Association between conicity index and osteoporosis/femoral bone mineral density in USA adults

Abstract

Aims

Osteoporosis poses a substantial public health burden. The conicity index (C-index), which integrates waist circumference, weight, and height, is a validated measure of abdominal obesity. However, its association with osteoporosis and femoral bone mineral density (BMD) remains unclear.

Methods

This study analyzed data from 16,218 USA adults (aged ≥ 20 years) in the 2005 to 2020 National Health and Nutrition Examination Survey (NHANES). Associations between C-index and osteoporosis were assessed by weighted multivariable logistic regression, while associations between C-index and femoral BMD (total femur, neck, trochanter, intertrochanter) were evaluated by weighted multivariable linear regression. Potential non-linearity was explored via generalized additive models with smooth curve fitting. Threshold effect and dose-response analyses were performed, and robustness was tested by subgroup analyses.

Results

After full adjustment for confounders, participants in the highest C-index quartile (Q4) had significantly higher odds of osteoporosis than those in the lowest quartile (Q1) (OR 1.67 (95% CI 1.23 to 2.27); p = 0.001). Each one-unit increase in C-index was associated with statistically significant decreases in BMD, as follows: total femur (−0.17 g/cm²), femoral neck (−0.18 g/cm²), trochanter (−0.17 g/cm²), and intertrochanter (−0.18 g/cm²). These associations persisted in subgroup analyses. A non-linear relationship was identified between C-index and femoral BMD.

Conclusion

Elevated C-index independently predicts osteoporosis risk and femoral BMD reduction in USA adults, with critical thresholds indicating accelerated bone loss. It thus serves as a clinically actionable metric for osteoporosis risk stratification in abdominal obesity management.

Cite this article: Bone Joint Res 2026;15(1):42–57.

Article focus

• We evaluated the association between conicity index (C-index) related to obesity and osteoporosis/femoral bone mineral density (BMD) in a nationally representative sample of adults in the USA.

Key messages

• C-index was a risk factor for osteoporosis, and exhibits a negative correlation with femoral BMD. In addition, the threshold effect of between C-index and total femur BMD was found to be 1.454.

• A non-linear relationship was identified, and each one-unit increase in C-index was associated with a clinically significant decrease in femoral BMD of 0.17 to 0.18 g/cm², providing a valuable reference for risk assessment.

Strengths and limitations

• This study used nationally representative NHANES data with rigorous methodology, including comprehensive covariate adjustments and advanced non-linear modelling, to ensure robust findings.

• Its cross-sectional design lacks causal reasoning, necessitating external validation.

• Additionally, potential recall bias from self-reported data from the USA adult population, and the exclusion of individuals under the age of 20 years, constrain the interpretation, age-related applicability of the results, and generalizability to other populations.

Introduction

Osteoporosis is a chronic systemic bone disease characterized by deteriorated bone microstructure as well as reduced bone mass and density, leading to enhanced bone fragility and elevated fracture risk with associated mortality.^1-3 It is widely assessed through measurement of bone mineral density (BMD),⁴ and poses a considerable global public health burden.⁵ Among individuals aged ≥ 50 years worldwide, one in five men and one in two women experience osteoporosis-related fractures.^6,7 Projections suggest that by 2040, the number at high risk for osteoporotic fractures will double compared with 2010 levels.⁸

The femur is the longest tubular bone in the human body and articulates with the pelvis via the hip joint.⁹ There has been a persistent rise in the global incidence of femoral fractures.¹⁰ Given the clinical significance of femoral BMD in osteoporosis diagnosis and fracture prediction, identification of its modifiable risk factors is crucial.

A complex relationship exists between obesity measures and bone health. Evidence suggests an inverse association between waist circumference and osteoporosis risk in adults.¹¹ In adults aged ≥ 50 years, rapid BMI increases accelerate bone loss, while maintaining stable overweight from early adulthood may mitigate loss.¹² In adolescents, BMI positively impacts bone density via saturation effects.¹³ The weight-adjusted-waist index (WWI)¹⁴—calculated based on weight and waist circumference—shows inverse relationships with BMD across age groups.^15,16 These findings indicate contradictory correlations across obesity metrics.

The conicity index (C-index) integrates waist circumference, weight, and height for comprehensive abdominal obesity assessment.¹⁷ The C-index is calculated using waist circumference, weight, and height to assess abdominal obesity. Abdominal obesity is considered to be a more perilous form of obesity, and the advantage of using the C-index ratio lies in its ability to effectively assess fat accumulation around the waist and evaluate the degree of abdominal obesity in individuals.¹⁷ The C-index has been confirmed to have a significant association with various health conditions, including gallstones,¹⁸ sarcopenia, cardiovascular diseases,¹⁹ type 2 diabetes mellitus,²⁰ hypertension,²¹ erectile dysfunction,²² urinary incontinence,²³ osteoarthritis,²⁴ chronic kidney disease,²⁵ metabolic syndrome,²⁶ and all-cause mortality.²⁷ In postmenopausal women, the C-index is positively correlated with osteoporosis.²⁸ Furthermore, each component of the C-index can be easily determined at low cost, thereby reducing the expense associated with evaluating abdominal obesity. This index also demonstrates high sensitivity (ranging from 62.5% to 100.0%) and specificity (ranging from 78.2% to 100.0%) in evaluating excess fat, making it suitable for widespread application in future epidemiological research.²⁹

However, studies confirming the relationship between C-index and bone mineral density or osteoporosis across all adult populations are lacking. Additionally, it remains unclear whether the correlation observed in female populations applies similarly to other demographic groups. To address this gap, using NHANES data from 2005 to 2020, this study investigates the associations of C-index with osteoporosis and site-specific femoral BMD (neck, trochanter, intertrochanter, total femur) in USA adults aged ≥ 20 years.

Methods

Study population

Data from the National Health and Nutrition Examination Survey (NHANES) were analyzed. The NHANES, conducted by the National Center for Health Statistics (NCHS) of the Centers for Disease Control and Prevention (CDC), assesses the health and nutritional status of USA civilians to generate national statistical data. Trained healthcare professionals collected all data, and participants provided informed consent. The study received NCHS Ethics Review Board (ERB) approval. Secondary analysis required no additional approval.

This study included adults aged ≥ 20 years from five NHANES cycles: 2005 to 2006, 2007 to 2008, 2009 to 2010, 2013 to 2014, and 2017 to 2020 (2011 to 2012 and 2015 to 2016 were excluded owing to absence of BMD data). Participants with missing variables were excluded.

Osteoporosis and femoral BMD definitions

Dependent variables included osteoporosis and femoral BMD (total femur, neck, trochanter, intertrochanter). Certified radiological technologists measured BMD using Hologic QDR-4500A fan-beam densitometers via dual-energy X-ray absorptiometry (DXA). Osteoporosis was defined according to the World Health Organization (WHO) criteria^11,30,31 as BMD ≥ 2.5 SD below the young-adult reference mean at any femoral site: total femur: < 0.6830 g/cm²; femoral neck: < 0.5927 g/cm²; trochanter: < 0.4701 g/cm²; and intertrochanter: < 0.8066 g/cm².

