Sclerostin antibody treatment improves fracture outcomes in a Type I diabetic mouse model
Abstract
Type 1 diabetes mellitus (T1DM) patients have osteopenia and impaired fracture healing due to decreased osteoblast activity. Further, no adequate treatments are currently available that can restore impaired healing in T1DM; hence a significant need exists to investigate new therapeutics for treatment of orthopedic complications. Sclerostin (SOST), a WNT antagonist, negatively regulates bone formation, and SostAb is a potent bone anabolic agent. To determine whether SOST antibody (SostAb) treatment improves fracture healing in streptozotocin (STZ) induced T1DM mice, we administered SostAb twice weekly for up to 21 days post-fracture, and examined bone quality and callus outcomes at 21 days and 42 days post-fracture (11 and 14 weeks of age, respectively). Here we show that SostAb treatment improves bone parameters; these improvements persist after cessation of antibody treatment. Markers of osteoblast differentiation such as Runx2, collagen I, osteocalcin, and DMP1 were reduced, while an abundant number of SP7/osterix-positive early osteoblasts were observed on the bone surface of STZ calluses. These results suggest that STZ calluses have poor osteogenesis resulting from failure of osteoblasts to fully differentiate and produce mineralized matrix, which produces a less mineralized callus. SostAb treatment enhanced fracture healing in both normal and STZ groups, and in STZ +more »
- Authors:
-
- Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Univ. of California, Merced, CA (United States)
- Regeneron Pharmaceuticals, Tarrytown, NY (United States)
- Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)
- Univ. of California, Merced, CA (United States)
- Publication Date:
- Research Org.:
- Lawrence Livermore National Laboratory (LLNL), Livermore, CA (United States)
- Sponsoring Org.:
- USDOE
- OSTI Identifier:
- 1234603
- Report Number(s):
- LLNL-JRNL-666626
Journal ID: ISSN 8756-3282
- Grant/Contract Number:
- AC52-07NA27344
- Resource Type:
- Accepted Manuscript
- Journal Name:
- Bone
- Additional Journal Information:
- Journal Volume: 82; Journal Issue: C; Journal ID: ISSN 8756-3282
- Publisher:
- Elsevier
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES; Sclerostin; Type I diabetes; fracture repair; Streptozotocin; STZ; Osteoblast differentiation; Sclerostin antibody
Citation Formats
Yee, Cristal S., Xie, LiQin, Hatsell, Sarah, Hum, Nicholas, Murugesh, Deepa, Economides, Aris N., Loots, Gabriela G., and Collette, Nicole M. Sclerostin antibody treatment improves fracture outcomes in a Type I diabetic mouse model. United States: N. p., 2015.
Web. doi:10.1016/j.bone.2015.04.048.
Yee, Cristal S., Xie, LiQin, Hatsell, Sarah, Hum, Nicholas, Murugesh, Deepa, Economides, Aris N., Loots, Gabriela G., & Collette, Nicole M. Sclerostin antibody treatment improves fracture outcomes in a Type I diabetic mouse model. United States. https://doi.org/10.1016/j.bone.2015.04.048
Yee, Cristal S., Xie, LiQin, Hatsell, Sarah, Hum, Nicholas, Murugesh, Deepa, Economides, Aris N., Loots, Gabriela G., and Collette, Nicole M. Mon .
"Sclerostin antibody treatment improves fracture outcomes in a Type I diabetic mouse model". United States. https://doi.org/10.1016/j.bone.2015.04.048. https://www.osti.gov/servlets/purl/1234603.
