Indirect comparison of bazedoxifene vs oral bisphosphonates for the prevention of vertebral fractures in postmenopausal osteoporotic women.
OBJECTIVE
Compare the efficacy of bazedoxifene with oral bisphosphonates for reduction of vertebral fracture risk in postmenopausal osteoporotic (PMO) women and in higher-risk patients based on evidence from randomized controlled trials (RCTs).


METHODS
Eight RCTs assessing vertebral fracture risk reduction with oral bisphosphonates (n = 7) or bazedoxifene (n = 1) were identified by a systematic literature review. Individual study results were pooled in a network meta-analysis (NMA) to indirectly compare treatment effects for overall PMO women and a higher-risk subgroup (FRAX ≥ 20%). Three sets of NMA analyses were conducted: aggregate data (AD) from the bisphosphonate RCTs and bazedoxifene RCT for the full population or the FRAX ≥20% subgroup (NMA AD); bisphosphonate AD and bazedoxifene AD from each FRAX subgroup adjusted for baseline risk (NMA AD meta-regression); and bisphosphonate AD and bazedoxifene individual patient data (IPD) adjusted for baseline risk/FRAX (NMA AD/IPD meta-regression).


RESULTS
For the overall population, bisphosphonates had lower fracture risks versus bazedoxifene although there is considerable uncertainty in supporting one intervention over another. The relative risk reduction (RRR) for bazedoxifene was -0.23 (95% CrI: -1.11, 0.27) versus ibandronate, -0.17 (-0.76, 0.22) versus alendronate, and -0.06 (-0.62, 0.30) versus risedronate. RESULTS from the meta-regression analyses were similar. For the FRAX ≥20% population, estimated fracture rates with bazedoxifene were lower than with bisphosphonates, but again the uncertainty limits strong interpretation. The RRR for bazedoxifene was 0.51 (-0.31, 0.83) versus ibandronate, 0.53 (-0.18, 0.83) versus alendronate, and 0.57 (-0.07, 0.85) versus risedronate. The meta-regression analyses showed comparable findings.


CONCLUSIONS
The analyses only considered vertebral fractures for oral bisphosphonates versus bazedoxifene, and IPD was available only for bazedoxifene. In light of this, bazedoxifene is comparable to bisphosphonates in the overall PMO population and at least as effective as bisphosphonates for preventing vertebral fractures among higher-risk PMO patients. The findings suggest bazedoxifene performs better in higher-risk PMO than in the overall PMO.
Formerly at Mapi , Boston, MA , USA.
Alexandra G
AG
Ellis
Jean-Yves
JY
Reginster
Xuemei
X
Luo
Andrew G
AG
Bushmakin
Robert
R
Williams
Santosh
S
Sutradhar
Sebastian
S
Mirkin
Jeroen P
JP
Jansen
D000284:Administration, Oral; D050071:Bone Density Conservation Agents / Q000627:therapeutic use*; D004164:Diphosphonates / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007211:Indoles / Q000627:therapeutic use*; D015663:Osteoporosis, Postmenopausal / Q000150:complications / Q000188:drug therapy*; D058866:Osteoporotic Fractures / Q000209:etiology / Q000517:prevention & control*; D016032:Randomized Controlled Trials as Topic; D012044:Regression Analysis; D016103:Spinal Fractures / Q000209:etiology / Q000517:prevention & control*; D016896:Treatment Outcome
D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007211:Indoles; C447119:bazedoxifene
Bazedoxifene; Bisphosphonates; Fractures; Indirect comparison; Osteoporosis