| PMC full text: | Published online 2012 May 17. doi: 10.1210/jc.2011-3328
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Table 1.
Characteristics of the eight randomized controlled trials included in the IPD analysis and 16 additional studies included in the trial level meta-analysis
| First author, year (Ref.) | Patient category; total no. of included participants (% females); median age (IQR) or mean ± sd; place of study | Randomization and duration | Study arms; no. of participants in each arm/total no. of deaths during the entire period of follow-upa (no. of deaths during the first 36 months of follow-upb) |
|---|---|---|---|
| Studies included in IPD analysis | |||
| Meyer, 2002 (11) | Nursing home residents; n = 1,144 (75.9%); age, 85 (81–90) yr; Norway | Q, 24 months, double-blind | Daily oral 10 μg D3, 569/246 (246), vs. placebo, 575/245 (245) |
| Larsen, 2004 (13) | Community-dwelling aged ≥66 yr; n = 9,605 (60.1%); age, 74 (70–79) yr; Denmark | C, 42 months, open-label | Daily oral 10 μg D3 + 1000 mg Ca, 4,957/832 (715), vs. no treatment, 4,648/839 (705) |
| Porthouse, 2005 (14) | GP patients with risk factors for fracture; n = 3,314 (100%); age, 76 (73–80) yr; UK | I, 18–42 (median, 22.5) months, open-label | Daily oral 20 μg D3 + 1000 mg Ca. 1,321/57 (57), vs. leaflet, 1,993/68 (67) |
| Grant (RECORD), 2005 (15) | Previous osteoporotic fracture; n = 5,292 (84.7%); age, 77 (73–81) yr; UK | I, 24–62 (median, 30.4) months, double-blind | Four groups with daily oral dose: 1) 20 μg D3 + 1000 mg Ca, 1,306/221 (161); 2) 20 μg D3, 1,343/217 (167); 3) 1000 mg Ca, 1,311/243 (198); 4) double placebo, 1,332/217 (172) |
| Smith, 2007 (18) | GP patients presenting for influenza vaccination; n = 9,440 (53.9%); age, 79 (77–83) yr; UK | I, up to 36 (median, 36.0) months, double-blind | Once a year im 300,000 IU D2, 4,727/316 (290), vs. placebo, 4,713/312 (291) (equal to an average D2 dose of 20.5 μg/d) |
| LaCroix (WHI), 2009 (19)c | Community-based postmenopausal women; n = 36,282 (100%); age, 62 (57–68) yr; USA | I, median, 85.4 months, double-blind | Daily oral 10 μg D3 + 1000 mg Ca, 18,176/755 (180), vs. placebo, 18,106/825 (220) |
| Sanders, 2010 (20)e | Community-dwelling aged ≥70 yr; n = 2,256 (100%); age, 76 (73–80) yr; Australia | I, up to 60 (median, 36) months, double-blind | Once a year oral 500,000 IU D3, 1,131/46 (39), vs. placebo, 1,125/54 (46) (equal to an average D3 dose of 34 μg/d) |
| Salovaara (OSTPRE-FPS), 2010 (21)d | Community-dwelling women aged 65–71 yr; n = 3,195 (100%); age, 67 (66–69) yr; Finland | I, up to 36 months; mean follow-up time, 3.01 (sd, 0.22) yr, open-label | Daily oral 20 μg D3 + 1000 mg Ca, 1,586/15 (15), vs. no treatment, 1,609/18 (18) |
| Additional medium- and large-sized (>500 participants) studies included in trial level meta-analysis | |||
| Chapuy, 1994 (9) | Nursing home residents; n = 3,270 (100%); age, 84 ± 6 yr; France | I, up to 36 months, double-blind | Daily oral 20 μg D3 + 1200 mg Ca, 1,634/601, vs. placebo, 1,636/597 |
| Lips, 1996 (10) | Living independently, in apartments/homes for elderly persons aged ≥70 yr; n = 2,578 (74%); age, 80 ± 6 yr; The Netherlands | I, up to 42 months, double-blind | Daily oral 10 μg D3, 1,291/223, vs. placebo, 1,287/251 |
| Chapuy, 2002 (27) | Ambulatory institutionalized women; n = 583 (100%); age, 85 ± 7 yr; France | I, up to 24 months, double-blind | Daily oral 20 μg D3 + 1200 mg Ca, 393/71, vs. placebo, 190/45 |
| Trivedi, 2003 (12) | Community-dwelling aged ≥65 yr; n = 2,686 (24%); age, 75 ± 5 yr; UK | I, up to 60 months, double-blind | Every fourth month, oral 100,000 IU D3, 1,345/224, vs. placebo, 1,341/247 (equal to an average D3 dose of 21 μg/d) |
| Flicker, 2005 (28) | Nursing home residents; n = 625 (95%); age, 83 ± 8 yr; Australia | I, up to 24 months, double-blind | Daily oral 600 mg Ca + D2, initially 10,000 IU weekly followed by 25 μg/d, 313/76, vs. placebo, 312/85 |
