Anti-Inflammatory Activities of Pentaherbs Formula, Berberine, Gallic Acid and Chlorogenic Acid in Atopic Dermatitis-Like Skin Inflammation.

Atopic dermatitis (AD) is a common allergic skin disease, characterized by dryness, itchiness, thickening and inflammation of the skin. Infiltration of eosinophils into the dermal layer and presence of edema are typical characteristics in the skin biopsy of AD patients. Previous in vitro and clinical studies showed that the Pentaherbs formula (PHF) consisting of five traditional Chinese herbal medicines, Flos Lonicerae, Herba Menthae, Cortex Phellodendri, Cortex Moutan and Rhizoma Atractylodis at w/w ratio of 2:1:2:2:2 exhibited therapeutic potential in treating AD. In this study, an in vivo murine model with oxazolone (OXA)-mediated dermatitis was used to elucidate the efficacy of PHF. Active ingredients of PHF water extract were also identified and quantified, and their in vitro anti-inflammatory activities on pruritogenic cytokine IL-31- and alarmin IL-33-activated human eosinophils and dermal fibroblasts were evaluated. Ear swelling, epidermis thickening and eosinophils infiltration in epidermal and dermal layers, and the release of serum IL-12 of the murine OXA-mediated dermatitis were significantly reduced upon oral or topical treatment with PHF (all p < 0.05). Gallic acid, chlorogenic acid and berberine contents (w/w) in PHF were found to be 0.479%, 1.201% and 0.022%, respectively. Gallic acid and chlorogenic acid could suppress the release of pro-inflammatory cytokine IL-6 and chemokine CCL7 and CXCL8, respectively, in IL-31- and IL-33-treated eosinophils-dermal fibroblasts co-culture; while berberine could suppress the release of IL-6, CXCL8, CCL2 and CCL7 in the eosinophil culture and eosinophils-dermal fibroblasts co-culture (all p < 0.05). These findings suggest that PHF can ameliorate allergic inflammation and attenuate the activation of eosinophils.

Anti-inflammatory and anti-allergic activities of Pentaherb formula, Moutan Cortex (Danpi) and gallic acid.

Pentaherb formula (PHF) has been proven to improve the quality of life of children with atopic dermatitis without side effects. The aim of this study was to elucidate the potential anti-inflammatory and anti-allergic activities of PHF, Moutan Cortex (Danpi/DP) and gallic acid (GA) using human basophils (KU812 cells), which are crucial effector cells in allergic inflammation. PHF, DP and GA could significantly suppress the expression of allergic inflammatory cytokine IL-33-upregulated intercellular adhesion molecule (ICAM)-1, and the release of chemokines CCL2, CCL5, CXCL8 and inflammatory cytokine IL-6 from KU812 cells (all p < 0.05). With the combined use of dexamethasone (0.01 µg/mL) and GA (10 µg/mL), the suppression of ICAM-1 expression and CCL5 and IL-6 release of IL-33-activated KU812 cells were significantly greater than the use of GA alone (all p < 0.05). The suppression of the IL-33-induced activation of intracellular signalling molecules p38 mitogen activated protein kinase, nuclear factor-kB and c-Jun amino-terminal kinase in GA-treated KU812 cells could be the underlying mechanism for the suppression on ICAM-1, chemokines and cytokines. The combined use of dexamethasone with the natural products PHF or DP or GA might therefore enhance the development of a novel therapeutic modality for allergic inflammatory diseases with high potency and fewer side effects.

Depressive symptoms and change in abdominal obesity in the elderly: positive or negative association?

