Osteoporosis New drugs Review
23.0K views | +31 today
Follow
 
Scooped by Krishan Maggon
onto Osteoporosis New drugs Review
Scoop.it!

Bone density and microarchitecture in hepatitis C and HIV-coinfected postmenopausal minority women

Bone density and microarchitecture in hepatitis C and HIV-coinfected postmenopausal minority women | Osteoporosis New drugs Review | Scoop.it
We found tha t HIV+/HCV+ women had 7–8% lower areal bone mineral densi ty (aBMD) by dual-energy x-ray absor p tiome try (DXA) a t the s pine, hi p, and radius ( p < 0.01) and 5–7% lower volume tric BM
more...
No comment yet.
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.
Curated by Krishan Maggon
Your new post is loading...
Your new post is loading...
Scooped by Krishan Maggon
Scoop.it!

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...
more...
No comment yet.
Scooped by Krishan Maggon
Scoop.it!

FDA Votes in Favor of Romosozumab Approval for Osteoporosis

FDA Votes in Favor of Romosozumab Approval for Osteoporosis | Osteoporosis New drugs Review | Scoop.it
The FDA Bone, Reproductive, and Urologic Drugs Advisory Committee voted in favor of approving romosozumab (EVENITY) for the treatment of postmenopausal women with osteoporosis at high risk for fracture.
more...
No comment yet.
Scooped by Krishan Maggon
Scoop.it!

Amgen And UCB Receive Positive Vote From FDA Advisory Committee In Favor Of Approval For EVENITY romosozumab

Amgen And UCB Receive Positive Vote From FDA Advisory Committee In Favor Of Approval For EVENITY romosozumab | Osteoporosis New drugs Review | Scoop.it

 Amgen (NASDAQ:AMGN) and UCB (Euronext Brussels: UCB) today announced strong support from the U.S. Food and Drug Administration (FDA) Bone, Reproductive and Urologic Drugs Advisory Committee (BRUDAC) for the approval of EVENITY™* (romosozumab) for the treatment of postmenopausal women with osteoporosis at high risk for fracture after reviewing safety and efficacy data from the pivotal Phase 3 studies. Eighteen of 19 members voted yes for approval. In their discussion, the Committee emphasized the need for post-marketing follow-up.

The EVENITY development program includes 19 clinical studies that enrolled approximately 14,000 patients.2 Notable Phase 3 studies include FRAME,3 a placebo-controlled study with 7,180 postmenopausal women with osteoporosis at risk for fracture; ARCH,4 an active comparator-controlled study with 4,093 postmenopausal women with osteoporosis and with prior history of fracture; and STRUCTURE,5 an active comparator-controlled study with 436 postmenopausal women with osteoporosis. The BRUDAC evaluated the FRAME and ARCH studies in its review of the clinical benefit:risk profile of EVENITY, including the cardiovascular safety finding seen in the ARCH study, for the potential to reduce the risk of fractures and increase bone mineral density (BMD) in postmenopausal women with osteoporosis.

Krishan Maggon 's insight:

About EVENITY™* (romosozumab)
EVENITY is an investigational bone-forming monoclonal antibody. It is designed to work by inhibiting the activity of sclerostin, which enables EVENITY to rapidly increase bone formation and reduce bone resorption simultaneously. The EVENITY development program includes 19 clinical studies that enrolled approximately 14,000 patients. EVENITY has been studied for its potential to reduce the risk of fractures in an extensive global Phase 3 program. This program included two large fracture trials comparing EVENITY to either placebo or active comparator in more than 11,000 postmenopausal women with osteoporosis. Amgen and UCB are co-developing EVENITY.

more...
No comment yet.
Scooped by Krishan Maggon
Scoop.it!

Stem cells regulate their fate by altering their stiffness

Stem cells regulate their fate by altering their stiffness | Osteoporosis New drugs Review | Scoop.it
In adults, mesenchymal stems cells (MSCs) are primarily found in bone marrow and they play a vital role in repair of damaged organs. The transformation of a single MSC into complex tissue like cartilage and bone starts with ...
more...
No comment yet.
Scooped by Krishan Maggon
Scoop.it!

