Iwamoto J, Takeda T, Katsumata T, Tanaka T, Ichimura S, Toyama Y
Department of Sports Medicine, Keio University School of Medicine, Tokyo, Japan.
Bone. 2002 Feb;30(2):360-7. doi: 10.1016/s8756-3282(01)00687-1.
The purpose of the present study was to determine whether etidronate treatment could prevent bone loss caused by orchidectomy (ORX) and unilateral sciatic neurectomy (NX) in adult male rats. Seventy-four male Wistar rats, aged 10 months, were randomly divided into eight groups: baseline controls (n = 10); age-matched sham-operated controls (AMC; n = 9); ORX (n = 9); NX (n = 10); ORX + NX (n = 9); ORX + etidronate treatment (ORX + E; n = 7); NX + E (n = 10); and ORX + NX + E (n = 10). Etidronate treatment (10 mg/kg per day subcutaneously) was initiated 2 weeks after surgery and was continued for 2 weeks. Four weeks after surgery, bone mineral density (BMD) of the proximal and middle tibia (PT and MT, respectively), distal and middle femur (DF and MF, respectively), and fourth lumbar vertebral body (LVB) was measured by dual-energy X-ray absorptiometry (Model DCS-600, Aloka, Tokyo, Japan). The mechanical properties of the MF and third LVB were measured by three-point bending and compression tests, respectively. Levels of urinary deoxypyridinoline (Dpd) and serum osteocalcin (Oc) were also measured by enzyme-linked immunosorbent assay. Four weeks of aging had no significant effects on BMD, bone mechanical properties, or bone markers. ORX significantly increased the levels of urinary Dpd and serum Oc, which resulted in significant decreases in BMD of the PT, MT, DF, MF, and fourth LVB, as well as the mechanical strength (maximum load) of the MF and third LVB. NX significantly increased levels of urinary Dpd and decreased levels of serum Oc, resulting in a significant decrease in BMD of the PT, DF, and fourth LVB. The ORX-induced decrease in BMD of the PT was more pronounced when combined with NX. Etidronate treatment for NX, ORX, and ORX + NX rats significantly decreased levels of urinary Dpd and serum Oc, resulting in complete prevention of loss of BMD and/or bone mechanical strength. The present study demonstrates the efficacy of etidronate treatment for prevention of bone loss caused by testosterone deficiency and immobilization in adult male rats.
本研究的目的是确定依替膦酸治疗是否能预防成年雄性大鼠因去势(ORX)和单侧坐骨神经切除术(NX)导致的骨质流失。74只10月龄雄性Wistar大鼠被随机分为八组:基线对照组(n = 10);年龄匹配的假手术对照组(AMC;n = 9);去势组(n = 9);神经切除组(n = 10);去势+神经切除组(n = 9);去势+依替膦酸治疗组(ORX + E;n = 7);神经切除+依替膦酸治疗组(NX + E;n = 10);以及去势+神经切除+依替膦酸治疗组(ORX + NX + E;n = 10)。手术后2周开始依替膦酸治疗(每天皮下注射10 mg/kg),持续2周。手术后4周,通过双能X线吸收法(型号DCS - 600,日本东京阿洛卡公司)测量胫骨近端和中段(分别为PT和MT)、股骨远端和中段(分别为DF和MF)以及第四腰椎椎体(LVB)的骨密度(BMD)。分别通过三点弯曲试验和压缩试验测量MF和第三腰椎椎体的力学性能。还通过酶联免疫吸附测定法测量尿脱氧吡啶啉(Dpd)水平和血清骨钙素(Oc)水平。四周的衰老对BMD、骨力学性能或骨标志物没有显著影响。去势显著增加了尿Dpd水平和血清Oc水平,导致PT、MT、DF、MF和第四腰椎椎体的BMD以及MF和第三腰椎椎体的力学强度(最大负荷)显著降低。神经切除显著增加了尿Dpd水平并降低了血清Oc水平,导致PT、DF和第四腰椎椎体的BMD显著降低。当与神经切除联合时,去势引起的PT的BMD降低更为明显。对神经切除组、去势组和去势+神经切除组大鼠进行依替膦酸治疗显著降低了尿Dpd水平和血清Oc水平,从而完全预防了BMD和/或骨力学强度的损失。本研究证明了依替膦酸治疗对预防成年雄性大鼠因睾酮缺乏和固定导致的骨质流失的有效性。