Effect of Dietary Composition of Weight Loss Diets on High Sensitivity C-Reactive Protein: The Randomized POUNDS LOST Trial

Overweight and obesity are associated with increased high sensitivity C-reactive protein (hsCRP) levels. The purpose of this study was to determine if weight loss diets differing in fat, protein, or carbohydrate composition differentially reduce hsCRP. POUNDS (Preventing Overweight Using Novel Dietary Strategies) LOST was a two-year trial of overweight and obese adults randomly allocated to one of four weight loss diets with targeted percentages of energy derived from fat, protein, and carbohydrates (20,15,65%;20,25,55%;40,15,45%;40,25,35%, respectively). hsCRP was measured at baseline, 6, and 24 months among 710 participants, and adiposity as measured by dual X-ray absorptiometry (N=340) or abdominal computed tomography (N=126) was correlated with hsCRP change. At 6 months, hsCRP was reduced in all trial participants by −24.7% (IQR +7%,−50%), weight by −6.7% (IQR −3%,−11%), and waist circumference by −6.0% (IQR −3%,−10%) (all P<.002), with no significant differences according to dietary composition. The percent change in hsCRP at 6 and 24 months correlated modestly with change in weight, waist circumference, fasting insulin, fasting glucose, HOMA, and most lipid levels. Reductions in hsCRP persisted despite an approximate 50% regain of weight by 24 months. The percent change in hsCRP at 24 months significantly correlated with changes in total body fat (r=0.42), total abdominal adiposity (r=0.52), subcutaneous abdominal adiposity (r=0.52), visceral adiposity (r=0.47), and hepatic tissue density (r=−0.34) (all P<0.0006). In conclusion, weight loss decreased hsCRP by similar magnitude, irrespective of dietary composition. Clinicians concerned about inflammation and cardiovascular risk should recommend weight loss diets most likely to succeed for their patients

Association of Physical Activity and Fracture Risk Among Postmenopausal Women

Importance: Physical activity is inversely associated with hip fracture risk in older women. However, the association of physical activity with fracture at other sites and the role of sedentary behavior remain unclear. Objective: To assess the associations of physical activity and sedentary behavior with fracture incidence among postmenopausal women. Design, Setting, and Participants: The Women\u27s Health Initiative prospective cohort study enrolled 77206 postmenopausal women aged 50 to 79 years between October 1993 and December 1998 at 40 US clinical centers. Participants were observed for outcomes through September 2015, with data analysis conducted from June 2017 to August 2019. Exposures: Self-reported physical activity and sedentary time. Main Outcomes and Measures: Hazard ratios (HRs) and 95% CIs for total and site-specific fracture incidence. Results: During a mean (SD) follow-up period of 14.0 (5.2) years among 77206 women (mean [SD] age, 63.4 [7.3] years; 66072 [85.6%] white), 25516 (33.1%) reported a first incident fracture. Total physical activity was inversely associated with the multivariable-adjusted risk of hip fracture ( \u3e 17.7 metabolic equivalent [MET] h/wk vs none: HR, 0.82; 95% CI, 0.72-0.95; P for trend \u3c .001). Inverse associations with hip fracture were also observed for walking ( \u3e 7.5 MET h/wk vs none: HR, 0.88; 95% CI, 0.78-0.98; P for trend = .01), mild activity (HR, 0.82; 95% CI, 0.73-0.93; P for trend = .003), moderate to vigorous activity (HR, 0.88; 95% CI, 0.81-0.96; P for trend = .002), and yard work (HR, 0.90; 95% CI, 0.82-0.99; P for trend = .04). Total activity was positively associated with knee fracture ( \u3e 17.7 MET h/wk vs none: HR, 1.26; 95% CI, 1.05-1.50; P for trend = .08). Mild activity was associated with lower risks of clinical vertebral fracture (HR, 0.87; 95% CI, 0.78-0.96; P for trend = .006) and total fractures (HR, 0.91; 95% CI, 0.87-0.94; P for trend \u3c .001). Moderate to vigorous activity was positively associated with wrist or forearm fracture (HR, 1.09; 95% CI, 1.03-1.15; P for trend = .004). After controlling for covariates and total physical activity, sedentary time was positively associated with total fracture risk ( \u3e 9.5 h/d vs \u3c 6.5 h/d: HR, 1.04; 95% CI, 1.01-1.07; P for trend = .01). When analyzed jointly, higher total activity mitigated some of the total fracture risk associated with sedentary behavior. Analysis of time-varying exposures resulted in somewhat stronger associations for total physical activity, whereas those for sedentary time were materially unchanged. Conclusions and Relevance: In older ambulatory women, higher total physical activity was associated with lower total and hip fracture risk but higher knee fracture risk. Mild activity and walking were associated with lower hip fracture risk, a finding with important public health implications because these activities are common in older adults. The positive association between sedentary time and total fracture risk requires further investigation

