keyword
MENU ▼
Read by QxMD icon Read
search

Anti sclerostin antibodies

keyword
https://www.readbyqxmd.com/read/28770650/osteoblast-as-a-target-of-anti-osteoporotic-treatment
#1
Addolorata Corrado, Eliana Rita Sanpaolo, Silvana Di Bello, Francesco Paolo Cantatore
Osteoblasts are mesenchymal cells that play a key role in maintaining bone homeostasis; they are responsible for the production of extracellular matrix proteins, regulation of matrix mineralization, control of bone remodeling and regulate osteoclast differentiation. Osteoblasts have an essential role in the pathogenesis of many bone diseases, particularly osteoporosis. For many decades, the main current available treatments for osteoporosis have been represented by anti-resorptive drugs, such as bisphosphonates, which act mainly by inhibiting osteoclasts maturation, proliferation and activity; nevertheless, in recent years much attention has been paid on anabolic aspects of osteoporosis treatment...
August 3, 2017: Postgraduate Medicine
https://www.readbyqxmd.com/read/28647818/assessment-of-the-effect-of-systemic-delivery-of-sclerostin-antibodies-on-wnt-signaling-in-distraction-osteogenesis
#2
Mohammad M Alzahrani, Asim M Makhdom, Frank Rauch, Dominique Lauzier, Maria Kotsiopriftis, Saber Ghadakzadeh, Reggie C Hamdy
Sclerostin is a known inhibitor of the Wnt signaling pathway which is involved in osteogenesis and, when inactivated, stimulates bone formation. To our knowledge, this effect has not been studied in the context of distraction osteogenesis (DO). Tibial DO was conducted on a total of 24 wild-type mice, which were then divided into 2 groups-a saline injection group (control) and an anti-sclerostin (Scl-Ab) injection group (treatment). The mice in the treatment group received 100 mg/kg intravenous injections of the antibody weekly until killing...
June 24, 2017: Journal of Bone and Mineral Metabolism
https://www.readbyqxmd.com/read/28628032/osteocyte-specific-wnt1-regulates-osteoblast-function-during-bone-homeostasis
#3
Kyu Sang Joeng, Yi-Chien Lee, Joohyun Lim, Yuqing Chen, Ming-Ming Jiang, Elda Munivez, Catherine Ambrose, Brendan H Lee
Mutations in WNT1 cause osteogenesis imperfecta (OI) and early-onset osteoporosis, identifying it as a key Wnt ligand in human bone homeostasis. However, how and where WNT1 acts in bone are unclear. To address this mechanism, we generated late-osteoblast-specific and osteocyte-specific WNT1 loss- and gain-of-function mouse models. Deletion of Wnt1 in osteocytes resulted in low bone mass with spontaneous fractures similar to that observed in OI patients. Conversely, Wnt1 overexpression from osteocytes stimulated bone formation by increasing osteoblast number and activity, which was due in part to activation of mTORC1 signaling...
June 30, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28543818/bone-formation-is-coupled-to-resorption-via-suppression-of-sclerostin-expression-by-osteoclasts
#4
Masanori Koide, Yasuhiro Kobayashi, Teruhito Yamashita, Shunsuke Uehara, Midori Nakamura, B Yukihiro Hiraoka, Yuki Ozaki, Tadahiro Iimura, Hisataka Yasuda, Naoyuki Takahashi, Nobuyuki Udagawa
Bone formation is coupled to bone resorption throughout life. However, the coupling mechanisms are not fully elucidated. Using Tnfrsf11b-deficient (OPG(-/-) ) mice, in which bone formation is clearly coupled to bone resorption, we found here that osteoclasts suppress the expression of sclerostin, a Wnt antagonist, thereby promoting bone formation. Wnt/β-catenin signals were higher in OPG(-/-) and RANKL-transgenic mice with a low level of sclerostin. Conditioned medium from osteoclast cultures (Ocl-CM) suppressed sclerostin expression in UMR106 cells and osteocyte cultures...
May 24, 2017: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/28540603/positioning-novel-biologicals-in-ckd-mineral-and-bone-disorders
#5
REVIEW
Lida Tartaglione, Marzia Pasquali, Silverio Rotondi, Maria Luisa Muci, Adrian Covic, Sandro Mazzaferro
Renal osteodystrophy (ROD), the histologic bone lesions of chronic kidney disease (CKD), is now included in a wider syndrome with laboratory abnormalities of mineral metabolism and extra-skeletal calcifications or CKD-mineral and bone disorders (CKD-MBD), to highlight the increased burden of mortality. Aging people, frequently identified as early CKD, could suffer from either the classical age-related osteoporosis (OP) or ROD. Distinguishing between these two bone diseases may not be easy without bone biopsy...
