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Biomedical subjects

Jane A Cauley

Publications and source records attributed to Jane A Cauley.

At least 19 recordsLinked to original sources

Effects of continuing or stopping alendronate after 5 years of treatment: the Fracture Intervention Trial Long-term Extension (FLEX): a randomized trial.

CONTEXT: The optimal duration of treatment of women with postmenopausal osteoporosis is uncertain. OBJECTIVE: To compare the effects of discontinuing alendronate treatment after 5 years vs continuing for 10 years. DESIGN AND SETTING: Randomized, double-blind trial conducted at 10 US clinical centers that participated in the Fracture Intervention Trial (FIT). PARTICIPANTS: One thousand ninety-nine postmenopausal women who had been randomized to alendronate in FIT, with a mean of 5 years of prior alendronate treatment. INTERVENTION: Randomization to alendronate, 5 mg/d (n = 329) or 10 mg/d (n = 333), or placebo (n = 437) for 5 years (1998-2003). MAIN OUTCOME MEASURES: The primary outcome measure was total hip bone mineral density (BMD); secondary measures were BMD at other sites and biochemical markers of bone remodeling. An exploratory outcome measure was fracture incidence. RESULTS: Compared with continuing alendronate, switching to placebo for 5 years resulted in declines in BMD at the total hip (-2.4%; 95% confidence interval [CI], -2.9% to -1.8%; P<.001) and spine (-3.7%; 95% CI, -4.5% to -3.0%; P<.001), but mean levels remained at or above pretreatment levels 10 years earlier. Similarly, those discontinuing alendronate had increased serum markers of bone turnover compared with continuing alendronate: 55.6% (P<.001) for C-telopeptide of type 1 collagen, 59.5% (P < .001) for serum n = propeptide of type 1 collagen, and 28.1% (P<.001) for bone-specific alkaline phosphatase, but after 5 years without therapy, bone marker levels remained somewhat below pretreatment levels 10 years earlier. After 5 years, the cumulative risk of nonvertebral fractures (RR, 1.00; 95% CI, 0.76-1.32) was not significantly different between those continuing (19%) and discontinuing (18.9%) alendronate. Among those who continued, there was a significantly lower risk of clinically recognized vertebral fractures (5.3% for placebo and 2.4% for alendronate; RR, 0.45; 95% CI, 0.24-0.85) but no significant reduction in morphometric vertebral fractures (11.3% for placebo and 9.8% for alendronate; RR, 0.86; 95% CI, 0.60-1.22). A small sample of 18 transilial bone biopsies did not show any qualitative abnormalities, with bone turnover (double labeling) seen in all specimens. CONCLUSIONS: Women who discontinued alendronate after 5 years showed a moderate decline in BMD and a gradual rise in biochemical markers but no higher fracture risk other than for clinical vertebral fractures compared with those who continued alendronate. These results suggest that for many women, discontinuation of alendronate for up to 5 years does not appear to significantly increase fracture risk. However, women at very high risk of clinical vertebral fractures may benefit by continuing beyond 5 years. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT 00398931.

Aged↗

Comparative effects of raloxifene and alendronate on fracture outcomes in postmenopausal women with low bone mass.

