| During the first five years of menopause, women lose approximately 2-3% of their bone each year. The decrease in estrogen that accompanies menopause leads to increased activity and maturation of osteoclasts, high rates of bone resorption and eventually to osteoporosis. The rate of osteoclast development depends on the number of osteoclast progenitors and the production of cytokines involved in osteoclast differentiation. Recent studies suggest that bone loss occurring during menopause results from an alteration of the immune system. Osteoclastogenic cytokines increase, thereby stimulating bone resorption. Concurrently, there is down-regulation of bone formation and therefore, a disruption of bone homeostasis, resulting in a net bone loss.;The purpose of this study was two-fold: (1) to examine the relationship between inflammatory cytokines, CRP, and cortisol to bone mineral density (BMD) and bone mineral content (BMC) of the total hip, femoral neck, and lumbar spine; and (2) to investigate two methods (serum analysis and stimulated whole blood cultures) of assessment of cytokine production in a cohort of healthy, postmenopausal women to determine which method would best capture the relationship between inflammatory status and bone.;The relationship of cytokines to BMD and BMC of the three bone sites varied depending on the type of methodology used. Consistently, IL-1beta had a positive relationship with BMC of the femoral neck and lumbar spine. Interleukin-4 was positively associated with femoral neck BMC. Interleukin-6, TNF-alpha, and IL-7 had a negative relationship with femoral neck BMC. CRP was negatively associated with the femoral neck and lumbar spine BMC. Results of this study indicated that whole blood stimulation was more precise than serum analysis of cytokine production.;Findings of this project indicated that there was a clear relationship between inflammation and bone, demonstrated by the negative association of TNF-alpha, IL-6, and CRP with BMC. In addition, since cytokine production measured in serum may not be reflective of what is occurring in the micro environment of the bone, stimulated cytokines may better represent potential in vivo events and have the ability to capture low levels of cytokine production often seen in a healthy population. |