OBJECTIVES: Recent evidence suggests that depression can result in abdominal obesity in the elderly. Few longitudinal studies are available and none has been conducted outside the United States. METHODS: To examine the relationship between depressive symptoms and abdominal obesity, data from 3,998 community-dwelling Chinese elderly men and women age 65 years and older with 4-year follow-up were analyzed. Depression was defined by a Geriatric Depression Scale score of 8 or higher. At baseline and after 4 years, overall obesity measures included body mass index, percentage of body fat, and general adiposity or body fat index (expressed by total body fat mass measured by DEXA (dual-energy x-ray absorptiometry) in kilograms divided by the square of stature in meters). Abdominal obesity measures included waist circumference, waist to hip ratio, and relative truncal fat (ratio of truncal fat mass to total fat mass measured by DEXA). RESULTS: After adjustment for sociodemographics, lifestyle, and medical factors, the presence of clinically relevant depressive symptoms at baseline was associated with significant decrease in waist circumference at follow-up after adjusting for sociodemographic factors, baseline obesity, lifestyle, and medical factors (ß = -1.801, t = -2.93, df = 1564, p = 0.0034), although this relationship disappeared in older age women in further age-stratified analysis. CONCLUSIONS: This study shows that depressive symptoms may result in a decrease in abdominal obesity, suggesting that more research is needed to further explore this relationship. Similar studies conducted in different cultural groups may help to explain these conflicting findings.

Prediction of bone loss in elderly female subjects by MR perfusion imaging and spectroscopy.

OBJECTIVE: To determine whether MR perfusion indices or marrow fat content at baseline can predict areal bone mineral density (BMDa) loss. METHODS: Repeat dual x-ray absorptiometry (DXA) of the hip was performed in female subjects at 2 years (n = 52) and 4 years (n = 45) following baseline MR perfusion imaging and spectroscopy of the hip. RESULTS: Percentage reduction in femoral neck BMDa at 4 years post-baseline was greater in subjects with below median acetabulum enhancement slope (E(slope)) (-5.6 ± 1.2 Vs -1.1 ± 1.2 (mean ± standard error) p = 0.014) or muscle maximum enhancement (E(max)) (-5.7 ± 1.2 Vs -0.23 ± 1.2, p = 0.009) after adjusting for baseline co-variables. Baseline MR parameters correlated with reduction in BMDa at 4 years (acetabulum E(slope) r = 0.517, p = 0.0003; muscle E(max) r = 0.306, p = 0.043) as well as traditionally applied clinical risk factors. Acetabulum E(slope), femoral neck E(max) and marrow fat content at baseline had sensitivities of 89%, 81% and 72% respectively at distinguishing between fast (>1%/annum) (n = 18) and slow (<1%/annum) (n = 27) BMD losers. CONCLUSION: Elderly female subjects with reduced perfusion indices at baseline had increased femoral neck bone loss at 4 years. Selected perfusion indices and marrow fat content have a moderate to high sensitivity in discriminating between fast and slow bone losers.

Depressive symptoms and lifestyle factors as risk factors of lower urinary tract symptoms in Southern Chinese men: a prospective study.

BACKGROUND: Few prospective studies have been conducted to identify risk factors associated with lower urinary tract symptoms (LUTS). Our objective is to evaluate the dietary, lifestyle and medical risk factors of LUTS. METHODS: Data were collected from a large prospective cohort of elderly Chinese men in Hong Kong. Eight hundred seventy-one subjects provided response to a structured interviewer-administered questionnaire and physical examination at baseline and at 4-year follow-up. LUTS and depressive symptoms were assessed using International Prostate Symptom Score (IPSS) and Geriatric Depressive Symptom Scale (GDS). RESULTS: The GDS score was independently associated with increased risk of having moderate to severe LUTS (odd ratios (OR) = 2.08; confidence interval (CI) = 1.28-3.40; Wald chi-square test = 9.52 and p = 0.023). A history of coronary heart disease was independently associated with increased risk of moderate to severe LUTS (OR = 1.65, CI: 1.05-2.59; Wald chi-square test = 4.74 and p = 0.029). Alcohol consumption of seven drinks or more per week was independently associated with increased risk of moderate to severe LUTS (OR = 2.51; CI: 1.32-4.79; Wald chi-square test = 8.01 and p = 0.018). LIMITATIONS: We have studied LUTS but not surgical BPH. CONCLUSIONS: The results showed that medical and lifestyle factors may increase the risk of LUTS in Chinese elderly men.

