Osteoporosis New drugs Review
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Osteoporosis New drugs Review
Denosumab is a breakthrough fully human monoclonal antibody approved by both the FDA and EMA in 2010. It had been fast tracked by FDA for treatment and prevention of postmenopausal osteoporosis, treatment and prevention of bone loss in hormone treated prostate and breast cancer patients. The FDA advisory committee (August 13, 2009) to review the safety and efficacy had recommend approval for treatment of high risk bone loss postmenopausal osteoporosis in women and hormone ablation treated men with prostate cancer, with black box warnings for serious side effects and under REMS program. Denosumab may have peak sales in the range of $5 billion within 5 years after approval in US, Europe, Japan and other major markets. New additional indications may follow and it may cross sales of $1 billion in 2012 due to unmet medical need from patients and healthcare providers. Clinical data published and in public domain indicates a superior safety and efficacy profile. FDA has asked for modifications and details of the REMS for treatment of osteoporosis. Denosumab (Prolia, Amgen) after FDA Review was approved under REMS on 1 June 2010. For prevention of osteoporosis and cancer indications, FDA has asked for new studies to show that there was no incidence of increased cancer. Amgen has submitted the BLA for prevention of bone loss in cancer patients on 14 June 2010. FDA had granted it the priority review status and approved the use for reducing fractures and other bone problems in cancer patients on 18 November, 2010. The European Committee for Human Medicinal Products CHMP recommended its approval in December 2009. It was approved by the EMA on 28 may 2010 and was launched there in the 3Q2010. Data presented at the ASCO and ESMO 2010 meetings has been added. The UK cost control agency NICE has recommended the clinical use of Prolia in osteoporosis. Data presented at EULAR showed increased bone density in women taking denosumab for 6 years and significantly reduced risk of fractures in elderly patients. The drug is approved in Switzerland for the prevention of bone loss in breast and prostate cancer patients undergoing hormone therapy besides osteoporosis. Sales of the drug were $33 million in 2010 and peak potential sales of over $ 5 billion per year.
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Denosumab (Prolia, Amgen) FDA Review & Approval - Krishan Maggon

Denosumab (Prolia, Amgen) FDA Review & Approval - Krishan Maggon | Osteoporosis New drugs Review | Scoop.it
Denosumab is a breakthrough fully human monoclonal antibody approved by both the FDA and EMA in 2010. It had been fast...
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Clinical and pathological results of denosumab treatment for giant cell tumors of bone: Prospective study of 14 cases

Clinical and pathological results of denosumab treatment for giant cell tumors of bone: Prospective study of 14 cases | Osteoporosis New drugs Review | Scoop.it
Conclusion Denosumab has been shown to be a successful drug in treatment of GCT. Denosumab can be used as neoadjuvant for all recurrent lesions, grade II lesions with high surgical risk, grade III lesions, and metastatic cases of GCT.
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Acta Orthopaedica et Traumatologica Turcica Available online 24 October 2016 In Press, Corrected Proof
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Hand bone loss in early rheumatoid arthritis during a methotrexate-based treat-to-target strategy with or without adalimumab-a substudy of the opti... - PubMed - NCBI

Hand bone loss in early rheumatoid arthritis during a methotrexate-based treat-to-target strategy with or without adalimumab-a substudy of the opti... - PubMed - NCBI | Osteoporosis New drugs Review | Scoop.it
Clin Rheumatol. 2016 Dec 5. [Epub ahead of print]
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National Bone Health Alliance | Strong Bones America

National Bone Health Alliance | Strong Bones America | Osteoporosis New drugs Review | Scoop.it
NBHA supports health care professionals by supporting bone health, sharing knowledge and improving bone disease diagnoses and treatments.
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Dysregulation of macrophage polarization is associated with the metastatic process in osteosarcoma

Dysregulation of macrophage polarization is associated with the metastatic process in osteosarcoma | Osteoporosis New drugs Review | Scoop.it
Dysregulation of macrophage polarization is associated with the metastatic process in osteosarcoma
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Denosumab bested risedronate in bone mineral density in osteoporosis

Denosumab bested risedronate in bone mineral density in osteoporosis | Osteoporosis New drugs Review | Scoop.it
Patients with osteoporosis showed greater improvement in key bone mineral density parameters after treatment with denosumab than with risedronate, according to data presented at the American College of Rheumatology Annual Meeting, here.