UNLABELLED: The double-blind, randomized raloxifene alendronate comparison trial was the first study designed to compare two osteoporosis therapies head-to-head for fracture risk reduction. The original protocol planned to treat 3000 postmenopausal women with alendronate 10 mg/day (ALN) or raloxifene 60 mg/day (RLX) for 5 years, and to recruit women (50-80 years old) with a femoral neck bone mineral density (BMD) T-score between -2.5 and -4.0, inclusive, no prevalent vertebral fractures, and no prior bone-active agent use. The trial was stopped early, due to difficulty in finding treatment-naïve women to meet enrollment goals within the planned timeline, resulting in insufficient power to show non-inferiority between therapies in the primary endpoint (number of women with >or=1 new osteoporotic vertebral or nonvertebral fracture). Except for vertebral fractures, fracture analyses were based upon 1412 of the 1423 women randomized (mean age of 66 years). After 312+/-254 days (mean+/-SD), 22 women in the ALN group and 20 in the RLX group had new vertebral or nonvertebral fractures. Four women in the ALN group and none in the RLX group had moderate/severe vertebral fractures, a pre-specified endpoint (P=0.04). Lumbar spine, femoral neck, and total hip BMD were increased from baseline at 2 years in each group (P<0.001), with greater increases in the ALN group (each P<0.05). Similar numbers of women in each group had >or=1 adverse event and discontinued due to an adverse event. The only adverse events with an incidence that differed between groups were colonoscopy, diarrhea, and nausea; each was more common with ALN treatment (each P<0.05). One woman in each group had a venous thromboembolic event. One case of breast cancer occurred in each group. In summary, as this trial was terminated early, there was insufficient power to compare the fracture risks between alendronate and raloxifene. Safety profiles were as expected from clinical trial and post-marketing reports. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT00035971.

Aged↗

Patterns and correlates of muscle strength loss in older women.

BACKGROUND: The aging process is associated with progressive declines in muscle strength, resulting in functional disability and reduced quality of life. OBJECTIVE: The purpose of this epidemiological study was to examine the age-related loss of grip strength both cross-sectionally and longitudinally and the risk factors associated with the decline in muscle strength in a large population of community-living older women (aged 65-91 years). METHODS: Clinical visits, including physical examinations and lifestyle assessment, were conducted at baseline and biennially afterwards for a total of 10 years of follow-up. The upper-body muscle strength was measured by grip strength using a hand-held dynamometer. RESULTS: The muscle strength decreased cross-sectionally (n = 9,372) as well as longitudinally (n = 5,214), as age increased, and the decline in muscle strength measured during follow-up was greater than that measured cross-sectionally at baseline. The average loss of grip strength during 10 years of follow-up was 5.1 kg, equivalent to a rate of 2.4% decline per year, with the greatest loss seen in the oldest age group (80 years or older). Cross-sectional analysis revealed that the correlates of lower muscle strength included older age, greater weight, greater height loss since age 25 years, lower protein intake, difficulties in functional tasks, and lower physical activity. In longitudinal analysis, older age, baseline strength, weight and height loss during follow-up, difficulties in functional tasks, and lower physical activity were found to be significantly and independently associated with greater loss in grip strength during follow-up. CONCLUSIONS: Cross-sectional and longitudinal analyses of age-related loss of muscle strength yielded different rates of decline. In addition to older age and difficulties in functional tasks, a number of modifiable factors, including weight and physical activity, are associated with increased decline in muscle strength among older women.

Age Factors↗

Risk factors for breast cancer in older women: the relative contribution of bone mineral density and other established risk factors.

AIM: To determine the contribution of bone mineral density (BMD) to breast cancer risk relative to other established breast cancer risk factors in postmenopausal women with osteoporosis. METHODS: Data for this analysis comprised those collected from women randomized to placebo in the MORE and CORE trials (N = 2,576). Risk factors measured at baseline included age, family history of breast cancer, estradiol level, body mass index, prior hormone therapy, BMD and vertebral fracture status. Cox proportional hazards regression models were used to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: Over a total of 13,698 woman-years of follow-up, 65 incident breast cancers occurred. In univariate analyses, older age and family history of breast cancer were the strongest predictors of breast cancer risk, associated with a 2.4- and 2.6-fold increase in breast cancer incidence. A higher estradiol level was associated with a 1.9-fold increase in breast cancer incidence. The association between femoral neck BMD and breast cancer incidence was only significant after adjustment for age (P = 0.03). The final multivariable model included age, family history, estradiol, BMD, and the BMD-estradiol interaction since the effect of BMD on breast cancer varied by estradiol level (interaction P-value, 0.04); in those with a lower estradiol level, a higher BMD was associated with a 2.6-fold increased in breast cancer. CONCLUSION: Overall, BMD is a relatively weak predictor of breast cancer risk in these postmenopausal women with osteoporosis, after taking into consideration age, family history and endogenous estradiol level.

