Association between Dietary Intake of Phosphorus and Measures of Obesity in the Jackson Heart Study.

BACKGROUND: The relation between phosphorus (P) intake and obesity is equivocal, with hypotheses in both directions. OBJECTIVES: We investigated the relationship between P intake, assessed from a current database, and calculated bioavailable P intake, and obesity among African American adults. METHODS: We examined associations between original and bioavailable P (total, added, and natural), and body mass index (BMI) and waist circumference (WC) in a cross-sectional study of 5306 African American adults (21-84 y) from the Jackson Heart Study. A total of 3300 participants had complete interviews, valid dietary data, and normal kidney function. Diet was assessed by FFQ. A novel algorithm was used to estimate P bioavailability. BMI or WC was regressed on each P variable, adjusting for total energy intake and potential confounders. RESULTS: After adjusting for covariates, original P (total and added) and bioavailable P (total and added) intakes (expressed/100 mg) were associated with BMI (ß = 0.11, 0.67, 0.31, and 0.71, respectively, all P < 0.0001). Neither original nor bioavailable natural P were significantly associated, (ß = -0.03 and 0.09, respectively, both P > 0.05). When added and natural P were included in the same model, added P (original and bioavailable) intakes remained strongly associated with BMI (0.70 and 0.73, respectively, both P < 0.0001). Similar results were seen for WC. Intake of original added P tended to be more strongly associated with BMI, in females (ß = 0.72, P < 0.0001) than in males (ß = 0.56, P = 0.003) (Pinteraction = 0.06). CONCLUSION: We found that greater intake of added, not natural, which may be a proxy for intake of processed foods was associated with higher BMI and WC. These were somewhat stronger when bioavailability was considered, and for women than for men. Further investigation is needed to fully understand the mechanisms driving these associations.

Genome-wide association study of osteoporosis identifies genetic risk and interactions with DASH diet and sugar sweetened beverages in a Hispanic cohort of older adults.

BACKGROUND: Osteoporosis (OP) and low bone mass can be debilitating and costly conditions if not acted on quickly. This disease is also difficult to diagnose as symptoms develop unnoticed until fracture occurs. Therefore, gaining understanding of the genetic risk associated with these conditions could be beneficial for healthcare professionals in early detection and prevention. METHODS: The Boston Puerto Rican Osteoporosis (BPROS) study, an ancillary study to the Boston Puerto Rican Health Study (BPRHS), collected information regarding bone and bone health. All bone measurements were taken during regular BPROS visits using dual-energy x-ray absorptiometry. Osteoporosis was defined as T-score ≤ -2.5 (2.5 SD or more below peak bone mass). Dietary variables were collected at the second wave of the BPRHS via food frequency questionnaire. We conducted genome-wide associations with bone outcomes including bone mineral density (BMD) and OP for 978 participants. We also examined interactions with dietary quality on the relationships between genotype and bone outcomes. We further tested if candidate genetic variants described in previous GWAS on OP and BMD contribute to OP risk in this population. RESULTS: Four variants were associated with OP: rs114829316 (IQCJ), rs76603051, rs12214684 (MCHR2), and rs77303493 (RIN2), and two variants with BMD of lumbar spine (rs11855618, CGNL1) and hip (rs73480593, NTRK2), reaching the genome-wide significance threshold of P ≤ 5E-08. In a gene-diet interaction analysis, we found that one SNP showed a significant interaction with the overall DASH score, and 7 SNPs with sugar-sweeten beverages, a major contributor to the DASH score. CONCLUSION: This study identifies new genetic markers related to osteoporosis and BMD in older Hispanic adults. Additionally, we uncovered unique genetic markers that interact with dietary quality, specifically sugar-sweetened beverages, in relation to bone health. These findings may be useful to guide early detection and preventative care.

Daily yogurt consumption does not affect bone turnover markers in men and postmenopausal women of Caribbean Latino descent: a randomized controlled trial.