@article{osti_1234603,
title = {Sclerostin antibody treatment improves fracture outcomes in a Type I diabetic mouse model},
author = {Yee, Cristal S. and Xie, LiQin and Hatsell, Sarah and Hum, Nicholas and Murugesh, Deepa and Economides, Aris N. and Loots, Gabriela G. and Collette, Nicole M.},
abstractNote = {Type 1 diabetes mellitus (T1DM) patients have osteopenia and impaired fracture healing due to decreased osteoblast activity. Further, no adequate treatments are currently available that can restore impaired healing in T1DM; hence a significant need exists to investigate new therapeutics for treatment of orthopedic complications. Sclerostin (SOST), a WNT antagonist, negatively regulates bone formation, and SostAb is a potent bone anabolic agent. To determine whether SOST antibody (SostAb) treatment improves fracture healing in streptozotocin (STZ) induced T1DM mice, we administered SostAb twice weekly for up to 21 days post-fracture, and examined bone quality and callus outcomes at 21 days and 42 days post-fracture (11 and 14 weeks of age, respectively). Here we show that SostAb treatment improves bone parameters; these improvements persist after cessation of antibody treatment. Markers of osteoblast differentiation such as Runx2, collagen I, osteocalcin, and DMP1 were reduced, while an abundant number of SP7/osterix-positive early osteoblasts were observed on the bone surface of STZ calluses. These results suggest that STZ calluses have poor osteogenesis resulting from failure of osteoblasts to fully differentiate and produce mineralized matrix, which produces a less mineralized callus. SostAb treatment enhanced fracture healing in both normal and STZ groups, and in STZ + SostAb mice, also reversed the lower mineralization seen in STZ calluses. Micro-CT analysis of calluses revealed improved bone parameters with SostAb treatment, and the mineralized bone was comparable to Controls. Additionally, we found sclerostin levels to be elevated in STZ mice and β-catenin activity to be reduced. Consistent with its function as a WNT antagonist, SostAb treatment enhanced β-catenin activity, but also increased the levels of SOST in the callus and in circulation. Lastly, our results indicate that SostAb treatment rescues the impaired osteogenesis seen in the STZ induced T1DM fracture model by facilitating osteoblast differentiation and mineralization of bone.},
doi = {10.1016/j.bone.2015.04.048},
journal = {Bone},
number = C,
volume = 82,
place = {United States},
year = {Mon May 04 00:00:00 EDT 2015},
month = {Mon May 04 00:00:00 EDT 2015}
}
Free Publicly Available Full Text
Publisher's Version of Record
Other availability
Search WorldCat to find libraries that may hold this journal
Cited by: 46 works
Citation information provided by
Web of Science
Web of Science
Save to My Library
You must Sign In or Create an Account in order to save documents to your library.
Works referenced in this record:
Coordination of kidney organogenesis by Wnt signaling
journal, January 2014
- Halt, Kimmo; Vainio, Seppo
- Pediatric Nephrology, Vol. 29, Issue 4
Targeted Deletion of the Sclerostin Gene in Mice Results in Increased Bone Formation and Bone Strength
journal, February 2008
- Li, Xiaodong; Ominsky, Michael S.; Niu, Qing-Tian
- Journal of Bone and Mineral Research, Vol. 23, Issue 6
Systemic administration of sclerostin monoclonal antibody accelerates fracture healing in the femoral osteotomy model of young rats
journal, January 2015
- Feng, Gao; Chang-Qing, Zhang; Yi-Min, Chai
- International Immunopharmacology, Vol. 24, Issue 1
Impact of Diabetes on Fracture Healing
journal, February 2011
- Graves, Dana T.; Alblowi, Jazia; Paglia, David N.
- Journal of Experimental & Clinical Medicine, Vol. 3, Issue 1
The emerging challenge in diabetes: The “metabolic memory”
journal, November 2012
- Ceriello, Antonio
- Vascular Pharmacology, Vol. 57, Issue 5-6
Bone structure and turnover in type 2 diabetes mellitus
journal, March 2011
- Shu, A.; Yin, M. T.; Stein, E.
- Osteoporosis International, Vol. 23, Issue 2
Sclerostin Binds to LRP5/6 and Antagonizes Canonical Wnt Signaling
journal, March 2005
- Li, Xiaofeng; Zhang, Yazhou; Kang, Heeseog
- Journal of Biological Chemistry, Vol. 280, Issue 20
Exendin-4 increases bone mineral density in type 2 diabetic OLETF rats potentially through the down-regulation of SOST/sclerostin in osteocytes
journal, March 2013
- Kim, Ju-Young; Lee, Seong-Kyu; Jo, Kyung-Jin
- Life Sciences, Vol. 92, Issue 10
Activation of Wnt/β-Catenin Signaling Increases Insulin Sensitivity through a Reciprocal Regulation of Wnt10b and SREBP-1c in Skeletal Muscle Cells
journal, December 2009
- Abiola, Mounira; Favier, Maryline; Christodoulou-Vafeiadou, Eleni
- PLoS ONE, Vol. 4, Issue 12
Temporal changes in systemic and local expression of bone turnover markers during six months of sclerostin antibody administration to ovariectomized rats
journal, October 2014
- Stolina, Marina; Dwyer, Denise; Niu, Qing-Tian
- Bone, Vol. 67
Bone Loss and Increased Bone Adiposity in Spontaneous and Pharmacologically Induced Diabetic Mice
journal, January 2007
- Botolin, Sergiu; McCabe, Laura R.
