Skeletal effects of raloxifene after 8 years: results from the continuing outcomes relevant to Evista (CORE) study.
In the CORE breast cancer trial of 4011 women continuing from MORE, the incidence of nonvertebral fractures at 8 years was similar between placebo and raloxifene 60 mg/day. CORE had limitations for assessing fracture risk. In a subset of 386 women, 7 years of raloxifene treatment significantly increased lumbar spine and femoral neck BMD compared from the baseline of MORE.


BACKGROUND
The multicenter, double-blind Continuing Outcomes Relevant to Evista (CORE) trial assessed the effects of raloxifene on breast cancer for 4 additional years beyond the 4-year Multiple Outcomes of Raloxifene Evaluation (MORE) osteoporosis treatment trial.


METHODS
In CORE, placebo-treated women from MORE continued with placebo (n = 1286), whereas those previously given raloxifene (60 or 120 mg/day) received raloxifene 60 mg/day (n = 2725). As a secondary endpoint, new nonvertebral fractures were analyzed as time-to-first event in 4011 postmenopausal women at 8 years. A substudy assessed lumbar spine and femoral neck BMD at 7 years, with the primary analysis based on 386 women (127 placebo, 259 raloxifene) who did not take other bone-active agents from the fourth year of MORE and who were > or =80% compliant with study medication in CORE.


RESULTS
The risk of at least one new nonvertebral fracture was similar in the placebo (22.9%) and raloxifene (22.8%) groups (hazard ratio [HR], 1.00; Bonferroni-adjusted CI, 0.82, 1.21). The incidence of at least one new nonvertebral fracture at six major sites (clavicle, humerus, wrist, pelvis, hip, lower leg) was 17.5% in both groups. Posthoc Poisson analyses, which account for multiple events, showed no overall effect on nonvertebral fracture risk, and a decreased risk at six major nonvertebral sites in women with prevalent vertebral fractures (HR, 0.78; 95% CI, 0.63, 0.96). At 7 years after MORE randomization, the differences in mean lumbar spine and femoral neck BMD with raloxifene were 1.7% (p = 0.30) and 2.4% (p = 0.045), respectively, from placebo. Compared with MORE baseline, after 7 years, raloxifene treatment significantly increased lumbar spine (4.3% from baseline, 2.2% from placebo) and femoral neck BMD (1.9% from baseline, 3.0% from placebo). BMDs were significantly increased from MORE baseline at all time-points at both sites with raloxifene.


CONCLUSIONS
Raloxifene therapy had no effect on nonvertebral fracture risk after 8 years, although CORE had limitations for fracture risk assessment. BMD increases were maintained after 7 years of raloxifene.
Siris
Ethel S
ES
Toni Stabile Osteoporosis Center, Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA. es27@columbia.edu
Harris
Steven T
ST
Eastell
Richard
R
Zanchetta
Jose R
JR
Goemaere
Stefan
S
Diez-Perez
Adolfo
A
Stock
John L
JL
Song
Jingli
J
Qu
Yongming
Y
Kulkarni
Pandurang M
PM
Siddhanti
Suresh R
SR
Wong
Mayme
M
Cummings
Steven R
SR
D000368:Aged; D015519:Bone Density; D050071:Bone Density Conservation Agents / Q000627:therapeutic use*; D016723:Bone Remodeling; D001842:Bone and Bones / Q000528:radiation effects*; D001943:Breast Neoplasms / Q000473:pathology; D004311:Double-Blind Method; D005260:Female; D005265:Femoral Neck Fractures / Q000473:pathology; D005272:Femur Neck / Q000473:pathology*; D017102:Fracture Healing; D050723:Fractures, Bone / Q000517:prevention & control*; D006801:Humans; D008159:Lumbar Vertebrae / Q000473:pathology; D008875:Middle Aged; D010024:Osteoporosis / Q000473:pathology; D015663:Osteoporosis, Postmenopausal / Q000188:drug therapy; D010919:Placebos; D016012:Poisson Distribution; D017698:Postmenopause; D016016:Proportional Hazards Models; D020849:Raloxifene Hydrochloride / Q000627:therapeutic use*; D012306:Risk; D013997:Time Factors; D016896:Treatment Outcome
D050071:Bone Density Conservation Agents; D010919:Placebos; D020849:Raloxifene Hydrochloride