BACKGROUND: Caribbean Latino adults are at high risk for osteoporosis yet remain underrepresented in bone research. This increased risk is attributed to genetics, diet, and lifestyle known to drive inflammation and microbial dysbiosis. OBJECTIVE: The primary objective of this study was to determine whether consuming 5 oz of yogurt daily for 8wks improves bone turnover markers (BTMs) among Caribbean Latino adults > 50 years; and secondarily to determine the impact on the gut microbiota and markers of intestinal integrity and inflammation. METHODS: Following a 4wk baseline period, participants were randomized to an 8wk whole fat yogurt intervention (n = 10) daily, containing only Streptococcus thermophilus and Lactobacillus bulgaricus, or to an untreated control group that did not consume yogurt (n = 10). Blood and stool samples collected at week-0 and week-8 were used to assess BTMs, inflammation, intestinal integrity biomarkers, and gut microbiota composition, short chain fatty acids (SCFAs), respectively. Data were evaluated for normality and statistical analyses were performed. RESULTS: Participants were 55% women, with a mean age of 70 ± 9 years, BMI 30 ± 6 kg/m2, and serum C-reactive protein 4.8 ± 3.6 mg/L, indicating chronic low-grade inflammation. Following 8wks of yogurt intake, absolute change in BTMs did not differ significantly between groups (P = 0.06-0.78). Secondarily, absolute change in markers of inflammation, intestinal integrity, and fecal SCFAs did not differ significantly between groups (P range 0.13-1.00). Yogurt intake for 8wks was significantly associated with microbial compositional changes of rare taxa (P = 0.048); however, no significant alpha diversity changes were observed. CONCLUSIONS: In this study, daily yogurt did not improve BTMs, inflammation, intestinal integrity, nor SCFAs. However, yogurt did influence beta diversity, or the abundance of rare taxa within the gut microbiota of the yogurt group, compared to controls. Additional research to identify dietary approaches to reduce osteoporosis risk among Caribbean Latino adults is needed. TRIAL REGISTRATION: This study is registered to ClinicalTrials.gov, NCT05350579 (28/04/2022).

The longitudinal impact of the SARS-CoV-2 pandemic on participants from the Boston Puerto Rican Health Study.

Objective: to investigate the impact of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic on older Hispanic adults. Methods: A total of 522 participants (or their family member, if deceased) from the Boston Puerto Rican Health Study were asked whether they had been diagnosed with SARS-CoV-2, across 2 survey phases. In phase 1 (May - Aug 2020, n=497), participants answered survey questions related to SARS-CoV-2 exposure, diagnosis, and transmission and 5 family members reported deaths. In phase 2, participants were again surveyed (January - June 2021; n=420, and 2 family members reported deaths). SARS-CoV-2 diagnosis and/or death apparently from SARS-CoV-2 was self-reported. Results: In 2020, 5.2% reported that they had been SARS-CoV-2 positive; by June 2021, a cumulative 11.0% reported having been SARS-CoV-2 positive (including cases and deaths in the first survey). A total of 7 participants (1.3%) reportedly died from SARS-CoV-2. Language acculturation was significantly lower among participants with SARS-CoV-2 (13.7 ± 17.9) vs. without SARS-CoV-2 (20.0 ± 21.4; P = 0.049). Mean length of return to usual health was 28 ± 38 days (range: 0-210 days; median = 15 days). Depressive symptomatology was significantly lower during the pandemic (CES-D score: 13.4 ± 11.6) compared to the same participants pre-pandemic (17.8 ± 11.7; P = 0.001). Compared to the months before the pandemic, 32% (n=135) of participants reported greater communication with friends and family, and 41% (n=172) reported no change. Conclusions: Public health models should be personalized to communities, considering their unique structures and cultural beliefs. Social resiliency may be key for future programmatic responses to pandemics to reduce the mental health burden.

Association between a Calcium-to-Magnesium Ratio and Osteoporosis among Puerto Rican Adults.

BACKGROUND: The ratio of calcium-to-magnesium intake (Ca:Mg) may be important for bone due to their competitive absorption. The Ca:Mg ratio has been related to health outcomes, but few studies have related it to bone. OBJECTIVES: The purpose of this analysis was to examine associations between the Ca:Mg intake with bone mineral density (BMD) and osteoporosis among Puerto Rican adults. METHODS: Adults, aged 47-79 y, from the Boston Puerto Rican Osteoporosis Study, with complete BMD and dietary data (n = 955) were included. BMD was assessed with dual-energy X-ray absorptiometry and diet by a food frequency questionnaire. Calcium and magnesium intakes from food were energy adjusted, and the Ca:Mg was calculated. Adjusted linear and logistic regression models were utilized for testing associations between Ca:Mg and bone outcomes. RESULTS: Calcium intake was greater in the highest compared with lowest tertile, whereas magnesium intake was similar across tertiles. Mean BMD at hip sites was higher in the middle, compared with the lowest, tertile. Higher odds of osteoporosis were observed for the highest and lowest tertiles, compared with the middle tertile, after adjustment (T3 compared with T2 OR: 2.79; 95% CI: 1.47, 5.3; T1 compared with T2 OR: 2.01; 95% CI: 1.03, 3.92). Repeated analyses without supplement users (n = 432) led to stronger differences and ORs, but lost significance for some comparisons. CONCLUSIONS: Dietary calcium and magnesium are important for bone, perhaps not independently. The Ca:Mg intake ratio appeared most protective within a range of 2.2-3.2, suggesting that a balance of these nutrients may be considered in recommendations for osteoporosis..

Validity of a Smartphone Application in Calculating Measures of Heart Rate Variability.

