Rest-activity circadian rhythms and bone mineral density in elderly men.

BACKGROUND: Disrupted rest-activity circadian rhythm (RAR) patterns have been associated with poor health outcomes (i.e. diminished cognitive function, increased risk of dementia and falls). Circadian time cues in bone influence the differentiation of osteoblasts and osteoclasts, and bone turnover markers exhibit circadian variation; relationships between bone outcomes and RAR are emerging areas of research. We evaluated associations between RAR and areal bone mineral density (aBMD) at the total hip and femoral neck in older men from the Osteoporotic Fractures in Men (MrOS) cohort. We hypothesized that weaker RAR patterns would be associated with lower aBMD. METHODS: MrOS is an ongoing prospective cohort study following ambulatory men ≥ 65 years (n = 5994) at 6 U.S. clinics (baseline enrollment 3/2000-4/2002); participants for this analysis are from an ancillary study, Outcomes of Sleep Disorders in Older Men (MrOS Sleep). We included data from men who had technically adequate measures of RAR and aBMD at Sleep Visit 1 (12/2003-3/2005), with repeat aBMD at core Visit 3 (3/2007-3/2009) (n = 2412; mean age at Sleep Visit 1: 75.7 ± 5.2 years). aBMD was measured by dual energy x-ray absorptiometry (DXA). Actigraphs worn on the non-dominant wrist were used to collect circadian activity data over 4.8 ± 0.8 consecutive 24-hour periods. An extension of the traditional cosine curve was used to fit RAR to the activity data [Ancoli-Israel et al., 2003; Marler et al., 2006]. Six RAR parameters were evaluated: acrophase (time of peak activity), amplitude (rhythm strength), mesor (mean of activity fitted curve), pseudo F-statistic (overall circadian rhythmicity of rest and activity), alpha statistic (daytime to nighttime activity ratio), and beta statistic (daytime activity). Associations between RAR and aBMD (Sleep Visit 1), and RAR and ΔaBMD (Sleep Visit 1-Visit 3) were assessed with generalized linear models. Covariates included age, clinic site, physical activity, race, comorbidity, body mass index (BMI), smoking, alcohol, caffeine, beta blocker use, serum 25(OH) vitamin D and urinary melatonin and calcium. RESULTS: Pseudo F-statistic was significantly associated with total hip aBMD (p-trend = 0.009), femoral neck aBMD (p-trend = 0.007) and total hip ΔaBMD (p-trend = 0.017) in minimally adjusted models but not after multivariate (MV) adjustment. Alpha statistic was significantly associated with femoral neck aBMD (p-trend = 0.029) and femoral neck ΔaBMD (p-trend = 0.019) in minimally adjusted models; significance was retained in the femoral neck ΔaBMD model (p-trend = 0.034) after MV adjustment. There were no consistent, significant associations between the other RAR variables and aBMD or ΔaBMD. CONCLUSIONS: The data demonstrate modest associations between overall circadian rhythmicity of rest and activity (measured by pseudo F-statistic), as well as daytime to nighttime activity ratio (measured by alpha statistic), aBMD and ΔaBMD, but adjustment for covariates related to lifestyle, BMI and comorbidities attenuated most of these associations. These results suggest that RAR patterns are not independently associated with aBMD or four-year ΔaBMD at the total hip or femoral neck in older men, but additional research is needed.

The role of a dairy fraction rich in milk fat globule membrane in the suppression of postprandial inflammatory markers and bone turnover in obese and overweight adults: an exploratory study.