Nucleic acids and analogs for bone regeneration

Nucleic acids and analogs for bone regeneration | Osteoporosis New drugs Review | Scoop.it
Abstract
With the incidence of different bone diseases increasing, effective therapies are needed that coordinate a combination of various technologies and biological materials. Bone tissue engineering has also been considered as a promising strategy to repair various bone defects. Therefore, different biological materials that can promote stem cell proliferation, migration, and osteoblastic differentiation to accelerate bone tissue regeneration and repair have also become the focus of research in multiple fields. Stem cell therapy, biomaterial scaffolds, and biological growth factors have shown potential for bone tissue engineering; however, off-target effects and cytotoxicity have limited their clinical use. The application of nucleic acids (deoxyribonucleic acid or ribonucleic acid) and nucleic acid analogs (peptide nucleic acids or locked nucleic acids), which are designed based on foreign genes or with special structures, can be taken up by target cells to exert different effects such as modulating protein expression, replacing a missing gene, or targeting specific gens or proteins. Due to some drawbacks, nucleic acids and nucleic acid analogs are combined with various delivery systems to exert enhanced effects, but current studies of these molecules have not yet satisfied clinical requirements. In-depth studies of nucleic acid or nucleic acid analog delivery systems have been performed, with a particular focus on bone tissue regeneration and repair. In this review, we mainly introduce delivery systems for nucleic acids and nucleic acid analogs and their applications in bone repair and regeneration. At the same time, the application of conventional scaffold materials for the delivery of nucleic acids and nucleic acid analogs is also discussed.
more...
No comment yet.
Scooped by Krishan Maggon
Scoop.it!

Efficacy of an orally active small-molecule inhibitor of RANKL in bone metastasis

Efficacy of an orally active small-molecule inhibitor of RANKL in bone metastasis | Osteoporosis New drugs Review | Scoop.it
Abstract
Bone is one of the preferred sites for the metastasis of malignant tumours, such as breast cancer, lung cancer and malignant melanoma. Tumour cells colonizing bone have the capacity to induce the expression of receptor activator of nuclear factor-κB ligand (RANKL), which promotes osteoclast differentiation and activation. Tumour-induced osteoclastic bone resorption leads to a vicious cycle between tumours and bone cells that fuels osteolytic tumour growth, causing bone pain and hypercalcaemia. Furthermore, RANKL contributes to bone metastasis by acting as a chemoattractant to bone for tumour cells that express its receptor, RANK. Thus inhibition of the RANKL–RANK pathway is a promising treatment for bone metastasis, and a human monoclonal anti-RANKL antibody, denosumab, has been used in the clinic. However, orally available drugs targeting RANKL must be developed to increase the therapeutic benefits to patients. Here we report the efficacy of the small-molecule RANKL inhibitor AS2676293 in treating bone metastasis using mouse models. Oral administration of AS2676293 markedly inhibited bone metastasis of human breast cancer cells MDA-MB-231-5a-D-Luc2 as well as tumour-induced osteolysis. AS2676293 suppressed RANKL-mediated tumour migration in the transwell assay and inhibited bone metastasis of the murine cell line B16F10, which is known not to trigger osteoclast activation. Based on the results from this study, RANKL inhibition with a small-molecule compound constitutes a promising therapeutic strategy for treating bone metastasis by inhibiting both osteoclastic bone resorption and tumour migration to bone.
more...
No comment yet.
Scooped by Krishan Maggon
Scoop.it!

GORAB scaffolds COPI at the trans -Golgi for efficient enzyme recycling and correct protein glycosylation

GORAB scaffolds COPI at the trans -Golgi for efficient enzyme recycling and correct protein glycosylation | Osteoporosis New drugs Review | Scoop.it
Here, we identify GORAB, the protein mutated in the skin and bone disorder gerodermia osteodysplastica, as a component of the COPI machinery. GORAB forms stable domains at the trans-Golgi that, via interactions with the COPI-binding protein Scyl1, promote COPI recruitment to these domains. Pathogenic GORAB mutations perturb Scyl1 binding or GORAB assembly into domains, indicating the importance of these interactions. Loss of GORAB causes impairment of COPI-mediated retrieval of trans-Golgi enzymes, resulting in a deficit in glycosylation of secretory cargo proteins. Our results therefore identify GORAB as a COPI scaffolding factor, and support the view that defective protein glycosylation is a major disease mechanism in gerodermia osteodysplastica.
more...
No comment yet.
Scooped by Krishan Maggon
Scoop.it!