The purpose of the current study was to determine the concurrent validity of the Elite HRV smartphone application when calculating heart rate variability (HRV) metrics in reference to an independent software criterion. A total of 5 minutes of R−R interval and natural log of root mean square of the successive differences (lnRMSSD) resting HRV data were simultaneously collected using two Polar H10 heart rate monitors (HRMs) in both the seated and supine positions from 22 participants (14 males, 8 females). One H10 HRM was paired with a Polar V800 watch and one with the Elite HRV application. When no artifact correction was applied, significant, but small, differences in the lnRMSSD data were observed between the software in the seated position (p = 0.022), and trivial and nonstatistically significant differences were observed in the supine position (p = 0.087). However, significant differences (p > 0.05) in the lnRMSSD data were no longer identifiable in either the seated or the supine positions when applying Very Low, Low, or Automatic artifact-correction filters. Additionally, excellent agreements (ICC3,1 = 0.938 − 0.998) and very strong to near-perfect (r = 0.889 − 0.997) relationships were observed throughout all correction levels. The Elite HRV smartphone application is a valid tool for calculating resting lnRMSSD HRV metrics.

Efficacy and Safety of Elexacaftor/Tezacaftor/Ivacaftor in Children 6 Through 11 Years of Age with Cystic Fibrosis Heterozygous for F508del and a Minimal Function Mutation: A Phase 3b, Randomized, Placebo-controlled Study.

Rationale: The triple-combination regimen elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) was shown to be safe and efficacious in children aged 6 through 11 years with cystic fibrosis and at least one F508del-CFTR allele in a phase 3, open-label, single-arm study. Objectives: To further evaluate the efficacy and safety of ELX/TEZ/IVA in children 6 through 11 years of age with cystic fibrosis heterozygous for F508del and a minimal function CFTR mutation (F/MF genotypes) in a randomized, double-blind, placebo-controlled phase 3b trial. Methods: Children were randomized to receive either ELX/TEZ/IVA (n = 60) or placebo (n = 61) during a 24-week treatment period. The dose of ELX/TEZ/IVA administered was based on weight at screening, with children <30 kg receiving ELX 100 mg once daily, TEZ 50 mg once daily, and IVA 75 mg every 12 hours, and children ⩾30 kg receiving ELX 200 mg once daily, TEZ 100 mg once daily, and IVA 150 mg every 12 hours (adult dose). Measurements and Main Results: The primary endpoint was absolute change in lung clearance index2.5 from baseline through Week 24. Children given ELX/TEZ/IVA had a mean decrease in lung clearance index2.5 of 2.29 units (95% confidence interval [CI], 1.97-2.60) compared with 0.02 units (95% CI, -0.29 to 0.34) in children given placebo (between-group treatment difference, -2.26 units; 95% CI, -2.71 to -1.81; P < 0.0001). ELX/TEZ/IVA treatment also led to improvements in the secondary endpoint of sweat chloride concentration (between-group treatment difference, -51.2 mmol/L; 95% CI, -55.3 to -47.1) and in the other endpoints of percent predicted FEV1 (between-group treatment difference, 11.0 percentage points; 95% CI, 6.9-15.1) and Cystic Fibrosis Questionnaire-Revised Respiratory domain score (between-group treatment difference, 5.5 points; 95% CI, 1.0-10.0) compared with placebo from baseline through Week 24. The most common adverse events in children receiving ELX/TEZ/IVA were headache and cough (30.0% and 23.3%, respectively); most adverse events were mild or moderate in severity. Conclusions: In this first randomized, controlled study of a cystic fibrosis transmembrane conductance regulator modulator conducted in children 6 through 11 years of age with F/MF genotypes, ELX/TEZ/IVA treatment led to significant improvements in lung function, as well as robust improvements in respiratory symptoms and cystic fibrosis transmembrane conductance regulator function. ELX/TEZ/IVA was generally safe and well tolerated in this pediatric population with no new safety findings.

Red meat consumption, incident CVD and the influence of dietary quality in the Jackson Heart Study.

OBJECTIVES: We investigated the prospective associations between meat consumption and CVD and whether these relationships differ by dietary quality among African American (AA) adults. DESIGN: Baseline diet was assessed with a regionally specific FFQ. Unprocessed red meat included beef and pork (120 g/serving); processed meat included sausage, luncheon meats and cured meat products (50 g/serving). Incident total CVD, CHD, stroke and heart failure were assessed annually over 9·8 years of follow-up. We characterised dietary quality using a modified Healthy Eating Index-2010 score (m-HEI), excluding meat contributions. SETTING: Jackson, MS, USA. PARTICIPANTS: AA adults (n 3242, aged 55 y, 66 % female). RESULTS: Mean total, unprocessed red and processed meat intakes were 5·7 ± 3·5, 2·3 ± 1·8 and 3·3 ± 2·7 servings/week, respectively. Mostly, null associations were observed between meat categories and CVD or subtypes. However, greater intake of unprocessed red meat (three servings/week) was associated with significantly elevated risk of stroke (hazard ratio = 1·43 (CI: 1·07,1·90)). With the exception of a more positive association between unprocessed meat consumption and stroke among individuals in m-HEI Tertile 2, the strength of associations between meat consumption categories and CVD outcomes did not differ by m-HEI tertile. In formal tests, m-HEI did not significantly modify meat-CVD associations. CONCLUSIONS: In this cohort of AA adults, total and processed meat were not associated with CVD outcomes, with the exception that unprocessed red meat was related to greater stroke risk. Dietary quality did not modfiy these associations. Research is needed in similar cohorts with longer follow-up and greater meat consumption to replicate these findings.

