Bolton‐Smith 2007.

Methods	Randomised, double‐blind, placebo controlled trial using 2 x 2 factorial design.
Participants	Country: United Kingdom. Number of participants randomised: 244 healthy, non‐osteoporotic women, aged 60 years or over (mean 68). Inclusion criteria: healthy, non‐osteoporotic women, aged 60 years or over. Exclusion criteria: clinical osteoporosis or chronic disease (e.g., diabetes mellitus, cardiovascular disease, cancer, fat malabsorption syndromes), routine medication that interferes with vitamin K, vitamin D, or bone metabolism (notably warfarin and steroids), and consumption of nutrient supplements that provided in excess of 30 µg vitamin K, 400 IU vitamin D, or 500 mg calcium daily.
Interventions	Participants were randomly assigned to receive: Intervention group 1: vitamin D3 (400 IU) plus calcium 1000 mg daily, (n = 62); Intervention group 2: vitamin D3 (400 IU) plus calcium 1000 mg plus vitamin K1 200 μg daily, (n = 61); Intervention group 3: vitamin K1 200 μg daily (n = 60); Intervention group 4 (Control group): matched placebo daily (n = 61); for a two‐year period.
Outcomes	The primary outcome measure was bone mineral density. Secondary outcome measure was possible interaction with vitamin K, of vitamin D and calcium.
Stated aim of study	"The putative beneficial role of high dietary vitamin K1 (phylloquinone) on bone mineral density and the possibility of interactive benefits with vitamin D were studied."
Notes	"Of the 244 eligible women randomised in the trial, 209 (85.6%) completed the two‐year trial. Compliance with the trial intervention was good based on pill count (median, 99; interquartile range, 97.3 to 99.8%)." Hoffmann‐La Roche (Basel, Switzerland) provided the supplementation tablets. Additional information on mortality, adverse events, and risk of bias domains was received through personal communication with Dr Martin J Shearer (03.02.2009; 05.02.2010).
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Sequence generation was achieved using computer random number generation.
Allocation concealment (selection bias)	Low risk	Allocation was controlled by a central and independent randomisation unit so that intervention allocations could not have been foreseen in advance of, or during, enrolment. "An independent statistician at Hoffmann‐La Roche, who had no other connection to the trial, provided a randomisation list to the researchers."
Blinding (performance bias and detection bias) All outcomes	Low risk	The trial was described as blinded, the parties that were blinded, and the method of blinding was described, so that knowledge of allocation was adequately prevented during the trial.
Incomplete outcome data (attrition bias) All outcomes	Low risk	The numbers and reasons for dropouts and withdrawals in all intervention groups were described.
Selective reporting (reporting bias)	Low risk	Pre‐defined, or clinically relevant and reasonably expected outcomes are reported on.
Industry bias	Unclear risk	Hoffmann‐La Roche (Basel, Switzerland) provided the supplementation tablets.
Other bias	Low risk	The trial appears to be free of other components that could put it at risk of bias.