Amgen and UCB's Evenity approved in Japan for osteoporosis | Pharmafile

Amgen and UCB's Evenity approved in Japan for osteoporosis | Pharmafile | Osteoporosis New drugs Review | Scoop.it
more...
No comment yet.
Scooped by Krishan Maggon
Scoop.it!

Researchers discover the signal that drives stem cells to form new bones | Hub

Researchers discover the signal that drives stem cells to form new bones | Hub | Osteoporosis New drugs Review | Scoop.it
The discovery is the first step in developing a stem cell therapy to help patients recover from bone fractures, spinal fusion, and osteoporosis...
more...
No comment yet.
Scooped by Krishan Maggon
Scoop.it!

Stem cell signal drives new bone building

Stem cell signal drives new bone building | Osteoporosis New drugs Review | Scoop.it
In experiments in rats and human cells, Johns Hopkins Medicine researchers say they have added to evidence that a cellular protein signal that drives both bone and fat formation in selected stem cells can be manipulated to ...
more...
No comment yet.
Scooped by Krishan Maggon
Scoop.it!

Epigenetics and Cartilage Regeneration | IntechOpen

Regenerative cartilage therapy has great potential for the treatment of debilitating diseases such as osteoarthritis and rheumatoid arthritis. Recent advances in the field of epigenetics have enabled us to understand more clearly the role of micro RNAs, DNA methylations and histone modification in...
more...
No comment yet.
Scooped by Krishan Maggon
Scoop.it!

Stem Cell Therapy in Osteonecrosis of the Femoral Head

Stem Cell Therapy in Osteonecrosis of the Femoral Head | Osteoporosis New drugs Review | Scoop.it

