Second-to-Fourth Digit (2D:4D) Ratio as A Risk Factor for Osteoporosis and Osteoarthritis: A Systematic Review
Abstract
Background: The second-to-fourth digit (2D:4D) ratio is an established marker of prenatal sex hormone exposure and has been associated with various health outcomes across the lifespan. Increasing evidence suggests that developmental factors reflected by the 2D:4D ratio may contribute to susceptibility to musculoskeletal disorders, including osteoarthritis (OA) and osteoporosis (OP).
Aim: This systematic review aimed to synthesize the available evidence regarding the association between 2D:4D ratio and the risk of OA and OP.
Methods: This systematic review was conducted according to the PRISMA guidelines and registered in PROSPERO (CRD420261439840). A comprehensive literature search was performed in PubMed, Web of Science, and Scopus between April and May 2026. Observational studies investigating the relationship between 2D:4D ratio and OA or OP related outcomes were included. Study selection, data extraction, and methodological quality assessment were independently performed by three reviewers. Methodological quality was evaluated using the Joanna Briggs Institute critical appraisal tools.
Results: Nine studies met the inclusion criteria, comprising eight studies on OA and one study on OP. Most studies reported that lower 2D:4D ratios or Type III finger patterns were associated with increased OA risk, greater radiographic severity, and a higher likelihood of severe knee OA requiring joint replacement. Associations were particularly evident for knee and hand OA, with several…
How strong is the evidence?
Evidence Hub reads this as a systematic review, done in people. Its evidence level is 1 of 5 (Highest · pooled evidence). Pooled evidence from several studies sits at the top of the evidence pyramid.
Read the paper
Related studies
- Effectiveness of Bisphosphonates and Denosumab on Risk of Vertebral Fractures in Prostate Cancer Patients Under Androgen Deprivation Therapies: A Real-World Prospective Study
- Osteoporosis-related fractures after spinal cord injury: a retrospective study from Brazil
- Serum 25-hydroxyvitamin D, parathyroid hormone, and mortality in older men
- Lack of Association between Vitamin D Insufficiency and Cardiovascular or Fracture Risk: A UK Biobank Study
- Muscle strength and body composition are clinical indicators of osteoporosis
- Incidence of bone protection and associated fragility injuries in patients with proximal femur fractures
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.