Cross-Sectional Associations of Serum Zinc with Bone Mineral Density in the NHANES 2011-2014 Cohort

Summary

This protocol aims to evaluate the association between serum zinc concentrations and total bone mineral density using nationally representative data from the NHANES 2011-2014 cohort.

Abstract

This cross-sectional study investigated the association between serum zinc concentrations and total bone mineral density (BMD) using data from 1,674 adults aged ≥ 20 years in the National Health and Nutrition Examination Survey (NHANES) 2011-2014. Participants with missing data on key variables were excluded, and analyses accounted for the NHANES complex survey design with 4-year fasting subsample weights (WTSAF4YR). Serum zinc levels were divided into quartiles, and multivariable linear regression models were applied to assess the relationship between serum zinc and total as well as site-specific BMD after adjustment for demographic, anthropometric, lifestyle, and biochemical confounders. Smooth curve fitting and threshold effect analyses based on generalized additive models (GAMs) were used to explore potential nonlinear associations. Serum zinc was positively associated with BMD after adjustment for covariates, with a nonlinear threshold effect observed at approximately 13.20 µmol/L, beyond which the positive association became more pronounced. These findings provide new insight into zinc's role in skeletal health, highlighting that maintaining serum zinc above this level may contribute to optimal bone density and inform strategies for osteoporosis prevention and nutritional assessment.

Introduction

Osteoporosis represents a major public health concern worldwide, affecting an estimated 18.3% of the global population^1,2. Epidemiological data indicate that this condition does not impact all demographic groups equally, with women experiencing a markedly higher burden compared to men, particularly after menopause due to hormonal changes that accelerate bone loss^1,2. Bone mineral density (BMD) serves as a fundamental indicator of skeletal health and is widely recognized as a crucial determinant of bone strength³. Clinically, it ....

Protocol

The National Center for Health Statistics (NCHS) Research Ethics Review Board (ERB) approved the NHANES data collection protocols. Since the NHANES datasets are publicly accessible, researchers are exempt from obtaining additional approval from their own institutional review boards (IRBs).

Study design and characteristics of the study population

In the present cross-sectional investigation, we sought to examine the potential independent association between serum zinc concentrations and BMD utilizing data derived from the 2011-2014 cycles of the NHANES. NHANES, which is administered by the Nationa....

Results

Descriptive characteristics and baseline profile of the participants included in the study

Since serum zinc concentrations were measured in a fasting subsample, the corresponding 4-year fasting subsample weight (WTSAF4YR) was applied in accordance with NHANES analytic guidelines. Because data from two survey cycles (2011-2012 and 2013-2014) were combined, the 4-year weight was derived by dividing each participant's 2-year fasting subsample weight (WTSAF2YR) by two, following t.......

Discussion

In this cross-sectional study of 1,674 adults from NHANES 2011-2014, higher serum zinc concentrations were positively associated with total and lumbar spine BMD, with the strongest effects observed in the highest zinc quartile. Multivariable analyses confirmed these associations after adjusting for demographic, lifestyle, anthropometric, and biochemical covariates, and subgroup analyses suggested a more pronounced effect in men. Site-specific results indicated that trabecular-rich sites like the lumbar spine were more re.......

Materials

List of materials used in this article

Name	Company	Catalog Number	Comments
APEX DXA Analysis Software	Hologic Inc.	Version 4.0	Used for DXA data acquisition and analysis.
EmpowerStats (for statistical analysis, regression, and threshold effect modeling)	X&Y Solutions, Boston, MA, USA	Version 4.1	Statistical software used for multivariable linear regression, smooth curve fitting, and threshold effect analysis. RRID if available.
Hologic QDR-4500A fan-beam densitometer	Hologic Inc., Bedford, MA, USA	https://www.hologic.com/file/403701/download?token=9xR5yyeg	Used for DXA scans to measure bone mineral density in NHANES participants.
ICP-DRC-MS (Inductively Coupled Plasma Dynamic Reaction Cell Mass Spectrometry)	NHANES Laboratory, CDC	https://wwwn.cdc.gov/nchs/data/nhanes/public/2017/labmethods/UM?J?MET?508.pdf	Used for quantification of serum zinc concentrations with high sensitivity and precision.
NHANES 2011–2014 Demographics & Socioeconomic dataset	CDC NHANES	DEMO	Publicly available dataset with demographic, socioeconomic, and lifestyle variables.
NHANES 2011–2014 DXA Bone Mineral Density dataset	CDC NHANES	DXXSPN	Publicly available dataset containing total and site-specific BMD measurements via DXA.
NHANES 2011–2014 Serum Zinc dataset	CDC NHANES	LBDZN	Publicly available dataset containing serum zinc measurements for U.S. adults.
NHANES 2011–2016 public datasets (LBDZN, DXXSPN, DEMO)	CDC NHANES	https://wwwn.cdc.gov/nchs/nhanes/tutorials/datasets.aspx	National Health and Nutrition Examination Survey datasets for serum zinc, DXA BMD, and demographic/socioeconomic data. Repository: https://www.cdc.gov/nchs/nhanes/
NHANES Official Website	National Center for Health Statistics (NCHS), CDC	https://www.cdc.gov/nchs/nhanes/	Official DXA examination protocol details are available at: https://www.cdc.gov/nchs/
QDR-4500A Fan-Beam Densitometer	Hologic Inc. (Bedford, MA, USA)	QDR-4500A	Used for DXA scans to obtain BMD measurements.