May 24, 2017: Journal of Nephrology
https://www.readbyqxmd.com/read/28529724/recent-advances-in-the-management-of-osteoporosis
#6
REVIEW
Seiji Fukumoto, Toshio Matsumoto
There has been substantial progress in the management of patients with osteoporosis and the prevention of osteoporotic fractures. Currently available strong anti-resorptive agents are bisphosphonates and an anti-receptor activator of nuclear factor-kappa B ligand (RANKL) antibody, denosumab. Although bisphosphonates and denosumab both inhibit bone resorption and prevent vertebral and non-vertebral fractures, their mechanisms of action are different. Whereas bisphosphonates' effects on bone mineral density and fracture peak around 3 to 5 years and become plateaued, those of denosumab are maintained for up to 10 years...
2017: F1000Research
https://www.readbyqxmd.com/read/28529307/genetic-deletion-of-sost-or-pharmacological-inhibition-of-sclerostin-prevent-multiple-myeloma-induced-bone-disease-without-affecting-tumor-growth
#7
J Delgado-Calle, J Anderson, M D Cregor, K W Condon, S A Kuhstoss, L I Plotkin, T Bellido, G D Roodman
Multiple myeloma (MM) causes lytic bone lesions due to increased bone resorption and concomitant marked suppression of bone formation. Sclerostin (Scl), an osteocyte-derived inhibitor of Wnt/β-catenin signaling, is elevated in MM patient sera and increased in osteocytes in MM-bearing mice. We show here that genetic deletion of Sost, the gene encoding Scl, prevented MM-induced bone disease in an immune-deficient mouse model of early MM, and that administration of anti-Scl antibody (Scl-Ab) increased bone mass and decreases osteolysis in immune-competent mice with established MM...
May 22, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28515094/inhibiting-the-osteocyte-specific-protein-sclerostin-increases-bone-mass-and-fracture-resistance-in-multiple-myeloma
#8
Michelle M McDonald, Michaela R Reagan, Scott E Youlten, Sindhu T Mohanty, Anja Seckinger, Rachael L Terry, Jessica A Pettitt, Marija K Simic, Tegan L Cheng, Alyson Morse, Lawrence M T Le, David Abi-Hanna, Ina Kramer, Carolyne Falank, Heather Fairfield, Irene M Ghobrial, Paul A Baldock, David G Little, Michaela Kneissel, Karin Vanderkerken, J H Duncan Bassett, Graham R Williams, Babatunde O Oyajobi, Dirk Hose, Tri G Phan, Peter I Croucher
Multiple myeloma (MM) is a plasma cell cancer that develops in the skeleton causing profound bone destruction and fractures. The bone disease is mediated by increased osteoclastic bone resorption and suppressed bone formation. Bisphosphonates used for treatment inhibit bone resorption and prevent bone loss but fail to influence bone formation and do not replace lost bone, so patients continue to fracture. Stimulating bone formation to increase bone mass and fracture resistance is a priority; however, targeting tumor-derived modulators of bone formation has had limited success...
June 29, 2017: Blood
https://www.readbyqxmd.com/read/28461254/combination-sclerostin-antibody-and-zoledronic-acid-treatment-outperforms-either-treatment-alone-in-a-mouse-model-of-osteogenesis-imperfecta
#9
David G Little, Lauren Peacock, Kathy Mikulec, Michaela Kneissel, Ina Kramer, Tegan L Cheng, Aaron Schindeler, Craig Munns
In this study, we examined the therapeutic potential of anti-Sclerostin Antibody (Scl-Ab) and bisphosphonate treatments for the bone fragility disorder Osteogenesis Imperfecta (OI). Mice with the Amish OI mutation (Col1a2 G610C mice) and control wild type littermates (WT) were treated from week 5 to week 9 of life with (1) saline (control), (2) zoledronic acid given 0.025mg/kg s.c. weekly (ZA), (3) Scl-Ab given 50mg/kg IV weekly (Scl-Ab), or (4) a combination of both (Scl-Ab/ZA). Functional outcomes were prioritized and included bone mineral density (BMD), bone microarchitecture, long bone bending strength, and vertebral compression strength...
