Dietary Inflammatory Potential and Bone Outcomes in Midwestern Post-Menopausal Women.

Little is known about the inflammatory potential of diet and its relation to bone health. This cross-sectional study examined the association between the inflammatory potential of diet and bone-related outcomes in midwestern, post-menopausal women enrolled in the Heartland Osteoporosis Prevention Study (HOPS) randomized controlled trial. Dietary intake from the HOPS cohort was used to calculate Dietary Inflammatory Index (DII®) scores, which were energy-adjusted (E-DIITM) and analyzed by quartile. The association between E-DII and lumbar and hip bone mineral density (BMD) and lumbar trabecular bone scores (TBS; bone structure) was assessed using ANCOVA, with pairwise comparison to adjust for relevant confounders (age, education, race/ethnicity, smoking history, family history of osteoporosis/osteopenia, BMI, physical activity, and calcium intake). The cohort included 272 women, who were predominately white (89%), educated (78% with college degree or higher), with a mean BMI of 27 kg/m2, age of 55 years, and E-DII score of -2.0 ± 1.9 (more anti-inflammatory). After adjustment, E-DII score was not significantly associated with lumbar spine BMD (p = 0.53), hip BMD (p = 0.29), or TBS at any lumbar location (p > 0.05). Future studies should examine the longitudinal impact of E-DII scores and bone health in larger, more diverse cohorts.

Risedronate use may blunt appendicular lean mass loss secondary to sleeve gastrectomy: Results from a pilot randomized controlled trial.

Background: Despite robust weight loss and cardiometabolic benefit, lean mass loss following sleeve gastrectomy (SG) confers health risk. Bisphosphonates are a potential therapeutic agent for lean mass maintenance. Thus, our objective was to explore the effect of six months of risedronate (vs placebo) on change in dual energy x-ray absorptiometry (DXA) and computed tomography (CT) derived lean mass metrics in the year following SG. Methods: 24 SG patients were randomized to six months of 150 mg oral risedronate or placebo capsules (NCT03411902). Body composition was assessed at baseline and six months with optional 12-month follow-up using whole-body DXA and CT at the lumbar spine and mid-thigh. Group treatment effects and 95% CIs were generated from a mixed model using contrast statements at six and 12 months, adjusted for baseline values. Results: Of 24 participants enrolled [55.7±6.7 years (mean±SD), 79% Caucasian, 83% women, body mass index (BMI) 44.7±6.3kg/m2], 21 returned for six-month testing, and 14 returned for 12-month testing. Six-month weight loss was -16.3 kg (-20.0, -12.5) and -20.9 kg (-23.7, -18.1) in the risedronate and placebo groups, respectively (p=.057). Primary analysis at six-months revealed a non-significant sparing of appendicular lean mass in the risedronate group compared to placebo [-1.2 kg (-2.3, -0.1) vs -2.1 kg (-3.0, -1.2)]; p=.20. By 12-months, the risedronate group displayed no change in appendicular lean mass from baseline [-0.5 kg (-1.5, 0.6)]; however, the placebo group experienced significantly augmented loss [-2.9 kg (-3.6, -2.1)]. Conclusion: Pilot data indicate risedronate treatment may mitigate appendicular lean mass loss following SG. Further study is warranted.

Bone-loading exercises versus risedronate for the prevention of osteoporosis in postmenopausal women with low bone mass: a randomized controlled trial.

PURPOSE: This randomized controlled trial compared changes in bone mineral density (BMD) and bone turnover in postmenopausal women with low bone mass randomized to 12 months of either risedronate, exercise, or a control group. METHODS: Two hundred seventy-six women with low bone mass, within 6 years of menopause, were included in analysis. Treatment groups were 12 months of (a) calcium and vitamin D supplements (CaD) (control), (b) risedronate + CaD (risedronate), or (c) bone-loading exercises + CaD (exercise). BMD and serum markers for bone formation (Alkphase B) and resorption (Serum Ntx) were analyzed at baseline, 6, and 12 months. RESULTS: Using hierarchical linear modeling, a group by time interaction was found for BMD at the spine, indicating a greater improvement in the risedronate group compared to exercise (p ≤ .010) or control groups (p ≤ .001). At 12 months, for women prescribed risedronate, changes in BMD at the spine, hip, and femoral neck from baseline were + 1.9%, + 0.9%, and + .09%; in exercise group women, + 0.2%, + 0.5%, and - 0.4%; and in control group women, - 0.7%, + 0.5%, and - 0.5%. There were also significant differences in reductions in Alkphase B (RvsE, p < .001, RvsC, p < .001) and Serum Ntx (RvsE, p = .004, RvsC, p = .007) in risedronate women compared to exercise and control groups. For risedronate, 12-month changes in Alkphase B and Serum Ntx were - 20.3% and - 19.0%; for exercise, - 6.7% and - 7.0%; and for control, - 6.3% and - 9.0%. CONCLUSION: Postmenopausal women with low bone mass should obtain adequate calcium and vitamin D and participate in bone-loading exercises. Additional use of BPs will increase BMD, especially at the spine.

