Brazier 2005.

Methods	Multicentre, randomised, double‐blind, placebo‐controlled trial using parallel group design (two intervention groups).
Participants	Country: France. Number of participants randomised: 192 women with a 25‐hydroxyvitamin D level ≤ 12 ng/mL, mean age 74.6 years. Inclusion criteria: community‐dwelling ambulatory women aged > 65 years who spontaneously consulted a practitioner and presented with vitamin D insufficiency (i.e., serum 25‐hydroxy vitamin D ≤ 12 ng/mL). Exclusion criteria: hypercalcaemia (serum calcium > 2.62 mmol/L), primary hyperparathyroidism, renal insufficiency (serum creatinine >130 pmol/L), hepatic insufficiency, treatment with a bisphosphonate, calcitonin, vitamin D or its metabolites, oestrogen, raloxifene, fluoride, anticonvulsives, or any other drug acting on bone metabolism (e.g., glucocorticoids) in the past six months.
Interventions	Participants were randomly assigned to receive: Intervention group 1: vitamin D3 (800 IU) plus calcium (1000 mg) daily (n = 95); Intervention group 2 (Control group): matched placebo tablets (n = 97); for a one‐year period.
Outcomes	The primary outcome was to assess the effects of vitamin D3 plus calcium on bone mineral density and biochemical markers of bone formation and resorption. Secondary outcome was to evaluate the clinical and laboratory safety of treatment.
Stated aim of study	"An evaluation of the clinical and laboratory safety of a one‐year course of treatment with a combination vitamin D and calcium tablets in ambulatory women aged > 65 years with vitamin D insufficiency."
Notes	Fifty women (21/95 vitamin D plus calcium, 29/97 placebo) were prematurely withdrawn from the trial for various reasons. Treatment‐related adverse events were reported in 21 and 23 women in the respective intervention groups. These events consisted mainly of metabolic disorders (9 and 10), particularly hypercalcaemia (6 and 8) and gastrointestinal disorders (9 and 8). "Treatment compliance was assessed at each visit based on counts of the number of tablets taken compared with the number that was to be taken. Compliance at each visit ranged from a median of 93% to 94% in the vitamin D plus calcium group and from 93% to 96.5% in the placebo group. Global compliance was 92% in the vitamin D plus calcium group and 92.5% in the placebo group. No significant difference in compliance was observed between the two groups at any visit." This trial was supported by Innothera Laboratories, Arcueil, France.
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)	Unclear risk	The trial was described as randomised but the method used to conceal the allocation was not described, so that intervention allocations may have been foreseen in advance of, or during, enrolment.
Blinding (performance bias and detection bias) All outcomes	Unclear risk	The trial was described as double blind, but the method of blinding was not described, so that knowledge of allocation was possible 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	High risk	This trial was supported by Innothera Laboratories, Arcueil, France.
Other bias	Low risk	The trial appears to be free of other components that could put it at risk of bias.