Bone mineralization is associated with differentiation of the osteoblast, which secretes osteopontin, one of the bone matrix proteins involved in bone formation. Rajamannan et al17
found that expression of osteopontin was stimulated by a high cholesterol diet, since cellular proliferation and bone matrix production were found to be mediated by hypercholesterolemia in in vivo experiments. Kha et al18
suggested that oxysterols, the products of cholesterol oxidation, contribute to the regulation of stem cell differentiation toward osteoblasts. A study by Brownbill et al19
showed that higher levels of serum lipids are positively associated with higher bone mineral density in postmenopausal women. Dennison et al20
demonstrated a relationship between BMD and lipids, but no relationship for BMD with total or LDL cholesterol. However, several studies have reported the opposite relationship, that lower BMD or osteoporosis is associated with higher total cholesterol levels in postmenopausal women.21,22
We also found a positive relationship between high cholesterol levels and osteoporosis and a weak inverse relationship between blood glucose and osteoporosis, but no relationship between osteoporosis and serum triglycerides and BMI in this study. Similarly, Samelson et al23
found an inverse relationship between elevated total cholesterol and lower BMD. These contradictory reports indicate that the mechanism of this association between lipid profile and BMD needs to be elucidated. They also lead to the conclusion that cholesterol is not a long-term clinical factor contributing to osteoporosis.
Osteoporosis is a common disease of the elderly, suggesting a possible link among various factors, including dietary saturated fat, physical activity, medical treatment and metabolic disorders. Osteoporosis is a polygenic disorder and is affected by the expression of several genes in the regulation of bone formation and osteoporotic fractures; for example, hormones and receptors, such as the vitamin D receptor (VDR) and estrogen receptor (ER); cytokines and receptors, such as IL-1α, IL-1β and IL-1ra, and transforming growth factor β1.23–27
Among genetic factors in the pathogenesis of osteoporosis, the IL-1 system was found to be the most important cytokine in modulating the growth of bone-resorptive cells in postmenopausal women.27–30
The IL-1 system is composed of IL-1α, IL-1β and IL-1ra. Both IL-1α and IL-β bond to the IL-1 receptor on the surface of blood cells, and they initiate a cascade of signal transduction to stimulate a potent pro-inflammatory response that initiates bone resorption. IL-1ra also bonds to the same IL-1 receptor, but is a competitive inhibitor of IL-1. However, these results are not consistent in different populations. For example, Langdahl et al12
reported that osteoporotic fractures were associated with IL-1ra, but not with polymorphism of IL-1β gene in whites. Kim et al31
reported that the association between IL-1ra VNTR polymorphism and BMD was identified in postmenopausal Korean women. Nevertheless, Bajnok et al11
observed a lack of association between the IL-1ra gene polymorphism and BMD in postmenopausal Hungarian women. Thus, the association between BMD and IL-1 cytokines is still unclear.32
In our study, the allelic and genotypic frequency results showed that IL-1β genotype was more frequent in postmenopausal Taiwanese women with osteoporosis. However, no significant differences were found in the distribution of IL-1α and IL-1ra genotype. This result is consistent with that of previous studies. For instance, Nemetz et al13
reported that allelic variation at the IL-1β gene was associated with reduction of bone mass in patients with inflammatory bowel disease. Chen et al14
reported similar findings, that IL-1β and IL-1ra gene polymorphisms were associated with BMD and osteoporosis in postmenopausal women.
In summary, the IL-1β polymorphism was found to be a genetic factor that might influence the maintenance of bone mass in postmenopausal Taiwanese woman. The relationship between IL-1α/ IL-1ra and bone mass is still unclear. Therefore, it is essential to carry out further studies in larger populations and other ethnic groups. Our experimental results suggest that a primary genetic analysis be part of a proper consultation so that precautions can be given to patients on familial genetics.