C-index definition

The independent variable in this study was C-index, which was derived from waist circumference, weight, and height using the formula below:¹⁷

$${\displaystyle {\displaystyle C-index=\frac{{\text{WC}}_{\left(m\right)}}{0.109\times \sqrt{\frac{Weigh{t}_{\left(kg\right)}}{Heigh{t}_{\left(m\right)}}}}.}}$$

Waist circumference, weight, and height were measured at mobile examination centres (MECs) by trained technicians under quality assurance protocols including direct observation and expert audits.

Covariate selection

Covariates were selected through comprehensive review of osteoporosis and the BMD literature.^32-34 The final adjustment set included sex (categorized as male or female); age, race/ethnicity (classified as Mexican American, Other Race, Non-Hispanic White, or Non-Hispanic Black); education level (less than high school graduate, high school graduate, or college/above); marital status (married, never married, or other (including divorced, widowed, cohabiting, or separated)); and poverty-income ratio (PIR). BMI was categorized as underweight (< 18.5 kg/m²), normal (18.5 to 24.9 kg/m²), or overweight/obese (≥ 25 kg/m²). Health behaviours included smoking status (defined as lifetime consumption of ≥ 100 cigarettes), alcohol consumption (annual intake of ≥ 12 alcoholic drinks), and vigorous physical activity (participation in cardiorespiratory-elevating activities ≥ 1 time/week). Medical conditions comprised physician-diagnosed hypertension and diabetes.³³ Medication use captured prednisone/cortisone intake. Biochemical covariates encompassed alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma glutamyl transferase (GGT), lactate dehydrogenase (LDH), phosphorus, total calcium, serum uric acid, total cholesterol, triglycerides, creatinine, and blood urea nitrogen—all quantified through standardized NHANES laboratory protocols.

Statistical analysis

Continuous variables were characterized using survey-weighted means with 95% CIs, while categorical variables were described by survey-weighted percentages with 95% CIs. Differences in continuous and categorical variables were assessed via survey-weighted linear regression and chi-squared tests, respectively.

Weighted logistic regression analyzed linear associations between C-index and osteoporosis using odds ratios (ORs), while weighted linear regression evaluated C-index relationships with femoral BMD through β coefficients, both reporting 95% CIs. Analyses employed four hierarchical models: an unadjusted model to assess independent associations and three progressively adjusted models. Model I adjusted for age, sex, and race; Model II added education level, marital status, PIR, and BMI; Model III further incorporated ALT, AST, ALP, GGT, LDH, phosphorus, total calcium, serum uric acid, total cholesterol, triglycerides, creatinine, blood urea nitrogen, smoking status, alcohol consumption, hypertension, diabetes, vigorous physical activity, and corticosteroid use.

The relationship between C-index and osteoporosis was additionally examined through quartile stratification. For femoral BMD, dual analytical approaches combined continuous and quartile-based methods. Nonlinear associations were investigated using generalized additive models with smooth fitting curves, supplemented by threshold effect analysis to identify inflection points in C-index-BMD relationships. Likelihood ratio tests confirmed the statistical significance of identified thresholds and characterized dose-response patterns across inflection points.

Subgroup analyses were performed to assess robustness across sex, age, race, BMI, smoking status, alcohol consumption, hypertension, diabetes, physical activity, and corticosteroid use strata, with interaction effects evaluated via likelihood ratio tests. All analyses were conducted using Empower software and R software (RStudio; Posit, USA), with statistical significance defined as two-sided p < 0.05.

Results

Participant selection

From 56,769 participants across five NHANES cycles (2005 to 2020), we excluded 24,636 individuals aged < 20 years and 12,444 individuals with missing femur BMD or C-index data. After additional exclusion of individuals with incomplete covariates (age, race, education, marital status, PIR, BMI, ALT, AST, ALP, GGT, LDH, phosphorus, total calcium, serum uric acid, total cholesterol, triglyceride, creatinine, blood urea nitrogen, smoking, drinking, hypertension, diabetes, vigorous activity, prednisone/cortisone use), 16,218 participants with complete data were included for analysis (Figure 1).

Fig. 1.

Flow diagram of the study participants included and excluded in National Health and Nutrition Examination Survey (NHANES) 2005 to 2020.

Baseline characteristics

This study ultimately included 16,218 participants, whose baseline characteristics are presented in Table I according to the total number and osteoporosis status. Among all participants, males accounted for 50.20%, while females comprised 49.80%, with a mean age of 51.18 years; non-Hispanic whites represented 72.90% of the cohort. Within this population, 1,173 individuals were classified as patients with osteoporosis, whereas 15,045 were categorized as not living with osteoporosis. Notably, among those with osteoporosis, the proportion of females was higher than that of males, and a significant percentage of participants was aged over 60 years. Additionally, their BMI was relatively lower (p < 0.001, survey-weighted linear regression). Laboratory test results indicated statistically significant differences in ALT, ALP, blood urea nitrogen, LDH, phosphorus, triglycerides, and uric acid (p < 0.001, survey-weighted linear regression). Compared with individuals without osteoporosis, patients with osteoporosis exhibited a significantly elevated C-index (p < 0.001, survey-weighted chi-squared test), suggesting that a high C-index may play a facilitating role in the development of osteoporosis.

Table I.

Baseline characteristics of participants from National Health and Nutrition Examination Survey 2005 to 2020 study by osteoporosis, weighted.

