Associations of components of sarcopenia with risk of fracture in the Osteoporotic Fractures in Men (MrOS) study.

Our aim was to evaluate the associations between the individual components of sarcopenia and fracture types. In this cohort, the risk of experiencing any clinical, hip, or major osteoporotic fracture is greater in men with slow walking speed in comparison to normal walking speed. INTRODUCTION: The association between the components of sarcopenia and fractures has not been clearly elucidated and has hindered the development of appropriate therapeutic interventions. Our aim was to evaluate the associations between the individual components of sarcopenia, specifically lean mass, strength, and physical performance and fracture (any fracture, hip fracture, major osteoporotic fracture) in the Osteoporotic Fractures in Men (MrOS) study. METHODS: The Osteoporotic Fractures in Men study (MrOS) recruited 5995 men ≥ 65 years of age. We measured appendicular lean mass (ALM) by dual-energy X-ray absorptiometry (low as residual value < 20th percentile for the cohort), walking speed (fastest trial of usual pace, values < 0.8 m/s were low), and grip strength (max score of 2 trials, values < 30 kg were low). Information on fractures was assessed tri-annually over an average follow-up of 12 years and centrally adjudicated. Cox proportional hazard models estimated the hazard ratio (HR) (95% confidence intervals) for slow walking speed, low grip strength, and low lean mass. RESULTS: Overall, 1413 men had a fracture during follow-up. Slow walking speed was associated with an increased risk for any HR = 1.39, 1.05-1.84; hip HR = 2.37, 1.54-3.63; and major osteoporotic, HR = 1.89, 1.34-2.67 in multi-variate-adjusted models. Low lean mass and low grip strength were not significantly associated with fracture. CONCLUSIONS: In this cohort of older adult men, the risk of experiencing any, hip, or major osteoporotic fracture is greater in men with slow walking speed in comparison to men with normal walking speed, but low grip strength and low lean mass were not associated with fracture.

Body Composition Across the Adult Lifespan in African Caribbean Men: The Tobago Longitudinal Study of Aging.

Body composition and muscle strength change vary by age and ethnicity, and have a major impact on health and physical function. Little is known about the patterns of these changes in African-ancestry populations. Herein, we examined age-specific (5-year age groups) rates-of-change in lean and fat mass in 1918 African-ancestry men on the Caribbean island of Tobago (baseline age: 62.0±11.8 years, range: 40-99 years). Body composition (DXA) and grip strength were measured at three time points (baseline, 4- and 9-year follow-up). Annualized rates of change were calculated with all 3 time-points using Generalized Estimating Equations. We found that whole body lean mass declined at constant rate until age 65 (-0.72%/year; 95% CI: -0.76, -0.67), which accelerated to -0.92 %/year (-1.02, -0.82) among those 65-69, and again to -1.16 %/year (-1.30, -1.03 ) among those aged 70+. Whole body fat mass increased by a near constant rate of 2.93 %/year (2.72, 3.15%) across the lifespan. Finally, grip strength decline accelerated at age 50, and about 2x faster than lean mass through the lifespan after the age of 50. To conclude, in African-Caribbean men, the acceleration in muscle strength decline precedes the acceleration in lean mass decline by 10-15 years, suggesting decrements in factors other than lean mass drive this initial acceleration in muscle strength decline. We also found that African-Caribbean men undergo a constant shift to a more adipogenic phenotype throughout the adult lifespan (aged 40-99), which likely contributes to age-related loss of muscle and physical function.

Transition to a More even Distribution of Daily Protein intake Is Associated with Enhanced Fat Loss during a Hypocaloric and Physical Activity Intervention in Obese Older Adults.

