Four-month treatment with GLP-2 significantly increases hip BMD: a randomized, placebo-controlled, dose-ranging study in postmenopausal women with low BMD

TY - JOUR

T1 - Four-month treatment with GLP-2 significantly increases hip BMD: a randomized, placebo-controlled, dose-ranging study in postmenopausal women with low BMD

AU - Henriksen, Dennis B

AU - Alexandersen, Peter

AU - Hartmann, Bolette

AU - Adrian, Charlotte L

AU - Byrjalsen, Inger

AU - Bone, Henry G

AU - Holst, Jens J

AU - Christiansen, Claus

N1 - Keywords: Aged; Bone Density; Bone Resorption; Circadian Rhythm; Demography; Dose-Response Relationship, Drug; Female; Femur Neck; Glucagon-Like Peptide 2; Hip; Humans; Injections, Subcutaneous; Osteogenesis; Placebos; Postmenopause; Spine; Time Factors; Treatment Outcome

PY - 2009

Y1 - 2009

N2 - We have previously shown that repeated dosing of glucagon-like peptide-2 (GLP-2) at 10 p.m. in postmenopausal women for 14 days results in a dose-dependent decrease in the nocturnal bone resorption, as assessed by s-CTX. In contrast, bone formation, as assessed by serum osteocalcin, appeared to be unaffected by treatment with exogenous GLP-2, at least over 14 days. The present study extends the observation period to four months. The study was a double-blind placebo-controlled dose-ranging trial comparing three different doses of GLP-2 (0.4 mg, 1.6 mg and 3.2 mg GLP-2, administered nightly) against a saline control injection. We examined safety and tolerability, and the effects on biochemical markers of bone turnover and the effect on bone mineral density. Injection of 0.4 mg, 1.6 mg and 3.2 mg GLP-2 resulted in similar reduction in the nocturnal rise of s-CTX, at Treatment Day 120 the mean difference to placebo was approximately -150%*h at AUC(0-10H) (P<0.01). Osteocalcin levels were unaffected in the 10-hour period after injection indicating that injections of 0.4 mg, 1.6 mg and 3.2 mg GLP-2 do not exert any acute stimulatory or inhibitory effect on bone formation. Treatment with GLP-2 resulted in a significant dose-dependent increase in total hip BMD over the course of the study that for the 3.2 mg GLP-2 group reached 1.1% (P=0.007) from baseline. The overall rates of adverse events in the 4 treatment groups were similar and there were no signs of tachyphylaxis or antibodies against GLP-2. The results indicate that GLP-2 produces a substantial decrease in bone resorption without suppression of bone formation thereby changing the bone remodeling balance in favor of bone formation, particularly at the hip.

AB - We have previously shown that repeated dosing of glucagon-like peptide-2 (GLP-2) at 10 p.m. in postmenopausal women for 14 days results in a dose-dependent decrease in the nocturnal bone resorption, as assessed by s-CTX. In contrast, bone formation, as assessed by serum osteocalcin, appeared to be unaffected by treatment with exogenous GLP-2, at least over 14 days. The present study extends the observation period to four months. The study was a double-blind placebo-controlled dose-ranging trial comparing three different doses of GLP-2 (0.4 mg, 1.6 mg and 3.2 mg GLP-2, administered nightly) against a saline control injection. We examined safety and tolerability, and the effects on biochemical markers of bone turnover and the effect on bone mineral density. Injection of 0.4 mg, 1.6 mg and 3.2 mg GLP-2 resulted in similar reduction in the nocturnal rise of s-CTX, at Treatment Day 120 the mean difference to placebo was approximately -150%*h at AUC(0-10H) (P<0.01). Osteocalcin levels were unaffected in the 10-hour period after injection indicating that injections of 0.4 mg, 1.6 mg and 3.2 mg GLP-2 do not exert any acute stimulatory or inhibitory effect on bone formation. Treatment with GLP-2 resulted in a significant dose-dependent increase in total hip BMD over the course of the study that for the 3.2 mg GLP-2 group reached 1.1% (P=0.007) from baseline. The overall rates of adverse events in the 4 treatment groups were similar and there were no signs of tachyphylaxis or antibodies against GLP-2. The results indicate that GLP-2 produces a substantial decrease in bone resorption without suppression of bone formation thereby changing the bone remodeling balance in favor of bone formation, particularly at the hip.

U2 - 10.1016/j.bone.2009.07.008

DO - 10.1016/j.bone.2009.07.008

M3 - Journal article

C2 - 19631303

SN - 8756-3282

VL - 45

SP - 833

EP - 842

JO - Bone

JF - Bone

IS - 5

ER -