Avenell 2012.

Methods	Randomised Evaluation of Calcium Or vitamin D (RECORD). Multicentre, randomised, double‐blind, placebo‐controlled trial using 2 x 2 factorial design.
Participants	Country: United Kingdom. Number of participants randomised: 5292 people (85% women) aged 70 and over (mean 77 years) with low‐trauma, osteoporotic fracture in the previous 10 years. Inclusion criteria: elderly people aged 70 years or older, who were mobile before developing a low‐trauma fracture. Exclusion criteria: bed or chair bound before fracture; cognitive impairment indicated by an abbreviated mental test score of less than seven; cancer in the past 10 years that was likely to metastasise to bone; fracture associated with pre‐existing local bone abnormality; those known to have hypercalcaemia; renal stone in the past 10 years; life expectancy of less than 6 months; individuals known to be leaving the United Kingdom; daily intake of more than 200 IU vitamin D or more than 500 mg calcium supplements; intake in the past 5 years of fluoride, bisphosphonates, calcitonin, tibolone, hormone‐replacement therapy, selective oestrogen‐receptor modulators, or any vitamin D metabolite (e.g., calcitriol); and vitamin D by injection in the past year.
Interventions	Participants were randomly assigned to receive: Intervention group 1: vitamin D3 (800 IU) daily (n = 1343); Intervention group 2: calcium (500 mg) daily (n = 1311); Intervention group 3: vitamin D3 (800 IU) plus calcium (500 mg) daily (n = 1306); Intervention group 4 (Control group): matched placebo tablets (n = 1332); for a 45 month period. Participants were followed for a period of 6.2 years. Tablets varied in size and taste, and thus each had matching placebos.
Outcomes	The primary outcome measure was all‐new low‐energy fractures including clinical, radiologically confirmed vertebral fractures, but not those of the face or skull.
Stated aim of study	"To assess whether vitamin D3 and calcium, either alone or in combination, were effective in prevention of secondary fractures."
Notes	"Compliance was measured by a postal questionnaire sent every four months, in which participants were asked how many days of the past seven days they had taken tablets. A randomly selected 10% sample was asked to return unused tablets for pill counting. Based on questionnaire responses at 24 months, 2886 (54,5%) of 5292 were still taking tablets. Throughout the trial about 80% of those taking tablets did so on more than 80% of days, which is consistent with pill counts in the subsample (data not shown). However, the number who were taking any tablets fell over time. At 24 months, 2268 of 4841 (46,8%), who returned questionnaires, had taken pills on more than 80% of days." Shire Pharmaceuticals co‐funded the drugs, with Nycomed, who also manufactured the drugs. Additional information received through personal communication with Dr Alison Avenell (02.02.2009).
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. "Allocation was controlled by a central and independent randomisation unit. The allocation programme was written by the trial programmer and the allocation remained concealed until the final analyses (other than for confidential reports to the data monitoring committee)."
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	Shire Pharmaceuticals co‐funded the drugs, with Nycomed, who also manufactured the drugs.
Other bias	Low risk	The trial appears to be free of other components that could put it at risk of bias.