Abstract
Osteoporosis is a metabolic skeletal disease characterized by an imbalance between osteoclast-mediated bone resorption and osteoblast-mediated bone formation. We examined the beneficial effect of shock waves (SW) alone or in combination with raloxifene (RAL) on bone loss in ovariectomized rats (OVX). Sixteen weeks after surgery, OVX were treated for five weeks with SW at the antero-lateral side of the right hind leg, one session weekly, at 3 Hz (EFD of 0.33 mJ/mm2), or with RAL (5 mg/kg/die, per os) or with SW+RAL. Sera, femurs, tibiae and vertebrae were sampled for following biochemical and histological analysis. SW, alone or combined with RAL, prevented femur weight reduction and the deterioration of trabecular microarchitecture both in femur and vertebrae. All treatments increased Speed of Sound (SoS) values, improving bone mineral density, altered by OVX. Serum parameters involved in bone remodeling (alkaline phosphatase, receptor activator of nuclear factor kappa-B ligand, osteoprotegerin) and osteoblast proliferation (PTH), altered by ovariectomy, were restored by SW and RAL alone or in combination. In tibiae, SW+RAL significantly reduced cathepsin k and TNF-α levels, indicating the inhibition of osteoclast activity, while all treatments significantly increased runt-related transcription factor 2 and bone morphogenetic-2 expression, suggesting an increase in osteoblastogenic activity. Finally, in bone marrow from tibiae, SW or RAL reduced PPARγ and adiponectin transcription, indicating a shift of mesenchymal cells toward osteoblastogenesis, without showing a synergistic effect. Our data indicate SW therapy, alone and in combination with raloxifene, as an innovative strategy to limit the hypoestrogenic bone loss, restoring the balance between bone formation and resorption.
Highlights
Osteoporosis is a metabolic skeletal disease characterized by low bone mass, deterioration of bone micro-architecture and increased fracture risk [1]
In the present study we show the beneficial effect of shock waves (SW) therapy, alone or in combination with raloxifene, inducing bone formation and reducing bone resorption impaired by OVX
Our hypothesis regarding the benefits of SW treatment in osteoporosis was suggested by previous data demonstrating that a single SW application could be effective increasing trabecular bone volume and reducing bone loss [21], especially when it was combined with antiresorptive alendronate therapy [23]
Summary
Osteoporosis is a metabolic skeletal disease characterized by low bone mass, deterioration of bone micro-architecture and increased fracture risk [1]. The prominent prevalence of osteoporosis in Europe (approximately 21% of women aged 50–84 years) and increased mortality rate in patients with osteoporotic fractures represent a clinical emergency [2, 3]. Raloxifene, a selective estrogen receptor modulator (SERM), has been approved for the prevention and treatment of postmenopausal osteoporosis, especially because of its capability to prevent or reduce vertebral fractures [5]. The osteoporosis progression is due to an imbalance between osteoclast-mediated bone resorption and osteoblast-mediated bone formation. The recovery of this balance represents the rationale underlying the two more recent two anti-osteoporotic strategies: the inhibition of bone resorption and turnover, and the stimulation of bone formation [7, 8]. Two cathepsin k inhibitors, odanacatib and ONO5334, have been recently used in clinical trials [9, 10]
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