- Endocrinology, Vol. 148, Issue 1
Bone Density Ligand, Sclerostin, Directly Interacts With LRP5 but Not LRP5G171V to Modulate Wnt Activity
journal, August 2006
- Ellies, Debra L.; Viviano, Beth; McCarthy, John
- Journal of Bone and Mineral Research, Vol. 21, Issue 11
The C-terminal fragment of parathyroid hormone-related peptide promotes bone formation in diabetic mice with low-turnover osteopaenia: C-terminal PTHrP is anabolic for diabetic bone
journal, February 2011
- Lozano, D.; Fernández-de-Castro, L.; Portal-Núñez, S.
- British Journal of Pharmacology, Vol. 162, Issue 6
Beta-Catenin Signaling Plays a Disparate Role in Different Phases of Fracture Repair: Implications for Therapy to Improve Bone Healing
journal, July 2007
- Chen, Yan; Whetstone, Heather C.; Lin, Alvin C.
- PLoS Medicine, Vol. 4, Issue 7
Diabetes Mellitus: Does it Affect Bone?
journal, December 2003
- Schwartz, A. V.
- Calcified Tissue International, Vol. 73, Issue 6
Circulating Sclerostin Levels and Bone Turnover in Type 1 and Type 2 Diabetes
journal, May 2012
- Gennari, Luigi; Merlotti, Daniela; Valenti, Roberto
- The Journal of Clinical Endocrinology & Metabolism, Vol. 97, Issue 5
The emerging challenge in diabetes: The “metabolic memory”
journal, November 2012
- Ceriello, Antonio
- Vascular Pharmacology, Vol. 57, Issue 5-6
Genetic evidence that SOST inhibits WNT signaling in the limb
journal, June 2010
- Collette, Nicole M.; Genetos, Damian C.; Murugesh, Deepa
- Developmental Biology, Vol. 342, Issue 2
Bone Dysplasia Sclerosteosis Results from Loss of the SOST Gene Product, a Novel Cystine Knot–Containing Protein
journal, March 2001
- Brunkow, Mary E.; Gardner, Jessica C.; Van Ness, Jeff
- The American Journal of Human Genetics, Vol. 68, Issue 3
Bone Matrix Quality After Sclerostin Antibody Treatment: BONE MATRIX COMPOSITION AND SCLEROSTIN ANTIBODY
journal, June 2014
- Ross, Ryan D.; Edwards, Lindsey H.; Acerbo, Alvin S.
- Journal of Bone and Mineral Research, Vol. 29, Issue 7
Loss of wnt/β-catenin signaling causes cell fate shift of preosteoblasts from osteoblasts to adipocytes
journal, October 2012
- Song, Lige; Liu, Minlin; Ono, Noriaki
- Journal of Bone and Mineral Research, Vol. 27, Issue 11
Understanding the pathology and mechanisms of type I diabetic bone loss
journal, January 2007
- McCabe, Laura R.
- Journal of Cellular Biochemistry, Vol. 102, Issue 6
Prevalence and predictors of osteopenia and osteoporosis in adults with Type 1 diabetes
journal, January 2009
- Hamilton, E. J.; Rakic, V.; Davis, W. A.
- Diabetic Medicine, Vol. 26, Issue 1
The effects of blood glucose control upon fracture healing in the BB Wistar rat with diabetes mellitus
journal, November 2002
- Beam, Heather A.; Russell Parsons, J.; Lin, Sheldon S.
