Prophylactic Effects of Propranolol Versus the Standard Therapy on a New Model of Disuse Osteoporosis in Rats

Abstract

Disuse by bed rest, limb immobilization, or space flight causes rapid bone loss by arresting bone formation and accelerating bone resorption. Propranolol (a non-selective β-adrenergic antagonist) has been shown to improve bone properties by increasing bone formation and decreasing bone resorption in an ovariectomy-induced rat model. However, no studies have yet compared the osteoprotective properties of propranolol with well-accepted therapeutic interventions for the treatment and prevention of immobilization/disuse osteoporosis. To clarify this, we investigated the effects of propranolol compared with zoledronic acid and alfacalcidol in a new animal model of immobilization/disuse osteoporosis. Three-month-old male Wistar rats were divided into five groups with six animals in each group: (1) immobilized (IMM) control; (2) normal control; (3) IMM + zoledronic acid (50 μg/kg, intravenous single dose); (4) IMM + alfacalcidol (0.5 μg/kg, per oral daily); (5) IMM + propranolol (0.1 mg/kg, subcutaneously 5 days/week) for 10 weeks. In groups 1 and 3–5, the right hindlimb was immobilized. At the end of treatment, the femurs were removed and tested for bone porosity, bone mechanical properties, and cortical microarchitecture. Treatment with propranolol induced greater reductions in the bone porosity of the right femur and improved the mechanical properties of the femoral mid-shaft femur in comparison to the IMM control. Moreover, treatment with propranolol also improved the microarchitecture of cortical bones when compared with the IMM control, as indicated by scanning electron microscopy. The anti-osteoporotic property of propranolol was comparable with zoledronic acid and alfacalcidol. This study shows that the bone resorption induced by immobilization/disuse in rats can be suppressed by treatment with propranolol.

Effect of combined treatment with zoledronic acid and propranolol on mechanical strength in an rat model of disuse osteoporosis

“…Disuse (unloading) osteoporosis occurs in patients with spinal cord injuries, patients confined to prolonged bed rest, and astronauts exposed to microgravity during space flight. 2 Microgravity induced osteoporosis poses a major threat to the astronaut's health. Microgravity leads to the unloading of the skeleton especially weight bearing bones.…”

“…The immobilization procedure proposed was effective in producing long-term disuse in the hind-limbs of rats and is a good alternative to the traditional methods of immobilization. 2 Zoledronic acid (ZOL) is a third generation nitrogen containing bisphosphonate that binds to hydroxyapatite with the highest affinity and inhibits osteoclasts with the highest potency of all licensed bisphosphonates. 4,5 Therefore, ZOL needs only to be injected once annually in patients, while still efficiently inhibiting osteoclastic activity and thereby reducing the risk of fracture.…”

“…1 Disuse (unloading) is one of the important causes of osteoporosis. 2 Mechanical loading is essential for the normal functioning of bone tissue. Immobilization results in imbalance of bone metabolism followed by rapid bone loss and impairment of bone mechanical function.…”

Sensitive and Rapid RP-HPLC Quantification of Zoledronic Acid in a Hydroxyapatite-based Nanoparticles

“…ZOL chemically is [1-hydroxy-2-(1H-imidazol-1-yl)ethane-1,1-diyl]bis(phosphonic acid) hydrate ( fig. 1) [1][2][3] . Among bisphosphonates, ZOL has a higher binding affinity for the bone HA.…”

“…Bisphosphonates are one of the most important bone resorption inhibitor drugs, which are used extensively in the management of skeletal diseases like osteoporosis, malignant hypercalcemia, bone metastasis and Paget's disease [1][2][3] . Bisphosphonates are the endogenous arbitrator of bone mineralization, capable of being adsorbed onto hydroxyapatite (HA) crystals in bone, hence providing bone stabilization and hindering its dissolution.…”