Aged↗

Effect of raloxifene on the incidence of invasive breast cancer in postmenopausal women with osteoporosis categorized by breast cancer risk.

PURPOSE: To assess the effect of raloxifene, indicated for osteoporosis treatment and prevention, on invasive breast cancer in subgroups of postmenopausal women defined by risk factors for breast cancer. EXPERIMENTAL DESIGN: Data from the 4-year Multiple Outcomes of Raloxifene Evaluation (MORE) trial (N=7,705) and a follow-up study, the 4-year Continuing Outcomes Relevant to Evista (CORE) trial (N=4,011), were analyzed. Prespecified subgroups were defined by age (>or=65 versus<65 years), age at menopause (>or=49 versus<49 years), body mass index (>or=25 versus<25 kg/m2), family history of breast cancer (yes/no), serum estradiol level (5-10 versus<5, >10 versus<5 pmol/L), prior estrogen therapy (yes/no), and bone mass at MORE baseline, and 5-year predicted risk, assessed using the modified Gail model (>or=1.67 versus<1.67%), at CORE baseline. Time-to-first invasive breast cancer was analyzed using Cox proportional hazards models. RESULTS: In the placebo group, older age, higher estradiol level, and a family history of breast cancer were associated with an increased breast cancer risk (P<0.05). Raloxifene therapy was associated with a reduced breast cancer risk in both women at lower and those at higher breast cancer risk. Hazard ratio point estimates were 0.11 to 0.67, corresponding to a 33% to 89% reduction in breast cancer risk with raloxifene versus placebo. The therapy by family history interaction was significant (P=0.04). CONCLUSIONS: Raloxifene therapy was associated with a reduced risk of invasive breast cancer in postmenopausal women irrespective of the presence/absence of risk factors; its effect was greater in women with a family history of breast cancer.

Aged↗

Comparison of methods to measure low serum estradiol levels in postmenopausal women.

CONTEXT: Accurate measurement of low serum estradiol (E(2) < 30 pg/ml or < 110 pmol/liter) is needed to study relationships between endogenous E(2) and risks of diseases in older women. OBJECTIVE: The objective of this study was to determine whether an extraction-based (indirect) assay or a non-extraction-based (direct) assay correlates better with mass spectrometry and body mass index (BMI). DESIGN/SETTING: In a pilot study of 40 postmenopausal women, endogenous E(2) measurements from three indirect and four direct assay methods and gas chromatography-tandem mass spectrometry (GC-MS/MS) were compared. A confirmatory study compared an indirect and a direct assay, selected among those in the pilot study, to GC-MS/MS; this study was conducted in 374 postmenopausal women not taking hormone therapy from the Ultra Low-dose TRansdermal estrogen Assessment (ULTRA) trial. MAIN OUTCOMES: Pearson correlation coefficients among E(2) measurements by assay methods and BMI, and their confidence intervals, by bias-corrected bootstrap method, were used. RESULTS: In the pilot study, E(2) by three indirect assays correlated better (P < 0.03) with GC-MS/MS and with BMI than measurements by four direct assays. In the confirmatory study, the indirect assay correlated better (P < 0.01) with GC-MS/MS and BMI than the direct assay. Measurements by the indirect and direct assays were overestimated, but deviations in direct assay measurements were less precise. Mean E(2) by the indirect and direct assays were higher (by 14 and 68%, respectively) and less reproducible than by GC-MS/MS. CONCLUSION: Until mass spectrometry is practical for wide use, extraction-based indirect assays may be preferable for measuring low postmenopausal serum E(2).

Aged↗

Association of testosterone and estradiol deficiency with osteoporosis and rapid bone loss in older men.

