Early changes in biochemical markers of bone formation predict BMD response to teriparatide in postmenopausal women with osteoporosis.
The relationship between early changes in biochemical markers of bone turnover and the subsequent BMD response to daily teriparatide therapy in women with postmenopausal osteoporosis was studied. Changes in five biochemical markers, obtained from a subset of women enrolled in the Fracture Prevention Trial, were examined. Early increases in the PICP and the PINP were the best predictors of BMD response to teriparatide in this analysis.


BACKGROUND
Early reductions in biochemical markers of bone turnover with antiresorptive therapy negatively correlate with subsequent increases in BMD. We undertook this analysis to determine if early changes in biochemical markers with teriparatide therapy predict subsequent increases in BMD.


METHODS
In the Fracture Prevention Trial, 1637 postmenopausal women with osteoporosis were randomized to receive daily, self-administered, subcutaneous injections of placebo, teriparatide 20 microg/day, or teriparatide 40 microg/day. Serum concentrations of two bone formation markers (bone-specific alkaline phosphatase [bone ALP] and the carboxy-terminal extension peptide of procollagen type 1 [PICP]) and urinary concentrations of two bone resorption markers (free deoxypyridinoline [DPD] and N-terminal telopeptide [NTX]) were assessed in a trial population subset (n = 520) at baseline and at 1, 3, 6, and 12 months. We also assessed serum concentrations of another bone formation marker, the amino-terminal extension peptide of procollagen type 1 (PINP), in a subset of 771 women at baseline and 3 months. Lumbar spine (LS) BMD was measured by DXA at baseline and 18 months. Femoral neck BMD was measured at baseline and 12 months.


CONCLUSIONS
Baseline bone turnover status correlated positively and significantly with BMD response. The highest correlations occurred for the LS BMD response to teriparatide 20 microg/day. Among all studied biochemical markers, increases in PICP at 1 month and PINP at 3 months correlated best with increases in LS BMD at 18 months (0.65 and 0.61, respectively; p < 0.05). The relationships between these two biochemical markers and the LS BMD response were stronger than the corresponding relationships for the femoral neck BMD response. Using receiver operator curve analysis, we determined that the increases in PICP at 1 month and PINP at 3 months were the most sensitive and accurate predictors of the LS BMD response.
Chen
Peiqi
P
Eli Lilly and Company, Indianapolis, Indiana 46285, USA.
Satterwhite
Julie H
JH
Licata
Angelo A
AA
Lewiecki
E Michael
EM
Sipos
Adrien A
AA
Misurski
Derek M
DM
Wagman
Rachel B
RB
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000469:Alkaline Phosphatase / Q000097:blood; D000596:Amino Acids / Q000652:urine; D015519:Bone Density; D001846:Bone Development; D001862:Bone Resorption; D001842:Bone and Bones / Q000187:drug effects*; D015331:Cohort Studies; D003094:Collagen / Q000652:urine; D024042:Collagen Type I; D004305:Dose-Response Relationship, Drug; D005260:Female; D005272:Femur Neck / Q000473:pathology; D050723:Fractures, Bone / Q000517:prevention & control; D006801:Humans; D008875:Middle Aged; D010024:Osteoporosis / Q000188:drug therapy; D015663:Osteoporosis, Postmenopausal / Q000188:drug therapy*; D010455:Peptides / Q000737:chemistry / Q000652:urine; D010919:Placebos; D011347:Procollagen / Q000097:blood; D019379:Teriparatide / Q000494:pharmacology*; D013997:Time Factors; D016896:Treatment Outcome
D000596:Amino Acids; D024042:Collagen Type I; D010455:Peptides; D010919:Placebos; D011347:Procollagen; C052929:collagen type I trimeric cross-linked peptide; D019379:Teriparatide; C036020:deoxypyridinoline; D003094:Collagen; D000469:Alkaline Phosphatase