Abstract
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 μg/kg, i.v. single dose), (4) OVX + ZOL (50 μg/kg, i.v. single dose), (5) OVX + PRO (0.1 mg/kg, s.c. 5 days per week), and (6) OVX + ZOL (50 μg/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.
Highlights
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
We asked whether single intravenous dose of Zoledronic acid (ZOL) would (1) inhibit bone loss and microarchitectural changes associated with estrogen deficiency in adult rats and (2) enhance anabolic effects of PRO
We clearly demonstrated that combination therapy using ZOL and PRO preserves the trabecular microarchitecture better than singledrug therapy using ZOL or PRO in OVX rats
Summary
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. 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. Rodrigues et al demonstrated that low doses of PRO suppress bone resorption by inhibiting receptor activator of nuclear factor kappa-B ligand (RANKL) mediated osteoclastogenesis as well as inflammatory markers without affecting haemodynamic parameters [24] This result is supported by a previous finding, which showed that propranolol stimulates osteoprotegerin (OPG) on its own in osteoblast cells [25]. Owing to the different mechanisms of action of ZOL and PRO, our hypothesis was that the combination of ZOL and PRO would facilitate greater improvements in bone properties than either intervention alone
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