Kenneth S. Saag, MD, of the University of Alabama at Birmingham, and colleagues, conducted a phase 3, randomized, double-blind, active-controlled study to assess whether the drug was safe and effective in comparison with risedronate in patients with glucocorticoid-induced osteoporosis.
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References: Saag KS, et al. Abstract #2L. Presented at: American College of Rheumatology Annual Meeting; Nov. 11-16, 2016; Washington.
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Home : Bone biology and disease

Home : Bone biology and disease | Osteoporosis New drugs Review | Scoop.it
Bone biology and disease is a collection of articles from Nature Reviews Endocrinology and Nature Reviews Rheumatology on the latest advances in the bone field.
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Vitamin D receptor expression in human bone tissue and dose-dependent activation in resorbing osteoclasts

Vitamin D receptor expression in human bone tissue and dose-dependent activation in resorbing osteoclasts | Osteoporosis New drugs Review | Scoop.it
Bone Research, Published online: 11 October 2016; | doi:10.1038/boneres.2016.30
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Biological Treatment Approaches for Degenerative Disc Disease: A Review of Clinical Trials and Future Directions

Biological Treatment Approaches for Degenerative Disc Disease: A Review of Clinical Trials and Future Directions | Osteoporosis New drugs Review | Scoop.it
<p>Biologic-based treatment strategies for musculoskeletal diseases have gained traction over the past 20 years as alternatives to invasive, costly, and complicated surgical interventions.
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Imaging in osteoporosis in rheumatic diseases

Imaging in osteoporosis in rheumatic diseases | Osteoporosis New drugs Review | Scoop.it
Abstract Osteoporosis is a common comorbidity of all major rheumatic diseases, and manifests itself both systemically and locally. Systemic bone loss manifests because of several factors, primarily inflammation, immobility, and commonly used medical treatment for rheumatic diseases. Local bone loss manifests as periarticular demineralization and bone erosion due to local release of inflammatory agents and cytokines, which promote bone resorption. All these factors contribute to the phenomenon of arthritis-associated osteoporosis. This review summarized the currently available and used methods that play a role in the diagnosis and monitoring of osteoporosis and in the detection of osteoporotic fractures. Keywords
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Best Practice & Research Clinical Rheumatology Available online 20 October 2016 In Press, Corrected Proof

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Blood Cancer Journal - Overexpression of RANKL by invariant NKT cells enriched in the bone marrow of patients with multiple myeloma

Blood Cancer Journal - Overexpression of RANKL by invariant NKT cells enriched in the bone marrow of patients with multiple myeloma | Osteoporosis New drugs Review | Scoop.it
Blood Cancer Journal is a peer-reviewed, open access online journal publishing pre-clinical and clinical work in the field of hematology with ramifications into translational biology research down to new therapies
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Laboratory Investigation - CD68/macrosialin: not just a histochemical marker

Laboratory Investigation - CD68/macrosialin: not just a histochemical marker | Osteoporosis New drugs Review | Scoop.it

Laboratory Investigation 


Abstract CD68 is a heavily glycosylated glycoprotein that is highly expressed in macrophages and other mononuclear phagocytes. Traditionally, CD68 is exploited as a valuable cytochemical marker to immunostain monocyte/macrophages in the histochemical analysis of inflamed tissues, tumor tissues, and other immunohistopathological applications. CD68 alone or in combination with other cell markers of tumor-associated macrophages showed a good predictive value as a prognostic marker of survival in cancer patients. Lowression of CD68 was found in the lymphoid cells, non-hematopoietic cells (fibroblasts, endothelial cells, etc), and tumor cells. Cell-specific CD68 expression and differentiated expression levels are determined by the complex interplay between transcription factors, regulatory transcriptional elements, and epigenetic factors. Human CD68 and its mouse ortholog macrosialin belong to the family of LAMP proteins located in the lysosomal membrane and share many structural similarities such as the presence of the LAMP-like domain. Except for a second LAMP-like domain present in LAMPs, CD68/microsialin has a highly glycosylated mucin-like domain involved in ligand binding. CD68 has been shown to bind oxLDL, phosphatidylserine, apoptotic cells and serve as a receptor for malaria sporozoite in liver infection. CD68 is mainly located in the endosomal/lysosomal compartment but can rapidly shuttle to the cell surface. However, the role of CD68 as a scavenger receptor remains to be confirmed. It seems that CD68 is not involved in binding bacterial/viral pathogens, innate, inflammatory or humoral immune responses, although it may potentially be involved in antigen processing/presentation. CD68 could be functionally important in osteoclasts since its deletion leads to reduced bone resorption capacity. The role of CD68 in atherosclerosis is contradictory.