Short-term effects of teriparatide versus placebo on bone biomarkers, structure, and fracture healing in women with lower-extremity stress fractures: A pilot study

Aims In this pilot, placebo-controlled study, we evaluated whether brief administration of teriparatide (TPTD) in premenopausal women with lower-extremity stress fractures would increase markers of bone formation in advance of bone resorption, improve bone structure, and hasten fracture healing according to magnetic resonance imaging (MRI). Methods: Premenopausal women with acute lower-extremity stress fractures were randomized to injection of TPTD 20-µg subcutaneous (s.c.) (n = 6) or placebo s.c. (n = 7) for 8 weeks. Biomarkers for bone formation N-terminal propeptide of type I procollagen (P1NP) and osteocalcin (OC) and resorption collagen type-1 cross-linked C-telopeptide (CTX) and collagen type 1 cross-linked N-telopeptide (NTX) were measured at baseline, 4 and 8 weeks. The area between the percent change of P1NP and CTX over study duration is defined as the anabolic window. To assess structural changes, peripheral quantitative computed topography (pQCT) was measured at baseline, 8 and 12 weeks at the unaffected tibia and distal radius. The MRI of the affected bone assessed stress fracture healing at baseline and 8 weeks. Results: After 8 weeks of treatment, bone biomarkers P1NP and OC increased more in the TPTD- versus placebo-treated group (both p ≤ 0.01), resulting in a marked anabolic window (p ≤ 0.05). Results from pQCT demonstrated that TPTD-treated women showed a larger cortical area and thickness compared to placebo at the weight bearing tibial site, while placebo-treated women had a greater total tibia and cortical density. No changes at the radial sites were observed between groups. According to MRI, 83.3% of the TPTD- and 57.1% of the placebo-treated group had improved or healed stress fractures (p = 0.18). Conclusions: In this randomized, pilot study, brief administration of TPTD showed anabolic effects that TPTD may help hasten fracture healing in premenopausal women with lower-extremity stress fractures. Larger prospective studies are warranted to determine the effects of TPTD treatment on stress fracture healing in premenopausal women

Animal versus plant protein and adult bone health: A systematic review and meta-analysis from the National Osteoporosis Foundation