Bioavailability of phosphorus and kidney function in the Jackson Heart Study.

BACKGROUND: High phosphorus (P) exposure may have negative effects on kidney function. Nutrient databases provide total P, but bioavailability varies by source. OBJECTIVES: We aimed to assess natural, added, and bioavailable P intake, and to relate these to estimated glomerular filtration rate (eGFR) in the Jackson Heart Study (JHS). METHODS: A total of 3962 African-American participants of the JHS, aged 21-84 y, with urine albumin:creatinine ratio < 30 mg/g, and eGFR ≥ 60 mL · min-1 · 1.73 m-2, and without self-reported kidney disease, were included. Diet was assessed by FFQ. We assigned P in foods as naturally occurring or added, and weighted intake by P bioavailability, based on published literature. Relations between P variables and eGFR were assessed using multivariable regression. RESULTS: Mean ± SE intakes were 1178 ± 6.7 mg and 1168 ± 5.0 mg for total P, 296 ± 2.8 mg and 291 ± 2.1 mg for bioavailable added P, and 444 ± 2.9 mg and 443 ± 2.2 mg for bioavailable natural P, in participants with eGFR = 60-89 and ≥90 mL · min-1 · 1.73 m-2, respectively. Major sources of total P included fish, milk, beef, eggs, cheese, and poultry; and of added P, fish, beef, processed meat, soft drinks, and poultry. After adjustment for confounders, P intakes, including total (ß ± SE: -0.32 ± 0.15; P = 0.03), added (ß ± SE: -0.73 ± 0.27; P = 0.01), bioavailable total (ß ± SE: -0.62 ± 0.23; P = 0.01), and bioavailable added (ß ± SE: -0.77 ± 0.29; P = 0.01), were significantly associated with lower eGFR. However, neither total nor bioavailable P from natural sources were associated with eGFR. CONCLUSIONS: Added, but not natural, P was negatively associated with kidney function, raising concern about P additives in the food supply. Further studies are needed to improve estimation of dietary P exposure and to clarify the role of added P as a risk factor for kidney disease.

Inflammation biomarkers in sputum for clinical trials in cystic fibrosis: current understanding and gaps in knowledge.

RATIONALE: Sputum biomarkers hold promise as a direct measure of inflammation within the cystic fibrosis (CF) lung, but variability in study design and sampling methodology have limited their use. A full evaluation of the reliability, validity and clinical relevance of individual biomarkers is required to optimise their use within CF clinical research. OBJECTIVES: A biomarker Special Interest Working Group was established within the European Cystic Fibrosis Society-Clinical Trials Network Standardisation Committee, to perform a review of the evidence regarding sputum biomarkers in CF. METHODS: From the 139 included articles, we identified 71 sputum biomarkers to undergo evaluation of their clinimetric properties, responsiveness, discriminant, concurrent and convergent validity. RESULTS: Current evidence confirms the potential of sputum biomarkers as outcome measures in clinical trials. Inconsistency in responsiveness, concurrent and convergent validity require further research into these markers and processing standardisation before translation into wider use. Of the 71 biomarkers identified, Neutrophil Elastase (NE), IL-8, TNF-α and IL-1ß, demonstrated validity and responsiveness to be currently considered for use in clinical trials. Other biomarkers show future promise, including IL-6, calprotectin, HMGB-1 and YKL-40. CONCLUSION: A concerted international effort across the cystic fibrosis community is needed to promote high quality biomarker trial design, establish large population-based biomarker studies, and work together to create standards for collection, storage and analysis of sputum biomarkers.

Correlating genotype with phenotype using CFTR-mediated whole-cell Cl- currents in human nasal epithelial cells.