BACKGROUND: Optimization of intentional weight loss in obese older adults, through preferential fat mass reduction, is challenging, as the concomitant lean mass loss may exacerbate sarcopenia. Recent studies have suggested within-day distribution of protein intake plays a role in determining body composition remodeling. Here, we assessed whether changes in within-day protein intake distribution are related to improvements in body composition in overweight/obese older adults during a hypocaloric and exercise intervention. METHODS: Thirty-six community-dwelling, overweight-to-obese (BMI 28.0-39.9 kg/m2), sedentary older adults (aged 70.6±6.1 years) were randomized into either physical activity plus successful aging health education (PA+SA; n=15) or physical activity plus weight loss (PA+WL; n=21) programs. Body composition (by CT and DXA) and dietary intake (by three-day food records) were determined at baseline, 6-month, and 12-month follow-up visits. Within-day protein distribution was calculated as the coefficient of variation (CV) of protein ingested per defined time periods (breakfast [5:00-10:59], lunch [11:00-16:59] and dinner [17:00-1:00]). Secondary analysis was performed to determine associations between changes in protein intake distribution and body composition. RESULTS: In both groups, baseline protein intake was skewed towards dinner (PA+SA: 49.1%; PA+WL: 54.1%). The pattern of protein intake changed towards a more even within-day distribution in PA+WL during the intervention period, but it remained unchanged in PA+SA. Transition towards a more even pattern of protein intake was independently associated with a greater decline in BMI (P<0.05) and abdominal subcutaneous fat (P<0.05) in PA+WL. However, changes in protein CV were not associated with changes in body weight in PA+SA. CONCLUSION: Our results show that mealtime distribution of protein intake throughout the day was associated with improved weight and fat loss under hypocaloric diet combined with physical activity. This finding provides a novel insight into the potential role of within-day protein intake on weight management in obese older people.

Normative Values of Muscle Power using Force Plate Jump Tests in Men Aged 77-101 Years: The Osteoporotic Fractures in Men (MrOS) Study.

OBJECTIVE: To determine normative values for weight-bearing, countermovement leg extension ("jump") tests in the oldest men and characteristics of those not completing vs. completing tests. DESIGN: 2014-16 cross-sectional exam. SETTING: Six U.S. sites from the Osteoporotic Fractures in Men (MrOS) Study. PARTICIPANTS: Community-dwelling men (N=1,841) aged 84.5±4.2 (range: 77-101) years. INTERVENTIONS: N/A. MEASUREMENTS: Jump tests on a force plate measured lower-extremity muscle peak power/kg, velocity and force/kg at peak power, with normative values for 5-year age groups and by limitations in moderate-intensity activities of daily living (ADLs) and climbing several flights of stairs. RESULTS: Jump completion was 68.9% (N=1,268/1,841) and 98% (1,242/1,268) had ≥1 analyzable trial/participant. Exclusions primarily were due to poor mobility and/or balance: 24.8% (456/1,841) prior to and 6.4% (N=117/1,841) after attempting testing. Peak power was 20.8±5.3 W/kg, with 1.2±0.3 m/s for velocity, and 16.7±1.9 N/kg for force at peak power. Each 5-year age group >80 years had subsequently 10% lower power/kg, with 30% lower power/kg at >90 vs. ≤80 years (all p<0.05). Velocity and force/kg at peak power were 24% and 9% lower respectively, at >90 vs. ≤80 years (all p<0.05). Limitations in both moderate ADLs and climbing several flights of stairs were associated with 16% lower age-adjusted power/kg, equivalent to 5-10 years of aging, with 11% and 6% lower age-adjusted velocity and force/kg respectively, vs. those without limitation (all p<0.05). Men not completing vs. completing jumps had older age, higher BMI, lower physical activity, more comorbidities, worse cognition, more IADLs/ADLs and more falls in the past year (all p<0.05). Post-jump pain occurred in 4.6% (58/1,268), with 2 participants stopping testing due to pain. Only 24/1,242 (2%) had all trials/participant without flight (i.e., inability to lift feet), with 323/1,242 having ≥1 trial/participant without flight (total of 28%). No serious adverse safety events (e.g., injury) occurred. CONCLUSIONS: A multicenter cohort of oldest men with a range of function had higher declines in jump power/kg and velocity vs. force/kg across each 5-year age group >80 years. Future research should examine age- and functional-related declines in jump measures related to physical performance decline, falls, fractures, and disability.

Synovitis in knee osteoarthritis: a precursor of disease?

