Rapid and robust response of biochemical markers of bone formation to teriparatide therapy.
Teriparatide, a parathyroid hormone analogue, is a potent anabolic treatment for postmenopausal osteoporosis. Studies have shown that teriparatide induces large increases in biochemical markers of bone formation after 1 month of therapy followed by a delayed increase in bone resorption markers. The aims of this study were to (1) describe changes in bone turnover markers during 28 days of treatment with teriparatide; (2) identify the earliest time point by which most subjects showed a biochemical response to teriparatide; (3) identify potential biomarkers of positive bone response; (4) describe changes in bone turnover markers 4 weeks after stopping teriparatide. We recruited 15 osteopenic postmenopausal women, ages 55-69 (mean 62) years. All received 20 microg teriparatide subcutaneously for 28 days. Serum levels of the bone formation markers type I collagen N-terminal propeptide (PINP), type I collagen C-terminal propeptide (PICP), osteocalcin (OC), bone alkaline phosphatase (bone ALP), and the bone resorption markers crosslinked C-telopeptide of type I collagen (Sbeta-CTX), crosslinked N-telopeptide of type I collagen (S-NTX) and tartrate-resistant acid phosphatase type 5b (TRACP5b) were measured on 11 occasions: three times before dosing (baseline) and on days 3, 7, 10, 14, 19, 24 and 28 and at day 56 (i.e., 28 days after stopping teriparatide ). During the first 2 days of teriparatide treatment, PINP levels increased rapidly, by 8.2% (90% confidence interval (CI) 6.9%, 9.5%) and continued to increase until the end of treatment to 110.8%. PICP and OC showed a similar, but less pronounced, pattern. All three markers increased by at least 75% at day 28. A small, transient decrease in bone resorption markers occurred over the same period. Following cessation of treatment, concentrations of bone formation markers decreased to within 20% of baseline values by day 56. In conclusion, the bone formation markers PINP, PICP and OC show a rapid and robust increase in response to teriparatide, which is noticeable during the first week of therapy. PINP is the most responsive marker. These findings have important implications for monitoring patients treated with teriparatide and may also inform the design of studies of new anabolic agents for osteoporosis.
Glover
Sarah J
SJ
University of Sheffield, Sheffield, UK.
Eastell
Richard
R
McCloskey
Eugene V
EV
Rogers
Angela
A
Garnero
Patrick
P
Lowery
Jonathan
J
Belleli
Rossella
R
Wright
Timothy M
TM
John
Markus R
MR
D000368:Aged; D015415:Biomarkers / Q000378:metabolism*; D050071:Bone Density Conservation Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001862:Bone Resorption / Q000188:drug therapy / Q000503:physiopathology; D016001:Confidence Intervals; D005260:Female; D006801:Humans; D008875:Middle Aged; D010012:Osteogenesis / Q000187:drug effects*; D019379:Teriparatide / Q000494:pharmacology* / Q000627:therapeutic use
D015415:Biomarkers; D050071:Bone Density Conservation Agents; D019379:Teriparatide