Alendronate versus Raloxifene for Postmenopausal Women: A Meta-Analysis of Seven Head-to-Head Randomized Controlled Trials

Table 3

^$GRADE evidence profile: randomized controlled trials of comparison between Aln and Rlx for postmenopausal women.

No. of trials; (No. of women)	Summary of finding	Quality of evidence
	Magnitude of; effect (95% CI)	Risk of bias	Inconsistency	Indirectness	Imprecision	Publication; bias	Quality
Efficacy profile
Antifracture evaluation
Total fractures risk
6 trials (3742)	RR: 1.12; (0.75 to 168)	Low	No	Direct	Yes^c	Unlikely	Moderate
Vertebral fractures risk
3 trials (2634)	RR: 1.30; (0.66 to 2.54)	Low	No	Direct	Yes^c	Unlikely	Moderate
Nonvertebral fractures risk
4 trials (3455)	RR: 0.95; (0.54 to 1.68)	Low	No	Direct	Yes^c	Unlikely	Moderate
Surrogate anti-fracture evaluation
LS BMD at 12 months
6 trials (2396)	WMD: 2.92; (2.23 to 3.62)	Low	Inconsistency^b	Direct	No	Unlikely	Moderate
5 trials (2274)*	WMD: 2.37; (2.17 to 2.58)	Low	No	Direct	No	Unlikely	High
FN BMD at 12 months
4 trials (1174)	WMD: 0.84; (0.32, 1.36)	Low	Inconsistency^b	Direct	No	Unlikely	Moderate
TH BMD at 12 months
3 trials (1009)	WMD: 1.25; (1.02, 1.49)	Low	Inconsistency^b	Direct	No	Unlikely	Moderate
Safety profile
Risk of upper GI events
6 trials (2708)	RR: 1.10; (0.77 to 1.58)	Low	Inconsistency^b	No	Yes^c	Unlikely	Low
5 trials (2221)^#	RR: 1.30; (1.04 to 1.63)	Low	No	No	No	Unlikely	High
Risk of discontinuations
5 trials (2642)	RR: 1.03; (0.77 to 1.36)	Low	No	No	Yes^c	Unlikely	Moderate
Risk of VT events
3 trials (1934)	RR: 0.52; (0.10 to 2.86)	Low	No	No	Yes^c	Unlikely	Moderate
Risk of diarrhea events
3 trials (1600)	RR: 2.33; (1.21 to 4.49)	High^a	No	No	No	Unlikely	Moderate
Risk of vasomotor events
2 trials (943)	RR: 0.47; (0.27 to 0.81)	Low	No	No	No	Unlikely	High
Risk of vasodilatation events
3 trials (1643)	RR: 0.74; (0.54 to 1.01)	Low	No	No	Yes^c	Unlikely	Moderate

Aln: Alendronate; Rlx: Raloxifene; LS: lumbar spine; FN: femoral neck; TH: total hip; BMD: bone mineral density; WMD: weighted mean differences; RR: risk ratios; CI: confidence interval.
^aOnly 2 or 3 trials are included, of which 2 trials are with high risk of bias; then evidence was rated down.
^bStatistical heterogeneities (𝐼² > 50%) across studies are detected; therefore quality was decreased.
^c95% confidence interval included both important superiority and inferiority; then quality was downgraded.
*After excluding Iwamoto's study (the eldest women involved).
^#After excluding Sambrook's study (the youngest women involved).
^$GRADE Working Group grades of evidence: high quality: further research very unlikely to change confidence in estimate of effect; moderate quality: further research likely to have important impact on confidence in estimate of effect and may change estimate; low quality: further research very likely to have important impact on confidence in estimate of effect and likely to change estimate; very low quality: very uncertain about estimate.