Background: Protein may have both beneficial and detrimental effects on bone health depending on a variety of factors, including protein source. Objective: The aim was to conduct a systematic review and meta-analysis evaluating the effects of animal versus plant protein intake on bone mineral density (BMD), bone mineral content (BMC) and select bone biomarkers in healthy adults. Methods: Searches across five databases were conducted through 10/31/16 for randomized controlled trials (RCTs) and prospective cohort studies in healthy adults that examined the effects of animal versus plant protein intake on 1) total body (TB), total hip (TH), lumbar spine (LS) or femoral neck (FN) BMD or TB BMC for at least one year, or 2) select bone formation and resorption biomarkers for at least six months. Strength of evidence (SOE) was assessed and random effect meta-analyses were performed. Results: Seven RCTs examining animal vs. isoflavone-rich soy (Soy+) protein intake in 633 healthy peri-menopausal (n = 1) and post-menopausal (n = 6) women were included. Overall risk of bias was medium. Limited SOE suggests no significant difference between Soy+ vs. animal protein on LS, TH, FN and TB BMD, TB BMC, and bone turnover markers BSAP and NTX. Meta-analysis results showed on average, the differences between Soy+ and animal protein groups were close to zero and not significant for BMD outcomes (LS: n = 4, pooled net % change: 0.24%, 95% CI: -0.80%, 1.28%; TB: n = 3, -0.24%, 95% CI: -0.81%, 0.33%; FN: n = 3, 0.13%, 95% CI: -0.94%, 1.21%). All meta-analyses had no statistical heterogeneity. Conclusions: These results do not support soy protein consumption as more advantageous than animal protein, or vice versa. Future studies are needed examining the effects of different protein sources in different populations on BMD, BMC, and fracture

Comparison of Weight-Loss Diets with Different Compositions of Fat, Protein, and Carbohydrates

BACKGROUND: The possible advantage for weight loss of a diet that emphasizes protein, fat, or carbohydrates has not been established, and there are few studies that extend beyond 1 year. METHODS: We randomly assigned 811 overweight adults to one of four diets; the targeted percentages of energy derived from fat, protein, and carbohydrates in the four diets were 20, 15, and 65%; 20, 25, and 55%; 40, 15, and 45%; and 40, 25, and 35%. The diets consisted of similar foods and met guidelines for cardiovascular health. The participants were offered group and individual instructional sessions for 2 years. The primary outcome was the change in body weight after 2 years in two-by-two factorial comparisons of low fat versus high fat and average protein versus high protein and in the comparison of highest and lowest carbohydrate content. RESULTS: At 6 months, participants assigned to each diet had lost an average of 6 kg, which represented 7% of their initial weight; they began to regain weight after 12 months. By 2 years, weight loss remained similar in those who were assigned to a diet with 15% protein and those assigned to a diet with 25% protein (3.0 and 3.6 kg, respectively); in those assigned to a diet with 20% fat and those assigned to a diet with 40% fat (3.3 kg for both groups); and in those assigned to a diet with 65% carbohydrates and those assigned to a diet with 35% carbohydrates (2.9 and 3.4 kg, respectively) (P>0.20 for all comparisons). Among the 80% of participants who completed the trial, the average weight loss was 4 kg; 14 to 15% of the participants had a reduction of at least 10% of their initial body weight. Satiety, hunger, satisfaction with the diet, and attendance at group sessions were similar for all diets; attendance was strongly associated with weight loss (0.2 kg per session attended). The diets improved lipid-related risk factors and fasting insulin levels. CONCLUSIONS: Reduced-calorie diets result in clinically meaningful weight loss regardless of which macronutrients they emphasize

The relationship between focal erosions and generalized osteoporosis in postmenopausal women with rheumatoid arthritis

OBJECTIVE: Among rheumatoid arthritis (RA) patients who have had the disease for 10 years, more than half have focal erosions, and the risk of fracture is doubled. However, there is little information about the potential relationship between focal erosions and bone mineral density (BMD). The aim of this study was to determine whether lower BMD is associated with higher erosion scores among patients with RA. METHODS: We enrolled 163 postmenopausal women with RA, none of whom were taking osteoporosis medications. Patients underwent dual x-ray absorptiometry at the hip and spine and hand radiography, and completed a questionnaire. The hand radiographs were scored using the Sharp method, and the relationship between BMD and erosions was measured using Spearman\u27s correlation coefficients and adjusted linear regression models. RESULTS: Patients had an average disease duration of 13.7 years, and almost all were taking a disease-modifying antirheumatic drug. Sixty-three percent were rheumatoid factor (RF) positive. The median modified Health Assessment Questionnaire score was 0.7, and the average Disease Activity Score in 28 joints was 3.8. The erosion score was significantly correlated with total hip BMD (r = -0.33, P \u3c 0.0001), but not with lumbar spine BMD (r = -0.09, P = 0.27). Hip BMD was significantly lower in RF-positive patients versus RF-negative patients (P = 0.02). In multivariable models that included age, body mass index, and cumulative oral glucocorticoid dose, neither total hip BMD nor lumbar spine BMD was significantly associated with focal erosions. CONCLUSION: Our results suggest that hip BMD is associated with focal erosions among postmenopausal women with RA, but that this association disappears after multivariable adjustment. While BMD and erosions may be correlated with bone manifestations of RA, their relationship is complex and influenced by other disease-related factors

