Pereira F A, Mattar R, Facincani I, Defino H L A, Ramalho L N Z, Jorgetti V, Volpon J B, de Paula F J A
Departamento de Clínica Médica, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brasil.
Braz J Med Biol Res. 2012 Dec;45(12):1255-61. doi: 10.1590/s0100-879x2012007500143. Epub 2012 Sep 11.
Osteoporosis is a major complication of chronic cholestatic liver disease (CCLD). We evaluated the efficacy of using disodium pamidronate (1.0 mg/kg body weight) for the prevention (Pr) or treatment (Tr) of cholestasis-induced osteoporosis in male Wistar rats: sham-operated (Sham = 12); bile duct-ligated (Bi = 15); bile duct-ligated animals previously treated with pamidronate before and 1 month after surgery (Pr = 9); bile duct-ligated animals treated with pamidronate 1 month after surgery (Tr = 9). Rats were sacrificed 8 weeks after surgery. Immunohistochemical expression of IGF-I and GH receptor was determined in the proximal growth plate cartilage of the left tibia. Histomorphometric analysis was performed in the right tibia and the right femur was used for biomechanical analysis. Bone material volume over tissue volume (BV/TV) was significantly affected by CCLD (Sham = 18.1 ± 3.2 vs Bi = 10.6 ± 2.2%) and pamidronate successfully increased bone volume. However, pamidronate administered in a preventive regimen presented no additional benefit on bone volume compared to secondary treatment (BV/TV: Pr = 39.4 ± 12.0; Tr = 41.2 ± 12.7%). Moreover, the force on the momentum of fracture was significantly reduced in Pr rats (Sham = 116.6 ± 23.0; Bi = 94.6 ± 33.8; Pr = 82.9 ± 22.8; Tr = 92.5 ± 29.5 N; P < 0.05, Sham vs Pr). Thus, CCLD had a significant impact on bone histomorphometric parameters and pamidronate was highly effective in increasing bone mass in CCLD; however, preventive therapy with pamidronate has no advantage regarding bone fragility.
骨质疏松症是慢性胆汁淤积性肝病（CCLD）的主要并发症。我们评估了使用帕米膦酸二钠（1.0mg/kg体重）预防（Pr）或治疗（Tr）雄性Wistar大鼠胆汁淤积性骨质疏松症的疗效：假手术组（Sham = 12只）；胆管结扎组（Bi = 15只）；术前及术后1个月用帕米膦酸二钠治疗的胆管结扎动物（Pr = 9只）；术后1个月用帕米膦酸二钠治疗的胆管结扎动物（Tr = 9只）。术后8周处死大鼠。测定左胫骨近端生长板软骨中IGF-I和GH受体的免疫组化表达。对右胫骨进行组织形态计量学分析，右股骨用于生物力学分析。骨组织体积与组织总体积之比（BV/TV）受CCLD显著影响（假手术组=18.1±3.2%，胆管结扎组=10.6±2.2%），帕米膦酸二钠成功增加了骨体积。然而，与二次治疗相比，预防性给药方案的帕米膦酸二钠对骨体积没有额外益处（BV/TV：预防组=39.4±12.0；治疗组=41.2±12.7%）。此外，预防性给药组大鼠骨折瞬间的力显著降低（假手术组=116.6±23.0；胆管结扎组=94.6±33.8；预防组=82.9±22.8；治疗组=92.5±29.5N；P<0.05，假手术组与预防组相比）。因此，CCLD对骨组织形态计量学参数有显著影响，帕米膦酸二钠在增加CCLD大鼠骨量方面非常有效；然而，帕米膦酸二钠的预防性治疗在骨脆性方面没有优势。
