Effect of etidronate on three-dimensional trabecular structure in ovariectomized or sciatic neurectomized rats

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 ovariectomy (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 5mg/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; ( 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.     

Effect of ethane-1-hydroxy-1,1-bisphosphonate (EHBP) on endochondral ossification lesions induced by a lethal oral dose of uranyl nitrate

A 350 mg/kg body weight (b.w.) oral dose of uranyl nitrate (UN) caused 100% mortality in mice three days after administration, due to resulting kidney lesions. Mortality decreased 50% after an oral (o) or subcutaneous (sc) dose of bisodic etidronate (EHBP). Given that bone is also a target organ for uranium (U) in acute intoxication, the aim of this work was to study the effect of exposure to a lethal oral dose of UN on endochondral ossification, and the latter's response to EHBP treatment. One hundred male Balb/c mice weighing 25 g were assigned to one of ten groups. Group I served as control. Group II received a lethal 350 mg/kg b.w. oral dose of UN by gavage. Groups III, IV, VII, and VIII received an equal dose of UN immediately followed by a single 500 mg/kg oral dose of EHBP in groups III and VII and a single 50 mg/kg subcutaneous dose of EHBP in groups IV and VIII. Groups V and IX only received a single 500 mg/kg oral dose of EHBP, and groups VI and X received a single 50 mg/kg subcutaneous dose of EHBP. The animals in groups II, III, IV, V, and VI were sacrificed 48 h after the onset of the experiment, whereas those in groups VII, VIII, IX, and X were killed at 14 days. Histologic and histomorphometric studies were performed on the femurs to determine growth cartilage width, bone volume, and metaphyseal bone activity. Our results showed that all growth cartilage and metaphyseal bone histomorphometric parameters were significantly lower in animals exposed to UN at 48 h than in controls. EHPB administration was found to prevent this condition at 48 h reaching similar values to those of controls. Although histomorphometric values did not reach control values at 14 days, they were higher than those of animals exposed to UN at 48 h not treated with EHBP. It is noteworthy that these values also decreased in animals only receiving EHBP at 14 days. Our results show that EHBP effectively ameliorates the adverse effects of a lethal dose of UN on endochondral ossification.     

Idiopathic calciphylaxis

A 68-year-old woman presented with a painful necrotic ulcer on her right calf and necrotic breakdown of a left below-knee amputation stump as a result of calciphylaxis. No cause could be identified and corrected. Treatment comprised wound care, substituting low molecular weight heparin for warfarin, hyperbaric oxygenation and etidronate disodium, none of which were helpful and major limb amputations were considered the best option for this patient.     

Etidronate disodium for treating hypercalcaemia of malignancy: a double blind, placebo-controlled study

The efficacy of intravenous etidronate disodium in controlling hypercalcaemia of malignancy was evaluated in a double blind, placebo-controlled study. Twenty patients with known malignant disease and hypercalcaemia were randomly assigned on a 2:1 basis to etidronate 7.5 mg kg-1 body weight or placebo for 3-5 days. All patients received 3000 ml saline and 40 mg furosemide per day. Eighteen patients completed the study. Eleven of twelve in the etidronate group reached normocalcaemia compared to two of six in the placebo group (P = 0.05). The etidronate group showed a greater decrease in serum calcium than the placebo group (P less than 0.02). The renal calcium excretion decreased significantly in the etidronate group, but not in the placebo group. A slight increase in serum creatinine was observed in the etidronate group compared to placebo on the first day of treatment. The difference however disappeared the following days. Intravenous etidronate treatment in combination with rehydration and furosemide constitutes a safe and efficient alternative in the treatment of hypercalcaemia of malignancy, although a first approach always should be rehydration.     

对雌性大鼠切除卵巢后骨质疏松症防治的探讨

目的探讨雌性大鼠切除卵巢后施以不同药物对骨转换率和骨丢失的影响。方法３５只６０周龄雌性ＳＤ大鼠分为假性切除卵巢、单纯切除卵巢、切除卵巢后分别给予雌二醇、氟化钠及羟乙膦酸钠５组。第１４周末处死，胫骨不脱钙切片行形态计量等比较。结果单纯切除卵巢后，小梁骨吸收和形成参数均显著增加（Ｐ＜０．０１），小梁骨体积百分比（ＴＢＶ％，８．６５±３．６２）显著减少（Ｐ＜０．０１），呈高转换率骨质疏松；给予雌二醇或羟乙膦酸钠则抑制骨吸收，降低骨转换率，ＴＢＶ％（分别为１８．５７±７．３１及１６．８２±７．９０）较单纯切除卵巢显著增加（均为Ｐ＜０．０１）；给予氟化钠，骨吸收和骨形成显著增多，骨转换率维持高水平，ＴＢＶ％（１３．２５±３．０３）较单纯切除卵巢增加（Ｐ＜０．０５），丢失也相对较多。结论雌二醇和羟乙膦酸钠可有效抑制骨吸收，降低因切除卵巢而增高的骨转换率，减少骨丢失。     

Effect of the Controlled Delivery of Chelating Agents on the Pulp Tissue Dissolution Ability of Fresh Sodium Hypochlorite Solutions

IntroductionThe purpose of this study was to evaluate pulp tissue dissolution ability of sodium hypochlorite (NaOCl) when mixed with tetrasodic etidronate (Na₄HEBP) and disodic ethylenediaminetetraacetate (Na₂EDTA) under controlled flow.MethodsBovine pulp tissue was extracted from the lower incisors of 10 bovine jaws. Pulp specimens were standardized in size (1 × 3 × 10 mm), blotted dry, and weighed (initial weight [T0]: mean (SD) = 31.98 (1.18) mg). Specimens from the same jaw were randomly assigned to 2 control (n = 3 each) and 4 experimental groups (n = 10 each): NC (negative control/distilled water), PC (positive control/6%NaOCl), G1 (3%NaOCl), G2 (3%NaOCl-17% Na₂EDTA), G3 (3%NaOCl-18% Na₄HEBP), and G4 (3%NaOCl-9% Na₄HEBP). Distilled water and NaOCl were provided using a delivery pump under a continuous controlled rate (1 mL/min). A second pump alternately delivered either Na₂EDTA or Na₄HEBP at the same rate with a 30-second programmed interval. Percentage of tissue weight loss was calculated at 2, 5, and 10 minutes (T2, T5, and T10) and compared among groups with analysis of variance. Free available chlorine and pH were controlled at T0 and T10.ResultsNo tissue remained in PC at T5. No dissolution occurred in NC. There were no significant differences in the percentage of weight loss among experimental groups at any point of time. Some remnant tissue was found in G3 (1.4% ± 2.4) and G4 (1.6% ± 2.3) at T10, whereas nothing was left in G1 and G2.ConclusionsThe controlled delivery of Na₂EDTA and Na₄HEBP did not alter tissue dissolution ability of NaOCl when fresh solutions were mixed in the root canal.