Hip Pelvis. 2018 Sep; 30(3): 135–137. Published online 2018 Sep 4. doi: 10.5371/hp.2018.30.3.135 PMCID: PMC6123505 PMID: 30202746 Stem Cell Therapy in Osteonecrosis of the Femoral Head CURRENT STATUS OF STEM CELL THERAPY IN OSTEONECROSIS OF THE FEMORAL HEAD Stem cell research began as a potential means of identifying new treatment options for intractable and lethal diseases. In the orthopaedic field, diseases in which current treatment methods are unsatisfactory, inefficient, or incapable of providing durable results are targets for stem cell therapy1,2). Osteonecrosis of the femoral head (ONFH) is a cause of premature total hip arthroplasty in young patients. In ONFH, osteocytes die from an obstruction to the blood supply, thus preventing dead tissue from repairing microcracks and leading to a gross collapse of femoral head structural integrity3). Stem cell therapy for ONFH–first suggested by Hernigou et al.4)–started with the premise that no existing treatments could regenerate dead bone. They added bone marrow aspirate concentrate (BMAC) after core decompression, and in a sense, BMAC injection represents a primitive form of stem cell therapy. However, bone marrow aspirate contains various cell types, of which a low proportion is stem cells, and thus is not considered a genuine stem cell therapy1). Several studies from other groups followed on the application of BMACs or culture-expanded mesenchymal stem cells (MSCs) to treat ONFH, and most reported a beneficial effect of the implantation of BMACs or culture-expanded MSCs5,6). Except for a few controlled studies, the majority of reported studies are, unfortunately, uncontrolled case series. Local implantation of BMAC to the core decompression tract was most commonly used, however, some recent studies used culture-expanded BMSCs. Scaffolding materials include fibrin glue, platelet rich plasma, β-tricalcium phosphate, autologous bone, and tantalum rod. While it is difficult to compare individual studies because of heterogeneous methods of application, BMAC or bone marrow MSC (BMSC) treatment seems to have reasonable, if not remarkable, effects in early stage (Ficat I or II) ONFH in terms of symptomatic relief and preventing progression of femoral head collapse1). A recent meta-analysis of stem cell therapy in ONFH revealed a very low complication rate (2.8%); these complications were all minor (hematoma, wound infection and pain at the site of bone marrow aspiration)7). Transformation of implanted cells is a potential serious complication in implantation of culture expanded MSC; however, to date no major cell-related complications were reported in stem cell implantation for ONFH. POINTS FOR CONSIDERATION AND POTENTIAL WAYS TO IMPROVE STEM CELL THERAPY IN ONFH Like any treatment modality, stem cell therapy requires an understanding of the underlying pathophysiology of the disease. It is imperative that clinicians who adopt these new strategies into their practice possess a good understanding of the natural course of targeted disease1). One surprising aspect of stem cell application in ONFH is that the fate of implanted cells was not characterized in any studies. While stem cells are applied with the expectation that these cells will: i) survive, ii) be taken up in the recipient area, and iii) differentiate into bone, it is not known whether these implanted cells will survive. Stem cell tracking studies in other organs reveal that injected or implanted stem cells usually exert paracrine effects, and then perish from the site. In the case of osteonecrosis, reduced vascularity of the implantation site would make the local environment even more hostile to the survival of stem cells. The less-than-satisfactory results of stem cell implantation in controlled studies may be explained by this understanding. It is expected that most implanted cells will undergo massive cell death in a short period, probably exerting some paracrine effect before they die. Therefore, if we wish to increase the survival capacity of implanted cells and ensure that they become osteoblasts within the implanted area, some measures to enhance the vascularity and osteogenic potential of the stem cells area are necessary. While the most commonly used stem cell is BMSC, adipose stem cells (ASCs) have the advantage of promoting angiogenesis. Our group had previously demonstrated that co-culture of a BMSC and ASC had a synergistic effect on angiogenesis and osteogenesis in vitro compared with either one of the cells alone. When these cells were implanted into bone defects of rats, enhanced bone formation was also observed8). Our group had also implanted BMSC and ASC together in the ONFH model of minipig, and demonstrated significantly enhanced bone formation, compared with an unimplanted control9). Another potential mechanism of enhancing angiogenesis and prolonging implanted cell survival is to concomitantly introduce angiogenic factors with the stem cells. Vascular endothelial growth factor (VEGF) can be impregnated into various scaffolds, and released in a controlled way to enhance angiogenesis. VEGF can be also transfected to ASCs, and the transfected cells can release VEGF for a period of time, before blood supply is established, aiding implanted cell survival. Our group has transfected the VEFG gene to ASCs using electroporation. When co-cultured with BMSCs, as little as 5% of ASC to BMSCs were effective in enhancing angiogenesis and osteogenesis in vivo and in vitro10). SUMMARY AND PERSPECTIVES In summary, there are a handful of reports that investigated applying stem cells as a treatment for ONFH; however, more than half of these studies used BMAC, which are not true stem cells. Furthermore, there is a very limited number of well-controlled studies. Although many studies report positive results, it remains unclear whether stem cell implantation can genuinely alter the natural history of ONFH. In addition, the adequate dose of cells has yet to be determined. To understand the place of stem cell therapy and maximize its therapeutic effect, the mode of action should be determined. If the paracrine effect is not sufficient for bone regeneration in ONFH, methods to enhance the survival of implanted cells and support their differentiation into bony tissue should be employed. To prolong the survival of implanted cells, rapid vascularization of the implantation site is necessary. To prove the mode of action in stem cell implantation, robust animal models are necessary to track the implanted cells, and observe their therapeutic effects. The well-known difficulty in establishing an animal model in ONFH adds up to the obstacles to resolving the fate of implanted stem cells in ONFH. For bone regeneration, ONFH has been the greatest focus for cell therapy. More evidence will be required to confirm the effectiveness of stem cell treatment in arresting the progression of the disease. In addition to scientific matters, regulatory issues complicate cell therapies. The implantation of culture-expanded cells needs approval from regulation agencies in most developed countries. The process is even tougher for allogeneic or genetically modified cells, adding up the cost of cell therapy. For treating physicians, it is also important to have an enhanced understanding of different cell sources, with analysis of the reported population of native stem and progenitor cells. Precise use of definitions and nomenclatures regarding cell sources and cell types is mandatory, as is distinguishing between culture-expanded cells and native cells and between autologous and allogeneic sources. It will also help to have a basic knowledge on the use and availability of methods for the quantification and characterization of the cells, and the efficiency of harvest, processing, and delivery procedures. It is also highly recommended that the concomitant use of established measures is not thrust aside until stem cell therapy is proven worthy in terms of safety, efficacy and cost1). ACKNOWLEDGEMENTS This work was supported by a grant from the National Research Foundation, funded by the Korean government (2017M3A9B4064777). 

