This study initially explored the relationship between NHHR and BMD in adult men. Our multivariate linear regression analyses revealed a negative correlation between NHHR and lumbar BMD. Curve fitting and threshold effect analyses indicated a nonlinear relationship between the variables, with an inflection point at 4.76. Specifically, in the other race group and participants aged 30–39 years, we discovered a nonlinear relationship between NHHR and lumbar BMD, with inflection points at 5.00 and 2.83, respectively.
Despite the absence of direct evidence on the role of NHHR in osteoporosis, extensive research has explored the relationship between HDL-C, LDL-C, and TC with osteoporosis [17, 23, 24]. Recent studies have revealed that LDL-C is negatively associated with lumbar spine BMD in postmenopausal women when LDL-C levels are below 3.52 mmol/L [25]. Xiao et al. further demonstrated that elevated LDL-C levels are linked to reduced lumbar spine BMD, indicating a detrimental impact of LDL-C on bone health [23]. High LDL-C levels may impair osteoblast function and enhance osteoclast activity, leading to decreased bone mass. LDL-C and its oxidized form (ox-LDL) can activate osteoclasts, promoting bone resorption and further decreasing BMD [26, 27]. Similarly, numerous studies have shown that higher cholesterol levels are associated with an increased risk of lower BMD or osteoporosis [28, 29]. Cao et al. reported a significant negative association between total cholesterol and total BMD in US adults after adjusting for age, BMI, smoking, and alcohol consumption [30]. Potential mechanisms may include systemic inflammation and oxidative stress induced by high cholesterol levels, disrupting bone metabolism balance by increasing bone resorption and decreasing bone formation [31].
Conversely, HDL-C is renowned for its role in reverse cholesterol transport, which can reduce the risk of cardiovascular disease and osteoporosis [24, 32]. Some studies suggest a positive correlation between high HDL-C levels and higher BMD, indicating a protective effect on bone health. For instance, Zolfaroli et al. found HDL-C positively associated with BMD at both the lumbar spine and femoral neck in postmenopausal women [14]. HDL-C may mitigate the production of inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), reducing inflammatory damage to bone tissue [33]. Additionally, HDL-C decreases oxidative stress, protecting osteoblasts from free radical damage and supporting bone formation and maintenance [34]. However, other studies have reported that HDL-C is either negatively correlated with BMD or shows no association, suggesting complex mechanisms through which HDL-C influences bone density. Hussain et al. found that higher HDL-C levels are associated with lower BMD, independent of common fracture risk factors [10]. Two cross-sectional surveys in China revealed a negative relationship between HDL-C and BMD, suggesting a potential adverse impact on bone health [35, 36]. Furthermore, another cross-sectional study found no association between HDL-C levels and osteoporosis in various locations [15]. The heterogeneity among studies, potentially arising from differences in study designs, sampling methodologies, confounding variables, and racial distribution, may explain these conflicting results.
Our research, after adjusting for covariates, indicates that a higher NHHR is significantly associated with lower BMD in adult men aged 20–59 years according to weighted multiple linear regression models. In line with the STROBE statement, we performed a subgroup analysis to identify specific groups exhibiting varied trends [37]. Among the total cohort, other race individuals, and participants aged 30–39 years, we discovered a nonlinear relationship with inflection points at 4.76, 5.00, and 2.83, respectively. Considering this relationship, regulating NHHR by lowering LDL-C and TG levels while maintaining or increasing HDL-C levels could offer a more comprehensive approach to preventing and treating osteoporosis.
Strengths and limitations
The study has several strengths. First, it is the first to explore the relationship between NHHR and lumbar BMD in American adult men, utilizing a nationally representative sample that reflects the general American population. Second, it suggests that NHHR may serve as a novel marker for bone health, highlighting the role of lipid metabolism disorders in bone loss mechanisms. Third, the use of multivariate linear regression, stratified analyses, smooth curve fitting, and threshold effect analysis, adjusted for numerous confounders, enhances the reliability of the results. However, the study has limitations. First, the sample is restricted to American men aged 20–59 years, and the relevance of the NHHR-BMD relationship to other populations or ethnicities remains uncertain due to genetic, environmental, and cultural differences, necessitating further mechanistic research and large-scale prospective studies. Additionally, the cross-sectional design limits the ability to establish causality between NHHR levels and BMD. Second, despite adjusting for many confounders, potential factors may still impact the outcomes. Third, the cross-sectional nature of the study restricts the ability to determine causality between NHHR and lumbar BMD in adult men. Therefore, further prospective clinical and basic research is needed to validate causal inferences.