Publisher Correction: GWAS of bone size yields twelve loci that also affect height, BMD, osteoarthritis or fractures.

The original HTML version of this Article was updated shortly after publication to add links to the Peer Review file.In addition, affiliations 16 and 17 incorrectly read 'School of Medicine Sydney, University of Notre Dame Australia, Sydney, WA, 6160, Australia' and 'St Vincent's Clinical School, University of New South Wales Medicine, University of New South Wales, Sydney, NSW, 2052, Australia.' This has now been corrected in both the PDF and HTML versions of the Article.

GWAS of bone size yields twelve loci that also affect height, BMD, osteoarthritis or fractures.

Bone area is one measure of bone size that is easily derived from dual-energy X-ray absorptiometry (DXA) scans. In a GWA study of DXA bone area of the hip and lumbar spine (N ≥ 28,954), we find thirteen independent association signals at twelve loci that replicate in samples of European and East Asian descent (N = 13,608 - 21,277). Eight DXA area loci associate with osteoarthritis, including rs143384 in GDF5 and a missense variant in COL11A1 (rs3753841). The strongest DXA area association is with rs11614913[T] in the microRNA MIR196A2 gene that associates with lumbar spine area (P = 2.3 × 10-42, ß = -0.090) and confers risk of hip fracture (P = 1.0 × 10-8, OR = 1.11). We demonstrate that the risk allele is less efficient in repressing miR-196a-5p target genes. We also show that the DXA area measure contributes to the risk of hip fracture independent of bone density.

Analysis of bone marrow fatty acid composition using high-resolution proton NMR spectroscopy.

High-resolution 1H NMR spectroscopy as a complementary method in the analysis of human bone marrow fatty acid (FA) composition was examined. Marrow FA composition in 10 bone samples measured by NMR and gas chromatography (GC) were compared. NMR T1 relaxation time of FA was determined and reproducibility tests were performed to assess the variability. Good correlations were obtained between the NMR and GC results for omega-6 polyunsaturated fatty acid (PUFA) (Spearman r, 0.878), omega-3 PUFA (0.895), monounsaturated FA (0.964) and saturated FA (0.939). The NMR method tended to overestimate saturated FA and underestimate omega-3/omega-6 ratio compared to GC results. T1 relaxation time of marrow FA was 0.56-3.65s. Coefficient of variation of the NMR method was 0.6-8.2% in intra-experimental and 0.2-8.4% in inter-experimental measurements. This study demonstrates a complementary role for 1H NMR spectroscopy as an additional analytical tool in human lipid research.

The effects of Fructus Xanthii extract on cytokine release from human mast cell line (HMC-1) and peripheral blood mononuclear cells.

In the present study, human mast cell line (HMC-1) and peripheral blood mononuclear cells (PBMNC) were pre-incubated with various concentrations of Fructus xanthii extract solution followed by being stimulated with phorbol myristate acetate and further incubated for 24 hours. The cytokines, in cell culture supernatants, of interleukin (IL)-4, IL-6, IL-8, GM-CSF, and TNF-alpha in the supernatant were measured by enzyme-linked immunosorbent assay. The results demonstrated that Fructus xanthii could modulate the mast cell-mediated and PBMNC-mediated inflammatory and immunological reactions modulated by cytokines. And our study supplied the evidence of the mechanisms of Fructus Xanthii in treating inflammatory and allergic diseases.

Clinically relevant depressive symptoms and peripheral arterial disease in elderly men and women. Results from a large cohort study in Southern China.