more...
No comment yet.
Scooped by Krishan Maggon
Scoop.it!

Diagnosis and Monitoring of Osteoporosis With 18F-Sodium Fluoride PET: An Unavoidable Path for the Foreseeable Future - ScienceDirect

Diagnosis and Monitoring of Osteoporosis With 18F-Sodium Fluoride PET: An Unavoidable Path for the Foreseeable Future - ScienceDirect | Osteoporosis New drugs Review | Scoop.it
The prevalence of metabolic bone diseases particularly osteoporosis and its precursor, osteopenia, continue to grow as serious global health issues today. On a worldwide perspective, 200million people suffer from osteoporosis and in 2005, over 2million fracture incidents were estimated due to osteoporosis in the United States. Currently, osteoporosis and other metabolic bone diseases are evaluated primarily through dual energy X-ray absorptiometry, and rarely by bone biopsy with tetracycline labeling or Technetium-99m (99mTc) based bone scintigraphy. Deficiencies in these methods have prompted the use of more precise methods of assessment. This review highlights the use of 18F-sodium fluoride (NaF) with PET (NaF-PET), NaF-PET/CT, or NaF-PET/MRI in the evaluation of osteoporosis and osteopenia in the lumbar spine and hip. This imaging modality provides a molecular perspective with respect to the underlying metabolic alterations that lead to osseous disorders by measuring bone turnover through standardized uptake values. Its sensitivity and ability to examine the entire skeletal system make it a more superior imaging modality compared to standard structural imaging techniques. Further research is needed to determine its accuracy in reflecting the efficacy of therapeutic interventions in metabolic bone diseases.
more...
No comment yet.
Scooped by Krishan Maggon
Scoop.it!

Scientists find hidden blood vessels inside bone

Scientists find hidden blood vessels inside bone | Osteoporosis New drugs Review | Scoop.it
The findings might lead to new treatments for bone inflammation and tissue injuries.
more...
No comment yet.
Scooped by Krishan Maggon
Scoop.it!

Japan Approvals Include World Firsts For Romosozumab, Spinal Injury Cell Therapy

Japan Approvals Include World Firsts For Romosozumab, Spinal Injury Cell Therapy | Osteoporosis New drugs Review | Scoop.it
<p><span>The latest group of new product approvals in Japan includes the first marketing clearances worldwide for fracture-reducing osteoporosis antibody romosozumab, a stem cell-based therapy for spinal cord injury, two new Daiichi drugs, and Pfizer's lung cancer therapy dacomitinib.&nbsp; </span></p>...
more...
No comment yet.
Scooped by Krishan Maggon
Scoop.it!

RANKL Inhibits the Production of Osteoprotegerin from Smooth Muscle Cells under Basal Conditions and following Exposure to Cyclic Strain - FullText - Journal of Vascular Research 2018, Vol. 55, No....

RANKL Inhibits the Production of Osteoprotegerin from Smooth Muscle Cells under Basal Conditions and following Exposure to Cyclic Strain - FullText - Journal of Vascular Research 2018, Vol. 55, No.... | Osteoporosis New drugs Review | Scoop.it
Receptor activator of nuclear factor-κB ligand (RANKL) promotes vascular calcification, while osteoprotegerin (OPG) opposes it by blocking RANKL activity.It remains unclear which vascular cell popula...
more...
No comment yet.
Scooped by Krishan Maggon
Scoop.it!