- Journal of Orthopaedic Research, Vol. 20, Issue 6
Osteo-promoting effects of insulin-like growth factor I (IGF-I) in a mouse model of type 1 diabetes
journal, November 2013
- Fowlkes, John L.; Nyman, Jeffry S.; Bunn, R. Clay
- Bone, Vol. 57, Issue 1
Gone with the Wnts: β-Catenin, T-Cell Factor, Forkhead Box O, and Oxidative Stress in Age-Dependent Diseases of Bone, Lipid, and Glucose Metabolism
journal, November 2007
- Manolagas, Stavros C.; Almeida, Maria
- Molecular Endocrinology, Vol. 21, Issue 11
Inhibition of sclerostin by monoclonal antibody enhances bone healing and improves bone density and strength of nonfractured bones
journal, May 2011
- Ominsky, Michael S.; Li, Chaoyang; Li, Xiaodong
- Journal of Bone and Mineral Research, Vol. 26, Issue 5
Insulin-dependent diabetes mellitus decreases osteoblastogenesis associated with the inhibition of Wnt signaling through increased expression of Sost and Dkk1 and inhibition of Akt activation
journal, May 2011
- Tsukamoto, Ikuyo
- International Journal of Molecular Medicine
Osteo-promoting effects of insulin-like growth factor I (IGF-I) in a mouse model of type 1 diabetes
journal, November 2013
- Fowlkes, John L.; Nyman, Jeffry S.; Bunn, R. Clay
- Bone, Vol. 57, Issue 1
Targeted deletion of Sost distal enhancer increases bone formation and bone mass
journal, August 2012
- Collette, N. M.; Genetos, D. C.; Economides, A. N.
- Proceedings of the National Academy of Sciences, Vol. 109, Issue 35
Diabetes and Its Complications and Their Relationship with Risk of Fractures in Type 1 and 2 Diabetes
journal, December 2008
- Vestergaard, Peter; Rejnmark, Lars; Mosekilde, Leif
- Calcified Tissue International, Vol. 84, Issue 1
Increased callus mass and enhanced strength during fracture healing in mice lacking the sclerostin gene
journal, December 2011
- Li, Chaoyang; Ominsky, Michael S.; Tan, Hong-Lin
- Bone, Vol. 49, Issue 6
Age-Related Changes in Trabecular Architecture Differ in Female and Male C57BL/6J Mice
journal, May 2007
- Glatt, Vaida; Canalis, Ernesto; Stadmeyer, Lisa
- Journal of Bone and Mineral Research, Vol. 22, Issue 8
Sclerostin monoclonal antibody enhanced bone fracture healing in an open osteotomy model in rats: Scl-Ab ENHANCED RAT OSTEOTOMY HEALING
journal, April 2014
- Suen, Pui Kit; He, Yi-Xin; Chow, Dick Ho Kiu
- Journal of Orthopaedic Research, Vol. 32, Issue 8
Sclerostin Levels Associated with Inhibition of the Wnt/β-Catenin Signaling and Reduced Bone Turnover in Type 2 Diabetes Mellitus
journal, October 2012
- Gaudio, Agostino; Privitera, Filippo; Battaglia, Katia
- The Journal of Clinical Endocrinology & Metabolism, Vol. 97, Issue 10
Genetic evidence that SOST inhibits WNT signaling in the limb
journal, June 2010
- Collette, Nicole M.; Genetos, Damian C.; Murugesh, Deepa
- Developmental Biology, Vol. 342, Issue 2
Multiple Roles of the PI3K/PKB (Akt) Pathway in Cell Cycle Progression
journal, July 2003
- Liang, Jiyong; Slingerland, Joyce M.
- Cell Cycle, Vol. 2, Issue 4
Wnt Signaling and the Polarity of the Primary Body Axis
journal, December 2009
- Petersen, Christian P.; Reddien, Peter W.
- Cell, Vol. 139, Issue 6
Guidelines for assessment of bone microstructure in rodents using micro-computed tomography
journal, June 2010
- Bouxsein, Mary L.; Boyd, Stephen K.; Christiansen, Blaine A.
