Table 2.
Comparison of individual trials included in traditional systematic reviews/meta-analysesa and reasons for exclusionb of trials by some systematic reviews/meta-analyses investigating hip fracture risk with calcium and vitamin D supplementation
| Bergman et al (17) 2010 |
Avenell et al (15) 2014 |
Bolland et al (19) 2014 |
Weaver et al (29) 2016 |
Zhao et al (31) 2017 |
Barrionuevo et al (16) 2019 |
Hu et al (24) 2019 |
Yao et al (30) 2019 |
Eleni and Panagiotis (22) 2020 |
|
|---|---|---|---|---|---|---|---|---|---|
| Pooled RR | 0.72 (0.32-1.40) | 0.84 (0.74-0.96) | 0.84 (0.74-0.96) | 0.61 (0.46-0.82) | 0.81 (0.71-0.93) | 0.84 (0.72-0.97) | 0.61 (0.40-0.92) | ||
| Institutionalized RR | 0.75 (0.62-0.92)c | 0.69 (0.53-0.90)d | |||||||
| Community RR | 0.91 (0.77-1.09) | 1.09 (0.85-1.39) | 1.15 (0.81-1.62)e | 0.92 (0.77-1.10) | |||||
| AMSTAR Quality Assessment | Critically low | Moderate | Critically low | Critically low | Low | Critically low | Critically low | Critically low | Critically low |
| Included trials | |||||||||
| Chapuy et al (45) 1992 |
NA 80/1387 110/1403 NA |
38.24% 137/1634 178/1636 0.77 (0.62-0.95) |
38% 137/1634 178/1636 NA |
NA 21/877 37/888 0.57 (0.34-0.97) |
Excluded institutionalized trials | 42.77% NA NA 0.77 (0.62-0.95) |
Excluded institutionalized trials | 25.5% 80/1634 110/1636 0.72 (0.53-0.96) |
15.2% 21/1387 37/1403 0.57 (0.34-0.98) |
| Chapuy et al (46) 2002 |
NA 27/393 21/190 NA |
6.02% 27/389 21/194 0.64 (0.37-1.10) |
6% 27/389 21/194 NA |
NA 27/393 21/190 0.62 (0.36-1.07) |
Excluded institutionalized trials | 6.50% NA NA 0.64 (0.37-1.10) |
Excluded institutionalized trials | 5.5% 27/393 21/190 0.58 (0.31-1.08) |
15.0% 27/393 21/190 0.62 (0.36-1.07) |
| Dawson-Hughes et al (47) 1997 |
Excluded trials including men | 0.31% 0/187 1/202 0.36 (0.01-8.78) |
0.2% 0/187 1/202 NA |
NA 0/170 1/148 0.29 (0.01-7.08) |
0.6% 0/187 1/202 0.36 (0.01-8.78) |
Excluded trials including men | NA 0/187 1/202 NA |
Excluded trials with < 500 participants | 1.5% 0/187 1/202 0.36 (0.01-8.78) |
| Larsen et al (43) 2004 |
NA | “No treatment group received vitamin D & calcium alone”f | NA | NA | “no treatment group received vitamin D and calcium alone” | NA | NA | “Not randomized (cluster randomized factorial design)” | 18.6% 87/4957 114/2116 0.33 (0.25-0.43) |
| Avenell et al (40) 2004 |
Excluded trials including men | 0.21% 1/35 1/35 1.0 (0.07-15.36) |
0.2% 1/35 1/35 NA |
“Doesn’t qualify as an RCT of Calcium and vitamin D” | 0.8% 1/35 1/35 1.0 (0.07-15.36) |
Excluded trials including men | NA 1/35 1/35 NA |
Excluded trials with < 500 participants | “It assessed the open trial design and not explicitly the combination of Ca & vitamin D” |
| Harwood et al (NoNOF) (42) 2004 |
Excluded trials on post–hip fracture | 0.29% 1/75 1/37 0.49 (0.03-7.67) |
0.2% 1/75 1/37 NA |
No data on hip fracture per SR/MA definition | 0.8% 1/75 1/37 0.49 (0.03-7.67) |
0.26% NA NA 0.49 (0.03-7.67) |
NA 1/75 1/37 NA |
Excluded trials with < 500 participants | NA |
| Grant et al (RECORD) (41) 2005 |
Included in sensitivity analysis | 8.73% 46/1306 41/1332 1.14 (0.76-1.73) |
10% 46/1306 41/1332 NA |
No data on hip fracture per SR/MA definition | 35.2% 46/1306 41/1332 1.14 (0.76-1.73) |
