A review of denosumab for the treatment of osteoporosis

Miyazaki, Tsuyoshi; Tokimura, Fumiaki; Tanaka, Sakae

doi:10.2147/ppa.s46192

Cited by 58 publications

(44 citation statements)

References 84 publications

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“…Denosumab is currently used to treat osteoporosis and is a highly effective treatment for osteoporosis [85]. Inhibitors of SOST and DKK1 have been developed and seem to be promising drugs for the treatment of osteoporosis [86].…”

Section: Gwas Related To Osteoporosis and Osteoporotic Fracturesmentioning

confidence: 99%

Recent genetic discoveries in osteoporosis, sarcopenia and obesity [Review]

Urano

Inoue

2015

Endocr J

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Abstract. Osteoporosis is a skeletal disorder characterized by low bone mineral density (BMD) and an increased susceptibility to fractures. Evidence from genetic studies indicates that BMD, a complex quantitative trait with a normal distribution, is genetically controlled. Genome-wide association studies (GWAS) as well as studies using candidate gene approaches have identified single-nucleotide polymorphisms (SNPs) that are associated with BMD, osteoporosis and osteoporotic fractures. These SNPs have been mapped close to or within genes including those encoding WNT/β-catenin signaling proteins. Understanding the genetics of osteoporosis will help to identify novel candidates for diagnostic and therapeutic targets. Genetic factors are also important for the development of sarcopenia, which is characterized by a loss of lean body mass, and obesity, which is characterized by high fat mass. Hence, in this review, we discuss the genetic factors, identified by genetic studies, which regulate the body components related to osteoporosis, sarcopenia, and obesity.

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Section: Gwas Related To Osteoporosis and Osteoporotic Fracturesmentioning

confidence: 99%

Recent genetic discoveries in osteoporosis, sarcopenia and obesity [Review]

Urano

Inoue

2015

Endocr J

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“…However, in patients with massive renal dysfunction, denosumab administration increases the risk of hypocalcemia. Denosumab binds to a specific loop structure on the RANKL molecule and inhibits its interaction with its receptor, RANK [32]. When labeled with radioactivity, denosumab was detected in the lymph nodes and spleen after subcutaneous administration, indicating positive RANKL binding of the drug within those tissues.…”

Section: Biological Antibody Therapy For Bone Diseasementioning

confidence: 99%

“…TNF-α is produced primarily by activated macrophages and induces osteoclast formation via activated phosphorylation of P38, JNK, and AP-1. This cytokine likely plays a key role in RA pathogenesis [11,32,33]. Infliximab is a chimeric monoclonal IgG1 antibody against TNF-α [34].…”

Section: Biological Antibody Therapy For Bone Diseasementioning

confidence: 99%

Effect of Macrophage Colony-Stimulating Factor Receptor c-Fms Antibody on Lipopolysaccharide-Induced Pathological Osteoclastogenesis and Bone Resorption

Kimura

Kitaura

Ishida

et al. 2015

Interface Oral Health Science 2014

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Lipopolysaccharide (LPS) is a major component of Gram-negative bacteria cell walls and is a well-known potent inducer of inflammation and pathogens of inflammatory bone loss. Formation of osteoclasts is highly dependent on the presence of macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor kappa-B ligand (RANKL). Recent reports indicate that biological preparations, including anti-RANKL antibody and anti-tumor necrosis factor-α antibody, positively influence rheumatoid arthritis and osteoporosis. In this study, we aimed to investigate whether the M-CSF receptor c-Fms antibody would inhibit the formation of osteoclasts. C57BL6/J mice were injected with either LPS, LPS and anti-c-Fms antibody, anti-c-Fms antibody, or PBS into the supracalvariae. Animals were sacrificed and calvariae fixation and demineralization were performed. Histological sections of calvariae were stained for tartrate-resistant acid phosphatase (TRAP). In mice administered with both LPS and the anti-cFms antibody, osteoclast numbers were lower than those in mice administered with LPS alone. Moreover, levels of TRACP-5b, a bone resorption marker in mice serum, were lower in mice administered with both LPS and the anti-c-Fms antibody than in mice administered with LPS alone. These results suggest that M-CSF and its receptor are potential therapeutic targets in LPS-induced osteoclastogenesis, and that the anti-c-Fms antibody might be useful for inhibition of inflammation-induced bone erosion. In this study, we describe and discuss the effect the anti-c-Fms antibody has on pathological osteoclastogenesis and bone resorption.

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“…Denosumab does not have the potential for autoimmunization against the vital regulatory proteins and is characterized by a longer half-life, which permits less frequent dosing [41]. Each of these attributes makes denosumab a more attractive therapeutic agent than other forms of Osteoprogtegerin [42]. Denosumab significantly reduce the risk of Skeletal Related Events (SREs) compared with zoledronic acid.…”

Section: Denosumab Versus Bisphosphonatementioning

confidence: 99%

Could Denosumab Support Bone Integrity in Sickle Cell Disease

2015

J Hematol Thromb

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Sickle cell anaemia is a congenital disease characterized by painful vaso-occlusive crises. It is associated with vitamin D deficiency, osteoporosis and recurrent attacks of micro-infarctions lead to bone osteonecrosis. The most common sites of osteonecrosis in sickle cell disease are the femoral and humeral heads which could lead to severe pain and extensive physical disability. Denosumab is a new human monoclonal antibody product; it is a receptor activator of nuclear factor kappa B ligand RANKL. That decreases osteoclastic bone restoration. It is Food and Drug Administration FDA approved for osteoporosis for women with high risk of fracture; and it is also being used for the treatment and prevention of bone loss in patients undergoing hormone ablation therapy for breast and prostate cancer. Denosumab is not restricted for sickle cell disease patients within its approved indications. It has less nephrotoxicity effect than the bisphosphonates which is a big advantage for sickle cell patients. It also used as an adjuvant agent to reduce metastatic bone pain in solid tumors. The extension of Denosumab use for sickle cell patients' osteoporosis and osteonecrosis deserve a randomized multi central trail aiming to improve bone integrity and possible reduction of the devastating pain in sickle cell disease patients.

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A review of denosumab for the treatment of osteoporosis

Cited by 58 publications

References 84 publications

Recent genetic discoveries in osteoporosis, sarcopenia and obesity [Review]

Recent genetic discoveries in osteoporosis, sarcopenia and obesity [Review]

Effect of Macrophage Colony-Stimulating Factor Receptor c-Fms Antibody on Lipopolysaccharide-Induced Pathological Osteoclastogenesis and Bone Resorption

Could Denosumab Support Bone Integrity in Sickle Cell Disease

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