BACKGROUND: Inflammation is associated with increased bone resorption; the role of inflammation in postprandial bone turnover has not been explored. Consumption of milk fat globule membrane (MFGM) reduces inflammation in animal models. This study aimed to measure postprandial changes in bone turnover after intake of high saturated fat test meals, with- and without the anti-inflammatory ingredient MFGM. METHODS: Subjects (n = 36 adults) were obese (BMI 30-39.9 kg/m2) or overweight (BMI 25-29.9 kg/m2) with two traits of Metabolic Syndrome. Subjects consumed a different test meal on four occasions at random; blood draws were taken at baseline and 1, 3, and 6 h postprandial. Test meals included whipping cream (WC), WC + MFGM, palm oil (PO) and PO + MFGM. Biomarkers of bone turnover and inflammation were analyzed from all four time points. RESULTS: Test meal (treatment) by time interactions were significant for bone resorption marker C-telopeptide of type 1 collagen (CTX) (p < 0.0001) and inflammatory marker interleukin 10 (IL-10) (p = 0.012). Significant differences in overall postprandial response among test meals were found for CTX and soluble intercellular adhesion molecule (sICAM), with the greatest overall postprandial suppression of CTX occurring in meals containing MFGM. However, test meal by MFGM interactions were non- significant for bone and inflammatory markers. Correlations between CTX and inflammatory markers were non-significant. CONCLUSION: This exploratory analysis advances the study of postprandial suppression of bone turnover by demonstrating differing effects of high SFA meals that contained MFGM; however MFGM alone did not directly moderate the difference in postprandial CTX response among test meals in this analysis. These observations may be useful for identifying foods and ingredients which maximize the suppression of bone resorption, and for generating hypotheses to test in future studies examining the role of inflammation in postprandial bone turnover. TRIAL REGISTRATION: Clinicaltrials.gov NCT01811329. Registered 11 March 2013.

Rest-activity patterns and falls and fractures in older men.

Dysregulated rest-activity rhythm (RAR) patterns have been associated with several health conditions in older adults. This study showed that later acrophase was associated with a modestly greater risk of falls but not fractures in elderly men. Associations between dysregulated RAR patterns and osteoporosis risk warrant further investigation. PURPOSE: The purpose of this study was to investigate the relationship between rest-activity rhythm (RAR) patterns and risk of falls/fractures in older men. We hypothesized that dysregulated RAR would be associated with incident falls/fractures. METHODS: We used wrist-worn actigraphy to measure RAR over 4.8 ± 0.8 24-h periods in men (≥67 years) enrolled in the multicenter Outcomes of Sleep Disorders in Men (MrOS Sleep) Study (n = 3001). Men were contacted every 4 months to report occurrence of falls/fractures. RAR parameters included amplitude (difference between peak and nadir activity in counts/minute), mesor (activity counts/minute), acrophase (time of day of peak activity), and pseudo-F statistic (rhythm robustness) and were evaluated as continuous variables with associations reported per SD increase/decrease in models adjusted for confounders. Logistic regression was used to estimate the likelihood (odds ratio, OR) of recurrent falls in the year after the visit. Proportional hazards models were used to estimate the risk (hazard ratio, HR) of fractures. RESULTS: One year after the visit, 417 men (14%) had recurrent (≥2) falls. Later acrophase (OR 1.18, 95% CI 1.06-1.32) was associated with a modestly greater likelihood of falls. In 8.6 years (SD 2.6 years) of >97% complete follow-up, 256 men (8.53%) had a major osteoporotic fracture, 85 (2.8%) had a clinical spine fracture, and 110 (3.7%) had a hip fracture. No consistent, significant associations were observed between RAR patterns and fractures. CONCLUSIONS: Later acrophase was associated with a modestly greater risk of falls; this association did not translate into a higher fracture risk in this cohort of elderly men.

Is bone equally responsive to calcium and vitamin D intake from food vs. supplements? Use of (41)calcium tracer kinetic model.

BACKGROUND: Few interventions directly compare equivalent calcium and vitamin D from dairy vs. supplements on the same bone outcomes. The radioisotope calcium-41 ((41)Ca) holds promise as a tracer method to directly measure changes in bone resorption with differing dietary interventions. OBJECTIVE: Using (41)Ca tracer methodology, determine if 4 servings/day of dairy foods results in greater (41)Ca retention than an equivalent amount of calcium and vitamin D from supplements. Secondary objective was to evaluate the time course for the change in (41)Ca retention. METHODS: In this crossover trial, postmenopausal women (n = 12) were dosed orally with 100 nCi of (41)Ca and after a 180 day equilibration period received dairy (4 servings/day of milk or yogurt; ~ 1300 mg calcium, 400 IU cholecalciferol (vitamin D3/day)) or supplement treatments (1200 mg calcium carbonate/day and 400 IU vitamin D3/day) in random order. Treatments lasted 6 weeks separated by a 6 week washout (WO). Calcium was extracted from weekly 24 h urine collections; accelerator mass spectrometry (AMS) was used to determine the (41/40)Ca ratio. Primary outcome was change in (41/40)Ca excretion. Secondary outcome was the time course for change in (41)Ca excretion during intervention and WO periods. RESULTS: The (41/40)Ca ratio decreased significantly over time during both treatments; there was no difference between treatments. Both treatments demonstrated a significant retention of (41)Ca within 1-2 weeks (p = 0.0007 and p < 0.001 for dairy and supplements, respectively). WO demonstrated a significant decrease (p = 0.0024) in (41)Ca retention within 1-2 weeks, back to pre-intervention levels. CONCLUSION: These data demonstrate that urinary (41)Ca retention is increased with an increase in calcium and vitamin D intake regardless of the source of calcium, and the increased retention occurs within 1-2 weeks.

