Comparison of new biochemical markers of bone turnover in late postmenopausal osteoporotic women in response to alendronate treatment.
To evaluate the clinical utility of recently developed biochemical markers of bone turnover to monitor the response of osteoporotic patients to antiresorptive therapy, we compared the results of three advanced assays for markers of bone resorption and four of bone formation to high pressure liquid chromatography (HPLC)-fluorometric assays for urinary pyridinoline and deoxypyridinoline. These assays were also used to resolve the uncertainties concerning the rate of bone turnover in late postmenopausal (late-PMP) osteoporotic women. The rate of bone turnover in 85 women (mean +/- SD age, 63 +/- 6 yr) with low bone mass and all more than 5 yr postmenopausal (mean +/- SD yr PMP, 16 +/- 7 yr) was compared to that in 46 premenopausal women (mean +/- SD age, 40 +/- 5 yr) randomly selected from a large cohort and all having a normal spine bone mineral density (BMD). The late-PMP osteoporotic patients were a subset of patients enrolled in a double blind, placebo-controlled, randomized study comparing the effects of several doses of oral alendronate, a potent and specific inhibitor of bone resorption. Periodically during the 2-yr study, the women's spinal BMD and the level of several markers of bone turnover were measured. Serum total and intact osteocalcin, bone-specific alkaline phosphatase, and carboxy-terminal propeptide of type I collagen measured by RIA were used to assess bone formation. To assess bone resorption, we measured the urinary excretion of total pyridinoline (HPLC Pyr) and deoxypyridinoline (HPLC D-Pyr) by HPLC, type I collagen cross-linked N-telopeptide and urinary free PYR (F-Pyr) by enzyme-linked immunosorbent assay, and the serum concentration of type I collagen cross-linked C-telopeptide (ICTP) by RIA. All bone formation markers, except carboxy-terminal propeptide of type I collagen, and all bone resorption markers, except ICTP, were significantly increased above normal (33-171%; P < 0.001) in late-PMP osteoporotic women. The long term within-patient variability assessed over a 15-month period in the placebo group was low and was somewhat lower for serum markers (12.5-17.4%) than for urinary markers (24-29%). Under treatment with alendronate, resorption markers decreased earlier than markers of bone formation, consistent with a direct action of the drug to inhibit osteoclastic bone resorption. With the exception of F-Pyr and ICTP, the levels of bone markers were reduced to the normal premenopausal range, and this steady state was maintained from 6-15 months.(ABSTRACT TRUNCATED AT 400 WORDS)
Garnero
P
P
INSERM U-403, Hôpital E. Herriot, Lyon, France.
Shih
W J
WJ
Gineyts
E
E
Karpf
D B
DB
Delmas
P D
PD
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019386:Alendronate; D000469:Alkaline Phosphatase / Q000097:blood; D000596:Amino Acids / Q000652:urine; D015415:Biomarkers / Q000032:analysis; D016723:Bone Remodeling; D003094:Collagen / Q000097:blood / Q000652:urine; D004164:Diphosphonates / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008875:Middle Aged; D015675:Osteocalcin / Q000097:blood; D015663:Osteoporosis, Postmenopausal / Q000188:drug therapy* / Q000503:physiopathology; D010919:Placebos; D017697:Premenopause / Q000502:physiology
D000596:Amino Acids; D015415:Biomarkers; D004164:Diphosphonates; D010919:Placebos; D015675:Osteocalcin; C015484:pyridinoline; D003094:Collagen; D000469:Alkaline Phosphatase; D019386:Alendronate