Inflammatory markers and bone health in postmenopausal women: a cross-sectional overview.

BACKGROUND: Cytokines, chemokines, C-reactive proteins (CRP) and ferritin are known inflammatory markers. However, cytokines such as interleukin (IL-1ß), (IL-6) and tumour necrosis factor (TNF-α) have been reported to interfere with both the bone resorption and bone formation processes. Similarly, immune cell cytokines are known to contribute to inflammation of the adipose tissue especially with obesity. IL-10 but not IL-33 has been linked to lower ferritin levels and anemia. In this study, we hypothesized that specific cytokine levels in the plasma of women with low bone mineral density (BMD) would be higher than those in the plasma of healthy women due to the actions of elevated levels of pro-inflammatory cytokines in inducing osteoclast formation and differentiation during senescence. RESULTS: Levels of cytokines (IFNα2, IFN-γ, IL-12p70, IL-33) and monocyte chemoattractant protein-1 (MCP-1) were significantly higher in the plasma of the osteoporotic group compared to the osteopenic and/or healthy groups. Meanwhile CRP levels were significantly lower in women with osteoporosis (P = 0.040) than the osteopenic and healthy groups. Hip BMD values were significantly lower in women with high/detectable values of IL-1ß (P = 0.020) and IL-6 (P = 0.030) compared to women where these were not detected. Similarly, women with high/detectable values of IL-1ß had significantly lower spine BMD than those where IL-1ß was not detected (P = 0.030). Participants' CRP levels were significantly positively correlated with BMI, fat mass and fat percentage (P < 0.001). In addition, ferritin levels of women with high/detectable values of anti-osteoclastogenic IL-10 (P = 0.012) and IL-33 (P = 0.017) were significantly lower than those where these were not detected. There was no statistically significant association between TNF-α and BMD of the hip and lumbar spine. CONCLUSIONS: High levels of cytokines (IFNα2, IFN-γ, IL-12p70, IL-33) and MCP-1 in apparently healthy postmenopausal women are associated with bone health issues. In addition, an increase in levels of IL-10 and IL-33 may be associated with low ferritin levels in this age group. TRIAL REGISTRATION: ANZCTR, ACTRN12617000802303. Registered May 31st, 2017, https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=373020.

Chasing a ghost?--Issues with the determination of circulating levels of endotoxin in human blood.

Reliable quantification of bacterial products such as endotoxin is important for the diagnosis of Gram-negative infection and for the monitoring of its treatment. Further, it is important to identify patients with persistent subclinical level of bacterial products in their systemic circulation as data from animal studies also suggest this may be correlated with the onset of metabolic syndrome. In this review, we first aim to describe the principles of the Limulus amoebocyte lysate (LAL) test, an assay that is used to quantify endotoxin, and the various shortcomings that must be addressed before it can become a reliable means of quantifying endotoxin in samples derived from blood. We then review published data regarding endotoxin levels in healthy subjects and those with sepsis, inflammatory bowel disease, liver disorders and metabolic disorders such as obesity and diabetes. We also review the evidence regarding influence of macronutrients in augmenting the levels of systemic endotoxin. The results of this review show that reported mean levels of endotoxin in the systemic circulation of healthy humans and of those with various clinical disorders vary over a wide range. Further, this review shows that a significant proportion of this variation can be related to the method that was used to prepare plasma and serum samples prior to assay and its ability to reduce the effect of various blood borne factors that interfere with the LAL assay.

Carvacrol Inhibits Osteoclastogenesis and Negatively Regulates the Survival of Mature Osteoclasts.