- Journal of Bone and Mineral Research, Vol. 25, Issue 7
Zinc supplementation inhibits the increase in osteoclastogenesis and decrease in osteoblastogenesis in streptozotocin-induced diabetic rats
journal, August 2013
- Iitsuka, Natsumi; Hie, Mamiko; Tsukamoto, Ikuyo
- European Journal of Pharmacology, Vol. 714, Issue 1-3
Histomorphometric analysis of diabetic osteopenia in streptozotocin-induced diabetic mice: A possible role of oxidative stress
journal, May 2007
- Hamada, Yasuhiro; Kitazawa, Sohei; Kitazawa, Riko
- Bone, Vol. 40, Issue 5
Zinc supplementation inhibits the increase in osteoclastogenesis and decrease in osteoblastogenesis in streptozotocin-induced diabetic rats
journal, August 2013
- Iitsuka, Natsumi; Hie, Mamiko; Tsukamoto, Ikuyo
- European Journal of Pharmacology, Vol. 714, Issue 1-3
Bone mineral density and fracture risk in type-2 diabetes mellitus: the Rotterdam Study.
journal, June 2005
- de Liefde, I. I.; van der Klift, M.; de Laet, C. E. D. H.
- Osteoporosis International, Vol. 16, Issue 12
Hyperglycemia Diverts Dividing Osteoblastic Precursor Cells to an Adipogenic Pathway and Induces Synthesis of a Hyaluronan Matrix That Is Adhesive for Monocytes
journal, April 2014
- Wang, Aimin; Midura, Ronald J.; Vasanji, Amit
- Journal of Biological Chemistry, Vol. 289, Issue 16
Inhibition of the canonical Wnt pathway by high glucose can be reversed by parathyroid hormone-related protein in osteoblastic cells
journal, June 2013
- López-Herradón, Ana; Portal-Núñez, Sergio; García-Martín, Adela
- Journal of Cellular Biochemistry, Vol. 114, Issue 8
Inhibition of the canonical Wnt pathway by high glucose can be reversed by parathyroid hormone-related protein in osteoblastic cells
journal, June 2013
- López-Herradón, Ana; Portal-Núñez, Sergio; García-Martín, Adela
- Journal of Cellular Biochemistry, Vol. 114, Issue 8
Identification of a 52 kb deletion downstream of the SOST gene in patients with van Buchem disease
journal, February 2002
- Balemans, W.
- Journal of Medical Genetics, Vol. 39, Issue 2
Hyperglycemia Enhances Adipogenic Induction of Lipid Accumulation: Involvement of Extracellular Signal-Regulated Protein Kinase 1/2, Phosphoinositide 3-Kinase/Akt, and Peroxisome Proliferator-Activated Receptor γ Signaling
journal, September 2007
- Chuang, Chia Chi; Yang, Rong Sen; Tsai, Keh Sung
- Endocrinology, Vol. 148, Issue 9
Anti-Sclerostin Antibody Inhibits Internalization of Sclerostin and Sclerostin-Mediated Antagonism of Wnt/LRP6 Signaling
journal, April 2013
- van Dinther, Maarten; Zhang, Juan; Weidauer, Stella E.
- PLoS ONE, Vol. 8, Issue 4
Production of a standard closed fracture in laboratory animal bone
journal, January 1984
- Bonnarens, Frank; Einhorn, Thomas A.
- Journal of Orthopaedic Research, Vol. 2, Issue 1
The bone marrow microenvironment contributes to type I diabetes induced osteoblast death
journal, November 2010
- Coe, Lindsay M.; Irwin, Regina; Lippner, Dennean
- Journal of Cellular Physiology, Vol. 226, Issue 2
Streptozotocin, Type I Diabetes Severity and Bone
journal, March 2009
- Motyl, Katherine; McCabe, Laura R.
- Biological Procedures Online, Vol. 11, Issue 1
Diabetes and Its Complications and Their Relationship with Risk of Fractures in Type 1 and 2 Diabetes
journal, December 2008
- Vestergaard, Peter; Rejnmark, Lars; Mosekilde, Leif
- Calcified Tissue International, Vol. 84, Issue 1
Increased callus mass and enhanced strength during fracture healing in mice lacking the sclerostin gene
journal, December 2011
- Li, Chaoyang; Ominsky, Michael S.; Tan, Hong-Lin
- Bone, Vol. 49, Issue 6
Wnt Signaling and the Polarity of the Primary Body Axis
journal, December 2009
- Petersen, Christian P.; Reddien, Peter W.
