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

Abstract

Background Cytokines, chemokines, C-reactive proteins (CRP) and ferritin are known inflammatory markers. However, cytokines such as interleukin (IL-1β), (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-1β ( 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-1β had significantly lower spine BMD than those where IL-1β 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

Relationship of Bone Mineral Density and Vascular Wall Condition With Biochemical Markers of Inflammation in Postmenopausal Women

“…С нарастанием продолжительно-О р и г и н а л ь н ы е и с с л е д о в а н и я была доказана в когорте молодых женщин, в отличие от мужчин [14]. А в одном исследовании были получены противоречивые данные о низком уровне СРБ у лиц с ОП по сравнению с остеопенией, в то время как высокий уровень ИЛ6 ассоциировался с низкой костной массой только в ПОБ [15].…”

IL-33/IL-31 Axis in Osteoporosis

“…Via the NF-kB and MAPK signaling pathways, IL-33 induces the production of IL-5, IL-13 and CCL5, CCL17, CCL24 chemokines [57,65]. The response to IL-33 depends on the cell type, the cellular composition of the tissue microenvironment, and the presence of co-stimulating cytokines [66][67][68][69].…”

“…An increase of IL-31 has been linked to decreased BMD in postmenopausal women. Binding of IL-31 to its receptor results in the phosphorylation and activation of STATs, MAPK, and JNK signaling pathways [66]. IL-31 plays a pathogenic role in tissue inflammation and bone destruction also during aging.…”

“…Unlike estrogens, IL-33 has little effect on TNF-α induced bone remodeling [58]. IL-33, together with the anti-inflammatory cytokine IL-10, is also related to the ferritin status in post-menopausal women, suggesting a role of these anti-inflammatory and anti-osteoclastogenic cytokines in the regulation of iron metabolism too [66]. Findings from IL-33 −/− and ST2 −/− mouse models of postmenopausal osteoporosis revealed that IL-33 and its receptor protects the maxilla and femur from bone loss during physiological bone remodeling.…”

Osteoporose und Frakturen bei Multipler Sklerose – unterschätzt und ignoriert?

“…Diese Abweichung war am ehesten zu korrigieren, wenn im Online-Tool zusätzlich die Angabe "rheumatoide Arthritis" bejaht wurde. Dies legt den Schluss nahe, dass die Entzündungsreaktion selbst in einem relevanten Ausmaß zur Entwicklung einer Osteoporose bei entzündlichen Systemerkrankungen beiträgt [21,22]. Zytokine selbst wirken negativ auf den Knochenstoffwechsel ein: direkte knochendestruktive Wirkungen konnten für mehrere im Rahmen der MS erhöhte Zytokine, Chemokine und Entzündungsmediatoren wie z.…”