Fracture risk reduction during treatment with teriparatide is independent of pretreatment bone turnover.
BACKGROUND
Teriparatide is a bone formation agent that increases bone turnover and mass, resulting in an increase in bone strength and a decrease in fracture risk.


METHODS
The primary purpose of this analysis was to evaluate the association between pretreatment bone turnover marker (BTM) concentrations and the absolute and relative fracture risks after adjusting for baseline femoral neck BMD, number of prevalent vertebral fractures, and age. Because femoral neck BMD is commonly attained in the assessment of patients at risk for osteoporosis, we examined the ability of a multivariate assessment including pretreatment BTM concentration and femoral neck BMD to predict future fracture risk after adjusting for the number of prevalent vertebral fractures. We examined data from the Fracture Prevention Trial, a study designed to determine the effect of teriparatide 20 mcg/day and teriparatide 40 mcg/day on vertebral and nonvertebral fracture risk in postmenopausal women with osteoporosis. BTM were analyzed in two subsets of women within the Fracture Prevention Trial, and included serum bone-specific alkaline phosphatase (BSAP), serum carboxy-terminal extension peptide of procollagen type I (PICP), serum amino-terminal extension peptide of procollagen type I (PINP), urinary free deoxypyridinoline (DPD), and urinary N-terminal telopeptide (NTX).


RESULTS
Teriparatide significantly reduced the risk of fracture [four BTM subset (n = 520), placebo = 14.3%, teriparatide = 5.8%, P < 0.05; PINP subset (n = 771), placebo = 17.7%, teriparatide = 5.5%, P < 0.05]. Subjects with the highest pretreatment BTM concentrations had the greatest fracture risk. Teriparatide-mediated absolute risk reduction was greatest for women with high pretreatment bone turnover; however, the relative fracture risk reduction was independent of pretreatment bone turnover. After adjusting for pretreatment BTM and number of prevalent vertebral fractures, baseline femoral neck BMD was not a significant predictor of fracture risk.


CONCLUSIONS
Teriparatide-mediated relative fracture risk reduction was independent of pretreatment bone turnover, demonstrating that this therapy offers clinical benefit to patients across a range of disease severity.
INSERM Research Unit 403, Claude Bernard University of Lyon, Lyon, France. delmas@lyon.inserm.fr
P D
PD
Delmas
A A
AA
Licata
J Y
JY
Reginster
G G
GG
Crans
P
P
Chen
D A
DA
Misurski
R B
RB
Wagman
B H
BH
Mitlak
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000469:Alkaline Phosphatase / Q000097:blood; D000596:Amino Acids / Q000652:urine; D015415:Biomarkers / Q000097:blood / Q000652:urine; D015519:Bone Density / Q000187:drug effects; D050071:Bone Density Conservation Agents / Q000627:therapeutic use*; D001842:Bone and Bones / Q000187:drug effects*; D015331:Cohort Studies; D024042:Collagen Type I / Q000097:blood / Q000652:urine; D004305:Dose-Response Relationship, Drug; D005260:Female; D005272:Femur Neck / Q000473:pathology; D050723:Fractures, Bone / Q000517:prevention & control*; D006801:Humans; D008875:Middle Aged; D015663:Osteoporosis, Postmenopausal / Q000188:drug therapy*; D010446:Peptide Fragments / Q000097:blood; D010455:Peptides / Q000652:urine; D011347:Procollagen / Q000097:blood; D012306:Risk; D012307:Risk Factors; D019379:Teriparatide / Q000627:therapeutic use*; D016896:Treatment Outcome
D000596:Amino Acids; D015415:Biomarkers; D050071:Bone Density Conservation Agents; D024042:Collagen Type I; D010446:Peptide Fragments; D010455:Peptides; D011347:Procollagen; C052929:collagen type I trimeric cross-linked peptide; C042813:procollagen type I carboxy terminal peptide; D019379:Teriparatide; C036020:deoxypyridinoline; D000469:Alkaline Phosphatase