CONTEXT: The clinical value of measuring testosterone and estradiol in older men with osteoporosis and of measuring bone mineral density (BMD) in older men with testosterone or estradiol deficiency is uncertain. OBJECTIVE: The objective of the study was to examine the association of testosterone and estradiol deficiency with osteoporosis and rapid bone loss in older men. DESIGN: This study was a cross-sectional and longitudinal analysis. SETTING: The study was conducted at six U.S. centers of the Osteoporotic Fractures in Men study. PARTICIPANTS: The study population consisted of 2447 community-dwelling men aged 65 yr or older. MAIN OUTCOME MEASURES: Total testosterone deficiency was defined as less than 200 ng/dl. Total estradiol deficiency was defined as less than 10 pg/ml. Osteoporosis was defined as femoral neck or total hip BMD T-score of -2.5 or less. Rapid bone loss was defined as 3%/yr or more. RESULTS: Prevalence of osteoporosis in men with deficient and normal total testosterone was 12.3 and 6.0% (P = 0.003) and 15.4 and 2.8% (P < 0.0001) in those with deficient and normal total estradiol. Among osteoporotic men and those with normal BMD, prevalence of total testosterone deficiency was 6.9 and 3.2% (P = 0.01), and prevalence of total estradiol deficiency was 9.2 and 2.4% (P = 0.0001). Incidence of rapid hip bone loss in men with deficient and normal total testosterone was 22.5 and 8.6% (p = 0.007) and in those with deficient and normal total estradiol was 14.3 and 6.3% (p = 0.08). CONCLUSIONS: Older men with total testosterone or estradiol deficiency were more likely to be osteoporotic. Those with osteoporosis were more likely to be total testosterone or estradiol deficient. Rapid hip bone loss was more likely in men with total testosterone deficiency. BMD testing of older men with sex steroid deficiency may be clinically warranted.

Aged↗

Peroxisome proliferator-activated receptor-gamma polymorphism, body mass and prostate cancer risk: evidence for gene-environment interaction.

BACKGROUND: Peroxisome proliferator-activated receptor (PPAR)-gamma has been implicated in prostate cancer. In the present case-control study, we tested if a common Pro12Ala polymorphism in PPAR-gamma is associated with the risk of prostate cancer. METHODS: Ninety-one adult Caucasians with prostate cancer were recruited between 1994 and 1998. Blood samples were also obtained from 237 community-based Caucasian men without prostate cancer. RESULTS: Twenty-six percent of cases and 19% of controls carried at least one Ala allele (p = 0.16). There was a significant interaction between the PPAR-gamma polymorphism and body mass index (BMI) in age-adjusted analyses (p < 0.05). Among the subgroup of men with BMI above 27.2 kg/m2 (median in controls), carriers of the Ala allele had over 2-fold greater risk of prostate cancer compared to those with the Pro12Pro genotype (odds ratio, OR: 2.77; 95% confidence interval, CI: 1.25-6.16). No association was observed between the PPAR-gamma genotype and prostate cancer among men with BMI below the median (OR: 0.68; 95% CI: 0.23-1.97). CONCLUSIONS: Our results suggest a novel gene-environment interaction between the PPAR-gamma Pro12Ala polymorphism and body mass in prostate cancer. Further research, particularly prospective studies, is needed to confirm these findings and to clarify the underlying mechanisms involved.

Adult↗

Prevalence of symptoms of cervical and lumbar stenosis among participants in the Osteoporotic Fractures in Men Study.

STUDY DESIGN: Cross-sectional. OBJECTIVES: To determine the prevalence of symptoms typical of cervical and lumbar stenosis, evaluate the relationship between lumbar and cervical symptoms, and assess the impact of these symptoms on health status. SUMMARY OF BACKGROUND DATA: Degenerative changes of the spine frequently associated with aging, may result in stenosis, a narrowing of the spinal canal. Little is known about the prevalence or health impact of symptoms associated with stenosis in older individuals. METHODS: Between March 2000 and April 2002, 5995 men aged > or = 65 years participating in the Osteoporotic Fractures in Men Study completed a self-administered questionnaire and clinical examination. Information was collected on demographics, spinal/joint health, and general health status. RESULTS: Overall, 14.4% of men had had clinically relevant neck pain during the previous year, and almost half this group (6.5%) had numbness/tingling/weakness (NTW) extending into the arm; 26.2% reported clinically relevant lower back pain, which in 12.2%, was accompanied by NTW extending into the leg. Men with spinal pain (neck or lower back) accompanied by NTW radiating into a limb had poorer health status than those with milder pain. CONCLUSIONS: Symptoms suggestive of cervical and lumbar stenosis are relatively common among this cohort of older men, and generalized spinal stenosis may occur in as many as 4%.