Homocysteine levels and risk of hip fracture in postmenopausal women.

BackgroundRecent studies suggest that high homocysteine levels are associated with an increased risk of fractures. Homocysteine levels are known to be influenced by vitamin B and folate supply or status, and poor renal function can result in higher levels independent of nutritional adequacy.ObjectiveThe aim of the study was to determine the associations between fasting homocysteine levels and incident hip fractures, and the effects of other factors on hip fracture risk.DesignWe conducted a case-control study in the Women's Health Initiative Observational Study, a study of postmenopausal women (n = 93,676) recruited in the United States. We selected 400 incident cases of hip fracture and 400 controls matched on age, ethnicity, and blood draw date among women not on osteoporosis therapies. Outcome measures included physician-adjudicated, incident hip fractures. Baseline lifestyle and nutritional questionnaires were performed.ResultsThe risk of hip fracture increased 1.38-fold [95% confidence interval (CI), 1.14, 1.66] for each sd increase in serum homocysteine level after adjustment for fracture risk factors. This association was not affected by adjustment for dietary folate, B6, or B12 intake, but it diminished after adjustment for cystatin-C level (odds ratio, 1.08; 95% CI, 0.66-1.79), a measure of renal function not affected by muscle mass. Among women in the highest quartile of homocysteine and cystatin-C compared to those without elevations in either biomarker, the risk of hip fracture was substantially elevated (odds ratio, 2.8; 95% CI, 1.61-4.87).ConclusionsThis study indicates that high homocysteine levels are associated with an increased risk of hip fracture, which could be accounted for by poor renal function

Wrist Fracture and Risk of Subsequent Fracture: Findings from the Women\u27s Health Initiative Study

Wrist fractures are common in postmenopausal women and are associated with functional decline. Fracture patterns after wrist fracture are unclear. The goal of this study was to determine the frequency and types of fractures that occur after a wrist fracture among postmenopausal women. We carried out a post hoc analysis of data from the Women\u27s Health Initiative Observational Study and Clinical Trials (1993-2010) carried out at 40 US clinical centers. Participants were postmenopausal women aged 50 to 79 years at baseline. Mean follow-up duration was 11.8 years. Main measures included incident wrist, clinical spine, humerus, upper extremity, lower extremity, hip, and total non-wrist fractures and bone mineral density (BMD) in a subset. Among women who experienced wrist fracture, 15.5% subsequently experienced non-wrist fracture. The hazard for non-wrist fractures was higher among women who had experienced previous wrist fracture than among women who had not experienced wrist fracture: non-wrist fracture overall (hazard ratio [HR] = 1.40, 95% confidence interval [CI] 1.33-1.48), spine (HR = 1.48, 95% CI 1.32-1.66), humerus (HR = 1.78, 95% CI 1.57-2.02), upper extremity (non-wrist) (HR = 1.88, 95% CI 1.70-2.07), lower extremity (non-hip) (HR = 1.36, 95% CI 1.26-1.48), and hip (HR = 1.50, 95% CI 1.32-1.71) fracture. Associations persisted after adjustment for BMD, physical activity, and other risk factors. Risk of non-wrist fracture was higher in women who were younger when they experienced wrist fracture (interaction p value 0.02). Associations between incident wrist fracture and subsequent non-wrist fracture did not vary by baseline BMD category (normal, low bone density, osteoporosis). A wrist fracture is associated with increased risk of subsequent hip, vertebral, upper extremity, and lower extremity fractures. There may be substantial missed opportunity for intervention in the large number of women who present with wrist fractures

Aging Well Among Women Veterans Compared With Non-Veterans in the Women's Health Initiative.