Dysfunction of the epithelial anion channel cystic fibrosis transmembrane conductance regulator (CFTR) causes a wide spectrum of disease, including cystic fibrosis (CF) and CFTR-related diseases (CFTR-RDs). Here, we investigate genotype-phenotype-CFTR function relationships using human nasal epithelial (hNE) cells from a small cohort of non-CF subjects and individuals with CF and CFTR-RDs and genotypes associated with either residual or minimal CFTR function using electrophysiological techniques. Collected hNE cells were either studied directly with the whole-cell patch-clamp technique or grown as primary cultures at an air-liquid interface after conditional reprogramming. The properties of cAMP-activated whole-cell Cl- currents in freshly isolated hNE cells identified them as CFTR-mediated. Their magnitude varied between hNE cells from individuals within the same genotype and decreased in the rank order: non-CF > CFTR residual function > CFTR minimal function. CFTR-mediated whole-cell Cl- currents in hNE cells isolated from fully differentiated primary cultures were identical to those in freshly isolated hNE cells in both magnitude and behaviour, demonstrating that conditional reprogramming culture is without effect on CFTR expression and function. For the cohort of subjects studied, CFTR-mediated whole-cell Cl- currents in hNE cells correlated well with CFTR-mediated transepithelial Cl- currents measured in vitro with the Ussing chamber technique, but not with those determined in vivo with the nasal potential difference assay. Nevertheless, they did correlate with the sweat Cl- concentration of study subjects. Thus, this study highlights the complexity of genotype-phenotype-CFTR function relationships, but emphasises the value of conditionally reprogrammed hNE cells in CFTR research and therapeutic testing. KEY POINTS: The genetic disease cystic fibrosis is caused by pathogenic variants in the cystic fibrosis transmembrane conductance regulator (CFTR), an ion channel, which controls anion flow across epithelia lining ducts and tubes in the body. This study investigated CFTR function in nasal epithelial cells from people with cystic fibrosis and CFTR variants with a range of disease severity. CFTR function varied widely in nasal epithelial cells depending on the identity of CFTR variants, but was unaffected by conditional reprogramming culture, a cell culture technique used to grow large numbers of patient-derived cells. Assessment of CFTR function in vitro in nasal epithelial cells and epithelia, and in vivo in the nasal epithelium and sweat gland highlights the complexity of genotype-phenotype-CFTR function relationships.

Sufficient Plasma Vitamin C Is Related to Greater Bone Mineral Density among Postmenopausal Women from the Boston Puerto Rican Health Study.

BACKGROUND: Vitamin C may benefit bone as an antioxidant. OBJECTIVES: This cross-sectional study evaluated associations between dietary, supplemental, and plasma vitamin C with bone mineral density (BMD) among Puerto Rican adults. METHODS: Diet was assessed by food-frequency questionnaire (n = 902); plasma vitamin C, measured in fasting blood (n = 809), was categorized as sufficient (≥50 µmol/L), insufficient (20-49 µmol/L), or low (<20 µmol/L). Associations between vitamin C and BMD (measured by DXA) were tested, with false discovery rate correction for multiple comparisons, and interactions by smoking, sex, and estrogen status. Least-squares mean BMDs were compared across tertiles of diet and plasma vitamin C. RESULTS: Participants' mean age was 59 ± 7 y (range: 46-78 y), 72% were women, mean dietary vitamin C was 95 ± 62 mg/d, and plasma vitamin C ranged from 1.7 to 125 µmol/L. No associations were observed between dietary vitamin C and BMD (P-value range: 0.48-0.96). BMD did not differ by vitamin C supplement use (P-value range: 0.07-0.29). Total femur BMD was higher (P = 0.04) among plasma vitamin C-sufficient participants (mean: 1.06; 95% CI: 1.035, 1.076 g/cm2) compared with low plasma vitamin C participants (1.026; 0.999, 1.052 g/cm2) in adjusted models. Findings at the trochanter were similar (P = 0.04). Postmenopausal women without estrogen therapy, with sufficient plasma vitamin C, showed greater total femur BMD (1.004 ± 0.014 g/cm2) compared to those with low plasma vitamin C (0.955 ± 0.017 g/cm2; P = 0.001). Similar findings were observed at the trochanter (P < 0.001). No significant associations were observed among premenopausal women or those with estrogen therapy or men. Interactions with smoking status were not significant. CONCLUSIONS: Dietary vitamin C was not associated with BMD. Low plasma vitamin C, compared with sufficiency, was associated with lower hip BMD, particularly among postmenopausal women without estrogen therapy. Future research is needed to determine whether vitamin C status is associated with change in BMD or reduction in fracture risk.

Metabolite patterns link diet, obesity, and type 2 diabetes in a Hispanic population.

