Short-term changes in body composition after surgical repair of hip fracture.

BACKGROUND: the deleterious changes in body composition that occur during the year after hip fracture are associated with increased disability, recurrent fracture, and mortality. While the majority of these unfavourable changes have been shown to occur during the first 2 months after fracture, potential changes in body composition occurring earlier than 2 months post-fracture have not been studied. Accordingly, the aim of this study was to rigorously assess short-term changes in body composition after hip fracture. METHODS: total body mass, lean mass, fat mass and total hip and femoral neck bone mineral density (BMD) were assessed via dual energy X-ray absorptiometry at 3 days, 10 days and 2 months post-fracture among 155 hip fracture patients from the Baltimore Hip Studies. Longitudinal regression analysis using mixed models was conducted to model short-term changes in body composition. RESULTS: no significant changes in body composition were revealed from 3- to 10 days post-fracture. However, significant decreases from 10 days to 2 months post-fracture were noted in the total body mass (-1.95 kg, P < 0.001), lean mass (-1.73 kg, P < 0.001), total hip BMD (-0.00812 g/cm(2), P = 0.04) and femoral neck BMD (-0.015 g/cm(2), P = 0.03). No meaningful changes in fat mass were uncovered. CONCLUSIONS: the adverse changes in body composition during the first 2 months after hip fracture appear to have occurred primarily between 10 days and 2 months post-fracture. More research is needed to determine how these findings might help inform the optimal timing of interventions aimed at improving body composition and related outcomes after hip fracture.

Higher serum concentrations of dietary antioxidants are associated with lower levels of inflammatory biomarkers during the year after hip fracture.

BACKGROUND & AIMS: Chronic inflammation impairs recovery among the 1.6 million people who suffer from hip fracture annually. Vitamin E and the carotenoids are two classes of dietary antioxidants with profound anti-inflammatory effects, and the goal of this study was to assess whether higher post-fracture concentrations of these antioxidants were associated with lower levels of interleukin 6 (IL-6) and the soluble receptor for tumor necrosis factor-alpha (sTNF-αR1), two common markers of inflammation. METHODS: Serum concentrations of the dietary antioxidants and inflammatory markers were assessed at baseline and 2, 6, and 12 month follow-up visits among 148 hip fracture patients from The Baltimore Hip Studies. Generalized estimating equations modeled the relationship between baseline and time-varying antioxidant concentrations and inflammatory markers. RESULTS: Higher post-fracture concentrations of vitamin E and the carotenoids were associated with lower levels of inflammatory markers. Associations were strongest at baseline, particularly between the α-tocopherol form of vitamin E and sTNF-αR1 (p = 0.05) and total carotenoids and both sTNF-αR1(p = 0.01) and IL-6 (p = 0.05). Higher baseline and time-varying α-carotene and time-varying lutein concentrations were also associated with lower sTNF-αR1 at all post-fracture visits (p ≤ 0.05). CONCLUSIONS: These findings suggest that a clinical trial increasing post-fracture intake of vitamin E and the carotenoids may be warranted.

Serum vitamin E concentrations and recovery of physical function during the year after hip fracture.

BACKGROUND: Poor nutritional status after hip fracture is common and may contribute to physical function decline. Low serum concentrations of vitamin E have been associated with decline in physical function among older adults, but the role of vitamin E in physical recovery from hip fracture has never been explored. METHODS: Serum concentrations of α- and γ-tocopherol, the two major forms of vitamin E, were measured in female hip fracture patients from the Baltimore Hip Studies cohort 4 at baseline and at 2-, 6-, and 12-month postfracture follow-up visits. Four physical function measures-Six-Minute Walk Distance, Lower Extremity Gain Scale, Short Form-36 Physical Functioning Domain, and Yale Physical Activity Survey-were assessed at 2, 6, and 12 months postfracture. Generalized estimating equations modeled the relationship between baseline and time-varying serum tocopherol concentrations and physical function after hip fracture. RESULTS: A total of 148 women aged 65 years and older were studied. After adjusting for covariates, baseline vitamin E concentrations were positively associated with Six-Minute Walk Distance, Lower Extremity Gain Scale, and Yale Physical Activity Survey scores (p < .1) and faster improvement in Lower Extremity Gain Scale and Yale Physical Activity Survey scores (p < .008). Time-varying vitamin E was also positively associated with Six-Minute Walk Distance, Lower Extremity Gain Scale, Yale Physical Activity Survey, and Short Form-36 Physical Functioning Domain (p < .03) and faster improvement in Six-Minute Walk Distance and Short Form-36 Physical Functioning Domain (p < .07). CONCLUSIONS: Serum concentrations of both α- and γ-tocopherol were associated with better physical function after hip fracture. Vitamin E may represent a potentially modifiable factor related to recovery of postfracture physical function.