OBJECTIVE: Results from previous epidemiological studies on the relationship between depression and peripheral arterial diseases (PADs) were mixed. Therefore, a study was conducted to investigate this relationship in a large Chinese elderly sample. METHODS: Cross-sectional data from the baseline examination of a large cohort study on Chinese elderly were used in this current study. A stratified convenience sample of 3985 Hong Kong men and women aged 65 to 92 were recruited from the community. Clinically relevant depressive symptoms were assessed by the use of a validated screening instrument for depression: the Chinese version of the Short Form of Geriatric Depression Scale. PAD was assessed by the ankle-brachial index, with an index of <0.9 indicating the presence of PAD. Multiple logistic regression was used to compare the presence of PAD in depressed and nondepressed subjects, controlling for confounding variables for the relationship. RESULTS: In the total subject population, more severe peripheral atherosclerosis was associated with a higher prevalence of depressive disorders. The presence of peripheral atherosclerosis was associated with an adjusted odds ratio of 1.46 (95% confidence interval=1.01-2.10) of having clinically relevant depressive symptoms. CONCLUSION: We showed that depressive symptoms were associated with peripheral atherosclerosis in the Asian elderly after adjusting for stroke and cardiovascular diseases. Prospective studies are needed to provide conclusive evidence on the causality of the relationship between peripheral atherosclerosis and depressive symptoms.

Lower urinary tract symptoms and depressive symptoms in elderly men.

BACKGROUND: To evaluate the impact of moderate to severe lower urinary tract symptoms (LUTS) on clinically significant depressive symptoms in elderly Chinese men aged 65 and above. METHODS: In a large prospective cohort of 2000 Chinese men aged 65 to 92 years of age in Hong Kong, the association between moderate to severe lower urinary tract symptoms and clinically relevant depressive symptoms was studied. After excluding men with prostate or bladder cancer or surgery, 1980 subjects provided response to a structured interviewer-administered questionnaire and physical examination. A case-control analysis was performed, comparing subjects with clinically relevant depressive symptoms (cases) to those without depressive symptoms (controls). RESULTS: In multiple analyses adjusting for all factors that were shown to be significantly associated with having clinically relevant depressive symptoms in the initial bivariate analyses, being widowed, divorced or single were associated with increased risk of having clinically relevant depressive symptoms. Having a history of cardiac disease, being a current smoker and the use of corticosteroid were also associated with increased risk. Having moderate to severe LUTS was significantly associated with increased odds of having clinically relevant depressive symptoms (OR: 2.40; CI: 1.68-3.43) even after adjustment. LIMITATION: This study was cross-sectional and there were no clinician-based diagnostic interviews that were conducted to diagnose clinical depression and thus only clinically relevant depressive symptoms were assessed. CONCLUSIONS: In elderly men, moderate to severe LUTS are important public health problems that are associated with increased risk of having clinically relevant depressive symptoms. These findings suggest that physicians who deal with patients with moderate to severe LUTS should consider the psychological health of their patients as this population is at risk of having clinically relevant depressive symptoms.

Sequence variants in the PTCH1 gene associate with spine bone mineral density and osteoporotic fractures.

Bone mineral density (BMD) is a measure of osteoporosis and is useful in evaluating the risk of fracture. In a genome-wide association study of BMD among 20,100 Icelanders, with follow-up in 10,091 subjects of European and East-Asian descent, we found a new BMD locus that harbours the PTCH1 gene, represented by rs28377268 (freq. 11.4-22.6%) that associates with reduced spine BMD (P=1.0 × 10(-11), ß=-0.09). We also identified a new spine BMD signal in RSPO3, rs577721086 (freq. 6.8%), that associates with increased spine BMD (P=6.6 × 10(-10), ß=0.14). Importantly, both variants associate with osteoporotic fractures and affect expression of the PTCH1 and RSPO3 genes that is in line with their influence on BMD and known biological function of these genes. Additional new BMD signals were also found at the AXIN1 and SOST loci and a new lead SNP at the EN1 locus.

Short-Term Flavoxate Treatment Alters Detrusor Contractility Characteristics: Renewed Interest in Clinical Use?