OBJECTIVES: It is unknown whether joint inflammation precedes other articular tissue damage in osteoarthritis. Therefore, this study aims to determine if synovitis precedes the development of radiographic knee osteoarthritis (ROA). METHODS: The participants in this nested case-control study were selected from persons in the Osteoarthritis Initiative with knees that had a Kellgren Lawrence grading (KLG)=0 at baseline (BL). These knees were evaluated annually with radiography and non-contrast-enhanced MRI over 4 years. MRIs were assessed for effusion-synovitis and Hoffa-synovitis. Case knees were defined by ROA (KLG≥2) on the postero-anterior knee radiographs at any assessment after BL. Radiographs were assessed at P0 (time of onset of ROA), 1 year prior to P0 (P-1) and at BL. Controls were participants who did not develop incident ROA (iROA) from BL to 48 months). RESULTS: 133 knees of 120 persons with ROA (83 women) were matched to 133 control knees (83 women). ORs for occurrence of iROA associated with the presence of effusion-synovitis at BL, P-1 and P0 were 1.56 (95% CI 0.86 to 2.81), 3.23 (1.72 to 6.06) and 4.7 (1.10 to 2.95), respectively. The ORs for the occurrence of iROA associated with the presence of Hoffa-synovitis at BL, P-1 and P0 were 1.80 (1.1 to 2.95), 2.47 (1.45 to 4.23) and 2.40 (1.43 to 4.04), respectively. CONCLUSIONS: Effusion-synovitis and Hoffa-synovitis strongly predicted the development of iROA.

Effects of Changes in Regional Body Composition on Physical Function in Older Adults: A Pilot Randomized Controlled Trial.

BACKGROUND/OBJECTIVE: Obesity exacerbates age-related physical disability; however, observational studies show that any weight loss in old age is associated with greater risk of mortality. Conversely, randomized controlled trials in older adults show that weight loss is beneficial. The discrepancy may be due to weight loss intention and differential changes to regional body composition. The purpose of this research was to evaluate the independent role of regional body composition remodeling in improving physical function. DESIGN: Pilot Randomized Controlled Trial. SETTING: Community based research center. PARTICIPANTS: Thirty-six community dwelling, overweight to moderately obese (BMI 28.0-39.9 kg/m2) older adults (age 70.6±6.1 yrs). INTERVENTION: Physical activity plus weight loss (PA+WL, n=21) or PA plus successful aging (SA) education. PA consisted primary of treadmill walking supplemented with lower extremity resistance and balance training. The WL program was based on the Diabetes Prevention Project and aimed at achieving a 7% weight loss by cutting calories, specifically those from fat. MEASUREMENTS: At baseline, 6- and 12-months, body composition was measured using computerized tomography and dual x-ray absorptiometry. Abdominal visceral (VAT) and thigh intermuscular (IMAT) adipose tissue were quantified. Physical function was assessed using the short physical performance battery (SPPB). RESULTS: Separate multivariable linear regression models with both groups combined demonstrated that decreases in IMAT and VAT were significantly associated with improvements in SPPB (P<0.05) independent of change in total fat mass. PA+WL improved SPPB scores from baseline (0.8±1.4, P<0.05), whereas PA+SA did not; however no intergroup difference was detected. Of note, these effects were mainly achieved during the intensive intervention phase. CONCLUSION: Decreases in IMAT and VAT are important mechanisms underlying improved function following intentional weight loss plus physical activity.

Brief report: symmetricity of radiographic and MRI-detected structural joint damage in persons with knee pain--the Joints on Glucosamine (JOG) Study.

OBJECTIVE: Most MRI-based osteoarthritis (OA) studies have focused on a single knee per person and thus, data on bilaterality is sparse. Study aim was to describe symmetricity of MRI-detected OA features in a cohort of subjects with knee pain. DESIGN: Participants were 169 subjects with chronic knee pain who had 3 T MRI of both knees using the same protocol as in the Osteoarthritis Initiative. Knees were read for cartilage damage, bone marrow lesions (BMLs), and meniscal damage according to the Whole-Organ Magnetic Resonance Imaging Score (WORMS) system. Chi(2) tests were used to compare the proportion of knees with unilateral tissue pathology to the proportion what would be expected if both knees were independent. We further used percent agreement and linear weighted kappa statistics to describe agreement of cartilage damage and BMLs in the same articular plates. RESULTS: 51.2% of participants were men, mean age was 52.1 (±6.2), mean BMI was 29.0 kg/m(2) (±4.1). All plates showed a significant higher degree of symmetricity for cartilage damage as evidenced by weighted kappas ranging from 0.32 to 0.59. For BMLs the degree of symmetricity was higher for the patella, trochlea, medial tibia, lateral femur, and medial femur; for meniscal damage the degree of unilaterality was lower for all medial meniscal subregions but not all lateral. Kappas ranged between 0.52 and 0.68 for cartilage and 0.30 and 0.55 for BMLs for the four subregions with highest agreement. CONCLUSION: A higher degree of symmetricity of tissue damage than expected by chance was observed in this cohort of subjects with knee pain.