Bone is a dynamic tissue that undergoes continuous remodeling coupled with the action of osteoblasts and osteoclasts. Osteoclast activity is elevated during osteoporosis and periodontitis resulting in excessive loss of trabecular and alveolar bone. Osteoclasts are formed in an inflammatory response to cytokine production receptor activator of nuclear factor-kappaB (NF-κB) ligand (RANKL) and bacterial challenge lipopolysaccharide (LPS). Carvacrol, a monoterpenic phenol present in Origanum vulgare and Thymus vulgaris, is a natural compound with known medicinal properties. We investigated the effects of carvacrol on osteoclast formation induced by RANKL and LPS. Carvacrol suppressed RANKL-induced formation of tartrate resistant acid phosphatase (TRAP)-positive multinucleated cells in RAW264.7 macrophages and human CD14(+) monocytes. Furthermore, carvacrol inhibited LPS-induced osteoclast formation in RAW264.7 macrophages. Investigation of the underlying molecular mechanisms revealed that carvacrol downregulated RANKL-induced NF-κB activation in a dose-dependent manner. Furthermore, the suppression of NF-κB activation correlated with inhibition of inhibitor of kappaB (IκB) kinase (IKK) activation and attenuation of inhibitor of NF-κB (IκBa) degradation. Carvacrol potentiated apoptosis in mature osteoclasts by caspase-3 activation and DNA fragmentation. Moreover, carvacrol did not affect the viability of proliferating MC3T3-E1 osteoblast-like cells. Collectively, these results demonstrate that carvacrol mitigates osteoclastogenesis by impairing the NF-κB pathway and induction of apoptosis in mature osteoclasts.

Associations between Self-Reported Physical Activity, Heel Ultrasound Parameters and Bone Health Measures in Post-Menopausal Women.

Physical activity plays an important role in the maintenance of bone health from childhood through adulthood. This study aimed to explore the associations between self-reported physical activity (PA), activity energy expenditure (AEE), heel ultrasound parameters and bone health measures among older adult women. The AEE was estimated from the responses of questionnaires for 125 older adult women aged 54-81 years. The bone parameters were measured by dual energy x-ray absorptiometry (DXA) and heel ultrasound parameters by the heel quantitative ultrasound (QUS). This study showed that AEE and the metabolic equivalent task (MET) were positively correlated with the bone and heel ultrasound parameters. However, fat mass (FM) and fat percentage were negatively correlated with AEE and MET. In addition, the regression analysis showed that higher AEE was a strong predictor of a higher spine T-score (ß = 0.212, p = 0.015), QUS T-score (ß = 0.239, p = 0.011) and stiffness index (ß = 0.240, p = 0.010) after adjusting for age, fat mass, lean mass, height and calcium intake. These results contribute to our understanding of the importance of physical activity in postmenopausal women by reiterating the benefits of physical activity for older adult women. Physical activity is an important tool for the prevention and management of osteoporosis.

The Relationship between Nutrient Patterns and Bone Mineral Density in Postmenopausal Women.

In women, the menopausal transition is characterized by acid-base imbalance, estrogen deficiency and rapid bone loss. Research into nutritional factors that influence bone health is therefore necessary. In this study, the relationship between nutrient patterns and nutrients important for bone health with bone mineral density (BMD) was explored. In this cross-sectional analysis, 101 participants aged between 54 and 81 years were eligible. Body composition and BMD analyses were performed using dual-energy X-ray absorptiometry (DXA). Nutrient data were extracted from a 3-day diet diary (3-DDD) using Foodworks 9 and metabolic equivalent (MET-minutes) was calculated from a self-reported New Zealand physical activity questionnaire (NZPAQ). Significant positive correlations were found between intakes of calcium (p = 0.003, r = 0.294), protein (p = 0.013, r = 0.246), riboflavin (p = 0.020, r = 0.232), niacin equivalent (p = 0.010, r = 0.256) and spine BMD. A nutrient pattern high in riboflavin, phosphorus and calcium was significantly positively correlated with spine (p < 0.05, r = 0.197) and femoral neck BMD (p < 0.05, r = 0.213), while the nutrient pattern high in vitamin E, α-tocopherol, ß-carotene and omega 6 fatty acids was negatively correlated with hip (p < 0.05, r = -0.215) and trochanter BMD (p < 0.05, r = -0.251). These findings support the hypothesis that a nutrient pattern high in the intake of vitamin E, α-tocopherol and omega 6 fatty acids appears to be detrimental for bone health in postmenopausal women.

