%0 Journal Article
%T The Combination Therapy with Zoledronic Acid and Propranolol Improves the Trabecular Microarchitecture and Mechanical Property in an Rat Model of Postmenopausal Osteoporosis
%A Deepak Kumar Khajuria
%A Rema Razdan
%A D. Roy Mahapatra
%J Journal of Osteoporosis
%D 2014
%I Hindawi Publishing Corporation
%R 10.1155/2014/586431
%X We conducted the present study to investigate the therapeutic effects of propranolol (PRO), alone and in combination with the antiresorptive agent ZOL, in a rat model of postmenopausal osteoporosis. Female Wistar rats were OVX or sham-operated at 3 months of age. Twelve weeks after surgery, rats were randomized into six groups: (1) sham + vehicle, (2) OVX + vehicle, (3) OVX + ZOL (100£¿¦Ìg/kg, i.v. single dose), (4) OVX + ZOL (50£¿¦Ìg/kg, i.v. single dose), (5) OVX + PRO (0.1£¿mg/kg, s.c. 5 days per week), and (6) OVX + ZOL (50£¿¦Ìg/kg, i.v. single dose) + PRO (0.1£¿mg/kg, s.c. 5 days per week) for 12 weeks. At the end of treatment study, various bone parameters were evaluated. With respect to improvement in the mechanical strength of the lumbar spine and the femoral mid-shaft, the combination treatment of ZOL and PRO was more effective than each drug administered as a monotherapy. Moreover, combination therapy using ZOL and PRO preserved the trabecular microarchitecture better than single-drug therapy using ZOL or PRO in OVX rats. These data suggest that combination therapy with ZOL plus PRO represents a potentially useful therapeutic option for patients with osteoporosis. 1. Introduction Osteoporosis is a degenerative disease characterized by low bone mass and microarchitectural deterioration of bone tissue, leading to enhanced bone fragility and increased fracture risk. Osteoporosis is considered an important public health issue increasing rapidly in the elderly population [1, 2]. The fractures caused by osteoporosis have clinical and public health impacts, as they are often associated with increased morbidity, mortality, and enormous healthcare expenditure [1]. For those already affected by osteoporosis, timely diagnosis of bone loss, assessment of fracture risk, and selection of optimal treatment at appropriate stages of the disease are very important for effective management of osteoporosis. Zoledronic acid (ZOL) is a third generation nitrogen-containing bisphosphonate that has been shown to significantly reduce the risk of fractures in patients who receive the once-yearly dosing regimen for the treatment of postmenopausal osteoporosis [3]. ZOL interferes with osteoclastic activity by inhibiting osteoclast formation and osteoclast bone resorptive activities and by inducing osteoclast apoptotic cell death. On osteoclast stimulation of bone resorption, the bisphosphonate is released and internalized by the osteoclasts, interfering with osteoclast formation, function, and survival [4¨C6]. Moreover, the results obtained from several histologic and
%U http://www.hindawi.com/journals/jos/2014/586431/