Loss of anterior cruciate ligament integrity and the development of radiographic knee osteoarthritis: a sub-study of the osteoarthritis initiative.

INTRODUCTION: The aim of this study was to determine whether loss of ACL integrity in an older cohort precedes the onset of radiographic OA (ROA). METHODS: Participants in this nested case-control study were selected from the Osteoarthritis Initiative (OAI) study who had risk factors for OA development but did not have ROA (Kellgren-Lawrence grading (KLG) of 0 or 1) in both knees at baseline. The MRIs were assessed for the presence of ACL tears. Case knees were defined by the development of ROA on knee radiographs between the 12 and 48 month visits. Their radiographs were assessed at P0 (time of onset of radiographic knee OA), 1 year prior to P0 (P-1) and at baseline. Controls were selected from amongst those who did not develop incident ROA and were matched to cases. RESULTS: 355 persons who developed ROA were matched to 355 controls. No relationship between loss of ACL integrity and incident ROA was found at any assessment time point. Odds ratios (OR) for baseline, 1 year prior to incident ROA (P1) and at point of occurrence of incident ROA (P0) were 2.00 (0.66-6.06), 2.5 (0.76-8.24) and 2.75 (0.85-8.88) respectively. A significant risk of incident ROA was found in participants who had a history of knee injury with an OR of 1.51 (1.05-2.16). CONCLUSION: Loss of ACL integrity does not confer a significantly increased risk of incident ROA in an older adult cohort. In contrast, a history of knee injury was associated with an increased risk of incident ROA.

Trajectory of cartilage loss within 4 years of knee replacement--a nested case-control study from the osteoarthritis initiative.

OBJECTIVE: Knee replacement (KR) represents a clinically important endpoint of knee osteoarthritis (KOA). Here we examine the 4-year trajectory of femoro-tibial cartilage thickness loss prior to KR vs non-replaced controls. METHODS: A nested case-control study was performed in Osteoarthritis Initiative (OAI) participants: Cases with KR between 12 and 60 month (M) follow-up were each matched with one control (without KR through 60M) by age, sex, and baseline radiographic stage. Femoro-tibial cartilage thickness was measured quantitatively using magnetic resonance imaging (MRI) at the annual visit prior to KR occurrence (T0), and at 1-4 years prior to T0 (T-1 to T-4). Cartilage loss between cases and controls was compared using paired t-tests and conditional logistic regression. RESULTS: One hundred and eighty-nine knees of 164 OAI participants [55% women; age 64 ± 8.7; body mass index (BMI) 29 ± 4.5] had KR and longitudinal cartilage data. Comparison of annualized slopes of change across all time points revealed greater loss in the central medial tibia (primary outcome) in KRs than in controls [94 ± 137 vs 55 ± 104 µm; P = 0.0017 (paired t); odds ratio (OR) 1.36 (95% confidence interval (CI): 1.08-1.70)]. The discrimination was stronger for T-2 → T0 [OR 1.61 (1.33-1.95), n = 127] than for T-1 → T0, and was not statistically significant for intervals prior to T-2 [i.e., T-4 → T-2, OR 0.97 (0.67-1.41), n = 60]. Results were similar for total medial femoro-tibial cartilage loss (secondary outcome), and when adjusting for pain and BMI. CONCLUSIONS: In knees with subsequent replacement, cartilage loss accelerates in the 2 years, and particularly in the year prior to surgery, compared with controls. Whether slowing this cartilage loss can delay KR remains to be determined.

