Emerging Anabolic Therapies for Osteoporosis
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Osteoporosis is defined as low bone mineral density (BMD) associated with fragility fractures. It is characterized by unbalanced bone remodeling activity leading to bone loss and eventually fractures. Osteoporosis-related fractures are one of the leading causes of significant morbidity and disability in elderly and increase burden to patients, society, and healthcare systems. The goal of osteoporosis treatment is to prevent fractures. Present antiresorptive agents are effective, but they have relative lack of efficacy on nonvertebral fractures because their effects are restricted to remodeling-based activities. Also, there is a great need for additional and reasonable anabolic agents in situations of severe osteoporosis and extensive bone loss. The two main bone anabolic pathways are parathyroid hormone (PTH) signaling and canonical wingless-int (Wnt)/β-catenin signaling. These pathways stimulate bone formation through increasing the activation frequency or direct activation of bone modeling or a combination of both. Especially, the discovery of the Wnt signaling pathway and its activity in bone tissue has led to the development of novel anabolic agents that can enhance Wnt signaling in skeletal cells. This review aims at providing an overview of the currently available anabolic agents and an insight into promising investigational anabolic agents for the treatment of osteoporosis.
Abstract
Osteoporosis is defined as low bone mineral density (BMD) associated with fragility fractures. It is characterized by unbalanced bone remodeling activity leading to bone loss and eventually fractures. Osteoporosis-related fractures are one of the leading causes of significant morbidity and disability in elderly and increase burden to patients, society, and healthcare systems. The goal of osteoporosis treatment is to prevent fractures. Present antiresorptive agents are effective, but they have relative lack of efficacy on nonvertebral fractures because their effects are restricted to remodeling-based activities. Also, there is a great need for additional and reasonable anabolic agents in situations of severe osteoporosis and extensive bone loss. The two main bone anabolic pathways are parathyroid hormone (PTH) signaling and canonical wingless-int (Wnt)/β-catenin signaling. These pathways stimulate bone formation through increasing the activation frequency or direct activation of bone modeling or a combination of both. Especially, the discovery of the Wnt signaling pathway and its activity in bone tissue has led to the development of novel anabolic agents that can enhance Wnt signaling in skeletal cells. This review aims at providing an overview of the currently available anabolic agents and an insight into promising investigational anabolic agents for the treatment of osteoporosis.
참고문헌 (50)
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