Change in bone turnover and hip, non-spine, and vertebral fracture in alendronate-treated women: the fracture intervention trial.
We used data from the Fracture Intervention Trial to assess the relationship change in bone turnover after 1 year of alendronate or placebo treatment and subsequent hip, non-spine, and spine fracture risk among 6186 postmenopausal women. In the alendronate group (n = 3105), greater reductions in one or more biochemical marker were associated with a lower risk of fracture.


BACKGROUND
There are few data on the relationship between short-term change in biochemical markers of bone turnover and non-spine fracture risk among bisphosphonate-treated women, and the clinical use of such measurements is unknown.


METHODS
We measured biochemical markers of bone turnover (bone-specific alkaline phosphatase [bone ALP], intact N-terminal propeptide of type I collagen, and C-terminal crosslinked telopeptide of type 1 collagen) and BMD of the spine and hip at baseline and after 1 year of alendronate or placebo. During a mean follow-up of 3.6 years, 72 hip, 786 non-spine, and 336 vertebral fractures were documented.


CONCLUSIONS
Each 1 SD reduction in 1-year change in bone ALP was associated with fewer spine (odds ratio = 0.74; CI: 0.63, 0.87), non-spine (relative hazard [RH] = 0.89; CI: 0.78, 1.00; p < 0.050), and hip fractures (RH = 0.61; CI: 0.46, 0.78). Alendronate-treated women with at least a 30% reduction in bone ALP had a lower risk of non-spine (RH = 0.72; CI: 0.55, 0.92) and hip fractures (RH = 0.26; CI: 0.08, 0.83) relative to those with reductions <30%. We conclude that greater reductions in bone turnover with alendronate therapy are associated with fewer hip, non-spine, and vertebral fractures, and the effect is at least as strong as that observed with 1-year change in BMD.
Bauer
Douglas C
DC
Department of Medicine, Epidemiology and Biostatistics, University of California, San Francisco, California 94105, USA. dbauer@psf.ucsf.edu
Black
Dennis M
DM
Garnero
Patrick
P
Hochberg
Marc
M
Ott
Susan
S
Orloff
John
J
Thompson
Desmond E
DE
Ewing
Susan K
SK
Delmas
Pierre D
PD
D000368:Aged; D000369:Aged, 80 and over; D019386:Alendronate / Q000494:pharmacology / Q000627:therapeutic use*; D000469:Alkaline Phosphatase / Q000097:blood; D015415:Biomarkers / Q000097:blood; D015519:Bone Density / Q000187:drug effects; D001842:Bone and Bones / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D003094:Collagen / Q000097:blood; D024042:Collagen Type I; D004311:Double-Blind Method; D005260:Female; D050723:Fractures, Bone / Q000517:prevention & control*; D006620:Hip Fractures / Q000453:epidemiology / Q000517:prevention & control; D006801:Humans; D016015:Logistic Models; D008875:Middle Aged; D018579:Patient Selection; D010384:Pelvic Bones / Q000737:chemistry; D010446:Peptide Fragments / Q000097:blood; D010455:Peptides / Q000097:blood; D011347:Procollagen / Q000097:blood; D012307:Risk Factors; D016103:Spinal Fractures / Q000517:prevention & control; D013131:Spine / Q000737:chemistry; D016896:Treatment Outcome
D015415:Biomarkers; D024042:Collagen Type I; D010446:Peptide Fragments; D010455:Peptides; D011347:Procollagen; C052929:collagen type I trimeric cross-linked peptide; C047202:procollagen Type I N-terminal peptide; D003094:Collagen; D000469:Alkaline Phosphatase; D019386:Alendronate