Abdominal body composition measured by quantitative computed tomography and risk of non-spine fractures: the Osteoporotic Fractures in Men (MrOS) Study.

UNLABELLED: The effect of abdominal adiposity and muscle on fracture is unclear in older men; therefore, we examined the association among 749 men aged 65+. Among various adipose tissues and muscle groups, lower psoas muscle volume and higher fatty infiltration of abdominal muscle contribute to higher fracture risk independent of BMD. INTRODUCTION: The association of abdominal adiposity and muscle composition with incident fracture is unclear, especially in older men. Therefore, we examined the relationship of subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), abdominal intermuscular adipose tissue (IMAT), and muscle volume with incident non-spine fractures among 749 men aged 65 and older. METHODS: A case-cohort study design was used with a total of 252 fracture cases and 497 non-cases. We measured volumes (in centimeters) of adipose and muscle tissues obtained from quantitative computed tomography scan at the L4-5 intervertebral space. Three groups of muscle and IMAT were evaluated: total abdominal, psoas, and paraspinal. Cox proportional hazards regression with a robust variance estimator was used to estimate the hazard ratio (HR) of non-spine fractures per standard deviation (SD) increase in the abdominal body composition measures. The mean age among men in the random subcohort was 74.2 ± 6.1 years, and the average follow-up time was 5.2 ± 1.1 years. RESULTS: After adjusting for age, race, clinic site, percent body fat, and femoral neck bone mineral density (BMD), no significant relationship was found between incident fractures and SAT or VAT. One SD increase in muscle volume at the psoas, but not paraspinal, was associated with 28 % lower fracture risk (95 % CI = 0.55-0.95). When IMAT models were further adjusted for corresponding muscle volumes, only abdominal IMAT was significantly associated with fracture risk (HR = 1.30 (95 % CI = 1.04-1.63)). CONCLUSION: Our findings suggest that lower total psoas muscle volume and higher IMAT of the total abdominal muscle contribute to higher fracture risk in older men independent of BMD.

Renal function and nonvertebral fracture risk in multiethnic women: the Women's Health Initiative (WHI).

UNLABELLED: To examine the association between renal function and fracture in multiethnic women, we studied postmenopausal women enrolled in the Women's Health Initiative. Postmenopausal White women with mild renal dysfunction were at increased risk of nonvertebral fracture; this association was at least partially explained by effects of renal dysfunction on chronic inflammation. Reduced renal function appeared to increase fracture risk among Black women, but there was little evidence to support this association among other racial/ethnic groups. INTRODUCTION: The purpose of this study was to determine whether renal function is associated with fracture risk within racial/ethnic groups. METHODS: A nested case-control study was conducted among 93,673 postmenopausal women; incident nonvertebral fractures were identified in 362 Black, 183 Hispanic, 110 Asian, and 45 American-Indian women. A random sample of 395 White women with incident nonvertebral fracture was chosen. One nonfracture control for each case was selected (matched on age, race/ethnicity, and blood draw date). Cystatin C levels were measured using baseline serum, and estimated glomerular filtration rate calculated (eGFR(cys-c)). RESULTS: Each 1 SD increase in cystatin C was associated with a 1.2-fold increased risk of fracture among White women (adjusted odds ratios [OR], 1.23; 95% confidence intervals [CI], 1.04-1.46). The OR of fracture was 1.16 (95% CI, 0.85-1.58) among women with eGFR(cys-c) 60-90 mL/min/1.73 m(2) and 2.46 (95% CI, 1.16-5.21) among those with eGFR(cys-c) <60 mL/min/1.73 m(2) compared to the reference group (eGFR(cys-c) >90 mL/min/1.73 m(2)) (p trend = 0.05). The association was reduced after adjustment for cytokine TNFα soluble receptors (OR, 1.62; 95% CI, 0.59-4.46 for eGFR(cys-c) <60 mL/min/1.73 m(2)). Among Blacks, there was an association between cystatin C and fracture risk (OR per 1 SD increase, 1.15; 95% CI, 1.00-1.32); after adjustment, this association was only modestly attenuated, but no longer statistically significant. There was no evidence of significant associations among Hispanic, Asian, or American-Indian women. CONCLUSION: Postmenopausal White women with mild renal dysfunction are at increased risk of nonvertebral fracture. Effects of renal function on chronic inflammation may mediate this association. Reduced renal function may increase fracture risk among Black women, but there was little evidence to support this association among other racial/ethnic groups.

