Disassociation of bone resorption and formation by GLP-2: a 14-day study in healthy postmenopausal women
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Disassociation of bone resorption and formation by GLP-2 : a 14-day study in healthy postmenopausal women. / Henriksen, Dennis B; Alexandersen, Peter; Hartmann, Bolette; Adrian, Charlotte L; Byrjalsen, Inger; Bone, Henry G; Holst, Jens Juul; Christiansen, Claus.
In: Bone, Vol. 40, No. 3, 03.2007, p. 723-9.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Disassociation of bone resorption and formation by GLP-2
T2 - a 14-day study in healthy postmenopausal women
AU - Henriksen, Dennis B
AU - Alexandersen, Peter
AU - Hartmann, Bolette
AU - Adrian, Charlotte L
AU - Byrjalsen, Inger
AU - Bone, Henry G
AU - Holst, Jens Juul
AU - Christiansen, Claus
PY - 2007/3
Y1 - 2007/3
N2 - 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.
AB - 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.
KW - Aged
KW - Area Under Curve
KW - Bone Resorption
KW - Calcium
KW - Collagen Type I
KW - Creatinine
KW - Dose-Response Relationship, Drug
KW - Double-Blind Method
KW - Female
KW - Glucagon-Like Peptide 2
KW - Humans
KW - Injections, Subcutaneous
KW - Osteocalcin
KW - Osteogenesis
KW - Osteoporosis, Postmenopausal
KW - Peptide Fragments
KW - Peptides
KW - Phosphates
KW - Premenopause
KW - Procollagen
U2 - 10.1016/j.bone.2006.09.025
DO - 10.1016/j.bone.2006.09.025
M3 - Journal article
C2 - 17081815
VL - 40
SP - 723
EP - 729
JO - Bone
JF - Bone
SN - 8756-3282
IS - 3
ER -
ID: 132050902