Human Cartilage‐Derived Progenitors Resist Terminal Differentiation and Require CXCR4 Activation to Successfully Bridge Meniscus Tissue Tears - Jayasuriya - 2019 - STEM CELLS - Wiley Online Library

Human Cartilage‐Derived Progenitors Resist Terminal Differentiation and Require CXCR4 Activation to Successfully Bridge Meniscus Tissue Tears - Jayasuriya - 2019 - STEM CELLS - Wiley Online Library | Osteoporosis New drugs Review | Scoop.it
STEM CELLS, a peer reviewed journal published monthly, provides a forum for prompt publication of original investigative papers and concise reviews. STEM CELLS is read and written by clinical and basic scientists whose expertise encompasses the rapidly expanding fields of stem and progenitor cell...
more...
No comment yet.
Scooped by Krishan Maggon
Scoop.it!

An atlas of genetic influences on osteoporosis in humans and mice

An atlas of genetic influences on osteoporosis in humans and mice | Osteoporosis New drugs Review | Scoop.it
Abstract
Osteoporosis is a common aging-related disease diagnosed primarily using bone mineral density (BMD). We assessed genetic determinants of BMD as estimated by heel quantitative ultrasound in 426,824 individuals, identifying 518 genome-wide significant loci (301 novel), explaining 20% of its variance. We identified 13 bone fracture loci, all associated with estimated BMD (eBMD), in ~1.2 million individuals. We then identified target genes enriched for genes known to influence bone density and strength (maximum odds ratio (OR) = 58, P = 1 × 10−75) from cell-specific features, including chromatin conformation and accessible chromatin sites. We next performed rapid-throughput skeletal phenotyping of 126 knockout mice with disruptions in predicted target genes and found an increased abnormal skeletal phenotype frequency compared to 526 unselected lines (P < 0.0001). In-depth analysis of one gene, DAAM2, showed a disproportionate decrease in bone strength relative to mineralization. This genetic atlas provides evidence linking associated SNPs to causal genes, offers new insight into osteoporosis pathophysiology, and highlights opportunities for drug development.
more...
No comment yet.
Scooped by Krishan Maggon
Scoop.it!

NOTUM inhibition increases endocortical bone formation and bone strength

NOTUM inhibition increases endocortical bone formation and bone strength | Osteoporosis New drugs Review | Scoop.it
The disability, mortality and costs caused by non-vertebral osteoporotic fractures are enormous. Existing osteoporosis therapies are highly effective at reducing vertebral but not non-vertebral fractures. Cortical bone is a major determinant of non-vertebral bone strength. To identify novel osteoporosis drug targets, we phenotyped cortical bone of 3 366 viable mouse strains with global knockouts of druggable genes. Cortical bone thickness was substantially elevated in Notum−/− mice. NOTUM is a secreted WNT lipase and we observed high NOTUM expression in cortical bone and osteoblasts but not osteoclasts. Three orally active small molecules and a neutralizing antibody inhibiting NOTUM lipase activity were developed. They increased cortical bone thickness and strength at multiple skeletal sites in both gonadal intact and ovariectomized rodents by stimulating endocortical bone formation. Thus, inhibition of NOTUM activity is a potential novel anabolic therapy for strengthening cortical bone and preventing non-vertebral fractures.
more...
No comment yet.
Scooped by Krishan Maggon
Scoop.it!

JCI Insight - 1,25-Dihydroxyvitamin D suppresses M1 macrophages and promotes M2 differentiation at bone injury sites

JCI Insight - 1,25-Dihydroxyvitamin D suppresses M1 macrophages and promotes M2 differentiation at bone injury sites | Osteoporosis New drugs Review | Scoop.it
Research ArticleBone biology Free access | 10.1172/jci.insight.98773 1,25-Dihydroxyvitamin D suppresses M1 macrophages and promotes M2 differentiation at bone injury sites Samiksha Wasnik,1 Charles H. Rundle,2 David J. Baylink,1 Mohammad Safaie Yazdi,1 Edmundo E. Carreon,1 Yi Xu,1 Xuezhong Qin,1,2 Kin-Hing William Lau,1,2 and Xiaolei Tang1 First published September 6, 2018 - More info

 

 