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Laboratory Investigation advance online publication 21 November 2016; doi: 10.1038/labinvest.2016.116 
 CD68/macrosialin: not just a histochemical marker 

 Dimitry A Chistiakov, Murry C Killingsworth, Veronika A Myasoedova, Alexander N Orekhov and Yuri V Bobryshev
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Effects of ospemifene on bone parameters including clinical biomarkers in postmenopausal women. - PubMed - NCBI

Effects of ospemifene on bone parameters including clinical biomarkers in postmenopausal women. - PubMed - NCBI | Osteoporosis New drugs Review | Scoop.it
Menopause. 2016 Jun;23(6):638-44. doi: 10.1097/GME.0000000000000619.

Abstract OBJECTIVE: Ospemifene is an estrogen-receptor agonist/antagonist (also known as a selective estrogen-receptor modulator) that is FDA approved for the treatment of moderate-to-severe dyspareunia, a symptom of vulvovaginal atrophy, due to menopause. Preclinical and clinical data suggest that ospemifene may also have an effect on bone health in postmenopausal women. METHODS: Relevant articles, including cellular and preclinical studies and clinical trials written in English pertaining to ospemifene and bone health, were identified from a database search of PubMed (from its inception to June 2015) and summarized in this comprehensive review. 
RESULTS: In vitro data suggest that ospemifene may mediate a positive effect on bone through osteoblasts. Ospemifene effectively reduced bone loss and resorption in ovariectomized rats, with activity comparable to estradiol and raloxifene. Clinical data from three phase 1 or 2 clinical trials (2 placebo- and 1 raloxifene-controlled) found ospemifene 60 mg/d to have a positive effect on the biochemical markers for bone turnover in healthy, postmenopausal women with significant improvements relative to placebo and comparable to raloxifene. 
CONCLUSIONS: Ospemifene 60 mg/d may have a protective effect on the bone health of women being treated for dyspareunia. The initial clinical data for ospemifene follows a trend similar to raloxifene and bazedoxifene, suggesting that ospemifene may have bone-protective effects in postmenopausal women. However, additional rigorous clinical trials are necessary to confirm any positive effects ospemifene may have on vertebral fractures and bone mineral density in healthy and osteoporotic women.
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Menopause. 2016 Jun;23(6):638-44. doi: 10.1097/GME.0000000000000619. 

Effects of ospemifene on bone parameters including clinical biomarkers in postmenopausal women. 

Constantine GD1, Kagan R, Miller PD.
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Efficacy and safety of denosumab versus zoledronic acid in delaying skeletal-related events in patients with gastrointestinal cancer, pancreas-biliary system cancer, and other rare cancers

Efficacy and safety of denosumab versus zoledronic acid in delaying skeletal-related events in patients with gastrointestinal cancer, pancreas-biliary system cancer, and other rare cancers | Osteoporosis New drugs Review | Scoop.it
From the perspective of the efficacy and safety of denosumab for delaying the time to SREs, denosumab should be used to prevent SREs in patients with bone metastases from gastrointestinal cancer, pancreas-biliary system cancer, and other rare cancers.
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Artesunate suppresses RANKL-induced osteoclastogenesis through inhibition of PLCγ1-Ca2+–NFATc1 signaling pathway and prevents ovariectomy-induced bone loss

Artesunate suppresses RANKL-induced osteoclastogenesis through inhibition of PLCγ1-Ca2+–NFATc1 signaling pathway and prevents ovariectomy-induced bone loss | Osteoporosis New drugs Review | Scoop.it
Artesunate was able to reverse the bone loss in an ovariectomized mouse model in vivo accompanied with reduced RANKL, RANKL/OPG, and TRAP-5b levels. This study indicates that artesunate inhibits RANKL-induced osteoclastogenesis and bone loss by inhibiting PLCγ1-Ca2+-calcineurin-NFATc1 pathway. Collectively, our data suggest that artesunate is a potential treatment option against RANKL-mediated osteolytic bone disease.
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Treatment - National Osteoporosis Foundation

