Aminohydroxybutane bisphosphonate inhibits bone loss due to immobilization in rats.
The purpose of this study was to document the effects of aminobutane bisphosphonate (AHBuP) on bone remodeling during immobilization in rats. Male Sprague-Dawley rats underwent unilateral sciatic neurectomy after receiving two daily subcutaneous injections of 0, 0.01, 0.10, or 1.0 mg P per kg AHBuP. Rats were sacrificed at 24 h or 10 or 20 days postimmobilization. Femora were ashed and tibiae were prepared for histomorphometric analysis. AHBuP was effective in inhibiting bone loss due to immobilization in a dose-dependent manner. The percentage loss of femoral ash weight due to immobilization decreased in a dose-dependent manner. In vehicle-treated rats, there was a significant decrease in trabecular bone volume (TBV) in the immobilized tibiae compared to the normal tibiae; in AHBuP-treated rats there was a dose-dependent increase in TBV both in the immobilized and control tibiae. The osteoid surface extent was decreased in AHBuP-treated rats in a dose-dependent manner. The mineral apposition rate was altered only in the intact leg of rats treated with 0.1 and 1.0 mg P AHBuP per kg compared to vehicle treated. Osteoclast number per mm was reduced by AHBuP treatment. In conclusion, aminohydroxybutane bisphosphonate effectively prevented the bone loss due to immobilization in this system.
Thompson
D D
DD
Department of Bone Biology/Osteoporosis Research, Merck Sharp & Dohme Research Laboratories, West Point, PA 19486.
Seedor
J G
JG
Weinreb
M
M
Rosini
S
S
Rodan
G A
GA
D019386:Alendronate; D000818:Animals; D015519:Bone Density / Q000502:physiology; D001851:Bone Diseases, Metabolic / Q000209:etiology / Q000517:prevention & control*; D003714:Denervation; D004164:Diphosphonates / Q000627:therapeutic use*; D007103:Immobilization / Q000009:adverse effects*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012584:Sciatic Nerve / Q000502:physiology
D004164:Diphosphonates; D019386:Alendronate