Adolescent↗

Statin use and breast cancer: prospective results from the Women's Health Initiative.

BACKGROUND: Despite experimental observations suggesting that 3-hydroxy-3-methylglutaryl coenzyme A inhibitors (statins) have antitumor activity, clinical studies have reached mixed conclusions about the relationship between statin use and breast cancer risk. METHODS: To investigate associations between potency, duration of use, and type of statin used and risk of invasive breast cancer, we examined data for 156,351 postmenopausal women who were enrolled in the Women's Health Initiative. Information was collected on breast cancer risk factors and on the use of statins and other lipid-lowering drugs. Cox proportional hazards regression was used to calculate hazard ratios (HRs) with 95% confidence intervals (CIs). Statistical tests were two-sided. RESULTS: Over an average follow-up of 6.7 years, 4383 invasive breast cancers were confirmed by medical record and pathology report review. Statins were used by 11,710 (7.5%) of the cohort. Breast cancer incidence was 4.09 per 1000 person-years (PY) among statin users and 4.28 per 1000 PY among nonusers. In multivariable models, the hazard ratio of breast cancer among users of any statin, compared with nonusers, was 0.91 (95% CI = 0.80 to 1.05, P = .20). There was no trend in risk by duration of statin use, with HR = 0.80 (95% CI = 0.63 to 1.03) for < 1 year of use, HR = 0.99 (95% CI = 0.80 to 1.23) for 1- < 3 years of use, and HR = 0.94 (95% CI = 0.75 to 1.18) for > or = 3 years of use. Hydrophobic statins (i.e., simvastatin, lovastatin, and fluvastatin) were used by 8106 women, and their use was associated with an 18% lower breast cancer incidence (HR = 0.82, 95% CI = 0.70 to 0.97, P = .02). Use of other statins (i.e., pravastatin and atorvastatin) or nonstatin lipid-lowering agents was not associated with breast cancer incidence. CONCLUSIONS: Overall statin use was not associated with invasive breast cancer incidence. Our finding that use of hydrophobic statins may be associated with lower breast cancer incidence suggests possible within-class differences that warrant further evaluation.

Aged↗

Calcium plus vitamin D supplementation and the risk of fractures.

BACKGROUND: The efficacy of calcium with vitamin D supplementation for preventing hip and other fractures in healthy postmenopausal women remains equivocal. METHODS: We recruited 36,282 postmenopausal women, 50 to 79 years of age, who were already enrolled in a Women's Health Initiative (WHI) clinical trial. We randomly assigned participants to receive 1000 mg of elemental [corrected] calcium as calcium carbonate with 400 IU of vitamin D3 daily or placebo. Fractures were ascertained for an average follow-up period of 7.0 years. Bone density was measured at three WHI centers. RESULTS: Hip bone density was 1.06 percent higher in the calcium plus vitamin D group than in the placebo group (P<0.01). Intention-to-treat analysis indicated that participants receiving calcium plus vitamin D supplementation had a hazard ratio of 0.88 for hip fracture (95 percent confidence interval, 0.72 to 1.08), 0.90 for clinical spine fracture (0.74 to 1.10), and 0.96 for total fractures (0.91 to 1.02). The risk of renal calculi increased with calcium plus vitamin D (hazard ratio, 1.17; 95 percent confidence interval, 1.02 to 1.34). Censoring data from women when they ceased to adhere to the study medication reduced the hazard ratio for hip fracture to 0.71 (95 percent confidence interval, 0.52 to 0.97). Effects did not vary significantly according to prerandomization serum vitamin D levels. CONCLUSIONS: Among healthy postmenopausal women, calcium with vitamin D supplementation resulted in a small but significant improvement in hip bone density, did not significantly reduce hip fracture, and increased the risk of kidney stones. (ClinicalTrials.gov number, NCT00000611.).

