Effect of insulin-like growth factor-1 (IGF-1) plus alendronate on bone density during puberty in IGF-1-deficient MIDI mice.
Insulin-like growth factor-1 (IGF-1) increases both bone formation and bone resorption processes. To test the hypothesis that treatment with an antiresorber along with IGF-1, during the pubertal growth phase, would be more effective than IGF-1 alone to increase peak bone mass, we used an IGF-1 MIDI mouse model, which exhibits a >60% reduction in circulating IGF-1 levels. We first determined an optimal IGF-1 delivery by evaluating IGF-1 administration (2 mg/kg body weight/day) by either a single daily injection, three daily injections, or by continuous delivery via a minipump during puberty. Of the three regimens, the three daily IGF-1 injections and IGF-1 through a minipump produced a significant increase in total body bone mineral density (BMD) (6.0% and 4.4%, respectively) and in femoral BMD (4.3% and 6.2%, respectively) compared with the control group. Single subcutaneous (s.c.) administration did not increase BMD. We chose IGF-1 administration three times daily for testing the combined effects of IGF-1 and alendronate (100 microg/kg per day). The treatment of IGF-1 + alendronate for a period of 2 weeks increased total body BMD at 1 week and 3 weeks after treatment (21.1% and 20.5%, respectively) and femoral BMD by 29% at 3 weeks after treatment. These increases were significantly greater than those produced by IGF-1 alone. IGF-1, but not alendronate, increased bone length. IGF-1 and/or alendronate increased both periosteal and endosteal circumference. Combined treatment caused a greater increase in the total body bone mineral content (BMC) and periosteal circumference compared with individual treatment with IGF-1 or alendronate. Our data demonstrate that: (1) inhibition of bone turnover during puberty increases net bone density; and (2) combined treatment with IGF-1 and alendronate is more effective than IGF-1 or alendronate alone in increasing peak bone mass in an IGF-1-deficient MIDI mouse model.
Stabnov
L
L
Musculoskeletal Disease Center, Jerry L. Pettis Veterans Administration Medical Center, Loma Linda, CA 92357, USA.
Kasukawa
Y
Y
Guo
R
R
Amaar
Y
Y
Wergedal
J E
JE
Baylink
D J
DJ
Mohan
S
S
D019386:Alendronate / Q000494:pharmacology*; D000818:Animals; D015519:Bone Density / Q000187:drug effects* / Q000502:physiology; D004357:Drug Synergism; D005260:Female; D007334:Insulin-Like Growth Factor I / Q000008:administration & dosage* / Q000172:deficiency* / Q000235:genetics; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D012741:Sexual Maturation / Q000187:drug effects* / Q000502:physiology
D007334:Insulin-Like Growth Factor I; D019386:Alendronate