Serum vitamin E concentrations among highly functioning hip fracture patients are higher than in nonfracture controls.

Malnutrition after hip fracture is common and associated with poor outcomes and protracted recovery. Low concentrations of vitamin E have been associated with incident decline in physical function among older adults and may, therefore, be particularly important to functionally compromised patients hip fracture patients. Serum concentrations of α-tocopherol and γ-tocopherol, the 2 major forms of vitamin E, were assessed in 148 female hip fracture patients 65 years or older from the Baltimore Hip Studies cohort 4 around the time of fracture (baseline) and at 2, 6, and 12 month postfracture follow-up visits (recovery). It was hypothesized that mean concentrations of both forms of vitamin E among these hip fracture patients would be lowest at the baseline visit and increase at each study visit during the year after fracture. Linear regression and generalized estimating equations were used to assess changes in vitamin E concentrations after adjustment for covariates and to determine predictors of vitamin E concentrations at baseline and throughout recovery. It was also hypothesized that vitamin E concentrations shortly after hip fracture would be lower than those in nonfracture controls after adjustment for covariates. To evaluate this hypothesis, linear regression was used to perform adjusted comparisons of baseline vitamin E concentrations among Baltimore Hip Studies cohort 4 participants to 1076 older women without history of hip fracture from the Women's Health and Aging Study I, Invecchiare in Chianti Study, and the National Health and Nutrition Examination Surveys. Mean α-tocopherol was lowest at baseline, and time from fracture to blood draw was positively associated with baseline α-tocopherol (P = .005). Mean γ-tocopherol did not change appreciably throughout the year after fracture, although it fluctuated widely within individuals. Serum concentrations of α-tocopherol and γ-tocopherol were highest among the hip fracture population after adjustment (P < .0001). In general, highly cognitively and physically functioning hip fracture patients demonstrated higher vitamin E concentrations. Thus, the relatively high degree of function among this cohort of hip fracture patients may explain their higher-than-expected vitamin E concentrations.

Delivery and outcomes of a yearlong home exercise program after hip fracture: a randomized controlled trial.

BACKGROUND: Hip fracture affects more than 1.6 million persons worldwide and causes substantial changes in body composition, function, and strength. Usual care (UC) has not successfully restored function to most patients, and prior research has not identified an effective restorative program. Our objective was to determine whether a yearlong home-based exercise program initiated following UC could be administered to older patients with hip fracture and improve outcomes. METHODS: A randomized controlled trial of 180 community dwelling female patients with hip fracture, 65 years and older, randomly assigned to intervention (n = 91) or UC (n = 89). Patients were recruited within 15 days of fracture from 3 Baltimore-area hospitals from November 1998 through September 2004. Follow-up assessments were conducted at 2, 6, and 12 months after fracture. The Exercise Plus Program was administered by exercise trainers that included supervised and independently performed aerobic and resistive exercises with increasing intensity. Main outcome measures included bone mineral density of the contralateral femoral neck. Other outcomes included time spent and kilocalories expended in physical activity using the Yale Physical Activity Scale, muscle mass and strength, fat mass, activities of daily living, and physical and psychosocial functioning. The effect of intervention for each outcome was estimated by the difference in outcome trajectories 2 to 12 months after fracture. RESULTS: More than 80% of participants received trainer visits, with the majority receiving more than 3 quarters (79%) of protocol visits. The intervention group reported more time spent in exercise activity during follow-up (P < .05). Overall, small effect sizes of 0 to 0.2 standard deviations were seen for bone mineral density measures, and no significant patterns of time-specific between-group differences were observed for the remaining outcome measures. CONCLUSION: Patients with hip fracture who participate in a yearlong, in-home exercise program will increase activity level compared with those in UC; however, no significant changes in other targeted outcomes were detected. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00390741.