Aged↗

High bone density is associated with prostate cancer in older Afro-Caribbean men: Tobago prostate survey.

OBJECTIVE: To test the hypothesis that bone mineral density (BMD), a possible surrogate of lifetime exposure to hormone/growth factor/vitamin D/calcium exposure, is higher in prostate cancer cases than controls. METHODS: Hip BMD was measured by dual X-ray absorptiometry in 222 Afro-Caribbean screening-detected prostate cancer cases and 1,503 screened non-cases, aged 45-79, in the population-based Tobago Prostate Survey. Because possible skeletal metastases may modulate BMD, men with prostate specific antigen >20 ng/ml or highly undifferentiated tumors (Gleason score > or = 8) were excluded. Mean BMD, adjusted for age and body mass index, was compared in cases and non-cases by analysis of variance. Risk across age group-specific BMD quartiles was compared using logistic regression. RESULTS: Overall, adjusted mean hip BMD was higher in cases (1.157 g/cm2) than non-cases (1.134 g/cm2) (p = 0.02). In men aged 60-79, prostate cancer risk was two-fold higher (OR, 2.12; 95% CI: 1.21-3.71) in the highest BMD quartile compared to the lowest. There was no association in younger men (interaction, p = 0.055). CONCLUSIONS: High bone density is associated with prostate cancer among older men, consistent with an etiological role for lifetime exposure to factors which modulate bone density. However, other etiologies may dominate prostate cancer risk among younger men.

Adult↗

Osteoporosis in men: prevalence and investigation.

In the past, osteoporosis was thought to affect only women; however, in the last decade it has become apparent that osteoporosis is common in men, particularly elderly men. Osteoporosis affects as many as 2 million men in the United States. Osteoporosis most commonly affects the hip and the lumbar vertebrae, but other bones, such as the radius, tibia, and ribs, may also fracture. The main feature of the etiology of the disease is that low bone mineral density results in increased susceptibility to bone fracture. The World Health Organization has defined osteoporosis as a bone mineral density T-score value >2.5 SDs below the mean observed in young adult women. Although the validity of this score for evaluating men has been questioned and it is not clear whether a male or female reference database should be used, it is nonetheless often used in this way. The disease affects men differently than women in a number of respects. It manifests itself later in life in men than in women, probably because men initially have greater bone mass. Mortality and morbidity associated with hip fractures are high in all elderly individuals, but they are substantially higher in men than in women. Unlike in women, there is an underlying cause for the osteoporosis in almost half of affected men. Thus, for elderly men, a complete history and physical examination may reveal some remediable conditions; treating these may stop further progression of the disease and prevent further morbidity or mortality. Corticosteroid therapy for arthritis or asthma is a common cause of osteoporosis in elderly men. Hypogonadism is a recognized cause of osteoporosis in men treated for carcinoma of the prostate with androgen withdrawal therapy; treatments to modify the effects of these agents on bone are available. Consumption of large amounts of alcohol will eventually result in osteoporosis in some elderly men. Moreover, alcohol can predispose confused elderly patients to falls and to fracture bones that are already osteoporotic. Hyperthyroidism is associated with a reduction in bone mineral density and an increased likelihood of bony fracture. A careful search for undiagnosed hyperthyroidism in elderly osteoporotic men may prove worthwhile. Vitamin D deficiency is common among older men and could contribute to an increase in fractures. Routine analyses of blood and biochemistry should be carried out in any older male patient with newly diagnosed osteoporosis. Dual x-ray energy absorptiometry should be performed on every new patient with newly diagnosed osteoporosis.

Bone Density↗

Correlates of decline in lower extremity performance in older women: A 10-year follow-up study.

