHBG levels (highest quartile < or = 2.3 micrograms/dI) experienced an average of 2.2% (95% confidence interval = 1.6%, 2.9%) calcaneal bone loss per year compared with 1.2% (0.7%, 1.2%) among women with low SHBG concentrations (lowest quartile < 1.1 micrograms/dI; p < 0.01). This association was independent of concentrations of other sex hormones. Women with estradiol levels > or = 10 pg/ml averaged only 0.1% (-0.7%, 0.5%) annual hip bone loss while women with levels below 5 pg/ml averaged 0.8% (0.3, 1.2) hip bone loss per year. Lower 25-hydroxyvitamin D levels were associated with increased hip but not calcaneal bone loss. Levels of parathyroid hormone, 1,25-dihydroxyvitamin D, and Calcium were not significantly associated with bone loss from the calcaneus or hip.

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PubMed1998

Prevention of hip fractures in older women: a population-based perspective.

We now have several means of reducing the risk of fractures. Expert medical treatment of individual patients by modifying risk factors and appropriately prescribing effective supplements and drugs substantially reduces the patient's fracture risk but is not commonly provided to patients. At the moment, women at the greatest risk of fracture appear to be only slightly more likely to receive treatment that reduces fracture risk than women who are at low risk. This strategy seems likely to miss the vast majority of women who account for most of the hip fractures. On the other hand, the impact of strategies to reduce rates of hip fractures in populations critically depends on the reach of the program and adherence with treatment. It is not yet clear that effective population based programs will be affordable or cost-effective. To have a substantial impact on the rates of fractures in populations, we will need to be as energetic and clever in developing these strategies during the next decade as we have been in developing screening devices and new pharmaceuticals during the past one.

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PubMed1997

Calcium intake and fracture risk: results from the study of osteoporotic fractures.

The relation between dietary calcium, calcium, and vitamin D supplements and the risk of fractures of the hip (n = 332), ankle (n = 210), proximal humerus (n = 241), wrist (n = 467), and vertebrae (n = 389) was investigated in a cohort study involving 9,704 US white women aged 65 years or older. Baseline assessments took place in 1986-1988 in four US metropolitan areas. Dietary calcium intake was assessed at baseline with a validated food frequency questionnaire. Data on new nonvertebral fractures were collected every 4 months during a mean of 6.6 years of follow-up; identification of new vertebral fractures was based on comparison of baseline and follow-up radiographs of the spine done a mean of 3.7 years apart. Results were adjusted for numerous potential confounders, including weight, physical activity, estrogen use, protein intake, and history of falls, osteoporosis, and fractures. There were no important associations between dietary calcium intake and the risk of any of the fractures studied. Current use of calcium supplements was associated with increased risk of hip (relative risk = 1.5, 95% confidence interval 1.1-2.0) and vertebral (relative risk = 1.4, 95% confidence interval 1.1-1.9) fractures; current use of Tums antacid tablets was associated with increased risk of fractures of the proximal humerus (relative risk = 1.7, 95% confidence interval 1.3-2.4). There was no evidence of a protective effect of vitamin D supplements. Although a true adverse effect of calcium supplements on fracture risk cannot be ruled out, it is more likely that our findings are due to inadequately controlled confounding by indications for use of supplements. In conclusion, this study did not find a substantial beneficial effect of calcium on fracture risk.

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