OBJECTIVES: Flavoxate has had a long history of use in the treatment of overactive bladder, despite the lack of documentation on its clinical efficacy and mechanism(s) of action. This study was conducted to understand how contractility characteristics of the detrusor are affected after a short period of flavoxate treatment. METHODS: Eight-week-old mice were treated with flavoxate for 5 days and detrusor contractile responses were examined ex vivo under different pharmacological and electrical stimuli. RESULTS: K(+) -Krebs'-induced contraction developed more slowly while 64 Hz electrical field stimulation-induced contraction developed faster in flavoxate-treated strips when compared to control. Amplitudes of maximal and steady-state contraction induced by 3 µmol/L carbachol were also larger after flavoxate treatment. Control strips showed an overall greater dependence on stimulus strength in eliciting the responses. CONCLUSIONS: These findings provided new information of how short-term flavoxate treatment altered contractility characteristics at the bladder level, which may instill new interest in investigating the use of this drug in bladder disorders not responding well to conventional treatments.

Does acupuncture therapy alter activation of neural pathway for pain perception in irritable bowel syndrome?: a comparative study of true and sham acupuncture using functional magnetic resonance imaging.

BACKGROUND/AIMS: Patients with irritable bowel syndrome (IBS) are characterized by abnormal central processing with altered brain activation in response to visceral nociceptive signals. The effect of electroacupuncture (EA) on IBS patients is unclear. The study is set to study the effect of EA on brain activation during noxious rectal distension in IBS patients using a randomized sham-controlled model. METHODS: Thirty IBS-diarrhea patients were randomized to true electroacupuncture or sham acupuncture. Functional MRI was performed to evaluate cerebral activation at the following time points: (1) baseline when there was rectal distension only, (2) rectal distension during application of EA, (3) rectal distension after cessation of EA and (4) EA alone with no rectal distension. Group comparison was made under each condition using SPM5 program. RESULTS: Rectal distension induced significant activation of the anterior cingulated cortex, prefrontal cortex, thalamus, temporal regions and cerebellum at baseline. During and immediately after EA, increased cerebral activation from baseline was observed in the anterior cingulated cortex, bilateral prefrontal cortex, thalamus, temporal regions and right insula in both groups. However, true electroacupuncture led to significantly higher activation at right insula, as well as pulvinar and medial nucleus of the thalamus when compared to sham acupuncture. CONCLUSIONS: We postulate that acupuncture might have the potential effect of pain modulation in IBS by 2 actions: (1) modulation of serotonin pathway at insula and (2) modulation of mood and affection in higher cortical center via ascending pathway at the pulvinar and medial nucleus of the thalamus.

Low DHEAS levels are associated with depressive symptoms in elderly Chinese men: results from a large study.

This study investigated the association between depressive symptoms in elderly Chinese men and the total testosterone, dehydroepiandrosterone (DHEA), DHEA sulphate (DHEAS), oestradiol and sex hormone-binding globulin (SHBG) levels, and the free androgen index. Cross-sectional data from 1147 community-dwelling elderly men, aged 65 and older, were used. Depressive symptoms were measured using the Chinese Geriatric Depression Scale (GDS). Total testosterone, free testosterone, DHEA, DHEAS, total oestradiol, the free androgen index and SHBG levels were assessed. DHEA was significantly associated with GDS score, and there was a trend towards DHEAS association, but this was not significant (ß=-0.110, P=0.015; ß=-0.074, P=0.055). However, no association was seen between depressive symptoms and total testosterone levels, free testosterone levels, oestradiol levels or SHBG levels. In terms of the presence of clinically relevant depressive symptoms, there were no statistically significant differences between patients in the lowest quartile of sex steroid hormone levels and those in other quartiles of sex steroid hormone levels. Similarly to Western studies, our study shows that DHEA and DHEAS levels are associated with depressive symptoms.

European bone mineral density loci are also associated with BMD in East-Asian populations.