April 29, 2017: Bone
https://www.readbyqxmd.com/read/28436937/efficacy-of-anti-sclerostin-monoclonal-antibody-bps804-in-adult-patients-with-hypophosphatasia
#10
Lothar Seefried, Jasmin Baumann, Sarah Hemsley, Christine Hofmann, Erdmute Kunstmann, Beate Kiese, Yue Huang, Simon Chivers, Marie-Anne Valentin, Babul Borah, Ronenn Roubenoff, Uwe Junker, Franz Jakob
BACKGROUND: Hypophosphatasia (HPP) is a rare genetic disorder resulting in variable alterations of bone formation and mineralization that are caused by mutations in the ALPL gene, encoding the tissue-nonspecific alkaline phosphatase (ALP) enzyme. METHODS: In this phase IIA open-label, single-center, intra-patient, dose-escalating study, adult patients with HPP received 3 ascending intravenous doses of 5, 10, and 20 mg/kg BPS804, a fully human anti-sclerostin monoclonal antibody, on days 1, 15, and 29, respectively...
June 1, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28370407/bps804-anti-sclerostin-antibody-in-adults-with-moderate-osteogenesis-imperfecta-results-of-a-randomized-phase-2a-trial
#11
Francis H Glorieux, Jean-Pierre Devogelaer, Michaela Durigova, Stefan Goemaere, Sarah Hemsley, Franz Jakob, Uwe Junker, Jon Ruckle, Lothar Seefried, Peter J Winkle
This 21-week, open-label, phase 2a trial aimed to evaluate the pharmacodynamics and safety of multiple, escalating infusions of BPS804, a neutralizing, anti-sclerostin antibody, in adults with moderate osteogenesis imperfecta (OI). Patients received BPS804 (three escalating doses each separated by 2 weeks [5, 10, and 20 mg/kg]) or no treatment (reference group). The primary efficacy endpoints were mean changes from baseline to day 43 in: procollagen type 1 N-terminal propeptide (P1NP), procollagen type 1 C-terminal propeptide (P1CP), bone-specific alkaline phosphatase (BSAP), osteocalcin (OC), and type 1 collagen cross-linked C-telopeptide (CTX-1)...
July 2017: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/28240364/n-cadherin-regulation-of-bone-growth-and-homeostasis-is-osteolineage-stage-specific
#12
Francesca Fontana, Cynthia L Hickman-Brecks, Valerie S Salazar, Leila Revollo, Grazia Abou-Ezzi, Susan K Grimston, Sung Yeop Jeong, Marcus Watkins, Manuela Fortunato, Yael Alippe, Daniel C Link, Gabriel Mbalaviele, Roberto Civitelli
N-cadherin inhibits osteogenic cell differentiation and canonical Wnt/β-catenin signaling in vitro. However, in vivo both conditional Cdh2 ablation and overexpression in osteoblasts lead to low bone mass. We tested the hypothesis that N-cadherin has different effects on osteolineage cells depending upon their differentiation stage. Embryonic conditional osteolineage Cdh2 deletion in mice results in defective growth, low bone mass, and reduced osteoprogenitor number. These abnormalities are prevented by delaying Cdh2 ablation until 1 month of age, thus targeting only committed and mature osteoblasts, suggesting they are the consequence of N-cadherin deficiency in osteoprogenitors...
June 2017: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/28115281/clinical-utility-of-anti-sclerostin-antibodies
#13
Michael R McClung
Based on a platform of strong preclinical data, several studies in humans have demonstrated that inhibiting sclerostin with specific antibodies results in a brisk albeit transient anabolic response in the skeleton without an accompanying increase in bone resorption. Impressive increases in bone mineral density and bone strength have been demonstrated. Other than mild injection site reactions, therapy for up to 2years has been well tolerated. The restriction of sclerostin expression almost exclusively to skeletal tissues, coupled with the absence of recognized medical problems in patients with heterozygous sclerostin deficiency, provides promise that the drug can be used safely...
March 2017: Bone
https://www.readbyqxmd.com/read/28030966/systemic-drugs-that-influence-titanium-implant-osseointegration
#14
Dragos Apostu, Ondine Lucaciu, Gheorghe Dan Osvald Lucaciu, Bogdan Crisan, Liana Crisan, Mihaela Baciut, Florin Onisor, Grigore Baciut, Radu Septimiu Câmpian, Simion Bran
Titanium implants are widely used on an increasing number of patients in orthopedic and dental medicine. Despite the good survival rates of these implants, failures that lead to important socio-economic consequences still exist. Recently, research aimed at improving implant fixation, a process called osseointegration, has focused on a new, innovative field: systemic delivery of drugs. Following implant fixation, patients receive systemic drugs that could either impair or enhance osseointegration; these drugs include anabolic and anti-catabolic bone-acting agents in addition to new treatments...
