Association of serum neurofilament light chain and bone mineral density in adults

Serum neurofilament light chain (sNFL) is a blood-based marker of neuroaxonal damage increasingly used in neurological research. Although sNFL has been linked to systemic aging and chronic disease, its relationship with bone mineral density (BMD) remains unclear.

We analyzed data from 1,344 participants aged ≥ 20 years in the 2013-2014 National Health and Nutrition Examination Survey (NHANES). Serum sNFL concentrations were measured using a high-sensitivity immunoassay. Lumbar BMD was assessed by dual-energy X-ray absorptiometry. Multivariable linear regression models were used to evaluate associations between log-transformed sNFL and BMD, adjusting for demographic, lifestyle, metabolic, renal, cognitive, and bone-related covariates. Sensitivity analyses examined osteoporosis, defined as physician diagnosis or T-score ≤ - 2.5, as a binary outcome.

Higher sNFL levels were significantly associated with lower lumbar BMD (fully adjusted β = - 0.02 g/cm² per 1-unit increase in ln-sNFL; 95% CI: - 0.04, - 0.01; P = 0.0089). Compared with the lowest quartile, participants in the highest quartile had a 0.04 g/cm² lower BMD (P for trend = 0.011). Sensitivity analyses confirmed higher odds of osteoporosis with increasing sNFL levels (Q4 vs. Q1 OR = 2.70, 95% CI: 1.69, 4.31, P < 0.001).

Elevated serum sNFL concentrations are independently associated with lower lumbar spine BMD in U.S. adults. These findings suggest that sNFL may serve as an exploratory marker of systemic vulnerability relevant to bone health, warranting further longitudinal and mechanistic investigation.