Most genome-wide association (GWA) studies have focused on populations of European ancestry with limited assessment of the influence of the sequence variants on populations of other ethnicities. To determine whether markers that we have recently shown to associate with Bone Mineral Density (BMD) in Europeans also associate with BMD in East-Asians we analysed 50 markers from 23 genomic loci in samples from Korea (n = 1,397) and two Chinese Hong Kong sample sets (n = 3,869 and n = 785). Through this effort we identified fourteen loci that associated with BMD in East-Asian samples using a false discovery rate (FDR) of 0.05; 1p36 (ZBTB40, P = 4.3×10(-9)), 1p31 (GPR177, P = 0.00012), 3p22 (CTNNB1, P = 0.00013), 4q22 (MEPE, P = 0.0026), 5q14 (MEF2C, P = 1.3×10(-5)), 6q25 (ESR1, P = 0.0011), 7p14 (STARD3NL, P = 0.00025), 7q21 (FLJ42280, P = 0.00017), 8q24 (TNFRSF11B, P = 3.4×10(-5)), 11p15 (SOX6, P = 0.00033), 11q13 (LRP5, P = 0.0033), 13q14 (TNFSF11, P = 7.5×10(-5)), 16q24 (FOXL1, P = 0.0010) and 17q21 (SOST, P = 0.015). Our study marks an early effort towards the challenge of cataloguing bone density variants shared by many ethnicities by testing BMD variants that have been established in Europeans, in East-Asians.

A study of bone marrow and subcutaneous fatty acid composition in subjects of varying bone mineral density.

Osteoporosis is associated with an increase in marrow fat. Fats, particularly polyunsaturated fats, either in co-cultures or diet, have been shown to significantly influence bone remodeling. Whether the increase in marrow fat seen in osteoporosis is also associated with a change in fatty acid composition is not known. This study was undertaken to investigate the fatty acid composition in subjects of varying bone mineral density (BMD). Samples of marrow fat and subcutaneous fat from 126 subjects (98 females, 34 males, mean age 69.7+/-10.5 years) undergoing orthopedic surgery were analyzed for fatty acid composition by gas chromatography. These results were correlated with BMD assessed by DXA. A total of 22 fatty acids were identified in marrow and subcutaneous fat. Significant differences in fatty acid composition existed between marrow and subcutaneous fat as well as between marrow fat samples obtained from the proximal femur and proximal tibia. Other than cis-7-hexadecenoic acid [C16:1 (n=9)] and docosanoic acid [C22:0], no difference in marrow fatty acid composition was evident between subject groups of varying BMD (normal, low bone mass, and osteoporosis). In conclusion, there exists a wide range of individual fatty acids in marrow fat. Marrow fatty acid composition differs from that of subcutaneous fat and varies between predominantly erythropoetic and fatty marrow sites. Other than cis-7-hexadecenoic acid [C16:1 (n=9)] and docosanoic acid [C22:0], no difference in marrow fatty acid composition was evident between subjects of varying BMD.

The efficacy and tolerability of adjunctive alternative herbal medicine (Salvia miltiorrhiza and Pueraria lobata) on vascular function and structure in coronary patients.

BACKGROUND: Danshen and gegen (D&G) have long been used in treatment of angina and other cardiac symptoms in Chinese materia medica. Recent pharmacological studies suggest their therapeutic values. We aimed to evaluate the efficacy and safety of Salvia miltiorrhiza (danshen) and Pueraria lobata (gegen) in secondary prevention. METHODS: One hundred (100) consecutive coronary patients (mean age 58 +/- 8 years) were randomized to adjunctive treatment with D&G combination (3 g) or placebo (6 capsules) for 24 weeks in double-blind parallel fashion, followed by optional open-label D&G (1.5 g/day) for 6 more months. Brachial flow-mediated dilation (FMD) and carotid intima-media thickness (IMT) were measured using ultrasound. RESULTS: Baseline characteristics were similar between the 2 groups. After 24 weeks and compared with baseline, there were no significant changes in blood pressures, blood hematological and biochemical profiles, or folate and homocysteine levels in both groups, but there was a mild decrease in low density lipoprotein (LDL) cholesterol in both groups (p < 0.05). Brachial FMD improved during D&G (p < 0.001) and less so during placebo treatment (p < 0.05), while improvement in carotid IMT was observed only in the D&G group (p < 0.05). After open-label D&G treatment for 6 more months (n = 45), further improvement in both brachial FMD (p < 0.0001) and carotid IMT (p < 0.0001) was observed. Eight (8) adverse events were reported-6 during placebo and 2 during D&G treatment-requiring treatment termination in 2 patients (on placebo). CONCLUSIONS: D&G adjunctive treatment in coronary patients was well tolerated and effective in improving vascular function and structure. These two herbs may become a novel agent for secondary prevention.