Purpose of the studyTo examine whether Veteran status influences (a) women's survival to age 80 years without disease and disability and (b) indicators of successful, effective, and optimal aging at ages 80 years and older.Design and methodsThe Women's Health Initiative (WHI) enrolled 161,808 postmenopausal women aged 50-79 years from 1993 to 1998. We compared successful aging indicators collected in 2011-2012 via mailed questionnaire among 33,565 women (921 Veterans) who reached the age of 80 years and older, according to Veteran status. A second analysis focused on women with intact mobility at baseline who could have reached age 80 years by December 2013. Multinominal logistic models examined Veteran status in relation to survival to age 80 years without major disease or mobility disability versus having prevalent or incident disease, having mobility disability, or dying prior to age 80 years.ResultsWomen Veterans aged 80 years and older reported significantly lower perceived health, physical function, life satisfaction, social support, quality of life, and purpose in life scale scores compared with non-Veterans. The largest difference was in physical function scores (53.0 for Veterans vs 59.5 for non-Veterans; p &lt; .001). Women Veterans were significantly more likely to die prior to age 80 years than non-Veteran WHI participants (multivariate adjusted odds ratio = 1.20; 95% confidence interval, 1.04-1.38). In both Veteran and non-Veteran women, healthy survival was associated with not smoking, higher physical activity, healthy body weight, and fewer depressive symptoms.ImplicationsIntervening upon smoking, low physical activity, obesity, and depressive symptoms has potential to improve chances for healthy survival in older women including Veterans

Optimism, Cynical Hostility, Falls, and Fractures: The Women\u27s Health Initiative Observational Study (WHI-OS)

Traits of optimism and cynical hostility are features of personality that could influence the risk of falls and fractures by influencing risk-taking behaviors, health behaviors, or inflammation. To test the hypothesis that personality influences falls and fracture risk, we studied 87,342 women enrolled in WHI-OS. Optimism was assessed by the Life Orientation Test-Revised and cynical hostility, the cynicism subscale of the Cook-Medley questionnaire. Higher scores indicate greater optimism and hostility. Optimism and hostility were correlated at r = -0. 31, p \u3c 0.001. Annual self-report of falling \u3e /=2 times in the past year was modeled using repeated measures logistic regression. Cox proportional hazards models were used for the fracture outcomes. We examined the risk of falls and fractures across the quartiles (Q) of optimism and hostility with tests for trends; Q1 formed the referent group. The average follow-up for fractures was 11.4 years and for falls was 7.6 years. In multivariable (MV)-adjusted models, women with the highest optimism scores (Q4) were 11% less likely to report \u3e /=2 falls in the past year (odds ratio [OR] = 0.89; 95% confidence intervals [CI] 0.85-0.90). Women in Q4 for hostility had a 12% higher risk of \u3e /=2 falls (OR = 1.12; 95% CI 1.07-1.17). Higher optimism scores were also associated with a 10% lower risk of fractures, but this association was attenuated in MV models. Women with the greatest hostility (Q4) had a modest increased risk of any fracture (MV-adjusted hazard ratio = 1. 05; 95% CI 1.01-1.09), but there was no association with specific fracture sites. In conclusion, optimism was independently associated with a decreased risk of \u3e /=2 falls, and hostility with an increased risk of \u3e /=2 falls, independent of traditional risk factors. The magnitude of the association was similar to aging 5 years. Whether interventions aimed at attitudes could reduce fall risks remains to be determined