Osteoclastogenesis inhibitory factor/osteoprotegerin ameliorates the decrease in both bone mineral density and bone strength in immobilized rats.
Rat models of immobilization-induced osteopenia are characterized by uncoupling of bone metabolism, i.e., increased bone resorption and decreased bone formation in trabecular bone. Using such a rat model, the efficacy of osteoclastogenesis inhibitory factor (OCIF)/osteoprotegerin, a novel secreted protein that inhibits osteoclastogenesis, in reducing bone loss was investigated. Male Fischer rats were neurectomized and injected intramuscularly with either OCIF (0.2, 1.0, or 5.0 mg/kg body weight) or vehicle once daily for 7 days. On the eighth day after sciatic neurectomy, significant bone loss was observed in the vehicle-injected rats. OCIF ameliorated the decrease in bone mineral density (BMD) of both the proximal and distal femur in a dose-dependent manner. OCIF also ameliorated the decrease in bone strength of the femoral neck at the highest dose. A high correlation (r = 0.805) was detected between the BMD of the distal femur and the bone strength of the femoral neck. When OCIF was administered intermittently to the immobilized rats twice weekly (on days 1 and 4) after immobilization, it also ameliorated the decrease in BMD of the distal femur. These results suggest that OCIF has therapeutic potential for the treatment of immobilization-induced osteopenia.
Mochizuki
Shin-ichi
S
Research Institute of Life Science, Snow Brand Milk Products, Tochigi, Japan.
Fujise
Nobuaki
N
Higashio
Kanji
K
Tsuda
Eisuke
E
D000818:Animals; D001835:Body Weight; D015519:Bone Density / Q000187:drug effects*; D001862:Bone Resorption / Q000517:prevention & control*; D004305:Dose-Response Relationship, Drug; D005269:Femur / Q000187:drug effects; D006023:Glycoproteins / Q000008:administration & dosage / Q000627:therapeutic use*; D007273:Injections, Intramuscular; D008297:Male; D053244:Osteoprotegerin; D051381:Rats; D011916:Rats, Inbred F344; D018160:Receptors, Cytoplasmic and Nuclear / Q000008:administration & dosage / Q000627:therapeutic use*; D018124:Receptors, Tumor Necrosis Factor; D012149:Restraint, Physical; D012584:Sciatic Nerve / Q000502:physiology
D006023:Glycoproteins; D053244:Osteoprotegerin; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; C506032:Tnfrsf11b protein, rat