Characteristic	Overall	Non-osteoporosis	Osteoporosis	p-value
Number of participants	16,218	15,045	1,173
Sex, %				< 0.001*
Male	50.20 (49.42 to 50.97)	52.52 (51.68 to 53.35)	18.18 (15.82 to 20.81)
Female	49.80 (49.03 to 50.58)	47.48 (46.65 to 48.32)	81.82 (79.19 to 84.18)
Mean age, yrs	51.18 (50.60 to 51.76)	50.05 (49.48 to 50.62)	66.73 (65.84 to 67.61)	< 0.001†
Age group, %				< 0.001*
20 to 40 yrs	24.63 (23.33 to 25.98)	26.23 (24.86 to 27.64)	2.67 (1.69 to 4.19)
40 to 60 yrs	43.38 (42.05 to 44.72)	44.69 (43.34 to 46.04)	25.39 (21.76 to 29.40)
> 60 yrs	31.99 (30.34 to 33.67)	29.09 (27.50 to 30.73)	71.94 (67.94 to 75.63)
Race, %				< 0.001*
Mexican American	7.04 (5.80 to 8.52)	7.34 (6.05 to 8.88)	2.90 (2.02 to 4.14)
Other race	10.68 (9.51 to 11.98)	10.60 (9.39 to 11.95)	11.78 (9.85 to 14.04)
Non-Hispanic White	72.90 (70.15 to 75.48)	72.28 (69.46 to 74.93)	81.48 (78.56 to 84.09)
Non-Hispanic Black	9.38 (8.15 to 10.76)	9.78 (8.51 to 11.22)	3.83 (3.03 to 4.84)
Education level, %				< 0.001*
Below high school	15.57 (14.33 to 16.89)	15.42 (14.14 to 16.78)	17.65 (15.11 to 20.52)
High school or graduated	24.49 (23.27 to 25.76)	24.14 (22.92 to 25.40)	29.38 (25.72 to 33.33)
College or above	59.94 (57.89 to 61.96)	60.44 (58.35 to 62.50)	52.97 (48.99 to 56.91)
Marital status, %				< 0.001*
Married	60.70 (59.16 to 62.22)	61.58 (59.97 to 63.18)	48.48 (43.98 to 53.00)
Never married	11.77 (10.80 to 12.82)	12.36 (11.33 to 13.46)	3.71 (2.55 to 5.36)
Other	27.53 (26.40 to 28.68)	26.06 (24.92 to 27.23)	47.81 (43.01 to 52.66)
PIR	3.19 (3.12 to 3.26)	3.22 (3.15 to 3.29)	2.78 (2.62 to 2.94)	< 0.001†
BMI, kg/m 2	28.30 (28.14 to 28.45)	28.53 (28.37 to 28.70)	25.00 (24.68 to 25.33)	< 0.001†
BMI group, %				< 0.001*
Underweight	1.36 (1.14 to 1.63)	1.07 (0.86 to 1.33)	5.34 (3.95 to 7.19)
Normal	28.83 (27.66 to 30.02)	27.24 (26.02 to 28.49)	50.77 (47.01 to 54.51)
Overweight or obese	69.81 (68.55 to 71.04)	71.69 (70.36 to 72.99)	43.89 (40.37 to 47.47)
ALT, U/L	25.12 (24.78 to 25.47)	25.45 (25.09 to 25.81)	20.57 (19.66 to 21.49)	< 0.001†
ALP, IU/L	69.04 (68.44 to 69.65)	68.32 (67.73 to 68.91)	79.02 (76.34 to 81.70)	< 0.001†
AST, U/L	25.17 (24.87 to 25.47)	25.20 (24.91 to 25.49)	24.79 (23.21 to 26.37)	0.608†
Blood urea nitrogen, mg/dL	13.80 (13.61 to 13.99)	13.66 (13.46 to 13.86)	15.73 (15.28 to 16.18)	< 0.001†
Creatinine, mg/dL	0.91 (0.90 to 0.92)	0.91 (0.90 to 0.91)	0.92 (0.90 to 0.95)	0.283†
GGT, R IU/L	28.70 (27.96 to 29.44)	28.80 (28.05 to 29.56)	27.25 (24.58 to 29.92)	0.270†
LDH, IU/L	134.52 (133.49 to 135.54)	133.54 (132.58 to 134.49)	148.03 (144.43 to 151.63)	< 0.001†
Phosphorus, mg/dL	3.74 (3.73 to 3.75)	3.74 (3.72 to 3.75)	3.84 (3.79 to 3.88)	< 0.001†
Total calcium, mg/dL	9.43 (9.41 to 9.45)	9.43 (9.41 to 9.45)	9.43 (9.40 to 9.46)	0.935†
Cholesterol, mg/dL	197.21 (196.22 to 198.21)	196.95 (195.97 to 197.93)	200.81 (196.44 to 205.17)	0.085†
Triglycerides, mg/dL	154.03 (151.39 to 156.66)	155.30 (152.53 to 158.06)	136.52 (130.61 to 142.43)	< 0.001†
Uric acid, mg/dL	5.43 (5.39 to 5.46)	5.46 (5.43 to 5.50)	4.96 (4.86 to 5.05)	< 0.001†
Smoking, %				0.649*
Yes	47.43 (45.83 to 49.03)	47.37 (45.69 to 49.05)	48.28 (44.59 to 51.99)
No	52.57 (50.97 to 54.17)	52.63 (50.95 to 54.31)	51.72 (48.01 to 55.41)
Drinking, %				< 0.001*
Yes	80.47 (79.06 to 81.81)	81.20 (79.77 to 82.55)	70.46 (67.16 to 73.56)
No	19.53 (18.19 to 20.94)	18.80 (17.45 to 20.23)	29.54 (26.44 to 32.84)
Hypertension, %				< 0.001*
Yes	34.28 (33.13 to 35.44)	33.46 (32.27 to 34.67)	45.49 (41.89 to 49.13)
No	65.72 (64.56 to 66.87)	66.54 (65.33 to 67.73)	54.51 (50.87 to 58.11)
Diabetes, %				0.250*
Yes	9.72 (9.08 to 10.41)	9.61 (8.97 to 10.30)	11.22 (9.21 to 13.61)
No	88.09 (87.39 to 88.75)	88.18 (87.49 to 88.84)	86.87 (84.41 to 88.99)
Borderline	2.19 (1.90 to 2.51)	2.21 (1.90 to 2.56)	1.91 (1.22 to 2.99)
Vigorous activity, %				< 0.001*
Yes	25.01 (23.87 to 26.18)	25.88 (24.69 to 27.10)	13.05 (10.07 to 16.74)
No	74.99 (73.82 to 76.13)	74.12 (72.90 to 75.31)	86.95 (83.26 to 89.93)
Taking prednisone or cortisone, %				< 0.001*
Yes	5.30 (4.85 to 5.78)	5.06 (4.60 to 5.56)	8.61 (6.51 to 11.31)
No	94.70 (94.22 to 95.15)	94.94 (94.44 to 95.40)	91.39 (88.69 to 93.49)
Body weight, kg	80.95 (80.50 to 81.40)	82.15 (81.67 to 82.63)	64.43 (63.51 to 65.36)	< 0.001†
Height, m	1.69 (1.69 to 1.69)	1.69 (1.69 to 1.70)	1.60 (1.60 to 1.61)	< 0.001†
WC, m	0.98 (0.98 to 0.99)	0.99 (0.98 to 0.99)	0.91 (0.90 to 0.92)	< 0.001†
C-index	1.31 (1.30 to 1.31)	1.30 (1.30 to 1.31)	1.32 (1.31 to 1.33)	< 0.001†
Quartiles of the C-index				< 0.001*
Q1 (< 1.2527)	27.62 (26.37 to 28.90)	27.93 (26.60 to 29.29)	23.36 (20.40 to 26.60)
Q2 (1.2527 to 1.3142)	25.33 (24.32 to 26.35)	25.31 (24.33 to 26.32)	25.51 (22.32 to 28.97)
Q3 (1.3142 to 1.3722)	24.31 (23.47 to 25.18)	24.56 (23.67 to 25.47)	20.89 (17.68 to 24.50)
Q4 (≥ 1.3722)	22.74 (21.66 to 23.86)	22.20 (21.09 to 23.35)	30.25 (26.87 to 33.86)
Total femur BMD, gm/cm 2	0.96 (0.96 to 0.97)	0.98 (0.98 to 0.99)	0.68 (0.68 to 0.69)	< 0.001†
Femoral neck BMD, gm/cm 2	0.82 (0.81 to 0.82)	0.83 (0.83 to 0.84)	0.56 (0.55 to 0.56)	< 0.001†
Trochanter BMD, gm/cm 2	0.73 (0.72 to 0.73)	0.74 (0.74 to 0.75)	0.52 (0.51 to 0.52)	< 0.001†
Intertrochanter BMD, gm/cm 2	1.14 (1.13 to 1.14)	1.16 (1.16 to 1.17)	0.81 (0.81 to 0.82)	< 0.001†

^*Survey-weighted chi-squared test.

^†Survey-weighted linear regression.

ALP, alkaline phosphatase; ALT, alanine aminotransferase; AST, aspartate aminotransferase; BMD, bone mineral density; C-index, conicity index; GGT, gamma glutamyl transferase; LDH, lactate dehydrogenase; PIR, ratio of family income to poverty; WC, waist circumference.

