The efficacy and safety of bazedoxifene in postmenopausal women by baseline kidney function status.
BACKGROUND
Two global, double-blind, placebo- and active-controlled, phase-3 studies (2-year prevention (n = 1583) and 3-year treatment (n = 7492)) have shown that bazedoxifene (BZA) is safe and effective for prevention and treatment of postmenopausal osteoporosis.


OBJECTIVE
To evaluate the efficacy/safety of BZA according to baseline kidney function.


METHODS
Data for the BZA 20- and 40-mg and placebo groups from both studies were integrated for assessment of bone turnover markers (BTMs), bone mineral density (BMD), and fracture incidence (treatment study only). Safety was assessed using integrated data for the BZA, placebo, and raloxifene 60-mg groups from both studies. Baseline glomerular filtration rate (GFR) was estimated by the Modification of Diet in Renal Disease Study equation; among subjects with baseline GFR, renal function categories were defined by GFR (ml/min per 1.73 m(2)): normal (GFR ≥ 90; n = 1982), mild impairment (60 ≤ GFR < 90; n = 6032), or moderate/severe impairment (GFR < 60; n = 723).


RESULTS
Demographics were similar across treatment groups and within GFR subgroups. Across GFR subgroups, BZA 20 and 40 mg reduced BTM levels and improved lumbar spine and total hip BMD versus placebo. At month 24, there were significant treatment-by-GFR (p = 0.003) and treatment-by-serum creatinine (p = 0.034) interactions for the increase in lumbar spine BMD versus placebo. Fracture incidence was lower with BZA than placebo across all GFR categories, with no treatment-by-GFR interaction. There were no significant differences among treatment groups in incidences of overall, serious, or renal-related adverse events across GFR subgroups.


CONCLUSIONS
Mild to moderate kidney impairment did not affect the efficacy and safety of BZA in postmenopausal women.
University of Verona , Verona , Italy.
S
S
Adami
S
S
Palacios
R
R
Rizzoli
A B
AB
Levine
S
S
Sutradhar
A A
AA
Chines
D000368:Aged; D015519:Bone Density / Q000187:drug effects; D050071:Bone Density Conservation Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001842:Bone and Bones / Q000503:physiopathology; D024042:Collagen Type I / Q000097:blood; D004311:Double-Blind Method; D005260:Female; D050723:Fractures, Bone / Q000517:prevention & control; D005919:Glomerular Filtration Rate; D006801:Humans; D007211:Indoles / Q000008:administration & dosage* / Q000009:adverse effects; D007674:Kidney Diseases / Q000139:chemically induced / Q000503:physiopathology; D008875:Middle Aged; D015675:Osteocalcin / Q000097:blood; D015663:Osteoporosis, Postmenopausal / Q000188:drug therapy* / Q000517:prevention & control*; D010455:Peptides / Q000097:blood; D017698:Postmenopause
D050071:Bone Density Conservation Agents; D024042:Collagen Type I; D007211:Indoles; D010455:Peptides; C052929:collagen type I trimeric cross-linked peptide; D015675:Osteocalcin; C447119:bazedoxifene
BAZEDOXIFENE; MENOPAUSE; OSTEOPOROSIS; RENAL IMPAIRMENT; SELECTIVE ESTROGEN RECEPTOR MODULATOR (SERM)