J Bone Miner Metab (2004) 22:335–340 DOI 10.1007/s00774-003-0491-x © Springer-Verlag 2004 Effect of etidronate on three-dimensional trabecular structure in ovariectomized or sciatic neurectomized rats Akifumi Nishida 1 , Masako Ito 1 , Masataka Uetani 1 , Tatsuo Nakayama 2 , and Tomoyuki Tanaka 2 1 Division of Radiological Science, Department of Radiology and Radiation Biology, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan 2 Sumitomo Pharmaceuticals Research Division, Osaka, Japan osteopenic models of estrogen deficiency and immobili- zation, respectively. Although bone loss always accom- panies trabecular deterioration, the degree or fashion of the deterioration may vary according to the osteopenic model. As both OVX and NX induce acceleration of bone resorption [1–6], the bisphosphonate, etidronate (EHDP) is expected to restore bone loss in these two conditions. Because the mechanism of bone loss is dif- ferent between OVX and NX [5], the effect of EHDP is presumed to vary between them. The purpose of this study was to evaluate the effect of EHDP on the tree- dimensional (3D) trabecular structure in the two differ- ent osteopenic models, OVX and NX rats. Materials and methods Animals Seven-week-old female Lewis rats were purchased from Charles River Japan (Yokohama, Japan) and accli- mated under standard laboratory conditions at 23  2°C and 50  10% humidity. Rats were maintained in ster- ilized cages, fed standard rodent chow containing 1.25% Ca and 1.06% phosphate (CE-2; CLEA Japan, Tokyo, Japan), and allowed free access to tap water. Rats were allowed to acclimate for 1 week before the experiment. Experimental design OVX animals A total of 29 female Lewis rats (8 weeks old) received ovariectomy (n = 19) or sham operation (OVX-sham; n = 10). Under pentobarbital anesthesia, rats were bilat- erally ovariectomized. The success of the ovariectomy was confirmed by inspecting atrophy of the uterus. Ovariectomized rats were further divided into groups, receiving either vehicle (OVX-control; n = 9) or EHDP (OVX-EHDP; n = 10). Abstract The purpose of this study was to evaluate the effect of etidronate (EHDP) on three-dimensional (3D) trabecular structure in ovariectomized (OVX) and sciatic neurectomized (NX) rats. Eight-week-old female Lewis rats received ovariec- tomy (n = 19) or sham operation (OVX-sham; n = 10). OVX rats received either vehicle (OVX-control; n = 9) or EHDP (OVX-EHDP; n = 10). Eight-week-old female Lewis rats received NX (n = 20) or sham operation (NX-sham; n = 10). NX rats received either vehicle (NX-control; n = 10) or EHDP (NX-EHDP; n = 10). EHDP at 5 mg/kg or vehicle was subcutaneously injected 5 days a week. The treatment was initiated 2 weeks after surgery and was continued for 2 weeks. At 12 weeks of age, the rats were killed, and we scanned the proximal metaphysis of the tibia; this was done using micro- CT; (μ CT20; SCANCO Medical). The recovery of structural parameters was not complete in NX rats compared to OVX rats. The 3D micro-CT images showed that the subcortical spongiosa, which was preserved in OVX rats, had marked loss in NX rats. Furthermore, these trabeculae were not restored after the EHDP treatment. In conclusion, the mechanical driving of the control of trabecular structure is inactive in NX, and EHDP treatment for 2 weeks does not restore this condition. Key words micro-CT · three-dimensional (3D) · ovariec- tomy · immobilization · etidronate Introduction Both sex hormone and mechanical loading play an im- portant role in the bone remodeling process. Ovariecto- mized (OVX) and sciatic neurectomized (NX) rats are Offprint requests to: A. Nishida (e-mail: d300039c@stcc.nagasaki-u.ac.jp) Received: March 31, 2003 / Accepted: November 20, 2003