| Law, 2006 (16)f | Nursing home residents; n = 2,641 (76%); mean age, 85 yr; UK | C, median, 10 (IQR, 7–14) months, open-label | Every third month, oral 100,000 IU D2, 1,252/247, vs. placebo, 1,389/229 (equal to an average D2 dose of 28 μg/d) |
| Lyons, 2007 (17) | Nursing home residents; n = 3,440 (76%); age, 84 ± 8 yr; UK | I, up to 36 months, double-blind | Every fourth month, oral 100,000 IU D2, 1,673/713, vs. placebo, 1,670/715 (equal to an average D2 dose of 21 μg/d) |
| Small-sized studies (<500 participants) included in trial level meta-analysis | |||
| Baeksgaard, 1998 (29) | Healthy women aged 58–67 yr; n = 240 (100%); mean age, 62 yr; Denmark | I, 24 months, double-blind | Daily oral 14 μg D3 + 1000 mg Ca, 160/1, vs. placebo, 80/1 |
| Krieg, 1999 (43) | Institutionalized women aged 62–98 yr; n = 248 (100%); age, NA; Switzerland | I, 24 months, open-label | Daily oral 22 μg D3 + 1000 mg Ca, 124/21, vs. no treatment, 124/26 |
| Komulainen, 1999 (44) | Early postmenopausal women; n = 458 (100%); mean age, 53 yr (Finland) | I, 60 months, open-label | Four treatment groups with daily oral: 1) HRT, 115/1; 2) 7.5 μg D3 (only 2.5 μg/d during the fifth year), 112/0; 3) HRT + D3 as above, 116/1; 4) placebo, 115/1 |
| Latham, 2003 (30) | Frail elderly aged >65 yr; n = 243 (53%); age, 79 ± 7 yr; New Zealand | I, 6-month follow-up, double-blind | Single oral dose 300,000 IU D3, 121/11, vs. placebo, 122/3 |
| Avenell, 2004 (45) | Aged >70 yr and a history of an osteoporotic fracture within the last 10 yr; n = 134 (82%); age, 77 ± 5 yr; UK | I, 12 months, open-label | Daily oral 20 μg D3 + 1000 mg Ca, 99/1, vs. no treatment, 35/1 |
| Harwood, 2004 (46) | Elderly with a recent hip fracture; n = 150 (100%); age, 81 (67–92) yr; UK | I, 12 months, open-label | Four study groups: 1) single injection of D2 300,000 IU, 38/7; 2) single injection D2 300,000 IU + 1000 mg/d Ca, 36/11; 3) oral D3 20 μg/d + 1000 mg/d Ca, 39/6; 4) no treatment, 37/5 |
| Meier, 2004 (47) | Healthy community dwelling aged 33–78 yr; n = 55 (65%); age, NA; Germany | I, 12 months, open-label | Daily oral 12.5 μg D3 + 500 mg Ca, 30/0, vs. no treatment, 25/1 |
| Brazier, 2005 (31) | Women >65 yr with plasma 25OHD <30 nmol/liter; n = 192 (100%); age, 75 ± 7 yr; France | I, 12 months, double-blind | Daily oral 20 μg D3 + 1000 mg Ca, 95/3, vs. placebo, 97/1 |
| Schleithoff, 2006 (32) | Patients with congestive heart failure; n = 123 (17%); median age, 55 yr; Germany | I, 9 months, double-blind | Daily oral 50 μg D3 + 500 mg Ca, 61/7, vs. 500 mg Ca, 62/6 |
I, Individually randomized; Q, quasi-randomized by birth date; C, cluster randomized; IQR, interquartile range; 25OHD, 25-hydroyvitamin D; GP, general practice; Ca, calcium supplement; NA, not available. To convert micrograms of vitamin D into international units, multiply by 40.
aTotal number of deaths during the entire follow-up period, i.e. not restricted to the 36 months of follow-up used in the IPD analysis.
bData only available for studies included in the IPD analysis.
cNumber of deaths is based on the WHI Investigator Data Set updated on September 12, 2005 (released on December 21, 2006), in which slightly more (n = 29) deaths have been recorded than in the original trial report.
dNumber of deaths is based on an updated data extraction (October, 2010) from the Finnish National Population Register in which slightly more (n = 5) deaths have been recorded than in the original trial report.
eNumber of deaths in the original trial report was based on subjects who died while actively participating, whereas the number of deaths stated in the table is based on treatment allocation independently of whether subjects participated actively or not in the study.
fAdjustments to the number of participants (1762 vs. 1995) with outcomes, and denominators in study were made using an intraclass correlation coefficient of 0.026—see Sensitivity section for further explanations.