Design and implementation of a home-based exercise program post-hip fracture: the Baltimore hip studies experience.

OBJECTIVE: The objectives are to describe for the first time a home-based exercise intervention for frail elderly hip fracture patients and to describe the feasibility of this exercise program. DESIGN: A home-based exercise program was used in a randomized controlled trial in which the authors investigated exercise intervention versus no exercise intervention in patients after hip fracture. SETTING: This program was implemented at the patients' own home or place of residence after discharge. PARTICIPANTS: Women 65 years of age or older were recruited within 15 days of hip fracture. Eligible patients were those with a nonpathologic fracture who were admitted within 72 hours of injury, had surgical repair of the hip fracture, and met medical inclusion criteria. Participants initially were randomized to exercise groups and then assigned to exercise trainers. INTERVENTION: The exercise contained strength training and aerobic components. Participants were expected to exercise 5 days per week by performing a combination of supervised and independently performed exercise sessions. Intensity and duration were increased gradually by trainers in a standardized way. The frequency of the supervised sessions decreased as participants became more independent. Treatment fidelity visits ensured that the intervention was being delivered as intended across trainers and across participants. MAIN OUTCOME MEASUREMENT: This work describes the feasibility and challenges of administering an intensive home-based exercise program in this population of older adults. RESULTS: Of those patients randomized to exercise, 82% were followed by a trainer and almost all advanced to higher levels in both aerobic and strength programs. Overall, participants received an average of 44 (78.5%) of the prescribed visits by the trainer. CONCLUSIONS: This study showed that it was possible to engage a frail older population of post-hip fracture patients in a program of aerobic and strength training exercise with a high rate of participation.

Association between interleukin-6 and lower extremity function after hip fracture--the role of muscle mass and strength.

OBJECTIVES: To examine whether an effect on muscle mass or strength explains the association between interleukin-6 (IL-6) and lower extremity function in the year after hip fracture. DESIGN: Analysis of data from a longitudinal cohort study. SETTING: Two Baltimore-area hospitals. PARTICIPANTS: Community-dwelling women aged 65 and older admitted to one of two hospitals in Baltimore with a new, nonpathological fracture of the proximal femur between 1992 and 1995. MEASUREMENTS: At 2, 6, and 12 months postfracture, serum IL-6, appendicular lean muscle mass (aLM), and grip strength were measured, and the Lower Extremity Gain Scale (LEGS), a summary measure of performance of nine lower extremity tasks was calculated. Generalized estimating equations were used to model the longitudinal relationship between IL-6 tertile and LEGS. Whether muscle mass or strength explained the relationship between IL-6 and LEGS was examined by adding measures of aLM, grip strength, or both into the model. RESULTS: Subjects in the lowest IL-6 group performed better on the LEGS than those in the highest tertile by 4.51 (95% confidence interval (CI)=1.50-7.52) points at 12 months postfracture. Adjusting for aLM and grip strength, this difference was 4.28 points (95% CI=1.14-7.43) and 3.81 points (95% CI=0.63-7.00), respectively. Adjusting for both aLM and grip strength, the mean difference in LEGS score was 3.88 points (95% CI=0.63-7.13). CONCLUSION: In older women, after hip fracture, reduced muscle strength, rather than reduced muscle mass, better explains the poorer recovery of lower extremity function observed with higher levels of the inflammatory marker IL-6.

Association of serotonin-1A and 2A receptor promoter polymorphisms with depressive symptoms and functional recovery in elderly persons after hip fracture.