Relationship between C-index and osteoporosis

Table II presents the results of logistic regression analysis examining the association between C-index and osteoporosis. Significant correlations were observed in various models. In reference to the Q1 group of subjects, the odds of osteoporosis in the Q4 group were significantly increased in both the unadjusted model (OR 1.63 (95% CI 1.30 to 2.04), p < 0.001) and Model II (OR 1.74 (95% CI 1.31 to 2.33), p < 0.001), as well as in Model III (OR 1.67 (95% CI 1.23 to 2.27), p = 0.001). Conversely, in Model I (OR 0.60 (95% CI 0.47 to 0.78), p < 0.001), the likelihood of osteoporosis among subjects in the Q4 group showed a decrease. When conducting trend tests across different models, all results remained statistically significant: for the unadjusted model (p for trend < 0.001); for Model I (p for trend < 0.001); for Model II (p for trend = 0.002); and for Model III (p for trend = 0.006). The relationship between C-index and osteoporosis, after adjusting for all covariates, is illustrated in Figure 2.

Table II.

The association between conicity index (C-index) and osteoporosis from the National Health and Nutrition Examination Survey 2005 to 2020, weighted.

C-index	Crude*		Model I†		Model II‡		Model III§
	OR (95% CI)	p-value	OR (95% CI)	p-value	OR (95% CI)	p-value	OR (95% CI)	p-value
Q1	Reference		Reference		Reference		Reference
Q2	1.20 (0.97 to 1.50)	0.095	0.77 (0.60 to 0.98)	0.038	1.21 (0.95 to 1.55)	0.119	1.18 (0.92 to 1.52)	0.194
Q3	1.02 (0.79 to 1.31)	0.899	0.51 (0.38 to 0.67)	< 0.001	1.01 (0.75 to 1.36)	0.961	0.97 (0.72 to 1.31)	0.858
Q4	1.63 (1.30 to 2.04)	< 0.001	0.60 (0.47 to 0.78)	0.002	1.74 (1.31 to 2.33)	< 0.001	1.67 (1.23 to 2.27)	0.001
p for trend	< 0.001		< 0.001		0.002		0.006

^*No covariates were adjusted.

^†Sex, age, and race were adjusted.

^‡Sex, age, race, education level, marital status, poverty-income ratio, and BMI were adjusted.

^§Sex, age, race, education level, marital status, poverty-income ratio, BMI, alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase, blood urea nitrogen, creatinine, gamma glutamyl transferase, lactate dehydrogenase, phosphorus, total calcium, cholesterol, triglycerides, uric acid, smoking, drinking, hypertension, diabetes, vigorous activity, and taking prednisone or cortisone were adjusted.

OR, odds ratio.

Fig. 2.

The relationship between the conicity index (C-index) and osteoporosis. The red line represents the smooth curve fit between variables. The blue line represents the 95% CI of the fit. Sex, age, race, education level, marital status, poverty-income ratio, BMI, alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase, blood urea nitrogen, creatinine, gamma glutamyl transferase, lactate dehydrogenase, phosphorus, total calcium, cholesterol, triglycerides, uric acid, smoking, drinking, hypertension, diabetes, vigorous activity, and taking prednisone or cortisone were adjusted.

Relationship between C-index and femoral BMD

Table III presents a linear regression analysis of C-index and femur BMD, and a correlation was observed in the various models. When analyzing C-index as a continuous variable, in Model III, there was a negative correlation between C-index and femoral BMD. For every one-unit increase in C-index, the total femur BMD decreased by a mean of 0.17 g/cm² (β = −0.17 (95% CI −0.21 to –0.14), p < 0.001); the femoral neck BMD decreased by an average of 0.18 g/cm² (β = −0.18 (95% CI −0.22 to –0.15), p < 0.001); the trochanter BMD decreased by an average of 0.17 g/cm² (β = −0.17 (95% CI −0.20 to –0.14), p < 0.001); and the intertrochanter BMD decreased by an average of 0.18 g/cm² (β = −0.18 (95% CI −0.22 to –0.13), p < 0.001). Figure 3 shows the smooth curve fit of the relationship between C-index and femur BMD after adjusting for all potential confounders. In the quartile classification analysis of C-index, with Q1 group as reference, for Q4 group, the total femur BMD decreased by an average of 0.03 g/cm² (β = −0.03 (95% CI −0.04 to –0.03), p < 0.001); the femoral neck BMD decreased by an average of 0.04 g/cm² (β = −0.04 (95% CI −0.04 to –0.03), p < 0.001); the trochanter BMD decreased by an average of 0.03 g/cm² (β = −0.03 (95% CI −0.04 to –0.03), p < 0.001); and the intertrochanter BMD decreased by an average of 0.03 g/cm² (β = −0.03 (95% CI −0.04 to –0.02), p < 0.001). These results remained statistically significant after trend tests (p for trend < 0.001). This negative correlation still existed in Model II.

Table III.

The association between conicity index (C-index) and femur bone mineral density (BMD) from National Health and Nutrition Examination Survey 2005 to 2020, weighted.

C-index	Crude*		Model I†		Model II‡		Model III§
	β (95% CI)	p-value	β (95% CI)	p-value	β (95% CI)	p-value	β (95% CI)	p-value
Total femur BMD
Continuous	0.05 (0.01 to 0.08)	0.017	0.27 (0.24 to 0.30)	< 0.001	–0.18 (–0.21 to –0.14)	< 0.001	–0.17 (–0.21 to –0.14)	< 0.001
Q1	Reference		Reference		Reference		Reference
Q2	0.01 (–0.003 to 0.01)	0.170	0.02 (0.02 to 0.03)	< 0.001	–0.02 (–0.02 to –0.01)	< 0.001	–0.01 (–0.02 to –0.01)	< 0.001
Q3	0.02 (0.01 to 0.03)	0.001	0.05 (0.04 to 0.05)	< 0.001	–0.02 (–0.03 to –0.01)	< 0.001	–0.01 (–0.02 to –0.01)	< 0.001
Q4	0.01 (0.0002 to 0.02)	0.046	0.06 (0.05 to 0.07)	< 0.001	–0.04 (–0.04 to –0.03)	< 0.001	–0.03 (–0.04 to –0.03)	< 0.001
p for trend	0.008		< 0.001		< 0.001		< 0.001
Femoral neck BMD
Continuous	–0.16 (–0.19 to –0.12)	< 0.001	0.19 (0.16 to 0.22)	< 0.001	–0.19 (–0.22 to –0.16)	< 0.001	–0.18 (–0.22 to –0.15)	< 0.001
Q1	Reference		Reference		Reference		Reference
Q2	–0.02 (–0.02 to –0.01)	< 0.001	0.02 (0.01 to 0.02)	< 0.001	–0.02 (–0.02 to –0.01)	< 0.001	–0.01 (–0.02 to –0.01)	< 0.001
Q3	–0.02 (–0.03 to –0.01)	0.002	0.04 (0.03 to 0.04)	< 0.001	–0.02 (–0.03 to –0.01)	< 0.001	–0.01 (–0.02 to –0.01)	< 0.001
Q4	–0.04 (–0.05 to –0.03)	< 0.001	0.04 (0.03 to 0.05)	< 0.001	–0.04 (–0.05 to –0.03)	< 0.001	–0.04 (–0.04 to –0.03)	< 0.001
p for trend	< 0.001		< 0.001		< 0.001		< 0.001
Trochanter BMD
Continuous	0.03 (0.01 to 0.06)	0.019	0.16 (0.13 to 0.19)	< 0.001	–0.18 (–0.21 to –0.15)	< 0.001	–0.17 (–0.20 to –0.14)	< 0.001
Q1	Reference		Reference		Reference		Reference
Q2	0.002 (–0.01 to 0.01)	0.589	0.01 (0.01 to 0.02)	0.001	–0.02 (–0.02 to –0.01)	< 0.001	–0.02 (–0.02 to –0.01)	< 0.001
Q3	0.01 (0.01 to 0.02)	0.001	0.03 (0.02 to 0.04)	< 0.001	–0.02 (–0.03 to –0.01)	< 0.001	–0.01 (–0.02 to –0.01)	< 0.001
Q4	0.01 (–0.0004 to 0.01)	0.063	0.04 (0.03 to 0.04)	< 0.001	–0.04 (–0.04 to –0.03)	< 0.001	–0.03 (–0.04 to –0.03)	< 0.001
p for trend	0.005		< 0.001		< 0.001		< 0.001
Intertrochanter BMD
Continuous	0.09 (0.05 to 0.14)	< 0.001	0.34 (0.30 to 0.37)	< 0.001	–0.18 (–0.22 to –0.14)	< 0.001	–0.18 (–0.22 to –0.13)	< 0.001
Q1	Reference		Reference		Reference		Reference
Q2	0.01 (0.003 to 0.02)	0.012	0.03 (0.02 to 0.04)	< 0.001	–0.02 (–0.02 to –0.01)	< 0.001	–0.01 (–0.02 to –0.01)	0.001
Q3	0.02 (0.01 to 0.04)	< 0.001	0.06 (0.05 to 0.07)	< 0.001	–0.02 (–0.03 to –0.01)	< 0.001	–0.01 (–0.02 to –0.01)	0.002
Q4	0.02 (0.01 to 0.03)	< 0.001	0.08 (0.07 to 0.08)	< 0.001	–0.04 (–0.04 to –0.03)	< 0.001	–0.03 (–0.04 to –0.02)	< 0.001
p for trend	< 0.001		< 0.001		< 0.001		< 0.001