Protocol for a pilot randomised controlled trial of zoledronic acid to prevent bone loss following sleeve gastrectomy surgery.

INTRODUCTION: Sleeve gastrectomy (SG) is an increasingly used and effective treatment for obesity; however, the rapid weight loss associated with SG adversely affects bone metabolism predisposing patients to skeletal fragility. Bisphosphonate medications have been evaluated for safety and efficacy in combating bone loss in patients with osteoporosis, but their use in SG-induced bone loss is limited. The goal of this study is to investigate how a one-time infusion of zoledronic acid compares to placebo, in its ability to combat SG-associated bone loss. METHODS AND ANALYSIS: This research protocol is a 9-month, pilot randomized controlled trial (RCT) involving 30 adult SG patients randomised to receive an infusion of either 5 mg of zoledronic acid or placebo, 6 weeks following surgery. To be included participants must be <350 lbs/158.8 kg, free of bone-impacting pathologies or medications, and must have adequate serum calcium and vitamin D levels at baseline. The primary outcome is change in areal bone mineral density (aBMD) at the total hip. Secondary outcomes include change in aBMD of the femoral neck, and lumbar spine, and change in volumetric BMD at the lumbar spine. The primary aim will be tested using a linear mixed model fit with total hip aBMD at 9 months as the outcome. Treatment, participant sex and menopausal status will be considered in analysis. Groups will be compared using contrast statements at 9 months, with change over 9 months being the primary comparison. ETHICS AND DISSEMINATION: This study was approved by the Institutional Review Board of the University of Nebraska Medical Center (IRB820-19). Written consent will be obtained from participants at enrolment by trained staff. Careful and thorough explanation are used in obtainment of consent and voluntariness is emphasised throughout the trial. The findings of this study will be presented locally, nationally, and published in peer-reviewed journals. Additional details will be reported on ClinicalTrials.gov. TRIAL REGISTRATION NUMBER: NCT04279392.

Social Data: An Underutilized Metric for Determining Participation in COVID-19 Vaccinations.

Many measures have been taken since late 2019 to combat the coronavirus disease (COVID-19) pandemic. National, state, and local governments employed precautions, including mask mandates, stay-at-home orders, and social distancing policies, to alleviate the burden on healthcare workers and slow the spread of the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) virus until an efficacious vaccine was made widely available. By early spring of 2021, three effective and well-tolerated SARS-CoV-2 vaccines emerged and underwent broad distribution. Throughout the course of the COVID-19 vaccination campaign, several key logistical and psychological issues surfaced. Of these, access to vaccines and vaccination hesitancy are cited as two substantial hindrances towards vaccination. Noting the demand for the SARS-CoV-2 vaccine and its highly sensitive storage requirements, accurate dose allocation is critical for vaccinating the population quickly and successfully. Here, we propose the use of social data as a tool to predict vaccination participation by correlating Google searches with state-level daily vaccination. We identified a temporal and regionally-ubiquitous Google search syntax that broadly captures daily vaccination trends. By correlating trends in the search syntax with daily vaccination rates, we were able to quantify the correlation and identify optimal lag periods between Google searches and daily vaccination. This work highlights the importance of analyzing social data as a metric to effectively arrange vaccination roll-outs, identify voluntary vaccination participation, and identify inflection points in vaccination participation. In addition, social data assessments can help direct dose allocation, identify geographic areas that may seek, but lack, access to the vaccines, and actively prepare for fluctuations in vaccination demands.

