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	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 < 7; 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 < 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 (1000 mg) daily (n = 1311) Intervention group 3: vitamin D₃ (800 IU) plus calcium (1000 mg) daily (n = 1306) Comparator 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	Outcomes reported in abstract of publication Primary outcomes: all‐new low‐energy fractures including clinical, radiologically‐confirmed vertebral fractures, but not those of the face or skull. Secondary outcomes: none defined.
Stated aim of study	Quote from the publication: "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." „The United Kingdom Medical Research Council funded the central organization of the RECORD Trial (Grant G9706483). In the last two years, Roger M. Francis has received lecture fees from Shire Pharmaceuticals Group plc. All other authors have nothing to declare in the last two years. Before this, all authors received research grant support to their institutions from the United Kingdom Medical Research Council, Shire Pharmaceuticals Group plc, and Nycomed AS for the RECORD Trial.“ 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	Quote from the publication: "Randomization was centralized, computer generated, stratified by canter, and minimized by age (under 80 yr or 80 yr and over), gender, time since fracture (previous 3 months or longer), and type of enrolling fracture (proximal femur, distal forearm, clinical vertebral, and other)." Comment: sequence generation was achieved using computer random number generation.
Allocation concealment (selection bias)	Low risk	Quote from the publication: "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)." Comment: 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.
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Quote from the publication: "All outcomes were reported or verified by people who were masked to the allocation scheme. Tablets varied in size and taste, and so each had matching placebos. Calcium and calcium and vitamin D tablets were large, and those for vitamin D were small. Placebos matched in size were provided for each of these three types of tablets." Comment: 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.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Quote from the publication: "All outcomes were reported or verified by people who were masked to the allocation scheme. Tablets varied in size and taste, and so each had matching placebos. Calcium and calcium and vitamin D tablets were large, and those for vitamin D were small. Placebos matched in size were provided for each of these three types of tablets." Comment: 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)	Low risk	Comment: the numbers and reasons for dropouts and withdrawals in all intervention groups were described.
Selective reporting (reporting bias)	High risk	Comment: predefined, or clinically relevant and reasonably expected outcomes were reported.
For‐profit bias	High risk	Quote from the publication: "Shire Pharmaceuticals co‐funded the drugs together with Nycomed who also manufactured the drugs." Comment: the trial was sponsored by the industry.
Other bias	Low risk	Comment: the trial appears to be free of other components that could put it at risk of bias.