^*No covariates were adjusted.

^†Sex, age, and race were adjusted.

^‡Sex, age, race, education level, marital status, poverty-income ratio, and BMI were adjusted.

^§Sex, age, race, education level, marital status, poverty-income ratio, BMI, alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase, blood urea nitrogen, creatinine, gamma glutamyl transferase, lactate dehydrogenase, phosphorus, total calcium, cholesterol, triglycerides, uric acid, smoking, drinking, hypertension, diabetes, vigorous activity, and taking prednisone or cortisone were adjusted.

Fig. 3.

The relationship between conicity index (C-index) and femur bone mineral density (BMD). a) Total femoral neck BMD. b) Femoral neck BMD. c) Trochanter BMD. d) Indicated intertrochanter BMD. The red line represents the smooth curve fit between variables. The blue line represents the 95% CI of the fit. Sex, age, race, education level, marital status, poverty-income ratio, BMI, alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase, blood urea nitrogen, creatinine, gamma glutamyl transferase, lactate hydrogenase, phosphorus, total calcium, cholesterol, triglycerides, uric acid, smoking, drinking, hypertension, diabetes, vigorous activity, and taking prednisone or cortisone were adjusted.

Intriguingly, in the unadjusted model, C-index was positively correlated with femoral BMD (except for femoral neck BMD). For every one-unit increase in C-index, the total femur BMD increased by an average of 0.05 g/cm² (β = 0.05 (95% CI 0.01 to 0.08), p = 0.017); the trochanter BMD increased by an average of 0.03 g/cm² (β = 0.03 (95% CI 0.01 to 0.06), p = 0.019); and the intertrochanter BMD increased by an average of 0.09 g/cm² (β = 0.09 (95% CI 0.05 to 0.14), p < 0.001). In Model I, the positive correlation persisted (total femur BMD, β = 0.27 (95% CI 0.24 to 0.30), p < 0.001; femoral neck BMD, β = 0.19 (95% CI 0.16 to 0.22), p < 0.001; trochanter BMD, β = 0.16 (95% CI 0.13 to 0.19), p < 0.001; and intertrochanter BMD, β = 0.34 (95% CI 0.30 to 0.37), p < 0.001). After stratifying C-index into quartiles as a categorical variable, trend tests for C-index and femoral BMD were performed in both the unadjusted model and Model I, revealing a persistent positive correlation (p for trend < 0.05).

Threshold effect analysis of C-index with femur density

After adjusting for all potential confounders, threshold effects were observed for C-index and femur BMD (p for likelihood ratio test < 0.05), as shown in Table IV. The inflection points for total femur BMD, femoral neck BMD, trochanter BMD, and intertrochanter BMD were 1.454, 1.382, 1.454, and 1.454, respectively. When C-index < 1.454, for each unit increased in C-index, the total femur BMD decreased by an average of 0.16 g/cm² (β = −0.16 (95% CI −0.20 to –0.12), p < 0.001), the trochanter BMD decreased by an average of 0.16 g/cm² (β = −0.16 (95% CI −0.19 to –0.12), p < 0.001), and the intertrochanter BMD decreased by an average of 0.17 g/cm² (β = −0.17 (95% CI −0.21 to –0.13), p < 0.001). When C-index ≥ 1.454, for each unit increased in C-index, the total femur BMD decreased by an average of 0.42 g/cm² (β = −0.42 (95% CI −0.67 to –0.16), p = 0.002), the trochanter BMD decreased by an average of 0.36 g/cm² (β = −0.36 (95% CI −0.59 to –0.14), p = 0.002), and the intertrochanter BMD decreased by an average of 0.43 g/cm² (β = −0.43 (95% CI −0.76 to –0.09), p = 0.015). When C-index < 1.382, for each unit increased in C-index, the femoral neck BMD decreased by an average of 0.14 g/cm² (β = −0.14 (95% CI −0.18 to –0.09), p < 0.001). When C-index ≥ 1.382, for each unit increased in C-index, the femoral neck BMD decreased by an average of 0.30 g/cm² (β = −0.30 (95% CI −0.43 to –0.17), p < 0.001).

Table IV.

Threshold effect analysis of conicity index and femur bone mineral density (BMD).

Outcome	Effect size, 95% CI	p-value
Total femur BMD - β
Inflection point	1.454
< 1.454	–0.16 (–0.20 to –0.12)	< 0.001
≥ 1.454	–0.42 (–0.67 to –0.16)	0.002
p for likelihood ratio test	0.008
Femoral neck BMD - β
Inflection point	1.382
< 1.382	–0.14 (–0.18 to –0.09)	< 0.001
≥ 1.382	–0.30 (–0.43 to –0.17)	< 0.001
p for likelihood ratio test	< 0.001
Trochanter BMD - β
Inflection point	1.454
< 1.454	–0.16 (–0.19 to –0.12)	< 0.001
≥ 1.454	–0.36 (–0.59 to –0.14)	0.002
p for likelihood ratio test	0.009
Intertrochanter BMD - β
Inflection point	1.454
< 1.454	–0.17 (–0.21 to –0.13)	< 0.001
≥ 1.454	–0.43 (–0.76 to –0.09)	0.015
p for likelihood ratio test	0.049

Sex, age, race, education level, marital status, poverty-income ratio, BMI, alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase, blood urea nitrogen, creatinine, gamma glutamyl transferase, lactate dehydrogenase, phosphorus, total calcium, cholesterol, triglycerides, uric acid, smoking, drinking, hypertension, diabetes, vigorous activity, and taking prednisone or cortisone were adjusted.

