Jiani Fan, Jiabao Cai, Shengguang Chen
Nails demonstrate clear clinical value as a non-invasive tool for primary osteoporosis screening, supplementary bone quality assessment, treatment response monitoring, and fracture risk prediction. Future research should focus on technical standardization, large-sample prospective validation, and in-depth mechanistic studies to further unlock their potential. Integrated with clinical evaluation and DXA, nail analysis is expected to become an important auxiliary tool in the global osteoporosis prevention and control system.
BACKGROUND: Osteoporosis is a widespread public health problem, yet Dual-Energy X-ray Absorptiometry (DXA)-the current diagnostic gold standard-has significant limitations, including high cost, radiation exposure, and inability to assess bone organic phase changes. As an easily accessible epidermal derivative, nails share high molecular homology with bone tissue and offer unique advantages of non-invasive collection and stable composition reflecting medium- to long-term metabolic status. This narrative review aimed to systematically collate the pathophysiological associations between nails and bone metabolism and comprehensively analyze the clinical application evidence of nails in osteoporosis diagnosis, treatment monitoring, and prognostic assessment.
METHODS: A systematic literature search was conducted across PubMed, Web of Science, and Elsevier databases from inception to 2026. The search strategy combined Medical Subject Headings (MeSH) and free-text keywords: (nail OR fingernail OR toenail OR keratin) AND (osteoporosis OR bone metabolism OR bone mineral density OR fracture risk OR bone quality). Inclusion criteria were: (1) peer-reviewed original studies, systematic reviews, or meta-analyses; (2) studies exploring relationships between nail characteristics (composition, structure, or morphology) and bone health; and (3) human studies or animal model studies with direct clinical implications. Two reviewers independently screened titles and abstracts, extracted data, and resolved discrepancies through consensus. Ultimately, 32 studies were included.
RESULTS: Nails and bones share profound homology in structural protein metabolism (cysteine-disulfide bond pathways), mineral deposition (calcium and magnesium), and hormone regulation (estrogen and thyroid hormones). Clinically, nail plate thickness reduction and keratin structural abnormalities have been observed in osteoporosis patients. In grassroots screening, Laser-Induced Breakdown Spectroscopy (LIBS) achieved a classification accuracy of 85.9% atone-tenth the cost of DXA. For supplementary bone quality diagnosis, Raman spectroscopy combined with clinical data evaluating keratin disulfide bonds achieved an AUC of 74%, effectively identifying 75% of fracture patients missed by DXA. In treatment monitoring, nail composition changes preceded DXA-detected bone mineral density alterations, providing molecular evidence for early efficacy evaluation. For prognostic assessment, nail-related indicators predicted fracture risk over 3-20 years (OR 2.2 alone; OR 3.8 combined with clinical risk factors). The REMS fragility score also independently predicted fracture risk (OR = 9.23 when FS 37.2). A tiered integration model combining clinical risk assessment with nail-based screening was proposed to optimize clinical workflow.
CONCLUSION: Nails demonstrate clear clinical value as a non-invasive tool for primary osteoporosis screening, supplementary bone quality assessment, treatment response monitoring, and fracture risk prediction. Future research should focus on technical standardization, large-sample prospective validation, and in-depth mechanistic studies to further unlock their potential. Integrated with clinical evaluation and DXA, nail analysis is expected to become an important auxiliary tool in the global osteoporosis prevention and control system.