BACKGROUND: Depression is common after hip fracture and is associated with poorer functional recovery. Polymorphisms of the serotonin 1a (5HTR1A) and 2a receptors (5HTR2A) are associated with depression; therefore, we examined their association with depressive symptoms and functional recovery after hip fracture. METHODS: 145 elderly women were followed for 12 months after hip fracture. Depressive symptoms were measured with the 15-item Geriatric Depression Scale (GDS). Functional status was measured by Lower Extremity Physical and Instrumental Activity of Daily Living scales (LPADLs and IADLs). Time-adjusted general linear regression models compared mean GDS between those with and without risk alleles for 5HTR1A and 5HTR2A. RESULTS: Women with 1-2 copies of the 5HTR1A (-1019) G allele had higher GDS scores (Adjusted Mean Difference=0.59; 95% CI, 0.12-1.06), and poorer IADL scores (Adjusted Mean Difference=0.24; 95%CI -0.002 to 0.49), compared to those without this allele, controlling for potential confounders and 5HTR2A. Depressive symptoms partly accounted for poorer IADL recovery. Women with 1-2 copies of the 5HTR2A (-1438) C allele did not have significantly higher GDS scores (Adjusted Mean Difference=0.34; 95%CI, -0.20 to 0.87) and had better IADL scores (Adjusted Mean Difference=-0.40; 95%CI -0.74 to 0.06) than those with A/A genotype. LIMITATIONS: The findings are limited by small sample size and the use of a screening scale to measure depression. CONCLUSIONS: The 5HTR1A (-1019) G allele is associated with increased depressive symptoms after hip fracture, which in turn accounts for poorer functional recovery. These results suggest a role for serotonergic genetic variation in elderly persons' resilience and recovery from medical events.

Adherence to an Exercise Intervention Among Older Women Post Hip Fracture.

The purpose of this study was to evaluate adherence to home-based exercise interventions among older women post hip fracture that were randomized to one of three exercise intervention groups or a routine care group. A total of 157 female hip fracture patients provided data for the intervention analysis. Factors evaluated baseline, 2, 6, and 12 months post hip fracture included demographic variables, adherence to treatment visits, self-efficacy, outcome expectations, stage of change for exercise, social support for exercise, mood, health status, pain, and fear of falling. The hypothesized model tested the direct and indirect impact of all study variables on adherence to exercise intervention sessions. Different factors appeared to influence adherence to visits across the recovery trajectory.

Factors that influence exercise activity among women post hip fracture participating in the Exercise Plus Program.

Using a social ecological model, this paper describes selected intra- and interpersonal factors that influence exercise behavior in women post hip fracture who participated in the Exercise Plus Program. Model testing of factors that influence exercise behavior at 2, 6 and 12 months post hip fracture was done. The full model hypothesized that demographic variables; cognitive, affective, physical and functional status; pain; fear of falling; social support for exercise, and exposure to the Exercise Plus Program would influence self-efficacy, outcome expectations, and stage of change both directly and indirectly influencing total time spent exercising. Two hundred and nine female hip fracture patients (age 81.0 +/- 6.9), the majority of whom were Caucasian (97%), participated in this study. The three predictive models tested across the 12 month recovery trajectory suggest that somewhat different factors may influence exercise over the recovery period and the models explained 8 to 21% of the variance in time spent exercising. To optimize exercise activity post hip fracture, older adults should be helped to realistically assess their self-efficacy and outcome expectations related to exercise, health care providers and friends/peers should be encouraged to reinforce the positive benefits of exercise post hip fracture, and fear of falling should be addressed throughout the entire hip fracture recovery trajectory.

Testing the effectiveness of the exercise plus program in older women post-hip fracture.

BACKGROUND: Exercise is an important strategy with potential to improve recovery in older adults following a hip fracture. PURPOSE: The purpose of this study was to test the impact of a self-efficacy based intervention, the Exercise Plus Program, and the different components of the intervention, on self-efficacy, outcome expectations, and exercise behavior among older women post-hip fracture. METHODS: Participants were randomized to one of four groups: exercise plus, exercise only, plus only (i.e., motivation), or routine care. Data collection was done at baseline (within 22 days of fracture), 2, 6, and 12 months post-hip fracture. RESULTS: A total of 209 women were recruited with an average age of 81.0 years (SD=6.9). The majority was White (97.1%), was widowed (57.2%), and had a high school education (66.7%). Generalized Estimating Equations were used to perform repeated measures analyses. No differences in trajectories of recovery were observed for self-efficacy or outcome expectations. A statistically significant difference in the overall trajectory of time in exercise was seen (p<.001), with more time spent exercising in all three treatment groups. CONCLUSIONS: The study demonstrated that it was possible to engage these women in a home-based exercise program and that the plus only, exercise only, and the exercise plus groups all increased exercise.

Association of serum vitamin D levels with inflammatory response following hip fracture: the Baltimore Hip Studies.

