Disassociation of bone resorption and formation by GLP-2: a 14-day study in healthy postmenopausal women.
We have previously shown that a single subcutaneous injection of glucagon-like peptide-2 (GLP-2) at 10 p.m. in postmenopausal women results in a dose-dependent decrease in the nocturnal serum and urine concentrations of fragments derived from the degradation of the C-terminal telopeptide region of collagen type I (s-CTX and u-CTX) and u-DPD, markers of bone resorption. In contrast, bone formation, as assessed by serum osteocalcin and procollagen type I N-terminal propeptide (PINP), appeared to be unaffected by treatment with exogenous GLP-2. These effects were further investigated in a 14-day study. The aim was to demonstrate that a parenteral formulation of GLP-2 is safe and well tolerated after repeated dosing in healthy postmenopausal women for 14 days. It was further investigated whether the effects on bone turnover markers were sustained throughout the study period. The study was a double-blind placebo-controlled trial with 60 postmenopausal women and 2 different doses of GLP-2 (1.6 mg and 3.2 mg GLP-2) against a saline control. The data for bone resorption revealed a similar reduction on Day 1 and Day 14, both based on time course and AUC. There were no signs of tachyphylaxis and no serious adverse reaction. Both GLP-2 doses resulted in similar and significant (p<0.001) reduction in bone resorption indicating that the maximum efficacious dose has been approached. Osteocalcin and PINP levels were unaffected at Day 1 and Day 14, suggesting a disassociation between bone resorption and bone formation during GLP-2 treatment.
Henriksen
Dennis B
DB
Sanos Bioscience, Glerupvej 2, 2610 Roedovre, Denmark. dbh@sanosbioscience.com
Alexandersen
Peter
P
Hartmann
Bolette
B
Adrian
Charlotte L
CL
Byrjalsen
Inger
I
Bone
Henry G
HG
Holst
Jens J
JJ
Christiansen
Claus
C
D000368:Aged; D019540:Area Under Curve; D001862:Bone Resorption / Q000517:prevention & control*; D002118:Calcium / Q000652:urine; D024042:Collagen Type I / Q000097:blood / Q000187:drug effects; D003404:Creatinine / Q000652:urine; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D053767:Glucagon-Like Peptide 2 / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D006801:Humans; D007279:Injections, Subcutaneous; D015675:Osteocalcin / Q000097:blood / Q000187:drug effects; D010012:Osteogenesis / Q000187:drug effects*; D015663:Osteoporosis, Postmenopausal / Q000517:prevention & control*; D010446:Peptide Fragments / Q000097:blood / Q000187:drug effects; D010455:Peptides / Q000097:blood / Q000187:drug effects; D010710:Phosphates / Q000652:urine; D017697:Premenopause / Q000502:physiology*; D011347:Procollagen / Q000097:blood / Q000187:drug effects
D024042:Collagen Type I; D053767:Glucagon-Like Peptide 2; D010446:Peptide Fragments; D010455:Peptides; D010710:Phosphates; D011347:Procollagen; C052929:collagen type I trimeric cross-linked peptide; C047202:procollagen Type I N-terminal peptide; D015675:Osteocalcin; D003404:Creatinine; D002118:Calcium