Low Energy Availability with and without a High-Protein Diet Suppresses Bone Formation and Increases Bone Resorption in Men: A Randomized Controlled Pilot Study.

Suppression of insulin-like growth factor 1 (IGF-1) and leptin secondary to low energy availability (LEA) may contribute to adverse effects on bone health. Whether a high-protein diet attenuates these effects has not been tested. Seven men completed three five-day conditions operationally defined as LEA (15 kcal kg fat-free mass (FFM)-1 day-1) with low protein (LEA-LP; 0.8 g protein·kg body weight (BW)-1), LEA with high protein (LEA-HP; 1.7 g protein·kg BW-1) and control (CON; 40 kcal·kg FFM-1·day-1, 1.7 g protein·kg BW-1). In all conditions, participants expended 15 kcal·kg FFM-1·day-1 during supervised cycling sessions. Serum samples were analyzed for markers of bone turnover, IGF-1 and leptin. The decrease in leptin during LEA-LP (-65.6 ± 4.3%) and LEA-HP (-54.3 ± 16.7%) was greater than during CON (-25.4 ± 11.4%; p = 0.02). Decreases in P1NP (p = 0.04) and increases in CTX-I (p = 0.04) were greater in LEA than in CON, suggesting that LEA shifted bone turnover in favour of bone resorption. No differences were found between LEA-LP and LEA-HP. Thus, five days of LEA disrupted bone turnover, but these changes were not attenuated by a high-protein diet.

Promoting adherence to bone-loading exercises in postmenopausal women with low bone mass.

BACKGROUND: We recently completed a parent study (Bone Loading Exercises versus Risedronate on Bone Health in Post-menopausal Women [NIH# R01NR015029]) examining bone-loading exercises to prevent bone loss in postmenopausal women with low bone mass. Forty-three million US women have low bone mass and increased risk for fractures. Bone-loading exercises (weight-bearing and resistance training) can preserve bone mass and decrease risk of fractures. However, multiple barriers prevent women from exercising and adherence rates are low. PURPOSE: This secondary analysis of the parent study (a) examined barriers specific to women participating in bone-loading exercises; (b) described effectiveness of self-efficacy strategies used in the parent study for increasing confidence in knowledge and reducing barriers; and (c) applied study findings and principles of self-efficacy and self-regulation in development of guidelines for promoting adherence to exercises. METHODS: Seventy-two women were randomized to the exercise group and completed 12 months of exercises. Instruments for self-efficacy were completed at 2 weeks and barriers interference at 6 months. Percent adherence was measured as the number of exercise sessions attended divided by the number prescribed. RESULTS: In the 12-month study, average adherence to exercises was 58.9%. Lower adherers reported lack of self-regulation skills such as "lack of time" as the most frequent barriers to exercise. IMPLICATIONS FOR PRACTICE: Guidelines developed included promotion of skills for self-regulation (such as regulation of time) as well as self-efficacy to improve adherence rates. Nurse practitioners may be the most motivated of all providers to use guidelines promoting exercise for women in their clinical practice.

Approaches to Recruitment of Postmenopausal Women for a Community-Based Study.

BACKGROUND: Few researchers have focused on the challenges of recruiting postmenopausal women for community-based research. Researchers have reported that multiple methods may be needed to recruit the required number of subjects. One contemporary approach to recruitment is use of Facebook. More studies are needed examining Facebook as a recruitment strategy. OBJECTIVE: The aim of the study was to examine which recruitment methods were most successful and cost-effective in recruiting postmenopausal women for a randomized controlled trial on bone loss. METHODS: Subjects were 276 postmenopausal women who had osteopenia and were within 5 years of menopause. Multiple methods were used to recruit women. To determine which methods were successful, women were asked how they learned about the study. Descriptive data were used to examine recruitment numbers as well as to determine the cost-effectiveness and enrollment efficiency of recruitment methods. RESULTS: Healthcare provider letters yielded the highest number of enrolled subjects (n = 58), followed by postcard mailings (n = 47), and Facebook posts (n = 44). Eleven subjects were referred by family and friends, five subjects were from newspaper or television, and two were from digital ads. Cost of recruitment per subject enrolled was highest with digital ads and postcard mailings. DISCUSSION: Recruitment could be more costly and time-consuming than anticipated. Recruitment using direct-targeted mailings, such as provider letters and postcards, was successful in our study and has been effective in previous studies reviewed. Facebook was successful for recruitment in our study and may continue to be useful for recruitment in the future, as the number of women accessing Facebook continues to increase.

