Most Significant Risk Factor for Fragility Fractures
Advancing age is the most significant risk factor for fragility fractures among the options listed, even more important than bone mineral density itself. 1
Evidence Hierarchy
The 2025 US Preventive Services Task Force guidelines in JAMA explicitly state that "although bone density is an important risk factor for fragility fractures, advancing age is a stronger determinant." 1 This represents the highest quality, most recent guideline evidence available.
Why Age Supersedes Other Risk Factors
- Older adults have much higher fracture rates than younger adults with identical BMD because of concurrent declining bone quality and increasing fall risk 1
- Age integrates multiple pathophysiologic mechanisms: deteriorating bone microarchitecture, declining bone material properties, increased propensity to fall, and reduced protective responses 2
- Advanced age is a strong risk factor for fractures at nearly all skeletal sites, independent of other risk factors 2
Ranking the Listed Risk Factors
1. Old Age (Strongest)
- Age-dependent intervention thresholds in European guidelines rise progressively with age, acknowledging that fracture probability increases exponentially 1
- The FRAX algorithm demonstrates that a 65-year-old white woman with BMI 25 and no other risk factors has 9.3% 10-year major osteoporotic fracture risk—this baseline risk increases substantially with each additional decade 1, 3
2. Female Sex (Second Strongest)
- Women have 45.2% prevalence of fragility fractures versus 16.3% in men at age 85 4
- Female sex confers an adjusted odds ratio of 4.62 for requiring osteoporosis treatment and 12.4 for needing BMD assessment 4
- Women are 1.79 times more likely to experience refracture after initial fragility fracture 5
3. High BMI (Protective)
- High BMI is actually protective against fragility fractures, not a risk factor 1, 3
- FRAX calculations use low body weight as a risk factor; higher BMI reduces fracture probability 1
- The intervention threshold examples consistently reference "average BMI" as the neutral baseline 1
4. Osteoarthritis (Not a Primary Risk Factor)
- Osteoarthritis is not mentioned as a significant risk factor in any of the major guidelines reviewed 1
- The primary risk factors consistently identified are: age, female sex, low body weight, prior fracture, parental hip fracture history, smoking, and excess alcohol 1
Clinical Application
When assessing fragility fracture risk, prioritize age first, then consider female sex, followed by other established risk factors like prior fracture, low BMI, smoking, and family history 1. High BMI should be recognized as protective rather than harmful in this context 1, 3.
Common Pitfall to Avoid
Do not assume high BMI increases fracture risk—this contradicts the evidence base underlying all major fracture risk assessment tools 1, 3. The confusion may arise from obesity's association with other health conditions, but for skeletal fragility specifically, higher body weight provides mechanical loading that preserves bone density 1.