BACKGROUND: Vitamin D, known for its role in calcium homeostasis, may also regulate immune function. Whether vitamin D deficiency at the time of hip fracture is associated with the inflammatory response postfracture is not known. METHODS: In a cohort from the Baltimore Hip Studies, women aged >or= 65 years were evaluated at baseline and 2, 6, and 12 months after hip fracture repair. Serum at baseline was analyzed for 25-hydroxyvitamin D [25(OH)D], and serum from all time points was analyzed for interleukin-6 (IL-6). Participants were divided into two groups based on their baseline 25(OH)D levels. Vitamin D deficiency was defined as a 25(OH)D level of

Persistent changes in interleukin-6 and lower extremity function following hip fracture.

BACKGROUND: A hip fracture often heralds a period of functional decline in elderly persons. Although an inflammatory reaction would be expected following a hip fracture, whether the degree of this response is associated with adverse functional outcomes is unknown. METHODS: In a cohort from the Baltimore Hip Studies, women aged 65 years or older with a hip fracture were evaluated at 3 or 10 days (baseline) and 2, 6, and 12 months (follow-up) postfracture. Serum was analyzed for interleukin-6 (IL-6) level. A score of timed performance of 9 tasks, the Lower Extremity Gain Scale (LEGS) was calculated at each evaluation. We divided participants into tertiles based on their cytokine levels at 2, 6, and 12 months, and examined the LEGS score trajectories as a function of IL-6 tertile using generalized estimating equations, adjusting for age, prefracture function, body fat, pain, cognitive function, type of surgical repair, the number of in-hospital complications, and the number of comorbid medical conditions. RESULTS: At baseline, 2, 6, and 12 months, respectively, 149, 95, 101, and 82 participants provided serum samples; of these participants 65, 78, and 59 also provided a LEGS measure at 2, 6, and 12 months, respectively. At 12 months postfracture the median (interquartile range) of serum IL-6 levels was 7.4 (4.0, 15.9) pg/mL. Participants in the lowest tertile of IL-6 level performed better on the LEGS than did those in the highest tertile (p =.008). At 12 months postfracture, participants in the lowest tertile scored 5.3 points better (95% confidence interval, 2.0-8.6) on the LEGS than did those in the highest tertile (p =.002). CONCLUSIONS: Higher IL-6 levels are adversely associated with recovery of lower extremity function after hip fracture. Factors that predict cytokine response and the potential mechanisms by which this effect is mediated warrant further study.

Predictors of bone loss after hip fracture.

Although accelerated bone mineral density (BMD) loss follows hip fracture, little is known about factors associated with this loss. We examined potential predictors of BMD loss in a cohort of community-dwelling women who had sustained hip fracture and who were followed for 1 year after fracture. BMD was measured at the femoral neck, intertrochanteric region, and total body, during hospitalization and 2, 6, and 12 months later. Demographic, health, lifestyle, clinical, surgical, and functional characteristics at baseline, and postfracture activity were evaluated for associations with baseline BMD and BMD 1 year later. To examine possible BMD-dependent effects, high and low baseline BMD groups were defined. None of the studied factors consistently predicted either baseline BMD or BMD at 1 year after fracture, among women with either high or low baseline BMD. Baseline BMD was the only factor that substantially and consistently predicted change, explaining 70% to 90% of variation. These results suggest that BMD will not be preserved by general rehabilitative measures and that prompt, specific intervention to minimize bone loss after hip fracture is an essential element of clinical management of the hip fracture patient.

Classification of heterotopic ossification (HO) in artificial disk replacement.

There is currently no structured classification system to quantitate heterotopic bone formation after artificial disk replacement procedures. The purpose of this work was to develop a method of classifying heterotopic bone formation that is reliable between investigators with different levels of training and easy to remember with only five gradations of severity. One hundred one radiographs of clinical patients and 17 microradiographs from nonhuman primates having undergone various types of disk replacement were classified by seven independent reviewers. The kappa statistics were calculated for interobserver variation between the seven participants with various levels of spinal training and the intraobserver error based on two assessments made at least 2 months apart. The interobserver reliability correlation coefficient for seven raters calculated using the intraclass kappa correlation coefficient and the Kish rho was r = 0.9683 (P < 0.0001). The intraobserver reliability based on readings at two time intervals at a minimum of 2 months apart was r = 0.8949 (P = 0.01). This classification of heterotopic ossification, periannular calcification, and ectopic bone formation associated with total disk arthroplasty proved to be highly reliable and reproducible.