Lean Body Mass in the Prediction of Bone Mineral Density in Postmenopausal Women.

Owing to conflicting results of the association between body composition and bone mineral density (BMD), we investigated the relationship between fat mass (FM), lean mass (LM), and BMD in New Zealand postmenopausal women. We hypothesized that increased LM will indicate a higher BMD. A cross-sectional study was performed examining the associations between body composition, anthropometric measures, activity energy expenditure, and bone health status (using dual-energy X-ray absorptiometry [DXA]). A total of 127 healthy postmenopausal women aged between 54 and 81 years. Both FM and LM were significantly associated with BMD at all sites. However, LM, not FM, was the strongest predictor of femoral neck (FN) BMD (ß = 0.497, p < 0.001), hip BMD (ß = 0.495, p < 0.001), spine BMD (ß = 0.449, p < 0.001), and whole body BMD (ß = 0.406, p < 0.001). Age was negatively associated with FN and hip BMD. LM was positively associated with FN, spine, hip, and whole body BMD. Our findings suggest the need to increase LM rather than FM highlighting the importance of physical activity for this age group.

Increased intake of selected vegetables, herbs and fruit may reduce bone turnover in post-menopausal women.

Increased consumption of vegetables/herbs/fruit may reduce bone turnover and urinary calcium loss in post-menopausal women because of increased intake of polyphenols and potassium, but comparative human studies are lacking. The main aim was to compare bone turnover markers and urinary calcium excretion in two randomised groups (n = 50) of healthy post-menopausal women consuming ≥ 9 servings of different vegetables/herbs/fruit combinations (three months). Group A emphasised a generic range of vegetables/herbs/fruit, whereas Group B emphasised specific vegetables/herbs/fruit with bone resorption-inhibiting properties (Scarborough Fair Diet), with both diets controlled for potential renal acid load (PRAL). Group C consumed their usual diet. Plasma bone markers, urinary electrolytes (24 h) and estimated dietary PRAL were assessed at baseline and 12 weeks. Procollagen type I N propeptide (PINP) decreased (-3.2 µg/L, p < 0.01) in the B group only, as did C-terminal telopeptide of type I collagen (CTX) (-0.065 µg/L, p < 0.01) in women with osteopenia compared to those with normal bone mineral density (BMD) within this group. Intervention Groups A and B had decreased PRAL, increased urine pH and significantly decreased urinary calcium loss. Urinary potassium increased in all groups, reflecting a dietary change. In conclusion, Group B demonstrated positive changes in both turnover markers and calcium conservation.

Effects of dietary fibre and tea catechin, ingredients of the Japanese diet, on equol production and bone mineral density in isoflavone-treated ovariectomised mice.

Equol is a metabolite of the isoflavone daidzein (Dz) and is produced by the bacterial microflora in the distal intestine and colon. Some epidemiological studies have reported an association between increased equol production and intakes of green tea or dietary fibre, which are ingredients of the standard Japanese diet. We examined the effects of a diet supplemented with Dz and tea catechin or dietary fibre on equol production and bone mineral density in ovariectomised (OVX) mice. Female mice of the ddY strain were either sham operated or OVX. OVX mice were fed a control diet, a 0·1 % Dz-supplemented diet or a 0·1 % Dz diet supplemented with one of the food components commonly consumed in the Japanese diet. The mice were given 1 % tea catechin (w/w) as part of the diet in Expt 1 or 5 % polydextrose (PD) and 5 % raffinose (Raf) (w/w) as part of the diet in Expt 2. Catechin reduced serum equol levels and attenuated the beneficial effect of Dz on femoral bone loss. The soluble dietary fibres PD and Raf stimulated equol production, and enhanced the bone-protective effects of Dz on femoral bone. These results suggest that dietary fibre, in particular, PD, may alter the bioavailability of isoflavones and prevent osteopenia in OVX mice.