Subgroup analysis of the relationship of C-index and osteoporosis with femoral BMD

Table V presents subgroup analysis examining the association between C-index and osteoporosis, as well as femoral bone density, across different variables. Furthermore, Supplementary Figures a to e display smooth curve fitting plots illustrating the relationship of C-index and osteoporosis with femoral bone density. Subgroup analysis revealed a significant interaction between C-index and osteoporosis only within different sexes (p for interaction = 0.041), while no significant interactions were observed in subgroup analyses of other variables (p for interaction > 0.05). In subgroups of different sexes, males exhibited heightened sensitivity to changes in C-index than females. In the female population, with each quartile increase in the C-index, the likelihood of developing osteoporosis rises (OR 1.16 (95% CI 1.04 to 1.30), p = 0.012) (Supplementary Figure a).

Table V.

Subgroup analysis of the relationship between conicity index with osteoporosis and femoral bone mineral density (BMD) from the National Health and Nutrition Examination Survey 2005 to 2020, weighted.

Characteristic	Osteoporosis (quartile)			Total femur BMD			Femoral neck BMD			Trochanter BMD			Intertrochanter BMD
	OR (95% CI)	p-value	PFI	β (95% CI)	p-value	PFI	β (95% CI)	p-value	PFI	β (95% CI)	p-value	PFI	β (95% CI)	p-value	PFI
Sex			0.041			0.214			0.106			0.022			0.270
Male	1.20 (0.94 to 1.52)	0.144		–0.42 (–0.48 to –0.35)	< 0.001		–0.37 (–0.42 to –0.31)	< 0.001		–0.33 (–0.38 to –0.28)	< 0.001		–0.45 (–0.52 to –0.37)	< 0.001
Female	1.16 (1.04 to 1.30)	0.012		–0.07 (–0.11 to –0.03)	0.001		–0.10 (–0.14 to –0.06)	< 0.001		–0.09 (–0.12 to –0.06)	< 0.001		–0.06 (–0.11 to –0.02)	0.010
Age group			0.479			0.004			0.243			< 0.001			0.004
20 to 40 yrs	1.52 (0.63 to 3.63)	0.352		–0.24 (–0.32 to –0.17)	< 0.001		–0.23 (–0.30 to –0.16)	< 0.001		–0.25 (–0.32 to –0.17)	< 0.001		–0.27 (–0.35 to –0.18)	< 0.001
40 to 60 yrs	1.10 (0.91 to 1.34)	0.316		–0.20 (–0.26 to –0.15)	< 0.001		–0.22 (–0.27 to –0.17)	< 0.001		–0.20 (–0.25 to –0.15)	< 0.001		–0.21 (–0.27 to –0.15)	< 0.001
> 60 yrs	1.17 (1.04 to 1.32)	0.011		–0.13 (–0.19 to –0.08)	< 0.001		–0.15 (–0.20 to –0.10)	< 0.001		–0.12 (–0.17 to –0.07)	< 0.001		–0.13 (–0.20 to –0.06)	0.001
Race			0.334			0.408			0.447			0.462			0.286
Mexican American	1.15 (0.92 to 1.43)	0.216		–0.23 (–0.32 to –0.14)	< 0.001		–0.21 (–0.30 to –0.12)	< 0.001		–0.21 (–0.29 to –0.13)	< 0.001		–0.26 (–0.37 to –0.15)	< 0.001
Other race	1.18 (0.92 to 1.51)	0.194		–0.18 (–0.27 to –0.09)	< 0.001		–0.19 (–0.27 to –0.11)	< 0.001		–0.18 (–0.27 to –0.10)	< 0.001		–0.18 (–0.28 to –0.08)	0.002
Non-Hispanic White	1.14 (1.01 to 1.28)	0.030		–0.17 (–0.21 to –0.13)	< 0.001		–0.19 (–0.23 to –0.15)	< 0.001		–0.17 (–0.21 to –0.13)	< 0.001		–0.17 (–0.23 to –0.12)	< 0.001
Non-Hispanic Black	1.05 (0.81 to 1.36)	0.729		–0.13 (–0.21 to –0.06)	0.001		–0.14 (–0.22 to –0.06)	0.001		–0.14 (–0.20 to –0.08)	< 0.001		–0.12 (–0.20 to –0.04)	0.006
BMI group			0.130			0.738			0.232			0.610			0.532
Underweight	1.48 (0.80 to 2.73)	0.210		–0.10 (–0.31 to 0.10)	0.326		–0.05 (–0.28 to 0.19)	0.713		–0.13 (–0.31 to 0.05)	0.168		–0.13 (–0.36 to 0.11)	0.311
Normal	1.13 (0.99 to 1.31)	0.081		–0.19 (–0.25 to –0.14)	< 0.001		–0.17 (–0.22 to –0.12)	< 0.001		–0.16 (–0.22 to –0.11)	< 0.001		–0.23 (–0.29 to –0.16)	< 0.001
Overweight or Obese	1.24 (1.07 to 1.45)	0.006		–0.20 (–0.24 to –0.16)	< 0.001		–0.22 (–0.26 to –0.18)	< 0.001		–0.19 (–0.23 to –0.16)	< 0.001		–0.20 (–0.25 to –0.15)	< 0.001
Vigorous activity			0.567			0.068			0.043			0.027			0.172
Yes	1.45 (0.99 to 2.11)	0.057		–0.24 (–0.30 to –0.18)	< 0.001		–0.27 (–0.32 to –0.21)	< 0.001		–0.22 (–0.27 to –0.17)	< 0.001		–0.26 (–0.32 to –0.19)	< 0.001
No	1.11 (1.01 to 1.22)	0.026		–0.15 (–0.19 to –0.11)	< 0.001		–0.16 (–0.20 to –0.12)	< 0.001		–0.15 (–0.19 to –0.12)	< 0.001		–0.15 (–0.20 to –0.11)	< 0.001
Smoking			0.831			0.082			0.248			0.065			0.084
Yes	1.15 (1.01 to 1.31)	0.032		–0.16 (–0.21 to –0.12)	< 0.001		–0.17 (–0.21 to –0.12)	< 0.001		–0.14 (–0.18 to –0.10)	< 0.001		–0.16 (–0.22 to –0.11)	< 0.001
No	1.14 (0.98 to 1.33)	0.084		–0.18 (–0.23 to –0.14)	< 0.001		–0.20 (–0.24 to –0.16)	< 0.001		–0.19 (–0.23 to –0.15)	< 0.001		–0.19 (–0.24 to –0.14)	< 0.001
Drinking			0.698			0.429			0.122			0.879			0.316
Yes	1.13 (1.00 to 1.27)	0.045		–0.19 (–0.22 to –0.15)	< 0.001		–0.19 (–0.23 to –0.16)	< 0.001		–0.18 (–0.21 to –0.14)	< 0.001		–0.20 (–0.24 to –0.16)	< 0.001
No	1.20 (1.00 to 1.43)	0.049		–0.12 (–0.18 to –0.06)	< 0.001		–0.15 (–0.20 to –0.09)	< 0.001		–0.14 (–0.20 to –0.09)	< 0.001		–0.10 (–0.18 to –0.03)	0.011
Hypertension			0.817			0.622			0.910			0.130			0.880
Yes	1.12 (0.98 to 1.27)	0.097		–0.16 (–0.22 to –0.10)	< 0.001		–0.15 (–0.20 to –0.10)	< 0.001		–0.15 (–0.19 to –0.10)	< 0.001		–0.17 (–0.24 to –0.10)	< 0.001
No	1.20 (1.06 to 1.36)	0.005		–0.19 (–0.23 to –0.15)	< 0.001		–0.21 (–0.25 to –0.17)	< 0.001		–0.19 (–0.23 to –0.15)	< 0.001		–0.20 (–0.25 to –0.15)	< 0.001
Diabetes			0.880			0.732			0.677			0.870			0.642
Yes	0.96 (0.76 to 1.20)	0.698		–0.18 (–0.28 to –0.07)	0.002		–0.17 (–0.28 to –0.06)	0.003		–0.15 (–0.24 to –0.07)	0.001		–0.22 (–0.34 to –0.10)	0.001
No	1.18 (1.06 to 1.31)	0.003		–0.17 (–0.21 to –0.14)	< 0.001		–0.19 (–0.22 to –0.15)	< 0.001		–0.17 (–0.21 to –0.14)	< 0.001		–0.17 (–0.22 to –0.13)	< 0.001
Borderline	0.78 (0.40 to 1.53)	0.474		–0.12 (–0.40 to 0.16)	0.394		–0.17 (–0.41 to 0.08)	0.188		–0.15 (–0.38 to 0.07)	0.187		–0.14 (–0.48 to 0.20)	0.433
Taking prednisone or cortisone			0.595			0.459			0.263			0.452			0.482
Yes	1.14 (0.84 to 1.54)	0.400		–0.09 (–0.24 to 0.05)	0.220		–0.15 (–0.28 to –0.01)	0.035		–0.13 (–0.24 to –0.02)	0.024		–0.06 (–0.24 to 0.12)	0.503
No	1.16 (1.04 to 1.28)	0.008		–0.18 (–0.21 to –0.14)	< 0.001		–0.19 (–0.22 to –0.15)	< 0.001		–0.17 (–0.20 to –0.14)	< 0.001		–0.19 (–0.23 to –0.14)	< 0.001