Evolution of semi-quantitative whole joint assessment of knee OA: MOAKS (MRI Osteoarthritis Knee Score).

OBJECTIVE: In an effort to evolve semi-quantitative scoring methods based upon limitations identified in existing tools, integrating expert readers' experience with all available scoring tools and the published data comparing the different scoring systems, we iteratively developed the magnetic resonance imaging (MRI) Osteoarthritis Knee Score (MOAKS). The purpose of this report is to describe the instrument and its reliability. METHODS: The MOAKS instrument refines the scoring of bone marrow lesions (BMLs) (providing regional delineation and scoring across regions), cartilage (sub-regional assessment), and refines the elements of meniscal morphology (adding meniscal hypertrophy, partial maceration and progressive partial maceration) scoring. After a training and calibration session two expert readers read MRIs of 20 knees separately. In addition, one reader re-read the same 20 MRIs 4 weeks later presented in random order to assess intra-rater reliability. The analyses presented here are for both intra- and inter-rater reliability (calculated using the linear weighted kappa and overall percent agreement). RESULTS: With the exception of inter-rater reliability for tibial cartilage area (kappa=0.36) and tibial osteophytes (kappa=0.49); and intra-rater reliability for tibial BML number of lesions (kappa=0.54), Hoffa-synovitis (kappa=0.42) all measures of reliability using kappa statistics were very good (0.61-0.8) or reached near-perfect agreement (0.81-1.0). Only intra-rater reliability for Hoffa-synovitis, and inter-rater reliability for tibial and patellar osteophytes showed overall percent agreement <75%. CONCLUSION: MOAKS scoring shows very good to excellent reliability for the large majority of features assessed. Further iterative development and research will include assessment of its validation and responsiveness.

The risk of Parkinson disease associated with urate in a community-based cohort of older adults.

BACKGROUND/AIMS: Studies suggest an inverse association between urate concentration and the risk of Parkinson disease (PD). We investigated this in the Cardiovascular Health Study in an elderly community-based cohort of adults. METHODS: The association of baseline urate (µmol/l) and incident PD over 14 years was assessed with locally weighted scatterplot smoothing (LOESS) regression from which categories of low (<300 µmol/l), middle (300-500 µmol/l), and high (>500 µmol/l) urate ranges were derived. Multivariate logistic regression models assessed the risk of PD for each urate range. Linear and quadratic terms were tested when modeling the association between urate and the risk of PD. RESULTS: Women had significantly lower urate concentrations than did men [316.8 µmol/l (SD 88.0) vs. 367.4 µmol/l (SD 87.7), p < 0.0001] and in women no associations between urate and PD risk were observed. In men, LOESS curves suggested a U-shaped or threshold effect between urate and PD risk. With the middle range as reference, the risk of developing PD was significantly increased for urate <300 µmol/l (OR 1.69, 95% CI 1.03-2.78) but not for urate >500 µmol/l (OR 1.55, 95% CI 0.72-3.32) in men. A negative linear term was significant for urate <500 µmol/l, and across the entire range a convex quadratic term was significant. CONCLUSIONS: Results suggest a more complex relationship than previously reported between urate levels and the risk of PD in men. Low urate concentrations were associated with a higher PD risk and high urate concentrations were not associated with a further decrease in PD risk.

Executive function, memory, and gait speed decline in well-functioning older adults.

BACKGROUND: In community-dwelling older adults, global cognitive function predicts longitudinal gait speed decline. Few prospective studies have evaluated whether specific executive cognitive deficits in aging may account for gait slowing over time. METHODS: Multiple cognitive tasks were administered at baseline in 909 participants in the Health, Aging, and Body Composition Study Cognitive Vitality Substudy (mean age 75.2 ± 2.8 years, 50.6% women, 48.4% black). Usual gait speed (m/s) over 20 minutes was assessed at baseline and over a 5-year follow-up. RESULTS: Poorer performance in each cognitive task was cross-sectionally associated with slower gait independent of demographic and health characteristics. In longitudinal analyses, each 1 SD poorer performance in global function, verbal memory, and executive function was associated with 0.003-0.004 m/s greater gait speed decline per year (p =.03-.05) after adjustment for baseline gait speed, demographic, and health characteristics. CONCLUSIONS: In this well-functioning cohort, several cognitive tasks were associated with gait speed cross-sectionally and predicted longitudinal gait speed decline. These data are consistent with a shared pathology underlying cognitive and motor declines but do not suggest that specific executive cognitive deficits account for slowing of usual gait in aging.