BACKGROUND: Decline in lower extremity performance increases the risk of functional disability. This study examined the correlates of decline in lower extremity performance in older women. METHODS: A total of 5178 women aged 65-91 years were recruited from population-based listings from four centers in the United States. Clinical examinations were performed and lifestyle information was obtained at baseline and 10 years later. Lower extremity performance was measured by walking speed (meters/second) and time (seconds) to complete five chair-stands. Changes were calculated by subtracting baseline values from follow-up values. RESULTS: During the 10-year follow-up period, walking speed declined 17% and time to complete five chair-stands increased 22% (p < .0001). The decline in performance during the follow-up increased with baseline age: women aged 65-69 years experienced an 11% decline in walking speed and a 16% increase in the time to complete five chair-stands, while women aged 80 years or older experienced a 37% decline in walking speed and a 38% increase in chair-stand time. After adjusting for age, baseline physical performance, greater weight, greater height loss, smoking, history of arthritis and diabetes, and use of thyroid and estrogen medications were independently related to greater declines in lower extremity performance. CONCLUSIONS: Lower extremity performance decreased dramatically with advancing age in older women. Effective management of common diseases, such as arthritis and diabetes, and a healthy lifestyle, including avoidance of smoking and weight control, could help older women maintain their lower extremity physical functions.

Aged↗

Poor sleep is associated with impaired cognitive function in older women: the study of osteoporotic fractures.

BACKGROUND: The association between objectively measured sleep and cognition among community-dwelling elderly persons remains understudied. This observational, cross-sectional analysis examined this association. METHODS: Results are from 2932 women (mean age 83.5 years) in the Study of Osteoporotic Fractures between 2002 and 2004. Cognitive function was measured by Mini-Mental State Examination (MMSE) and Trail Making B Test (Trails B). Cognitive impairment was defined as MMSE < 26 or Trails B > 278 seconds. Sleep parameters measured objectively using actigraphy included total sleep time, sleep efficiency, sleep latency, wake after sleep onset (WASO), and total nap time. RESULTS: There were 305 women (10.6%) with MMSE < 26 and 257 women (9.3%) with Trails B > 278 seconds. Compared with women with sleep efficiency > or = 70%, those with <70% had a higher risk of cognitive impairment (MMSE < 26 multivariate odds ratio [MOR] = 1.61; 95% confidence interval [CI], 1.20-2.16; Trails B > 278 MOR = 1.96; 95% CI, 1.43-2.67). Higher sleep latency was associated with higher risk of cognitive impairment (per half hour: MMSE < 26 MOR = 1.23; 95% CI, 1.13-1.33; Trails B > 278 MOR = 1.13; 95% CI, 1.04-1.24), as was higher WASO (per half hour: MMSE < 26 MOR = 1.15; 95% CI, 1.06-1.23; Trails B > 278 MOR = 1.24; 95% CI, 1.15-1.34). Women who napped > or = 2 hours per day had a higher risk (MMSE < 26 MOR = 1.42; 95% CI, 1.05-1.93; Trails B > 278 MOR = 1.74; 95% CI, 1.26-2.40). There was no significant relationship for total sleep time. CONCLUSION: Objectively measured disturbed sleep was consistently related to poorer cognition, whereas total sleep time was not. This finding may suggest that it is disturbance of sleep rather than quantity that affects cognition.

Aged↗

Kidney function predicts the rate of bone loss in older individuals: the Cardiovascular Health Study.

BACKGROUND: Results of cross-sectional analyses of the association of kidney function with bone mineral density (BMD) have been conflicting. We examined the association of cystatin-C, a new marker of kidney function that is unrelated to lean mass, with initial and follow-up BMD, in an ancillary study of the Cardiovascular Health Study, a population-based cohort of individuals > or = 65 years old. METHODS: Two years after measurement of cystatin-C and other covariates, the first BMD was measured in Pittsburgh, Pennsylvania and Davis, California, by using dual energy x-ray absorptiometry. Follow-up BMD was measured in Pittsburgh 4 years later. Associations of cystatin-C with initial BMD and the change in BMD (%/y) at the hip were examined with linear regression. Analyses were conducted separately for men and women. RESULTS: In 1519 participants who had cystatin-C and initial BMD assessed, 614 had follow-up BMD. The percent annual change in BMD at the total hip by cystatin-C quartiles was -0.24, -0.13, -0.40, and -0.66%/y (first to fourth quartile) in women and -0.02, -0.30, -0.18, and -0.94%/y in men. After adjusting for potential confounders, cystatin-C was marginally associated with initial BMD in men but not women. Cystatin-C was associated with bone loss in men; after adjustment for weight loss, cystatin-C was not associated with bone loss in women. CONCLUSION: Kidney dysfunction, as assessed by cystatin-C, is associated with a more rapid loss of BMD at the hip, especially in men. Further studies are needed to confirm these findings and to determine whether this loss leads to an elevated risk of fracture.