Sex, age, race, education level, marital status, poverty-income ratio, BMI, alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase, blood urea nitrogen, creatinine, gamma glutamyl transferase, lactate dehydrogenase, phosphorus, total calcium, cholesterol, triglycerides, uric acid, smoking, drinking, hypertension, diabetes, vigorous activity, and taking prednisone or cortisone were adjusted, but the model was not adjusted for the stratification variable itself.

OR, odds ratio; PFI, p for interaction.

Subgroup analysis revealed a significant interaction between C-index and total femur BMD only within different age groups (p for interaction = 0.004), while no such interaction was observed in other subgroups (p for interaction > 0.05). Specifically, participants aged 20 to 40 years exhibited heightened sensitivity to changes in C-index compared with participants of other ages, experiencing an average decrease of 0.24 g/cm² in total femur BMD for every unit increased in C-index (β = -0.24 (95% CI –0.32 to –0.17), p < 0.001) (Supplementary Figure b).

Subgroup analysis revealed a significant interaction between C-index and femoral neck BMD among participants engaging in vigorous activity (p for interaction = 0.043), while no significant interactions were observed under other variables (p for interaction > 0.05). In the subgroup analysis of presence or absence of vigorous activity, compared with the population that did not engage in vigorous activity, those who did exhibited a higher sensitivity to changes in C-index. Specifically, for every one-unit increase in C-index, there was an average decrease of 0.27 g/cm² in femoral neck BMD (β = −0.27 (95% CI −0.32 to –0.21), p < 0.001) (Supplementary Figure c).

Subgroup analysis revealed significant interactions between C-index and trochanter BMD in different sexes (p for interaction = 0.022), age groups (p for interaction < 0.001), and those who undertook vigorous activity (p for interaction = 0.027). No significant interactions were observed in subgroup analysis under other variables (p for interaction > 0.05). The male population exhibited a greater sensitivity to changes in C-index than their female counterparts. Specifically, for every one-unit increase in C-index, trochanter BMD decreased by an average of 0.33 g/cm² among the male population (β = −0.33 (95% CI −0.38 to –0.28), p < 0.001) (Supplementary Figure d). In the subgroup analysis of different age groups, it was observed that the population aged 20 to 40 years exhibited a heightened sensitivity to variations in C-index compared with others. Specifically, for each incremental unit increase in C-index, there was an average decrease of 0.25 g/cm² in trochanter BMD (β = −0.25 (95% CI −0.32 to –0.17), p < 0.001) (Supplementary Figure d). In the subgroup analysis of vigorous activity or not, compared with the population without vigorous activity, those who engaged in vigorous activity were found to exhibit a higher sensitivity to changes in C-index. Specifically, for every one-unit increase in C-index, there was an average decrease of 0.22 g/cm² in trochanter BMD among the population engaging in vigorous activity (β = −0.22 (95% CI −0.27 to –0.17), p < 0.001) (Supplementary Figure d) .

For the subgroup analysis of the relationship between C-index and intertrochanter BMD, only the subgroup analysis of different age groups had an interaction effect (p for interaction = 0.004), while the subgroup analysis of other variables showed no interaction effect (p for interaction > 0.05). Within the subgroups of different age groups, participants aged 20 to 40 years were more sensitive to changes in C-index than other participants. For every one-unit increase in C-index, intertrochanter BMD decreased by an average of 0.27 g/cm² (β = −0.27 (95% CI −0.35 to –0.18), p < 0.001).

Discussion

In this study, a cross-sectional analysis of the NHANES database was conducted from 2005 to 2020, with a study population consisting of men and women in the USA aged 20 years and older. After adjusting for all potential confounding factors, a positive correlation between C-index and the risk of osteoporosis was observed, along with a negative correlation with femoral bone density that remained consistent across different sites. Furthermore, a threshold effect for C-index at different sites of femoral bone density was identified, confirming not only a linear relationship but also a non-linear relationship between them. In the subgroup analysis across numerous variables, the correlation between C-index and osteoporosis was more significant in the male population. Additionally, for femoral BMD, C-index variation had a relatively more significant effect on the male population, individuals aged 20 to 40 years, and vigorously active individuals.