Protocol for a randomized controlled trial to compare bone-loading exercises with risedronate for preventing bone loss in osteopenic postmenopausal women.

BACKGROUND: In the United States, over 34 million American post-menopausal women have low bone mass (osteopenia) which increases their risk of osteoporosis and fractures. Calcium, vitamin D and exercise are recommended for prevention of osteoporosis, and bisphosphonates (BPs) are prescribed in women with osteoporosis. BPs may also be prescribed for women with low bone mass, but are more controversial due to the potential for adverse effects with long-term use. A bone loading exercise program (high-impact weight bearing and resistance training) promotes bone strength by preserving bone mineral density (BMD), improving bone structure, and by promoting bone formation at sites of mechanical stress. METHODS/DESIGN: The sample for this study will be 309 women with low bone mass who are within 5 years post-menopause. Subjects are stratified by exercise history (≥2 high intensity exercise sessions per week; < 2 sessions per week) and randomized to a control or one of two treatment groups: 1) calcium + vitamin D (CaD) alone (Control); 2) a BP plus CaD (Risedronate); or 3) a bone loading exercise program plus CaD (Exercise). After 12 months of treatment, changes in bone structure, BMD, and bone turnover will be compared in the 3 groups. Primary outcomes for the study are bone structure measures (Bone Strength Index [BSI] at the tibia and Hip Structural Analysis [HSA] scores). Secondary outcomes are BMD at the hip and spine and serum biomarkers of bone formation (alkaline phosphase, AlkphaseB) and resorption (Serum N-terminal telopeptide, NTx). Our central hypothesis is that improvements in bone strength will be greater in subjects randomized to the Exercise group compared to subjects in either Control or Risedronate groups. DISCUSSION: Our research aims to decrease the risk of osteoporotic fractures by improving bone strength in women with low bone mass (pre-osteoporotic) during their first 5 years' post-menopause, a time of rapid and significant bone loss. Results of this study could be used in developing a clinical management pathway for women with low bone mass at their peak period of bone loss that would involve lifestyle modifications such as exercises prior to medications such as BPs. TRIAL REGISTRATION: Clinicaltrials.gov NCT02186600 . Initial registration: 7/7/2014.

Changes in the frequencies of human hematopoietic stem and progenitor cells with age and site.

This study enumerated CD45(hi)/CD34(+) and CD45(hi)/CD133(+) human hematopoietic stem cells (HSCs) and progenitor granulocyte-macrophage colony forming cells (GM-CFCs) in blood and trochanteric and femoral bone marrow in 233 individuals. Stem cell frequencies were determined with multiparameter flow cytometry and using an internal control to determine the intrinsic variance of the assays. Progenitor cell frequency was determined using a standard colony assay technique. The frequency of outliers from undetermined methodological causes was highest for blood, but less than 5% for all values. The frequency of CD45(hi)/CD133(+) cells correlated highly with the frequency of CD45(hi)/CD34(+) cells in trochanteric and femoral bone marrow. The frequency of these HSC populations in trochanteric and femoral bone marrow rose significantly with age. In contrast, there was no significant trend of either of these cell populations with age in the blood. Trochanteric marrow progenitor GM-CFCs showed no significant trends with age, but femoral marrow GM-CFCs trended downward with age, potentially because of the reported conversion of red marrow at this site to fat with age. Hematopoietic stem and progenitor cells exhibited changes in frequencies with age that differed between blood and bone marrow. We previously reported that side population (SP) multipotential HSC, which includes the precursors of CD45(hi)/CD133(+) and CD45(hi)/CD34(+), decline with age. Potentially the increases in stem cell frequencies in the intermediate compartment between SP and GM progenitor cells observed in this study represent a compensatory increase for the loss of more potent members of the HSC hierarchy.

Inflammation associated with obesity: relationship with blood and bone marrow endothelial cells.