Treatment - National Osteoporosis Foundation | Osteoporosis New drugs Review | Scoop.it
Although there is no cure for osteoporosis, there are steps you can take to prevent, slow or stop its progress. In some cases, you may even be able to improve bone density and reverse the disorder to some degree. Getting enough calcium and vitamin D are essential to bone health. There are also medications available... Read more »
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Hyaluronic Acid Gel-Based Scaffolds as Potential Carrier for Growth Factors: An In Vitro Bioassay on Its Osteogenic Potential

Hyaluronic Acid Gel-Based Scaffolds as Potential Carrier for Growth Factors: An In Vitro Bioassay on Its Osteogenic Potential | Osteoporosis New drugs Review | Scoop.it
Hyaluronic acid (HA) has been utilized for a variety of regenerative medical procedures due to its widespread presence in connective tissue and perceived biocompatibility.
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Towards better hip replacements | Newsroom - McGill University

Towards better hip replacements | Newsroom - McGill University | Osteoporosis New drugs Review | Scoop.it
Creating a Better #3DPrinted Hip Replacement #3DPrinting https://t.co/ji3F4oeLhO
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Three dimensional electrospun PCL/PLA blend nanofibrous scaffolds with significantly improved stem cells osteogenic differentiation and cranial bone formation

Three dimensional electrospun PCL/PLA blend nanofibrous scaffolds with significantly improved stem cells osteogenic differentiation and cranial bone formation | Osteoporosis New drugs Review | Scoop.it
Publication date: January 2017
Source:Biomaterials, Volume 115
Author(s): Qingqing Yao, Jaqueline G.L. Cosme, Tao Xu, Jacob M. Miszuk, Paulo H.S.
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FASEB > Resources for the Public > Scientific Contests > BioArt > Past Winners > 2012 BioArt Winners

FASEB > Resources for the Public > Scientific Contests > BioArt > Past Winners > 2012 BioArt Winners | Osteoporosis New drugs Review | Scoop.it
https://t.co/DKYs6kFljH #hippocampus #neurons #synthesis #stemcells https://t.co/lqtiCOfov6
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Bone Healing and Hormonal Bioassay in Patients with Long-Bone Fractures and Concomitant Head Injury.

Bone Healing and Hormonal Bioassay in Patients with Long-Bone Fractures and Concomitant Head Injury. | Osteoporosis New drugs Review | Scoop.it
Abstract OBJECTIVE: The aim of this study is to investigate healing of fractures in patients with concomitant head injuries and to measure blood hormone levels to elucidate the mec..
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Regeneron Discovery on Cause of Rare Genetic Bone Disease Detailed in Science Translational Medicine Publication (NASDAQ:REGN)

Regeneron Discovery on Cause of Rare Genetic Bone Disease Detailed in Science Translational Medicine Publication (NASDAQ:REGN) | Osteoporosis New drugs Review | Scoop.it

Tarrytown, New York (September 2, 2015) - Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) today announced that Science Translational Medicine has published a paper describing the discovery and preclinical validation of a key biologic mechanism that drives the pathophysiology of the rare genetic disorder Fibrodysplasia Ossificans Progressiva (FOP). FOP is a progressive, severely disabling and ultimately fatal disease in which muscles, ligaments, tendons and other connective tissues are transformed into bone. 

 FOP is caused by mutations in ACVR1, a gene that encodes for the ACVR1 receptor protein. When a set of ligands (proteins that help regulate cell behavior) known as Bone Morphogenetic Proteins (BMPs) bind to the ACVR1 receptor, a cascade of intracellular events (referred to as "signaling") is induced. This signaling is critical in controlling the formation of the skeleton and ensuring normal bone growth. 

 Regeneron scientists found that another ligand, Activin-A, in combination with the ACVR1 protein, normally "turns off" signaling by the BMPs, and is thus believed to play a role in regulating the volume of bone growth. However, they also discovered that in the presence of the ACVR1 mutation, Activin-A instead "turns on" BMP signaling, driving the abnormal bone growth that is characteristic of FOP.
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People diagnosed with FOP are gradually debilitated and immobilized as the soft tissue throughout their body transforms into bone. Attempts to remove this extra bone through surgery only result in additional episodes of abnormal bone growth. There are approximately 800 confirmed cases of FOP in the world, including around 200 in the United States, and the current lack of effective treatments underscores the need for scientific exploration that may aid in the development of new therapies.

