The role of body composition on bone health has been extensively investigated, but the results regarding the effect of fat mass on the BMD have been controversial. In this study of adult Chinese individuals, we found that BMI has shortcomings as a predictor of the BMD because it does not separate lean mass from fat mass and does not explore the influence of the fat distribution on the bone mass. Therefore, we modelled the effect of the regional fat content on the bone mineral density in a large sample size within a healthy population. Our results showed that overall, there was a negative relationship between the regional fat percentage and the FN BMD or the LS BMD in both males and females. Moreover, the tendency and magnitude of this effect depended on the gender, fat content/distribution and bone site.
Our results revealed that the associations between BMI and FN BMD appear stronger than those of BMI and LS BMD in both females and males. A previous study showed that an increasing BMI tended to reduce the risk of hip fractures and the prevalence of vertebral deformity. When the fracture risk was adjusted for the BMD, the BMI appeared to be a predictor only for hip fracture. This might be attributed to the fact that cortical bone rather than trabecular bone is preferentially affected by obesity.
In this study, we confirmed that the regional fat content was negatively associated with the BMD in males and females using multiple linear regression models. To further investigate the dose-response relationship between the regional fat content and the BMD, generalized additive models were performed. In females, the data from our study showed that the relationship between the regional fat percentage and the two-site BMD appeared to be n-shaped, indicating that the effect of the regional fat percentage on the BMD is nonlinear. According to these data, we may infer that an increase in the regional body fat is weakly protective against bone loss, but this effect becomes detrimental as we move towards morbid obesity. This suggests that body fat accentuates the mechanical loading on the skeleton and subsequently increases bone mass to a certain extent, while morbid obesity induces systemic inflammation due to several conditions, such as metabolic syndrome or insulin resistance, thereby impairing the balance of the body composition, which leads to bone loss. Our results seem consistent with the conclusion from Kim who claimed that overweight may be protective against hip fractures in Asian adults but not morbid obesity, particularly in women. Regardless, more evidence is needed to draw a firm conclusion. For the regional fat content on the BMD in males, the association curve was comparatively complex. Generally, bone mass tends to decline according to the increase in the regional fat percentage. The mechanisms accounting for this association may be, for instance, that the increase of the fat tissue causes the transformation of more androgens into estrogens. Male bone loss is due to decreased circulating androgen, which is necessary for bone health. It was also reported that androgens are solely responsible for normal trabecular bone growth in males. Considering the literature shown above, our study revealed that the more fat tissue is in males, the more bone loss will occur.
Interestingly, through multiple linear regression models, we found that the associations between the hip fat percentage and the LS BMD appeared stronger than those of the hip fat percentage and the FN BMD in both females and males, especially for females, while the associations between the waist fat percentage and the FN BMD were stronger than those of the waist fat percentage and the LS BMD in both females and males, particularly for males. Additionally, in our multiple logistic regression analyses, we obtained similar results; that is, the risk of low LS BMD was most significant in the participants in the highest quartile of hip fat percentage for females, whereas the risk of low FN BMD was most significant in the highest quartile of waist fat percentage in males. These results were supported by a prospective cohort study from Norway of 23,061 men aged 60 to 79 years. In this study, men in the highest tertile of waist circumference had a 100% higher risk of hip fractures than men in the lowest tertile, which means that abdominal adiposity considerably increased the risk of hip fractures. In another cross-sectional study of 1,011 participants aged 50–80 years, it was reported that women who had at least one vertebral deformity had a greater percentage of trunk fat than women without vertebral deformities, which was also consistent with our findings above. Altogether, we may infer that there existed a cross-influence between the regional fat content and the bone mineral density. This result may pave the way for the development of predictive health education that is suitable for clinical practice, which means that men should care more about their waist circumference and avoid abdominal adiposity, while women should pay more attention to their hip circumference. Actually, not all fat depots are the same: site-specific effects rather than simply total body fat may be crucial in the assessment of the impact of obesity on the BMD.
Osteoporosis and obesity, which superficially have no obvious connection, share a common denominator, including a genetic predisposition and a common progenitor cell. Thus, several underlying mechanisms have been proposed to elucidate the harmful effect of fat tissue on bone health. At the molecular genetics level, a genome-wide bivariate analysis of Caucasians of European origin identified some suggestive shared genomic regions for both body fat mass and BMD, therefore implying that those two diseases might be influenced by some shared candidate genes or mutual crosstalk between their phenotypes’ gene regulatory networks. At the cellular level, adipocytes and osteoblasts have common progenitor cells, mesenchymal stem cells (MSCs). A shift of the cell differentiation of MSCs to adipocytes rather than osteoblasts will hinder osteogenesis and will consequently result in bone loss. Apart from the causations mentioned above, several adipokines, which are secreted by adipocytes, including adiponectin and leptin, have shown a negative effect on bone metabolism. Serum adiponectin is reported to be inversely correlated with the BMD in both males and females by inhibiting osteoblast proliferation and promoting apoptosis, altogether decreasing bone formation levels[26–28]. Leptin has a detrimental effect on bone formation mainly via the central nervous system, which appears to be mediated by the decreased production of serotonin in hypothalamic neurons[29, 30].
This study also has limitations mainly because it was a retrospective study, and any changes in the sex hormones and adipocytokines were not examined. Therefore, whether these changes are involved in the interactions is still unclear.
In conclusion, there is a cross-influence between the regional fat content and the bone mineral density. The mechanism by which the regional fat content exerts a cross-harmful effect on the hip/lumbar bone mass in females and males is not yet well known. Additional perspective and interventional studies are needed to unravel these gender- and location-dependent mechanisms in this area of study.