Osteoporosis therapies and their mechanisms of action (Review)

Abstract

Osteoporosis is a common disease that affects millions of patients worldwide and is most common in menopausal women. The main characteristics of osteoporosis are low bone density and increased risk of fractures due to deterioration of the bone architecture. Osteoporosis is a chronic disease that is difficult to treat; thus, investigations into novel effective therapeutic methods are required. A number of studies have focused on determining the most effective treatment options for this disease. There are several treatment options for osteoporosis that differ depending on the characteristics of the disease, and these include both well-established and newly developed drugs. The present review focuses on the various drugs available for osteoporosis, the associated mechanisms of action and the methods of administration.

Keywords: bone formation; bone remodeling; bone resorption; fracture; menopause; osteoblast; osteoclast; osteoporosis treatment.

Figure 1

Pharmacological action sites for osteoporosis. 1. Pre-osteoclast: Estrogen and SERMs. 2. Osteoclast: Calcitonin. 3. Bone resorption site: Cathepsin K inhibitor and bisphosphonates. 4. Osteoblast: Strontium ranelate, PTH and PTHrP analogues, and anti-sclerostin antibody. 5. Osteoclast and osteoblast: Denosumab. ER, estrogen receptor; SERM, selective estrogen receptor modulator; CT, calcitonin receptor; RANK, receptor activator of nuclear factor-κB; RANKL, receptor activator of nuclear factor-κB ligand; CaSR, calcium sensing receptor; LRP5/6, lipoprotein receptor-related protein 5 and 6; PTH, parathyroid hormone; PTHrP, PTH-related protein; OPG, osteoprotegerin.

Figure 2

Schematic diagram of mutant RANKL and inhibitory effect against RANKL during osteoclastogenesis. RANK, receptor activator of nuclear factor-κB; RANKL, receptor activator of nuclear factor-κB ligand; LGR4, leucine rich repeat containing G protein-coupled receptor 4; mt, mutant; wt, wild-type; NFATc1, nuclear factor of activated T-cells cytoplasmic 1.