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Sex differences in association of mixed exposure to blood cadmium, lead, mercury, selenium, manganese with osteoporosis

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Overview

Cross-sectional analysis using NHANES 2013-2014 and 2017-2018 cycles examining associations between blood concentrations of five metals (cadmium, lead, mercury, selenium, manganese) and osteoporosis at the femoral neck and vertebral spine, separately in men aged at least 50 and postmenopausal women. WQS and BKMR were used for mixture analysis. A dairy-consumption stratification analysis was included to explore protective effects.

Key numbers

NHANES 2013-2014 and 2017-2018. Men aged at least 50 and postmenopausal women analyzed separately.

Men aged at least 50 (multivariable logistic regression, fully adjusted):

  • Cadmium: positively associated with femoral neck osteoporosis: OR=8.563 (95% CI: 1.888, 38.845; p below 0.05).
  • Selenium: negatively associated with femoral neck osteoporosis: OR below 0.001 (95% CI: 0, 0.150; p below 0.05).
  • WQS: mixed metal exposure positively associated with vertebral osteoporosis in men: OR=1.452 (95% CI: 0.277, 2.626; p below 0.05).
  • BKMR: mixed metal exposure positively associated with osteoporosis at femoral neck and vertebrae in men; cadmium contributing most.

Postmenopausal women (fully adjusted):

  • Cadmium: OR=2.148 (95% CI: 1.038, 4.443; p below 0.05) for femoral neck osteoporosis.
  • Selenium: OR=0.027 (95% CI: 0.001, 0.986; p below 0.05) for femoral neck osteoporosis; inverse.
  • WQS and BKMR: no significant overall association in women.
  • Dairy stratification: Cd-osteoporosis association stronger in low-dairy-consumption women (OR=3.12, 95% CI: 1.84, 5.30) than in high-dairy-consumption women (OR=1.19, 95% CI: 0.51, 2.78), suggesting dairy consumption may attenuate the cadmium-osteoporosis association in women.

The divergence between men (positive mixture-osteoporosis association in BKMR) and women (no mixture association in BKMR) documents sex-specific patterns in metal mixture effects that single-metal analyses would not capture.

Evidence Fitness

Context only. Cross-sectional design. Sample sizes per sex not reported in extracted text; individual NHANES cycles. The finding that cadmium’s effect on bone is stronger in men aged at least 50 and is modified by dairy consumption in women has implications for understanding the sex-specific nature of cadmium toxicity, but cannot establish causality.

Methods (brief)

NHANES 2013-2014 and 2017-2018. Blood metals by ICP-MS, standard NHANES protocols. Bone mineral density by DXA. Osteoporosis defined as T-score below negative 2.5 at femoral neck or vertebral spine (WHO criteria). Generalized linear regression; WQS; BKMR. Dairy consumption stratified as at least 7 times/week (high) versus below 7 times/week (low).

Implications

Certification: Cadmium’s dominant role in bone toxicity, confirmed in both sexes and across two NHANES cycles, reinforces its Tier-1 status. The dairy-consumption moderation finding may be relevant to guidance for populations with low calcium intake.

Courses: Useful for demonstrating sex differences in metal mixture toxicokinetics and the role of dietary factors (calcium from dairy) in modulating metal toxicity.

App: No food concentration data.

Microbiome: Potential gut-calcium-bone axis thread; not primary focus.

Update history

No substantive edit history is available in this build. The full commit record is available in git.

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