Absorptiometry, Photon↗

Measurement of lumbar lordosis: inter-rater reliability, minimum detectable change and longitudinal variation.

STUDY DESIGN: Repeated measures design to examine reliability and longitudinal variation of lumbar lordosis measurement. OBJECTIVES: To determine the interrater reliability, minimum detectable change (MDC) and longitudinal variation of the Cobb method for measuring lumbar lordosis using standardized rules. SUMMARY OF BACKGROUND DATA: The reliability of the 4-line Cobb method for measuring lumbar lordosis was not examined when standardized rules were instituted for drawing the lines. METHODS: A random sample of participants was selected from the Pittsburgh clinic of the multicenter Study of Osteoporotic Fractures for radiographic measurement of lumbar lordosis reliability (n=48) and stability (n=109). A standardized version of the 4-line Cobb method was used for all measurements of lordosis. The Intraclass Correlation Coefficient (ICC) was used to calculate interrater reliability for lordosis and to measure the stability of this measure over an approximate 2-year-time period. The standard error of measurement and MDC were calculated for lordosis measurement based on the ICC value. RESULTS: The interrater reliability coefficient for lumbar lordosis was in the excellent range (ICC=0.98; 95% CI: 0.95, 0.99). The MDC based on measurements between raters was 3.90 degrees. The ICC value for the stability, or reliability from time 1 to time 2, of lordosis measurement over time was 0.81 (95% CI: 0.74, 0.87). CONCLUSION: This study demonstrates that the 4-line Cobb method can be a highly reliable and precise method for measuring lumbar lordosis if standardized procedures are used. The Cobb method has an MDC that is appropriate for clinical use. Also, there is minimal longitudinal variation in lordosis measurements over a 2-year period.

Aged↗

Measures of adiposity and risk of breast cancer in older postmenopausal women.

OBJECTIVES: To determine whether higher adiposity is associated with greater breast cancer risk in older postmenopausal women. DESIGN: Prospective cohort study with mean follow-up of 11.3 years. SETTING: Four U.S. clinical centers. PARTICIPANTS: Seven thousand five hundred twenty-three women (mean age 73.5) enrolled in the Study of Osteoporotic Fractures. MEASUREMENTS: Weight, height, and waist and hip circumference were measured at baseline. Body composition was determined using bioelectrical impedance. Risk factor information was obtained by interview and questionnaire. Bone mineral density was measured using dual energy x-ray absorptiometry. The outcome was incident invasive breast cancer, confirmed using medical records. RESULTS: After adjustment for multiple risk factors, including bone density, women in the uppermost quartiles of weight, weight gain since age 25, body mass index, waist circumference, and percentage of body fat had higher breast cancer rates than women in the first quartiles of each measure. For example, breast cancer rates were 49% higher for women in the uppermost quartile of weight (hazard ratio (HR)=1.49, 95% confidence interval (CI)=1.05-2.10), 64% higher for women in the top quartile of weight gain since age 25 (HR=1.64, 95% CI=1.15-2.34), and 58% higher for women in the top quartile of percentage of body fat (HR=1.58, 95% CI=1.11-2.23) than for women in the lowest quartile of each measure. The associations between adiposity measures and breast cancer rates were not altered when the analyses were limited to very elderly women (> or = 70). CONCLUSION: Higher adiposity is an independent risk factor for breast cancer in elderly women.

Adiposity↗