Addition of a dairy fraction rich in milk fat globule membrane to a high-saturated fat meal reduces the postprandial insulinaemic and inflammatory response in overweight and obese adults.

Meals high in SFA, particularly palmitate, are associated with postprandial inflammation and insulin resistance. Milk fat globule membrane (MFGM) has anti-inflammatory properties that may attenuate the negative effects of SFA-rich meals. Our objective was to examine the postprandial metabolic and inflammatory response to a high-fat meal composed of palm oil (PO) compared with PO with an added dairy fraction rich in MFGM (PO+MFGM) in overweight and obese men and women (n 36) in a randomised, double-blinded, cross-over trial. Participants consumed two isoenergetic high-fat meals composed of a smoothie enriched with PO with v. without a cream-derived complex milk lipid fraction ( dairy fraction rich in MFGM) separated by a washout of 1-2 weeks. Serum cytokines, adhesion molecules, cortisol and markers of inflammation were measured at fasting, and at 1, 3 and 6 h postprandially. Glucose, insulin and lipid profiles were analysed in plasma. Consumption of the PO + MFGM v. PO meal resulted in lower total cholesterol (P = 0·021), LDL-cholesterol (P = 0·046), soluble intracellular adhesion molecule (P = 0·005) and insulin (P = 0·005) incremental AUC, and increased IL-10 (P = 0·013). Individuals with high baseline C-reactive protein (CRP) concentrations (≥3 mg/l, n 17) had higher (P = 0·030) insulin at 1 h after the PO meal than individuals with CRP concentrations <3 mg/l (n 19). The addition of MFGM attenuated this difference between CRP groups. The addition of a dairy fraction rich in MFGM attenuated the negative effects of a high-SFA meal by reducing postprandial cholesterol, inflammatory markers and insulin response in overweight and obese individuals, particularly in those with elevated CRP.

Consumption of a high-fat meal containing cheese compared with a vegan alternative lowers postprandial C-reactive protein in overweight and obese individuals with metabolic abnormalities: a randomised controlled cross-over study.

Dietary recommendations suggest decreased consumption of SFA to minimise CVD risk; however, not all foods rich in SFA are equivalent. To evaluate the effects of SFA in a dairy food matrix, as Cheddar cheese, v. SFA from a vegan-alternative test meal on postprandial inflammatory markers, a randomised controlled cross-over trial was conducted in twenty overweight or obese adults with metabolic abnormalities. Individuals consumed two isoenergetic high-fat mixed meals separated by a 1- to 2-week washout period. Serum was collected at baseline, and at 1, 3 and 6 h postprandially and analysed for inflammatory markers (IL-6, IL-8, IL-10, IL-17, IL-18, TNFα, monocyte chemotactic protein-1 (MCP-1)), acute-phase proteins C-reactive protein (CRP) and serum amyloid-A (SAA), cellular adhesion molecules and blood lipids, glucose and insulin. Following both high-fat test meals, postprandial TAG concentrations rose steadily (P < 0·05) without a decrease by 6 h. The incremental AUC (iAUC) for CRP was significantly lower (P < 0·05) in response to the cheese compared with the vegan-alternative test meal. A treatment effect was not observed for any other inflammatory markers; however, for both test meals, multiple markers significantly changed from baseline over the 6 h postprandial period (IL-6, IL-8, IL-18, TNFα, MCP-1, SAA). Saturated fat in the form of a cheese matrix reduced the iAUC for CRP compared with a vegan-alternative test meal during the postprandial 6 h period. The study is registered at clinicaltrials.gov under NCT01803633.