INTRODUCTION: Obesity is a precursor of type 2 diabetes (T2D). OBJECTIVES: Our aim was to identify metabolic signatures of T2D and dietary factors unique to obesity. METHODS: We examined a subsample of the Boston Puerto Rican Health Study (BPRHS) population with a high prevalence of obesity and T2D at baseline (n = 806) and participants (without T2D at baseline) at 5-year follow-up (n = 412). We determined differences in metabolite profiles between T2D and non-T2D participants of the whole sample and according to abdominal obesity status. Enrichment analysis was performed to identify metabolic pathways that were over-represented by metabolites that differed between T2D and non-T2D participants. T2D-associated metabolites unique to obesity were examined for correlation with dietary food groups to understand metabolic links between dietary intake and T2D risk. False Discovery Rate method was used to correct for multiple testing. RESULTS: Of 526 targeted metabolites, 179 differed between T2D and non-T2D in the whole sample, 64 in non-obese participants and 120 unique to participants with abdominal obesity. Twenty-four of 120 metabolites were replicated and were associated with T2D incidence at 5-year follow-up. Enrichment analysis pointed to three metabolic pathways that were overrepresented in obesity-associated T2D: phosphatidylethanolamine (PE), long-chain fatty acids, and glutamate metabolism. Elevated intakes of three food groups, energy-dense takeout food, dairy intake and sugar-sweetened beverages, associated with 13 metabolites represented by the three pathways. CONCLUSION: Metabolic signatures of lipid and glutamate metabolism link obesity to T2D, in parallel with increased intake of dairy and sugar-sweetened beverages, thereby providing insight into the relationship between dietary habits and T2D risk.

Racial and Ethnic Disparities in Bone Health and Outcomes in the United States.

Osteoporosis is a bone disease classified by deterioration of bone microarchitecture and decreased bone strength, thereby increasing subsequent risk of fracture. In the United States, approximately 54 million adults aged 50 years and older have osteoporosis or are at risk due to low bone mass. Osteoporosis has long been viewed as a chronic health condition affecting primarily non-Hispanic white (NHW) women; however, emerging evidence indicates racial and ethnic disparities in bone outcomes and osteoporosis management. The primary objective of this review is to describe disparities in bone mineral density (BMD), prevalence of osteoporosis and fracture, as well as in screening and treatment of osteoporosis among non-Hispanic black (NHB), Hispanic, and Asian adults compared with NHW adults living on the US mainland. The following areas were reviewed: BMD, osteoporosis prevalence, fracture prevalence and incidence, postfracture outcomes, DXA screening, and osteoporosis treatments. Although there are limited studies on bone and fracture outcomes within Asian and Hispanic populations, findings suggest that there are differences in bone outcomes across NHW, NHB, Asian, and Hispanic populations. Further, NHB, Asian, and Hispanic populations may experience suboptimal osteoporosis management and postfracture care, although additional population-based studies are needed. There is also evidence that variation in BMD and osteoporosis exists within major racial and ethnic groups, highlighting the need for research in individual groups by origin or background. Although there is a clear need to prioritize future quantitative and qualitative research in these populations, initial strategies for addressing bone health disparities are discussed. © 2021 American Society for Bone and Mineral Research (ASBMR).

Associations between dietary fatty acid patterns and cognitive function in the Hispanic Community Health Study/Study of Latinos.

Our objective was to quantify the cross-sectional associations between dietary fatty acid (DFA) patterns and cognitive function among Hispanic/Latino adults. This study included data from 8,942 participants of the Hispanic Community Health Study/Study of Latinos, a population-based cohort study (weighted age 56.2 y and proportion female 55.2%). The NCI (National Cancer Institute) method was used to estimate dietary intake from two 24-hr recalls. We derived DFA patterns using principal components analysis with 26 fatty acid and total plant and animal monounsaturated fatty acid (MUFA) input variables. Global cognitive function was calculated as the average z-score of 4 neurocognitive tests. Survey linear regression models included multiple potential confounders such as age, sex, education, depressive symptoms, physical activity, energy intake, and cardiovascular disease. DFA patterns were characterized by consumption of long-chain saturated fatty acids (SFA), animal-based MUFA, and trans fatty acids (Factor 1); short to medium-chain SFA (Factor 2); very-long-chain omega-3 polyunsaturated fatty acids (PUFA) (Factor 3); very-long-chain SFA and plant-based MUFA and PUFA (Factor 4). Factor 2 was associated with greater scores for global cognitive function (ß=0.037 ± 0.012) and the Digit Symbol Substitution (DSS) (ß=0.56±0.17), Brief Spanish English Verbal Learning-Sum (B-SEVLT) (ß=0.23 ± 0.11), and B-SEVLT-Recall (ß=0.11 ± 0.05) tests (P<0.05 for all). Factors 1 (ß=0.04 ± 0.01) and 4 (ß=0.70 ± 0.18) were associated with the DSS test (P<0.05 for all). Consumption of short to medium-chain SFA may be associated with higher cognitive function among U.S.-residing Hispanic/Latino adults. Prospective studies are necessary to confirm these findings.

Risk Factors Associated with Vitamin D Status among Older Puerto Rican Adults.