Concurrent change in dehydroepiandrosterone sulfate and functional performance in the oldest old: results from the Cardiovascular Health Study All Stars study.

INTRODUCTION: The correlation between dehydroepiandrosterone sulfate (DHEAS) decline and age led to the hypothesis that DHEAS might be a marker of primary aging, though conflicting data from observational studies of mortality do not support this. We evaluated concurrent DHEAS and functional decline in a very old cohort to test if DHEAS change tracks with functional change during aging. METHODS: DHEAS and functional performance (gait speed, grip strength, Modified Mini-Mental State Examination [3MSE] score, and digit symbol substitution test [DSST] score) were measured in 1996-1997 and 2005-2006 in 989 participants in the Cardiovascular Health Study All Stars study (mean age 85.2 years in 2005-2006, 63.5% women and 16.5% African American). We used multivariable linear regression to test the association of DHEAS decline with functional decline. RESULTS: After adjustment, each standard deviation decrease in DHEAS was associated with greater declines in gait speed (0.12 m/s, p = .01), grip strength (0.09 kg, p = .03), 3MSE score (0.13 points, p < .001), and DSST score (0.14 points, p = .001) in women only. Additional adjustment for baseline DHEAS attenuated the association with grip strength but did not alter other estimates appreciably, and baseline DHEAS was unassociated with functional decline. CONCLUSIONS: In this cohort of very old individuals, DHEAS decline tracked with declines in gait speed, 3MSE score, and DSST score, but not grip strength, in women independent of baseline DHEAS level. DHEAS decline might be a marker for age-associated performance decline, but its relevance is specific to women.

Variation in the use of breast-conserving therapy for Medicare beneficiaries in Virginia: clinical, geographic, and hospital characteristics.

BACKGROUND: Treatment for early-stage breast cancer has evolved significantly in recent years. Breast-conserving therapy (BCT) has been shown to offer equivalent survival compared to traditional mastectomy. However, there is marked variation in the performance of BCT which may not reflect clinical appropriateness or patient preference. Little is known about the factors related to variation in BCT performance in older women with early-stage breast cancer. METHODS: Retrospective claims analysis of 1,512 Medicare patients using part-A data for the years 1992 to 1993, with additional explicit chart review. A clinical algorithm was developed to categorize patients according to their candidacy for BCT and compare this to their treatment. Demographic, clinical, and geographic variables were included in the model. RESULTS: The overall BCT rate in Virginia was 20%, with marked variation among providers of all types. BCT rates ranged from 0% to 44% among hospitals caring for more than 12 cases per year. Twenty-six percent of patients considered good candidates for BCT by current guidelines received this option. Large urban hospitals had significantly higher rates of BCT than smaller hospitals, regardless of the presence of radiation oncology capability. Distance from radiation oncology facilities was a factor in low BCT rates of rural populations, but low BCT rates also were present even in facilities with access to radiation oncology services. CONCLUSIONS: These data present a detailed analysis of the patterns of BCT for Virginia Medicare beneficiaries with early-stage breast cancer. Clinical contraindications to BCT for confirmed early-stage disease were uncommon. Despite similar patient profiles and hospital-reported range of cancer services, marked variation in BCT rates exists. A large number of patients chose traditional mastectomy over BCT due to fears of radiation, but few received radiation oncology consultation. BCT rates were highest in hospitals with radiation oncology facilities on grounds; hospitals with facilities nearby had rates similar to those without access to radiation facilities. Patient preferences are documented poorly. This study provides further evidence that many women are receiving BCT in patterns that may not reflect clinical appropriateness for BCT nor access to necessary facilities.