February 2017: Drug Metabolism Reviews
https://www.readbyqxmd.com/read/27888056/sclerostin-expression-and-functions-beyond-the-osteocyte
#15
Megan M Weivoda, Stephanie J Youssef, Merry Jo Oursler
Sclerostin, the product of the SOST gene, is a secreted inhibitor of Wnt signaling that is produced by osteocytes to regulate bone formation. While it is often considered an osteocyte-specific protein, SOST expression has been reported in numerous other cell types, including hypertrophic chondrocytes and cementocytes. Of interest, SOST/sclerostin expression is altered in certain pathogenic conditions, including osteoarthritis and rheumatic joint disease, and it is unclear whether sclerostin plays a protective role or whether sclerostin may mediate disease pathogenesis...
March 2017: Bone
https://www.readbyqxmd.com/read/27837171/preventing-painful-age-related-bone-fractures-anti-sclerostin-therapy-builds-cortical-bone-and-increases-the-proliferation-of-osteogenic-cells-in-the-periosteum-of-the-geriatric-mouse-femur
#16
Michelle L Thompson, Stephane R Chartier, Stefanie A Mitchell, Patrick W Mantyh
Age-related bone fractures are usually painful and have highly negative effects on a geriatric patient's functional status, quality of life, and survival. Currently, there are few analgesic therapies that fully control bone fracture pain in the elderly without significant unwanted side effects. However, another way of controlling age-related fracture pain would be to preemptively administer an osteo-anabolic agent to geriatric patients with high risk of fracture, so as to build new cortical bone and prevent the fracture from occurring...
2016: Molecular Pain
https://www.readbyqxmd.com/read/27780792/application-of-anti-sclerostin-therapy-in-non-osteoporosis-disease-models
#17
Christina M Jacobsen
Sclerostin, a known inhibitor of the low density lipoprotein related protein 5 and 6 (LRP5 and LRP6) cell surface signaling receptors, is integral in the maintenance of normal bone mass and strength. Patients with loss of function mutations in SOST or missense mutations in LRP5 that prevent Sclerostin from binding and inhibiting the receptor, have significantly increased bone mass. This observation leads to the development of Sclerostin neutralizing therapies to increase bone mass and strength. Anti-Sclerostin therapy has been shown to be effective at increasing bone density and strength in animal models and patients with osteoporosis...
March 2017: Bone
https://www.readbyqxmd.com/read/27742499/sclerostin-s-role-in-bone-s-adaptive-response-to-mechanical-loading
#18
Gabriel L Galea, Lance E Lanyon, Joanna S Price
Mechanical loading is the primary functional determinant of bone mass and architecture, and osteocytes play a key role in translating mechanical signals into (re)modelling responses. Although the precise mechanisms remain unclear, Wnt signalling pathway components, and the anti-osteogenic canonical Wnt inhibitor Sost/sclerostin in particular, play an important role in regulating bone's adaptive response to loading. Increases in loading-engendered strains down-regulate osteocyte sclerostin expression, whereas reduced strains, as in disuse, are associated with increased sclerostin production and bone loss...
March 2017: Bone
https://www.readbyqxmd.com/read/27742498/role-and-mechanism-of-action-of-sclerostin-in-bone
#19
Jesus Delgado-Calle, Amy Y Sato, Teresita Bellido
After discovering that lack of Sost/sclerostin expression is the cause of the high bone mass human syndromes Van Buchem disease and sclerosteosis, extensive animal experimentation and clinical studies demonstrated that sclerostin plays a critical role in bone homeostasis and that its deficiency or pharmacological neutralization increases bone formation. Dysregulation of sclerostin expression also underlies the pathophysiology of skeletal disorders characterized by loss of bone mass, as well as the damaging effects of some cancers in bone...
March 2017: Bone
https://www.readbyqxmd.com/read/27641475/single-dose-of-bisphosphonate-preserves-gains-in-bone-mass-following-cessation-of-sclerostin-antibody-in-brtl-osteogenesis-imperfecta-model
#20
Joseph E Perosky, Basma M Khoury, Terese N Jenks, Ferrous S Ward, Kai Cortright, Bethany Meyer, David K Barton, Benjamin P Sinder, Joan C Marini, Michelle S Caird, Kenneth M Kozloff
Sclerostin antibody has demonstrated a bone-forming effect in pre-clinical models of osteogenesis imperfecta, where mutations in collagen or collagen-associated proteins often result in high bone fragility in pediatric patients. Cessation studies in osteoporotic patients have demonstrated that sclerostin antibody, like intermittent PTH treatment, requires sequential anti-resorptive therapy to preserve the anabolic effects in adult populations. However, the persistence of anabolic gains from either drug has not been explored clinically in OI, or in any animal model...
December 2016: Bone
keyword
keyword
97777
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"