BACKGROUND: Vitamin D deficiency has been associated with health problems globally, but there is limited information on vitamin D status and associated risk factors among adults in underserved populations. OBJECTIVE: This study aimed to identify risk factors for vitamin D deficiency/insufficiency among Puerto Rican adults from the Boston Puerto Rican Health Study (BPRHS). METHODS: A total of 822 adults (45-75 y, at baseline) were included in these analyses. Deficiency was defined as serum 25-hydroxyvitamin D [25(OH)D] <30 and insufficiency as 30 to <50 nmol/L. Dietary intake was assessed with a validated FFQ. Associations between risk factors, including dietary vitamin D, supplement use, ancestry, skin pigmentation, months in the past year spent in a southern climate, and serum 25(OH)D were assessed with multivariable general linear models. RESULTS: Approximately 13% of participants were deficient in 25(OH)D and another 43% insufficient. Skin pigment was associated with 25(OH)D using 3 measures, greater African ancestry (ß ± SE) (-7.74 ± 2.91, P = 0.01); interviewer assessed dark or medium, compared with white, skin tone, (-5.09 ± 2.19, P = 0.02 and -5.89 ± 1.58, P < 0.001, respectively); and melanin index of the upper inner right arm, assessed using a spectrophotometer (-2.04 ± 0.84, P = 0.02). After adjusting for ancestry, factors associated with lower serum 25(OH)D included smoking (-4.49 ± 1.58, P = 0.01); BMI (-0.21 ± 0.10, P = 0.04); and spring compared with autumn blood draw (-4.66 ± 1.68, P = 0.004). Factors associated with higher serum 25(OH)D included female sex compared with male (4.03 ± 1.58, P = 0.01); dietary vitamin D intake µg/d (0.71 ± 0.25, P < 0.004); vitamin D supplement use (4.50 ± 1.87, P = 0.02); income to poverty ratio (0.01 ± 0.01, P = 0.06), and months in a southern climate during the past year (0.96 ± 0.56, P = 0.09). CONCLUSIONS: Vitamin D deficiency/insufficiency was prevalent in this Puerto Rican population living in the northeastern USA. Several factors were associated with this, which may assist in identifying those at risk. Interventions are needed to improve serum 25(OH)D concentration, particularly among those with limited exposure to sunlight.

A Phase 3 Open-Label Study of Elexacaftor/Tezacaftor/Ivacaftor in Children 6 through 11 Years of Age with Cystic Fibrosis and at Least One F508del Allele.

Rationale: Elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) was shown to be efficacious and safe in patients ≥12 years of age with cystic fibrosis and at least one F508del-CFTR (cystic fibrosis transmembrane conductance regulator) allele, but it has not been evaluated in children <12 years of age. Objectives: To assess the safety, pharmacokinetics, and efficacy of ELX/TEZ/IVA in children 6 through 11 years of age with F508del-minimal function or F508del-F508del genotypes. Methods: In this 24-week open-label phase 3 study, children (N = 66) weighing <30 kg received 50% of the ELX/TEZ/IVA adult daily dose (ELX 100 mg once daily, TEZ 50 mg once daily, and IVA 75 mg every 12 h) whereas children weighing ⩾30 kg received the full adult daily dose (ELX 200 mg once daily, TEZ 100 mg once daily, and IVA 150 mg every 12 h). Measurements and Main Results: The primary endpoint was safety and tolerability. The safety and pharmacokinetic profiles of ELX/TEZ/IVA were generally consistent with those observed in older patients. The most commonly reported adverse events included cough, headache, and pyrexia; in most of the children who had adverse events, these were mild or moderate in severity. Through Week 24, ELX/TEZ/IVA treatment improved the percentage of predicted FEV1 (10.2 percentage points; 95% confidence interval [CI], 7.9 to 12.6), Cystic Fibrosis Questionnaire-Revised respiratory domain score (7.0 points; 95% CI, 4.7 to 9.2), lung clearance index2.5 (-1.71 units; 95% CI, -2.11 to -1.30), and sweat chloride (-60.9 mmol/L; 95% CI, -63.7 to -58.2); body mass index-for-age z-score increased over the 24-week treatment period when compared with the pretreatment baseline. Conclusions: Our results show ELX/TEZ/IVA is safe and efficacious in children 6 through 11 years of age with at least one F508del-CFTR allele, supporting its use in this patient population. Clinical trial registered with www.clinicaltrials.gov (NCT03691779).

Patterns of change in cardiovascular risk assessments and ankle brachial index among Puerto Rican adults.