Sleep disturbances and frailty status in older community-dwelling men.

OBJECTIVES: To test the hypothesis that sleep disturbances are independently associated with frailty status in older men. DESIGN: Cross-sectional analysis of prospective cohort study. SETTING: Six U.S. centers. PARTICIPANTS: Three thousand one hundred thirty-three men aged 67 and older. MEASUREMENTS: Self-reported sleep parameters (questionnaire); objective parameters of sleep-wake patterns (actigraphy data collected for an average of 5.2 nights); and objective parameters of sleep-disordered breathing, nocturnal hypoxemia, and periodic leg movements with arousals (PLMAs) (in-home overnight polysomnography). Frailty status was classified as robust, intermediate stage, or frail using criteria similar to those used in the Cardiovascular Health Study frailty index. RESULTS: The prevalence of sleep disturbances, including poor sleep quality, excessive daytime sleepiness, short sleep duration, lower sleep efficiency, prolonged sleep latency, sleep fragmentation (greater nighttime wakefulness and frequent, long wake episodes), sleep-disordered breathing, nocturnal hypoxemia, and frequent PLMAs, was lowest in robust men, intermediate in men in the intermediate-stage group, and highest in frail men (P-for-trend < or =.002 for all sleep parameters). After adjusting for multiple potential confounders, self-reported poor sleep quality (Pittsburgh Sleep Quality Index > 5, multivariable odds ratio (MOR)=1.28, 95% confidence interval (CI)=1.09-1.50), sleep efficiency less than 70% (MOR=1.37, 95% CI=1.12-1.67), sleep latency of 60 minutes or longer (MOR=1.42, 95% CI=1.10-1.82), and sleep-disordered breathing (respiratory disturbance index > or =15, MOR=1.38, 95% CI=1.15-1.65) were each independently associated with higher odds of greater frailty status. CONCLUSION: Sleep disturbances, including poor self-reported sleep quality, lower sleep efficiency, prolonged sleep latency, and sleep-disordered breathing, are independently associated with greater evidence of frailty.

Compromised bone marrow perfusion in osteoporosis.

A link between bone blood flow and osteoporosis may exist. Outside of the spine, the proximal femur is the most common site of osteoporotic fracture and is also an area prone to avascular necrosis and fracture nonunion. This study of the proximal femur investigates the relationship between BMD, bone marrow fat content, bone perfusion, and muscle perfusion. One hundred twenty healthy female subjects (mean age, 74 yr; age range, 67-89 yr) underwent DXA examination of the hip, proton MR spectroscopy, and dynamic contrast-enhanced MR imaging of the right proximal femur, acetabulum, and adductor thigh muscle. In all bone areas examined (femoral head, femoral neck, femoral shaft, acetabulum), perfusion indices (maximum enhancement, enhancement slope) were significantly reduced in subjects with osteoporosis compared with subjects with osteopenia or normal BMD. Adductor muscle perfusion was not affected by change in BMD. As marrow perfusion decreased in the proximal femur, marrow fat increased (r = 0.827). This increase in fat content seemed to account for the decrease in marrow perfusion more than a reduction in BMD. For normal BMD subjects, perfusion parameters in the femoral head were one third of those in the femoral neck or shaft and one fifth of those in the acetabulum. Perfusion throughout the proximal femur is reduced in osteoporotic subjects compared with osteopenic and normal subjects. This reduction in perfusion only affects bone and not those tissues outside of bone with the same blood supply. As bone perfusion decreased, there was a corresponding increase in marrow fat.