- Cell, Vol. 139, Issue 6
Inhibition of sclerostin by systemic treatment with sclerostin antibody enhances healing of proximal tibial defects in ovariectomized rats
journal, March 2012
- McDonald, Michelle M.; Morse, Alyson; Mikulec, Kathy
- Journal of Orthopaedic Research, Vol. 30, Issue 10
Genomic deletion of a long-range bone enhancer misregulates sclerostin in Van Buchem disease
journal, June 2005
- Loots, G. G.
- Genome Research, Vol. 15, Issue 7
Effects of sclerostin antibody on healing of a non-critical size femoral bone defect
journal, August 2012
- Jawad, Muhammad U.; Fritton, Kate E.; Ma, Ting
- Journal of Orthopaedic Research, Vol. 31, Issue 1
Osteoporosis in Patients With Diabetes Mellitus
journal, May 2007
- Hofbauer, Lorenz C.; Brueck, Carolin C.; Singh, Shiv K.
- Journal of Bone and Mineral Research, Vol. 22, Issue 9
Single-dose, placebo-controlled, randomized study of AMG 785, a sclerostin monoclonal antibody
journal, June 2010
- Padhi, Desmond; Jang, Graham; Stouch, Brian
- Journal of Bone and Mineral Research, Vol. 26, Issue 1
Diabetes Interferes with the Bone Formation by Affecting the Expression of Transcription Factors that Regulate Osteoblast Differentiation
journal, January 2003
- Lu, Huafei; Kraut, Douglas; Gerstenfeld, Louis C.
- Endocrinology, Vol. 144, Issue 1
Localization of the Gene for Sclerosteosis to the van Buchem Disease–Gene Region on Chromosome 17q12–q21
journal, June 1999
- Balemans, Wendy; Van Den Ende, Jenneke; Freire Paes-Alves, Auristela
- The American Journal of Human Genetics, Vol. 64, Issue 6
Wnt/β-Catenin Signaling in Mesenchymal Progenitors Controls Osteoblast and Chondrocyte Differentiation during Vertebrate Skeletogenesis
journal, May 2005
- Day, Timothy F.; Guo, Xizhi; Garrett-Beal, Lisa
- Developmental Cell, Vol. 8, Issue 5
Guidelines for assessment of bone microstructure in rodents using micro-computed tomography
journal, June 2010
- Bouxsein, Mary L.; Boyd, Stephen K.; Christiansen, Blaine A.
- Journal of Bone and Mineral Research, Vol. 25, Issue 7
An in vivo experimental study on osteopenia in diabetic rats
journal, October 2011
- Musumeci, Giuseppe; Loreto, Carla; Clementi, Giuseppe
- Acta Histochemica, Vol. 113, Issue 6
Inhibition of sclerostin by monoclonal antibody enhances bone healing and improves bone density and strength of nonfractured bones
journal, May 2011
- Ominsky, Michael S.; Li, Chaoyang; Li, Xiaodong
- Journal of Bone and Mineral Research, Vol. 26, Issue 5
Sclerostin Deficiency Is Linked to Altered Bone Composition: SCLEROSTIN DEFICIENCY IS LINKED TO ALTERED BONE COMPOSITION
journal, September 2014
- Hassler, Norbert; Roschger, Andreas; Gamsjaeger, Sonja
- Journal of Bone and Mineral Research, Vol. 29, Issue 10
Management of Diabetes Mellitus: Could Simultaneous Targeting of Hyperglycemia and Oxidative Stress Be a Better Panacea?
journal, March 2012
- Erejuwa, Omotayo O.
- International Journal of Molecular Sciences, Vol. 13, Issue 3
Age-Related Changes in Trabecular Architecture Differ in Female and Male C57BL/6J Mice
journal, May 2007
- Glatt, Vaida; Canalis, Ernesto; Stadmeyer, Lisa
- Journal of Bone and Mineral Research, Vol. 22, Issue 8
Sclerostin antibody treatment improves bone mass, bone strength, and bone defect regeneration in rats with type 2 diabetes mellitus
journal, February 2013
- Hamann, Christine; Rauner, Martina; Höhna, Yvonne
- Journal of Bone and Mineral Research, Vol. 28, Issue 3
Two doses of sclerostin antibody in cynomolgus monkeys increases bone formation, bone mineral density, and bone strength
journal, January 2010
- Ominsky, Michael S.; Vlasseros, Fay; Jolette, Jacquelin
- Journal of Bone and Mineral Research, Vol. 25, Issue 5
Increasing duration of type 1 diabetes perturbs the strength–structure relationship and increases brittleness of bone
journal, April 2011
- Nyman, Jeffry S.; Even, Jesse L.; Jo, Chan-Hee
- Bone, Vol. 48, Issue 4
Intensive Insulin Therapy and Bone Mineral Density in Type 1 Diabetes Mellitus: A Prospective Study
journal, May 2000
- Campos Pastor, M. M.; López-Ibarra, P. J.; Escobar-Jiménez, F.