BACKGROUND: Puerto Rican adults have higher odds of peripheral artery disease (PAD) compared with Mexican Americans. Limited studies have examined relationships between clinical risk assessment scores and ABI measures in this population. METHODS: Using 2004-2015 data from the Boston Puerto Rican Health Study (BPRHS) (n = 370-583), cross-sectional, 5-y change, and patterns of change in Framingham Risk Score (FRS) and allostatic load (AL) with ankle brachial index (ABI) at 5-y follow-up were assessed among Puerto Rican adults (45-75 y). FRS and AL were calculated at baseline, 2-y and 5-y follow-up. Multivariable linear regression models were used to examine cross-sectional and 5-y changes in FRS and AL with ABI at 5-y. Latent growth mixture modeling identified trajectories of FRS and AL over 5-y, and multivariable linear regression models were used to test associations between trajectory groups at 5-y. RESULTS: Greater FRS at 5-y and increases in FRS from baseline were associated with lower ABI at 5-y (ß = -0.149, P = 0.010; ß = -0.171, P = 0.038, respectively). AL was not associated with ABI in cross-sectional or change analyses. Participants in low-ascending (vs. no change) FRS trajectory, and participants in moderate-ascending (vs. low-ascending) AL trajectory, had lower 5-y ABI (ß = -0.025, P = 0.044; ß = -0.016, P = 0.023, respectively). CONCLUSIONS: FRS was a better overall predictor of ABI, compared with AL. Puerto Rican adults, an understudied population with higher FRS over 5 years, may benefit from intensive risk factor modification to reduce risk of PAD. Additional research examining relationships between FRS and AL and development of PAD is warranted.

Influence of Body Composition on Post-Exercise Parasympathetic Reactivation of Firefighter Recruits.

Firefighters have a sustained risk for experiencing a sudden cardiac event after completing a fire call. Heart rate recovery (HRR) can be utilized to characterize autonomic nervous system (ANS) recovery and has been linked to cardiac events. Research suggests that body composition influences post-exercise HRR responses in non-firefighter populations. The purpose of this study was to examine the influence of body mass index (BMI), waist circumference (WC), and percent body fat (BF) on the HRR response of firefighter recruits. BMI (kg·m-2), WC (cm), and BF (%) data from 57 firefighter recruits were collected. HRR (b·min-1) data were collected at completion (HR0), as well as 15 (HR15), 30 (HR30), 45 (HR45), 60 (HR60), 120 (HR120), and 180 (HR180) seconds following a submaximal step test, and commonly utilized clinical HRR indices were calculated (ΔHRR30, ΔHRR60, ΔHRR120, and ΔHRR180). After controlling for sex, linear mixed regression models did not identify significant interactions between body composition (ps > 0.05) and HRR response across time. However, significant (ps < 0.05) indirect semi-partial correlations were identified between BF and ΔHRR30 (rsp = -0.31) and ΔHRR60 (rsp = -0.27), respectively. Reducing overall BF (vs. BMI or WC) should be prioritized to improve the post-exercise ANS recovery of firefighter recruits.

Diet-derived fruit and vegetable metabolites show sex-specific inverse relationships to osteoporosis status.

BACKGROUND: The impact of nutrition on the metabolic profile of osteoporosis (OS) is unknown. OBJECTIVE: Identify biochemical factors driving the association of fruit and vegetable (FV) intakes with OS prevalence using an untargeted metabolomics approach. DESIGN: Cross-sectional dietary, anthropometric and plasma metabolite data were examined from the Boston Puerto Rican Osteoporosis Study, n = 600 (46-79 yr). METHODS: Bone mineral density was assessed by DXA. OS was defined by clinical standards. A culturally adapted FFQ assessed usual dietary intake. Principal components analysis (PCA) of 42 FV items created 6 factors. Metabolomic profiles derived from plasma samples were assessed on a commercial platform. Differences in levels of 525 plasma metabolites between disease groups (OS vs no-OS) were compared using logistic regression; and associations with FV intakes by multivariable linear regression, adjusted for covariates. Metabolites significantly associated with OS status or with total FV intake were analyzed for enrichment in various biological pathways using Mbrole 2.0, MetaboAnalyst, and Reactome, using FDR correction of P-values. Correlation coefficients were calculated as Spearman's rho rank correlations, followed by hierarchical clustering of the resulting correlation coefficients using PCA FV factors and sex-specific sets of OS-associated metabolites. RESULTS: High FV intake was inversely related to OS prevalence (Odds Ratio = 0.73; 95% CI = 0.57, 0.94; P = 0.01). Several biological processes affiliated with the FV-associating metabolites, including caffeine metabolism, carnitines and fatty acids, and glycerophospholipids. Important processes identified with OS-associated metabolites were steroid hormone biosynthesis in women and branched-chain amino acid metabolism in men. Factors derived from PCA were correlated with the OS-associated metabolites, with high intake of dark leafy greens and berries/melons appearing protective in both sexes. CONCLUSIONS: These data warrant investigation into whether increasing intakes of dark leafy greens, berries and melons causally affect bone turnover and BMD among middle-aged and older adults at risk for osteoporosis via sex-specific metabolic pathways, and how gene-diet interactions alter these sex-specific metabolomic-osteoporosis links. ClinicalTrials.gov Identifier: NCT01231958.