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Revisiting the Role of Vitamin D in Fracture Prevention in the Era of Mega-Trials.

  • 2026-04-30
  • Endocrinology and metabolism (Seoul, Korea) 41(2)
    • Sung Hye Kong

Study Design

Type
Review
For decades, vitamin D has been a cornerstone of preventive medicine. However, recent large-scale randomized controlled trials have failed to replicate the broad benefits previously observed in epidemiological studies, particularly with respect to fracture and fall prevention in vitamin D-replete populations. Moreover, growing evidence suggesting an increased fall risk associated with high-dose bolus administration has necessitated a re-evaluation of safety assumptions. This review synthesizes these discordant findings to propose a framework grounded in precision medicine. We explore the 'divergent threshold' hypothesis, whereby a serum 25-hydroxyvitamin D level of 20 to 30 ng/mL may be sufficient for skeletal health, whereas a higher threshold of 40 to 50 ng/mL appears necessary to achieve metabolic benefits, such as diabetes prevention in non-obese individuals. Ultimately, we advocate a shift away from a 'one-size-fits-all' paradigm toward targeted strategies that maximize efficacy while minimizing the risks associated with excess supplementation.

Research Insights

  • Vitamin D→Increased Fall Risk

    growing evidence suggesting an increased fall risk associated with high-dose bolus administration has necessitated a re-evaluation of safety assumptions.

    Effect
    Harmful
    Effect size
    Small
    Dose
    high-dose bolus administration
  • Vitamin D→Reduced Fall Risk

    recent large-scale randomized controlled trials have failed to replicate the broad benefits previously observed in epidemiological studies, particularly with respect to fracture and fall prevention in vitamin D-replete populations.

    Effect
    Neutral
    Effect size
    Small
    Dose
    high-dose bolus administration
  • Vitamin D→Reduced Fracture Risk

    recent large-scale randomized controlled trials have failed to replicate the broad benefits previously observed in epidemiological studies, particularly with respect to fracture and fall prevention in vitamin D-replete populations.

    Effect
    Neutral
    Effect size
    Small
    Dose
    high-dose bolus administration

Adverse Events Reported

  • Vitamin D→fall

    growing evidence suggesting an increased fall risk associated with high-dose bolus administration

    Finding
    Increased risk
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