Khajuria Deepak Kumar, Razdan Rema, Mahapatra D Roy, Bhat M R
Department of Pharmacology, Al-Ameen College of Pharmacy, Bangalore, 560027, India,
J Orthop Sci. 2013 Sep;18(5):832-42. doi: 10.1007/s00776-013-0433-y. Epub 2013 Jul 9.
Currently β-adrenergic receptor blockers are considered to be potential drugs under investigation for preventive or therapeutic effect in osteoporosis. However, there is no published data showing the comparative study of β-blockers with well accepted agents for the treatment of osteoporosis. To address this question, we compared the effects of propranolol with well accepted treatments like zoledronic acid and alfacalcidol in an animal model of postmenopausal osteoporosis.
Five days after ovariectomy, 36 ovariectomized (OVX) rats were divided into 6 equal groups, randomized to treatments zoledronic acid (100 μg/kg, intravenous single dose); alfacalcidol (0.5 μg/kg, oral gauge daily); propranolol (0.1 mg/kg, subcutaneously 5 days per week) for 12 weeks. Untreated OVX and sham OVX were used as controls. At the end of treatment serum calcium and alkaline phosphatase were assayed. Femurs were removed and tested for bone density, bone porosity, bone mechanical properties and trabecular micro-architecture.
Propranolol showed a significant decrease in alkaline phosphatase levels and bone porosity in comparison to OVX control. Moreover, propranolol significantly improved bone density, bone mechanical properties and inhibited the deterioration of trabecular microarchitecture when compared with OVX control. The osteoprotective effect of propranolol was comparable with zoledronic acid and alfacalcidol.
Based on this comparative study, the results strongly suggest that propranolol can be a candidate therapeutic drug for the management of postmenopausal osteoporosis.
目前,β-肾上腺素能受体阻滞剂被认为是正在研究的对骨质疏松症具有预防或治疗作用的潜在药物。然而,尚无已发表的数据显示β-阻滞剂与公认的骨质疏松症治疗药物的比较研究。为解决这个问题,我们在绝经后骨质疏松症动物模型中比较了普萘洛尔与唑来膦酸和阿法骨化醇等公认治疗方法的效果。
卵巢切除术后5天,将36只去卵巢(OVX)大鼠分为6组,每组数量相等,随机接受以下治疗:唑来膦酸(100μg/kg,静脉注射单剂量);阿法骨化醇(0.5μg/kg,每日口服);普萘洛尔(0.1mg/kg,每周皮下注射5天),持续12周。未治疗的OVX大鼠和假手术OVX大鼠用作对照。治疗结束时,测定血清钙和碱性磷酸酶。取出股骨,检测骨密度、骨孔隙率、骨力学性能和小梁微结构。
与OVX对照组相比,普萘洛尔显著降低了碱性磷酸酶水平和骨孔隙率。此外,与OVX对照组相比,普萘洛尔显著提高了骨密度、骨力学性能,并抑制了小梁微结构的恶化。普萘洛尔的骨保护作用与唑来膦酸和阿法骨化醇相当。
基于这项比较研究,结果强烈表明普萘洛尔可以作为治疗绝经后骨质疏松症的候选治疗药物。