The purpose of this study was to assess the inflammatory nature of obesity and its effect on blood and bone marrow endothelial cell populations. Obese patients (BMI ≥30) had significantly higher concentrations of the inflammatory marker C-reactive protein (CRP) (P = 0.03) and lower concentrations of the anti-inflammatory cytokine interleukin-10 (IL-10) (P = 0.05). This cytokine profile is consistent with obesity being an inflammatory condition and is further supported by the significant correlation between total white blood cell count and BMI (r = 0.15; P = 0.035). High BMI was associated with significantly lower numbers of early endothelial cells (CD45(-)/CD34(+)) in the bone marrow (r = -0.20; P = 0.0068). There was also a significant inverse correlation between BMI and a more mature endothelial cell phenotype (CD45(-)/31(+)) in the blood (r = -0.17; P = 0.02). In addition, there was a significant correlation between BMI- and endothelial-related cells of hematopoietic origin (CD133(+)/VEGFR-2(+)) in the bone marrow (r = -0.26; P = 0.0007). Patients with higher plasma IL-10 and insulin-like growth factor (IGF) concentrations had higher numbers of endothelial phenotypes in the bone marrow suggesting a protective effect of these anti-inflammatory cytokines. In conclusion, this work confirms the inflammatory nature of obesity and is the first to report that obesity is associated with reduced endothelial cell numbers in the bone marrow of humans. These effects of obesity may be a potential mechanism for impaired tissue repair in obese patients.

Use of the Human Activity Profile for estimating fitness in persons with arthritis.

OBJECTIVE: To evaluate the usefulness of the Human Activity Profile (HAP) in predicting estimated maximal oxygen uptake (VO(2max)) in persons with arthritis and to evaluate the ability of 2 classification systems to distinguish individuals with arthritis who have poor fitness from those with average and above fitness. METHODS: Forty-four subjects with arthritis completed the HAP and a submaximal treadmill test. The adjusted activity score (AAS) was derived from responses on the HAP. VO(2max) was estimated from the submaximal treadmill test. The ability of the AAS and age to predict estimated VO(2max) was determined with multiple regression analysis. Subjects were also assigned to a fitness category based on their AAS and estimated VO(2max), and agreement of these categories was assessed using the kappa statistic. Two classification systems were used, including one proposed by the original authors and one we proposed based on more recent normative data. RESULTS: Sixty-six percent of the variance in estimated VO(2max) could be accounted for by the AAS and age. The kappa statistic for our proposed classification system was 0.35, indicating fair agreement, whereas the kappa statistic for the original classification system was incalculable. The sensitivity of the proposed classification system to identify persons with average and above fitness was 84%, with a specificity of 50%. CONCLUSION: We suggest that the HAP is useful in estimating fitness level when standard exercise testing is not feasible.

Evaluation of the human activity profile for use with persons with arthritis.

OBJECTIVE: To investigate the reliability, validity, and responsiveness to change of the Human Activity Profile (HAP), a questionnaire measuring physical activity, in persons with arthritis. METHODS: Twenty-eight subjects completed the following self-report questionnaires: HAP, Modified Health Assessment Questionnaire, Medical Outcomes Study 36-Item Short Form Health Survey, and Arthritis Impact Measurement Scale 2. Subjects also completed a submaximal treadmill test, Timed-Stands Test, and 50-Foot Walk Test. Responses on the HAP resulted in 2 scores: the maximum activity score (MAS) and the adjusted activity score (AAS). These scores were correlated with the other tests and examined for test-retest reliability. A subset of subjects participated in a 12-week exercise program, repeating the same tests when finished. RESULTS: For all subjects, the intraclass correlation coefficient (ICC) was 0.76 for the MAS and 0.87 for the AAS. Significant correlations were found between the HAP scores and the questionnaires, submaximal treadmill test, Timed-Stands Test, and 50-Foot Walk Test. In response to 12 weeks of exercise, both HAP scores had an effect size of 0.5, similar to that of the other questionnaires. CONCLUSION: The ICCs demonstrate that the HAP is reliable, and the correlations between the HAP and other questionnaires, Timed-Stands Test, and 50-Foot Walk Test demonstrate that the HAP is a valid measure of physical function in persons with arthritis. The HAP's correlation with maximum oxygen consumption estimated by the treadmill test validates it as a measure of physical activity. The medium effect size (0.5) demonstrates that the HAP is moderately responsive to change. Its ease of use and broad scope make it a valuable assessment tool for persons with arthritis.