To extend their findings in vivo, Regeneron scientists used the Company's proprietary VelociGene® technology to develop a genetically humanized and novel mouse model of FOP in which the hypothesized molecular pathophysiology of disease was confirmed. The team also used Regeneron's VelocImmune®, a platform that enables the rapid generation of fully human monoclonal antibodies, to generate and validate a potential therapeutic antibody chosen for its ability to potently and selectively block Activin-A. Regeneron continues active preclinical testing on this antibody.
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Bone microstructure in men assessed by HR-pQCT: Associations with risk factors and differences between men with normal, low, and osteoporosis-range areal BMD

Bone microstructure in men assessed by HR-pQCT: Associations with risk factors and differences between men with normal, low, and osteoporosis-range areal BMD | Osteoporosis New drugs Review | Scoop.it
 • Bone microstructure of the ultra-distal radius and tibia was analyzed by HR-pQCT. 
• The subjects consisted of 78 healthy male volunteers ranging from 50 to 84 years. 
• Cortical bone was more impaired with age compared with trabecular bone. 
• Cortical porosity was increased with age, particularly at the ultra-distal tibia.
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Bone Reports Volume 5, December 2016, Pages 312–319
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Identification of suitable reference gene and biomarkers of serum miRNAs for osteoporosis

Identification of suitable reference gene and biomarkers of serum miRNAs for osteoporosis | Osteoporosis New drugs Review | Scoop.it
Our objective was to identify suitable reference genes in serum miRNA for normalization and screen potential new biomarkers for osteoporosis diagnosis by a systematic study.
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Olives and Bone: A Green Osteoporosis Prevention Option

Olives and Bone: A Green Osteoporosis Prevention Option | Osteoporosis New drugs Review | Scoop.it
Skeletal degeneration due to aging, also known as osteoporosis, is a major health problem worldwide. Certain dietary components confer protection to our skeletal system against osteoporosis.
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Effects of a Combination Therapy of Sclerostin Antibody III and Raloxifene on Bone Formation Markers in Ovariectomized Rats. - PubMed - NCBI

Effects of a Combination Therapy of Sclerostin Antibody III and Raloxifene on Bone Formation Markers in Ovariectomized Rats. - PubMed - NCBI | Osteoporosis New drugs Review | Scoop.it
J Coll Physicians Surg Pak. 2016 Jan;26(1):46-50. doi: 01.2016/JCPSP.4650. Research Support, Non-U.S. Gov't

Abstract OBJECTIVE: To determine the systemic effect of sclerostin monoclonal antibody (Scl-AbIII) administration on markers of bone formation and compare it with a combination of sclerostin antibody and raloxifene. STUDY DESIGN: Experimental study. PLACE AND DURATION OF STUDY: Medical College Animal House at King Khaled University Hospital, Riyadh, Saudi Arabia, from January to November 2014. METHODOLOGY: Forty-five female rats were divided into 5 groups equally; 1 control group and 4 groups of ovariectomized (OVX) rats: control OVX rats and OVX rats treated by Scl-AbIII, raloxifene or Scl-AbIII+raloxifene one month after ovariectomy, continued for 4 weeks. At the end of treatment, serum levels of Bone Specific Alkaline Phosphatase (BSAP), alkaline phosphatase, osteocalcin, Insulin-like Growth Factor-1 (IGF-1), Parathyroid Hormone (PTH), Ca2+ and phosphorus were measured. Uterus was weighed and body weight change was calculated. RESULTS: Scl-AbIII or raloxifene treatment produced significant increase of serum BSAP, osteocalcin, IGF-1, PTH and Ca2+ levels. Raloxifene, either alone or combined with Scl-AbIII attenuated the decrease in uterus wet weight, and the increase in body weight seen in OVX rats. Combination therapy of Scl-AbIII, and raloxifene produced significant increase of serum alkaline phosphatase, osteocalcin and IGF-1 levels than treatment with either Scl-AbIII or raloxifene alone. CONCLUSION: Combination therapy of Scl-AbIII and raloxifene is an attractive strategy to enhance bone formation and can offer better gain over treatment with either one of them alone. Confirmation of these preliminary observations must await careful long-term studies.
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J Coll Physicians Surg Pak. 2016 Jan;26(1):46-50. doi: 01.2016/JCPSP.4650. 
PMID: 26787031 DOI: 01.2016/JCPSP.4650 [PubMed - in process]

Effects of a Combination Therapy of Sclerostin Antibody III and Raloxifene on Bone Formation Markers in Ovariectomized Rats. Gad Allam HI.
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