Abstract
Osteoporosis is a worldwide health problem with a high prevalence. Agents for the treatment of osteoporosis are classified as antiresorptives, anabolic agents and drugs with combined anabolic and anti-resorptive actions. Although many drugs with proven efficacy are available for the treatment of osteoporosis their effectiveness has been limited by side-effects, concurrent comorbidities, and inadequate long-term compliance. Additionally, conventional antiresorptives such as aminobisphosphonates profoundly suppress bone resorption and formation which might contribute to the pathogenesis of osteonecrosis of the jaw. Various novel antiresorptive agents are in development. This overview aims to discuss in brief some of the most promising novel treatments which include: bazedoxifene a new selective estrogen receptor modulator, denosumab, PTH rP (parathyroid hormone related protein), odanacatib and other bone anabolic agents such antibodies against sclerostin and dickkopf-1. Denosumab, a fully human monoclonal antibody to receptor activator of nuclear factor kappa B ligand (RANKL) an anti-resorptive agent with a low side effect profile has been proven efficacious. Bazedoxifene has also proven its efficacy. Odanacatib, an inhibitor of cathepsin K, which is an osteoclast enzyme required for resorption of bone matrix is under assessment as an anti-resorptive agent with no antianabolic effects and is showing promising results. Anabolic agents act by stimulating formation of new bone. Novel agents in development include: antibodies to sclerostin and dickkopf-1, proteins that target molecules involved in Wnt signaling, a pathway that regulates gene transcription of proteins that are important for osteoblast function; an antagonist to the calcium-sensing receptor; and an activin receptor fusion protein, which functions as an activin antagonist and has shown promise as an anabolic agent in early human trials. Sri Lanka Journal of Diabetes, Endocrinology and Metabolism 2012; 2 : 92-100 DOI: http://dx.doi.org/10.4038/sjdem.v2i2.4779
Highlights
Osteoporosis, the most common metabolic bone disease, is characterized by low bone mineral density (BMD) and microarchitectural deterioration of bone tissue leading to an increase in the susceptibility to fragility fractures
Concurrent treatment is not recommended it has been demonstrated that sequential treatment with antiresorptives after teriparatide or parathyroid hormone (PTH) prevents accelerated osteoclastic resorption of the new bone tissue built during teriparatide therapy, increases mineralization, and rapidly lowers cortical porosity; leading to further increases in BMD [15]
Bazedoxifene is a novel third-generation selective estrogen receptor modulator, a molecule developed to act as estrogen receptor agonists in some tissues and as estrogen receptor antagonists in others, such as breast and endometrium, in order to reduce the risk of breast and endometrial cancers that would be induced by hormone replacement therapy [17,18,19]
Summary
Osteoporosis, the most common metabolic bone disease, is characterized by low bone mineral density (BMD) and microarchitectural deterioration of bone tissue leading to an increase in the susceptibility to fragility fractures. Bone is a dynamic tissue, which has the ability to adapt its shape and size in response to mechanical loads through a phenomenon of remodeling. This process allows the skeleton to maintain mechanical integrity through constant osteoclastic resorption of damaged bone followed by osteoblast-mediated deposition and mineralization of new matrix. Even small increases in bone mass can substantially reduce the incidence of fracture. Antiresorptive drugs decrease bone resorption and reduce fractures by preserving skeletal microarchitecture. There are drugs that decouple the two processes, inhibiting bone resorption and stimulating bone formation (Table 1)
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