Shiraki · Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 2000 · randomized open-label trial · n=241

Vitamin K2 (menatetrenone) effectively prevents fractures and sustains lumbar bone mineral density in osteoporosis.

Cited 411 times in the scientific literature.

Level 2 - randomized trial

Individual randomized controlled trial

PubMed 10750566 · doi:10.1359/jbmr.2000.15.3.515 · record verified 2026-08-29

What was done

A 24-month randomized, open-label trial evaluated 241 osteoporotic patients assigned to an untreated control group (n = 121) or oral vitamin K2 (menatetrenone, 45 mg/day; n = 120). Outcomes included lumbar bone mineral density (LBMD via DXA) measured at 6, 12, and 24 months, occurrence of new clinical fractures, serum Glu-osteocalcin (Glu-OC), total osteocalcin (OC), and urinary deoxypyridinoline (DPD).

What was found

Clinical fracture incidence was significantly lower in the vitamin K2 group compared to controls over 2 years (chi-square = 10.935; p = 0.0273; exact fracture event counts were not reported in the abstract). LBMD decreased in controls (-1.8 ± 0.6% at 6 months, -2.4 ± 0.7% at 12 months, -3.3 ± 0.8% at 24 months) but was preserved in the K2 group (1.4 ± 0.7%, -0.1 ± 0.6%, and -0.5 ± 1.0%; between-group p = 0.0010, p = 0.0153, and p = 0.0339, respectively). Serum Glu-OC at follow-up was 1.6 ± 0.1 ng/ml in the treated group versus 3.0 ± 0.3 ng/ml in controls (p < 0.0001), while total OC rose by 42.4 ± 6.9% versus 18.2 ± 6.1% (p = 0.0081). Urinary DPD excretion showed no significant change.

Why it matters

This study provides evidence that pharmacological vitamin K2 sustains bone density and lowers clinical fracture rates in osteoporosis, likely via enhanced gamma-carboxylation of osteocalcin.

Limits

The trial utilized an open-label design with an untreated rather than placebo control group, introducing potential reporting and ascertainment bias. The abstract does not report baseline patient demographics, adverse events, or absolute numbers of fracture events.

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