Excluded trials including men | NA 46/1306 41/1332 NA |
12% 46/1306 41/1332 1.15 (0.75-1.76) |
NA |
| Porthouse et al (44) 2005 |
NA 8/1321 17/1993 NA |
2.91% 8/1321 17/1993 0.71 (0.31-1.64) |
2% 8/1321 17/1993 NA |
NA 5/607 2/602 2.48 (0.48-12.78)g |
8.6% 8/1321 17/1993 0.71 (0.31-1.64) |
2.74% NA NA 0.71 (0.31-1.64) |
NA 8/1321 17/1993 NA |
3.4% 8/1321 17/1993 0.72 (0.32-1.61) |
11.0% 8/1321 17/1993 0.71 (0.31-1.64) |
| Jackson et al (WHI) (48) 2006 |
Excluded interventions incorporating hormone therapy | 42.86% 175/18176 199/18106 0.88 (0.72-1.07) |
42% 175/18176 199/18106 NA |
Excluded because used WHI post hoc analysis by Prentice et al (50) instead | 52% 70/4015 61/3957 1.13 (0.8-1.59) |
47.06% NA NA 0.88 (0.72-1.07) |
NA 70/4015 61/3957 NA |
52.7% 175/18176 199/18106 0.87 (0.71-1.07) |
19.4% 175/18176 199/18106 0.88 (0.72-1.07) |
| Salovaara et al (OSTPRE-FPS) (49) 2010 |
Beyond search period | 0.43% 4/1586 2/1609 2.03 (0.37-11.06) |
0.6% 4/1718 2/1714 NA |
NA 4/1586 2/1609 2.03 (0.37-11.06) |
2.1% 4/1718 2/1714 2.0 (0.37-10.88) |
0.67% NA NA 2.03 (0.37-11.06) |
NA 4/1718 2/1714 NA |
0.9% 4/1586 2/1609 1.98 (0.40-9.81) |
4.5% 4/1586 2/1609 2.03 (0.37-11.06) |
| Prentice et al (50) 2013 |
Beyond search period | NA | NA | NA 19/7530 35/7406 0.53 (0.31-0.93) |
NA | Post hoc analysis of WHI trial | NA | NA | 14.8% 19/7530 35/7801 0.56 (0.32-0.98) |
The trials by Chapuy et al (45, 46) are the only ones conducted in institutionalized populations. All the other trials are conducted in community-dwelling populations. Individual rows within cells are filled with the following: Percentage is weight of each trial taken from the forest plot of the corresponding SR/MA, number of fractures/total number of participants in the treatment group, number of fractures/total number of participants in control group, and effect size estimate of the trial taken from the forest plot of the corresponding SR/MA.
Abbreviations: Ca, calcium; D, vitamin D; MA, meta-analysis; NA, not available; RCT, randomized clinical trial; RR, relative risk; SR, systematic review; WHI, Women’s Health Initiative.
a MAs not included in the matrix: DIPART, 2010: individual participant data without details about individual RCTs (23); Murad et al, 2012: Network MA without details about Ca/D vs placebo (28); Tricco et al, 2017: Network MA without details about individual RCTs (39).
b Reasons for exclusion of some trials by SRs/MAs either as exactly reported or derived from inclusion/exclusion criteria.
c “The test for subgroup differences was not significant (P = .15).”
d “P for heterogeneity: .07”; P value for interaction term was not provided.
e This RR is for high D (≥ 800 IU/day) + high Ca (≥ 800 mg/day) vs placebo. RR for low D (< 800 IU/day) + high Ca (≥ 800 mg/day) is 1.13 (0.78-1.63). RR for low D (< 800 IU/day) + low Ca (< 800 mg/day) is 0.36 (0.01-8.81).
f Avenell excluded Larsen because participants in each of the 3 treatment clusters received 1 or more cointerventions designed to reduce falls (medication review, environmental hazard, and health assessment, and osteoporosis/fall prevention leaflets) but the control group received no intervention. No treatment group received D and Ca alone.
g CI for “equally allocated” subgroup.