In recent years, numerous scholars have conducted in-depth studies on the correlation between various indices of body obesity and osteoporosis as well as BMD.³⁵ Research has indicated a negative correlation between WWI and BMD, a phenomenon that has been validated across American adolescent, adult, and elderly populations.^15,16,36 Among American adults and the elderly, moderate levels of visceral adiposity index (VAI) have been shown to effectively protect BMD; conversely, excessive VAI is regarded as a significant risk factor affecting BMD.^11,37 Moreover, a negative correlation between A Body Shape Index (ABSI) and BMD was found in American adolescent and elderly populations—a relationship that was also evident in Chinese populations.^38-40 Furthermore, there remained a consistent negative correlation between BRI and BMD.³⁴ Many researchers have also explored the correlation between BMI and BMD. Ouyang et al¹³ and Li,⁴¹ respectively, conducted a study on BMI and BMD in adolescents and middle-aged adults, with both studies reporting that maintaining high BMI helped to maintain higher BMD. Obesity is believed to lead to various complications.⁴² At present, there are various theories about the mechanism by which obesity leads to osteoporosis and increased bone fragility. Abdallah and Kassem⁴³ identified two secreted factors – secreted frizzled related protein 1 and delta-like 1 (preadipocyte factor 1) – within the bone marrow microenvironment. Through cellular models utilizing pluripotent mesenchymal stem cells along with preosteoblastic and preadipocytic cell populations, their study further revealed that both factors exert regulatory effects on osteoblastogenesis and adipogenesis. Recently, Faienza et al⁴⁴ suggested that obesity is associated with low-grade inflammation, which alters the expression of molecules such as adiponectin, leptin, monocyte chemoattractant protein-1, and interleukin-6, potentially accelerating the development of osteoporosis by affecting normal bone metabolism. Notably, recent evidence extends these observations to adolescent populations, using composite metabolic indices. Liu et al⁴⁵ demonstrated that the cardiometabolic index (CMI)—integrating triglyceride/HDL-C ratio with waist-to-height ratio—exhibited a significant linear inverse association with femoral neck and lumbar BMD in USA adolescents. Each unit increase in CMI corresponded to 0.052 g/cm² and 0.048 g/cm² reductions in respective BMD measurements, independent of BMI. This contrasts with the non-linear threshold effect of C-index observed in our adult cohort, suggesting that distinct age-dependent mechanisms, such as lipid metabolism and central obesity, impact bone accrual versus maintenance.

In 2000, Taylor et al⁴⁶ used dual-energy X-ray absorptiometry to quantify high trunk fat mass in children and adolescents aged three to 19 years, aiming to evaluate the suitability of waist circumference, waist-to-hip ratio, and the C-index as screening tools. Their findings indicated that waist circumference is a more effective measure of trunk adiposity in this population. Recently, a study conducted by Pan et al³³ investigated the correlation between waist circumference and BMD in American adults aged 18 years and older. The findings revealed a positive association between waist circumference and BMD, suggesting that waist circumference serves as a protective factor against osteoporosis. In contrast with these results, Chen et al⁴⁷ conducted a separate study on individuals aged 60 years and above, finding a threshold effect whereby a waist circumference < 95 cm was identified as a protective factor, while a waist circumference > 95 cm was deemed to be a risk factor. In light of these findings, we posit that the accrual of waist circumference might have deleterious effects on bone density reduction in young individuals, and potentially serves as a risk factor for older adults. It is therefore advisable for older individuals to maintain their waist circumference below the threshold point of 95 cm.

In this study, C-index was primarily used for the assessment of abdominal obesity. The results suggest that the accrual of abdominal obesity might expedite the decline in BMD among adults and also constitute a risk factor for osteoporosis. Ren et al²⁴ observed that an increase in the C-index accelerates the onset of osteoarthritis, suggesting that it is a significant indicator for assessing this condition. Similarly, Zhang et al²⁸ found that elevated C-index levels are a risk factor for osteoporosis in postmenopausal women. In a study of Brazilian rural workers, do Prado et al⁴⁸ showed that the C-index has high discriminative power for the identification of abdominal obesity, even in patients receiving haemodialysis.⁴⁹ The analysis of C-index indicates that the accumulation of abdominal fat could cause other diseases, and is predictive of the occurrence of cardiovascular outcomes and all-cause mortality, chronic kidney disease, and metabolic syndrome.^25,26 Zhang et al⁵⁰ conducted a ten-year community-based follow-up study among elderly Chinese participants and found that the C-index was an independent risk factor for all-cause mortality in those without cancer. Andrade et al⁵¹ found that the C-index is a risk factor for diabetes and hypertension in Brazilian women. Finally, Ning et al²⁷ pointed out that the C-index serves as an important prognostic marker for predicting cardiovascular diseases and all-cause mortality in patients with diabetes. Therefore, we propose that the C-index serves as an effective indicator for assessing abdominal obesity. Research on the C-index could facilitate prediction of the risk of various diseases. To maintain overall health, it is essential to regulate abdominal fat levels to within a moderate range. Achieving this objective necessitates further prospective studies focused on abdominal fat in the future. Further, our study explored the association of the C-index with osteoporosis and femur BMD, offering valuable scientific insights for clinical management of osteoporosis in the context of abdominal obesity.

Interestingly, the unadjusted model applied in this study revealed a significant positive correlation between taper index and the risk of osteoporosis and femoral bone density, even after controlling for sex, age, and race in Model I. However, upon further adjustment in Model II to include covariates such as marital status, PIR, and BMI based on Model I, this positive correlation was found to be reversed into a negative one. Notably, in Model III with comprehensive adjustment for confounding factors, this negative correlation persisted. We hypothesize that a specific covariate might exert a significant influence on the direction of the effect in weighted multiple linear and logistic regression, and potentially influenced by the demographic characteristics of the subjects. This pattern was also observed in the study of waist circumference and femoral neck BMD by Chen et al.⁴⁷ The results of subgroup interaction in this study were different for the femoral BMD of different parts; this might be related to the degree of femoral stress at different parts, population characteristics, and research methods. More prospective studies are needed to explore this finding. The results of this study indicate a significant interaction in the subanalysis related to vigorous activity, impacting both femoral neck BMD and trochanter BMD. It is our hypothesis that the human skeletal structure has a limited capacity to endure mechanical stress, and excessive loading might not be conducive to maintaining optimal BMD. The subgroup analysis of C-index and femoral bone density showed that there was an interaction in different sexes and age groups, with the impact of C-index being more significant in males and individuals aged 20 to 40 years. Research has demonstrated that men have higher BMD than women and that advancing age is a risk factor for osteoporosis.⁵² We therefore posit that men and young adults have higher BMD within a moderate range of C-index; however, at higher C-index levels, their BMD would continue to decrease, showing a good linear relationship. Therefore, men and young adults are more sensitive to changes in C-index. This is, however, only a theory; more prospective studies are needed to verify this in the future.

Our study possesses several strengths. First, we addressed a research gap by utilizing an unexplored index of abdominal adiposity – the C-index – to examine its correlation with osteoporosis and femur density. Second, our sample size was substantial and adjusted for various potential confounders, and the data analyses were weighted to ensure representation of the national population. Third, subgroup analyses were conducted to confirm the robustness of the findings. However, this study also had certain limitations. First, the population was limited to individuals in the USA, therefore our results might not be generalizable to populations in other countries. Second, some data in this study were obtained through questionnaires, which might introduce recall bias and inaccurate results. Third, because this is a cross-sectional study using data from different years of NHANES, a causal relationship between C-index and osteoporosis and femur density could not be established. Finally, given that the participants were all adults aged 20 years and older, this association might not be applicable to children and adolescents.

Our study identified a negative correlation between C-index and femur density, with an excessively high C-index potentially hastening the onset of osteoporosis. This association was consistently observed in subgroup analyses. In clinical practice, the C-index might serve as an exploratory tool for the prevention, diagnosis, and treatment of osteoporosis. Furthermore, maintaining a C-index within an appropriate range would be beneficial for bone health management. Further research is warranted to establish recommendations regarding the normal C-index range.

In conclusion, this study found that excessively high C-index accelerates the formation of osteoporosis in USA adults, and that C-index is negatively correlated with femur density at different sites. Further prospective studies are needed to investigate the causal relationship between C-index and osteoporosis, and more longitudinal and clinical studies are necessary to understand the mechanisms involved.

Data Availability

All data in the study are available at: https://wwwn.cdc.gov/nchs/nhanes/Default.aspx.