Abstract

An indispensable role of macrophages in bone repair has been well recognized. Previous data have demonstrated the copresence of M1 macrophages and mesenchymal stem cells (MSCs) during the proinflammatory stage of bone repair. However, the exact role of M1 macrophages in MSC function and bone repair is unknown. This study aimed to define the role of M1 macrophages at bone injury sites via the function of 1,25-Dihydroxyvitamin D (1,25[OH]2D) in suppressing M1 but promoting M2 differentiation. We showed that 1,25(OH)2D suppressed M1 macrophage–mediated enhancement of MSC migration. Additionally, 1,25(OH)2D inhibited M1 macrophage secretion of osteogenic proteins (i.e., Oncostatin M, TNF-α, and IL-6). Importantly, the 1,25(OH)2D-mediated suppression of osteogenic function in M1 macrophages at the proinflammatory stage was associated with 1,25(OH)2D-mediated reduction of MSC abundance, compromised osteogenic potential of MSCs, and impairment of fracture repair. Furthermore, outside the proinflammatory stage, 1,25(OH)2D treatment did not suppress fracture repair. Accordingly, our data support 2 conclusions: (a) M1 macrophages are important for the recruitment and osteogenic priming of MSCs and, hence, are necessary for fracture repair, and (b) under vitamin D–sufficient conditions, 1,25(OH)2D treatment is unnecessary and can be detrimental if provided during the proinflammatory stage of fracture healing.

more...
No comment yet.
Scooped by Krishan Maggon
Scoop.it!

Amgen and UCB's Evenity approved in Japan for osteoporosis | Pharmafile

Amgen and UCB's Evenity approved in Japan for osteoporosis | Pharmafile | Osteoporosis New drugs Review | Scoop.it
more...
No comment yet.
Scooped by Krishan Maggon
Scoop.it!

Osteoporosis in men: a serious public health problem

Osteoporosis in men: a serious public health problem | Osteoporosis New drugs Review | Scoop.it
One in eight men older than 50 years will have a fragility fracture during their lifetime, which will contribute to dependency, morbidity and a higher mortality in the first year.
more...
No comment yet.
Scooped by Krishan Maggon
Scoop.it!

Cell migration: implications for repair and regeneration in joint disease

Cell migration: implications for repair and regeneration in joint disease | Osteoporosis New drugs Review | Scoop.it
Improved understanding of cell migration in the synovial joint, including the associated cellular and environmental factors, might reveal new therapeutic strategies for joint diseases such as rheumatoid arthritis and osteoarthritis and have important implications for tissue engineering of the joint.
more...
No comment yet.
Scooped by Krishan Maggon
Scoop.it!

Relative contributions of adipose-resident CD146 + pericytes and CD34 + adventitial progenitor cells in bone tissue engineering

Relative contributions of adipose-resident CD146 + pericytes and CD34 + adventitial progenitor cells in bone tissue engineering | Osteoporosis New drugs Review | Scoop.it
Different kinds of cells found surrounding blood vessels in fat play a complementary and synergistic role in bone healing. Aaron James from Johns Hopkins University in Baltimore, MD, USA, and colleagues derived two subsets of cells from human fat tissue: contractile cells known as pericytes that...
more...
No comment yet.
Scooped by Krishan Maggon
Scoop.it!

Growing cartilage-like tissue using bone stem cells | 2017 Photomicrography Competition

Growing cartilage-like tissue using bone stem cells | 2017 Photomicrography Competition | Osteoporosis New drugs Review | Scoop.it
Catarina Moura - Growing cartilage-like tissue in the lab using bone stem cells (collagen fibers in green and fat deposits in red)...
more...
No comment yet.
Scooped by Krishan Maggon
Scoop.it!

Single-cell RNA-seq analysis reveals the progression of human osteoarthritis

Single-cell RNA-seq analysis reveals the progression of human osteoarthritis | Osteoporosis New drugs Review | Scoop.it
Objectives Understanding the molecular mechanisms underlying human cartilage degeneration and regeneration is helpful for improving therapeutic strategies for treating osteoarthritis (OA). Here, we report the molecular programmes and lineage progression patterns controlling human OA pathogenesis...
more...
No comment yet.