Emerging therapies for the treatment of osteoporosis

Abstract

Osteoporosis is a chronic disease of the osseous system characterized by decreased bone strength and increased fracture risk. It is due to an imbalance in the dynamic ongoing processes of bone formation and bone resorption. Currently available osteoporosis therapies like bisphosphonates, selective estrogen receptor modulators (SERMs), and denosumab are anti-resorptive agents. Parathyroid hormone analogs like teriparatide are the only anabolic agents currently approved for osteoporosis treatment. The side-effects and limited efficacy of the presently available therapies has encouraged extensive research into the pathophysiology of the disease and newer drug targets for its treatment. The novel anti-resorptive agents being developed are newer SERMs, osteoprotegerin, c-src (cellular-sarcoma) kinase inhibitors, αVβ3 integrin antagonists, cathepsin K inhibitors, chloride channel inhibitors, and nitrates. Upcoming anabolic agents include calcilytics, antibodies against sclerostin and Dickkopf-1, statins, matrix extracellular phosphoglycoprotein fragments activin inhibitiors, and endo-cannabinoid agonists. Many of these new drugs are still in development. This article provides an insight into the emerging drugs for the treatment of osteoporosis.

Elevated serum osteoprotegerin levels in women: friend or foe?

“…16 Due to its anti-osteoclastogenesis effect, OPG has been studied and employed as a treatment for bone loss and osteoporosis. 3 It has been shown that the production of OPG can be stimulated in vitro by agents used against osteoporosis, such as 17β-estradiol, 3 raloxifene, 17 bisphosphonates 18 and mechanical stimuli. 19 In vivo studies also demonstrate that parenteral administration of recombinant OPG in healthy rodents results in a marked increase in bone mass and volume, and a decrease in the number and activity of osteoclasts, in addition to completely preventing bone loss induced by ovariectomy, although without adverse effects.…”

“…2 Therefore, there is need for greater understanding of bone biology to devise new strategies and therapies to treat osteoporosis. 3 Knowledge of the molecular mechanisms involved in the bone remodeling process is of paramount importance.…”

“…Next, a monoclonal antibody against RANKL (Denosumab) was developed, which proved to be highly effective in the reduction of bone fractures, and is currently one of the best therapeutic options for the treatment of osteoporosis. 3,4 New treatments for osteoporosis are, therefore, based on a better understanding of bone biology and the development of new, highly specific compounds, with fewer side effects. This review aims to evaluate the role of osteoprotegerin on bone tissue and other local targets for better understanding of the physiology of this protein.…”

Restoration of osteogenic differentiation by overexpression of cannabinoid receptor 2 in bone marrow mesenchymal stem cells isolated from osteoporotic patients

“…According to the World Health Organization, patients diagnosed with OP demonstrate significantly decreased bone mineral density (BMD) compared with that of sex-matched adults (1). Osteoporotic fractures occur so frequently as to affect 1 in 3 women and 1 in 5 men over 50 years of age (2). The increasing number of osteoporotic fractures not only places a heavy economic burden on the medical care system but also leads to chronic pain, deformity, depression, disability and even death of patients.…”

Osteocyte culture in microfluidic devices

“…[3][4][5][6] Due to limited understandings on the underlying mechanisms, current osteoporosis therapies cannot address this imbalance properly. 7 Recent studies suggest a coordinating role of osteocytes (bone cells embedded in bone matrix) in bone metabolism by regulating activities of osteoblasts (bone formation cell) and osteoclasts (bone desorption cell), [8][9][10][11][12] which may shed new treatment strategies for osteoporosis. However, current studies of osteocytes are based on conventional cell culture, 13,14 which cannot recapitulate local in vivo microenvironments, due to its incapability to control the spatial/temporal distribution of cells and biomolecules.…”