- Osteoporosis International, Vol. 11, Issue 5
Bone and the regulation of global energy balance
journal, May 2015
- Zhang, Q.; Riddle, R. C.; Clemens, T. L.
- Journal of Internal Medicine, Vol. 277, Issue 6
Glimepiride Promotes Osteogenic Differentiation in Rat Osteoblasts via the PI3K/Akt/eNOS Pathway in a High Glucose Microenvironment
journal, November 2014
- Ma, Pan; Gu, Bin; Xiong, Wei
- PLoS ONE, Vol. 9, Issue 11
The Influence of Diabetes Mellitus on the Healing of Closed Fractures
journal, July 1988
- Loder, Randall T.
- Clinical Orthopaedics and Related Research, Vol. 232, Issue &NA;
Works referencing / citing this record:
Pulsed electromagnetic fields preserve bone architecture and mechanical properties and stimulate porous implant osseointegration by promoting bone anabolism in type 1 diabetic rabbits
journal, March 2018
- Cai, J.; Li, W.; Sun, T.
- Osteoporosis International, Vol. 29, Issue 5
Sclerostin Antibody Mitigates Estrogen Deficiency-Inducted Marrow Lipid Accumulation Assessed by Proton MR Spectroscopy
journal, March 2019
- Li, Shaojun; Huang, Bingcang; Jiang, Bo
- Frontiers in Endocrinology, Vol. 10
Sclerostin Antibody Therapy for the Treatment of Osteoporosis: Clinical Prospects and Challenges
journal, January 2016
- MacNabb, Claire; Patton, D.; Hayes, J. S.
- Journal of Osteoporosis, Vol. 2016
Altered expression of SDF-1 and CXCR4 during fracture healing in diabetes mellitus
journal, April 2017
- Arakura, Michio; Lee, Sang Yang; Takahara, Shunsuke
- International Orthopaedics, Vol. 41, Issue 6
Loss of mechanosensitive sclerostin may accelerate cranial bone growth and regeneration
journal, October 2018
- Kang, Kyung Shin; Lastfogel, Jeff; Ackerman, Laurie L.
- Journal of Neurosurgery, Vol. 129, Issue 4
The skeletal cell-derived molecule sclerostin drives bone marrow adipogenesis
journal, June 2017
- Fairfield, Heather; Falank, Carolyne; Harris, Elizabeth
- Journal of Cellular Physiology, Vol. 233, Issue 2
Clinical advantages and disadvantages of anabolic bone therapies targeting the WNT pathway
journal, September 2018
- Appelman-Dijkstra, Natasha M.; Papapoulos, Socrates E.
- Nature Reviews Endocrinology, Vol. 14, Issue 10
Differential effects of type 1 diabetes mellitus and subsequent osteoblastic β-catenin activation on trabecular and cortical bone in a mouse model
journal, December 2018
- Chen, Sixu; Liu, Daocheng; He, Sihao
- Experimental & Molecular Medicine, Vol. 50, Issue 12
Tumor necrosis factor-α antagonist diminishes osteocytic RANKL and sclerostin expression in diabetes rats with periodontitis
journal, December 2017
- Kim, Ji-Hye; Kim, Ae Ri; Choi, Yun Hui
- PLOS ONE, Vol. 12, Issue 12
Tumor necrosis factor-α antagonist diminishes osteocytic RANKL and sclerostin expression in diabetes rats with periodontitis
journal, December 2017
- Kim, Ji-Hye; Kim, Ae Ri; Choi, Yun Hui
- PLOS ONE, Vol. 12, Issue 12
Sclerostin influences body composition by regulating catabolic and anabolic metabolism in adipocytes
journal, December 2017
- Kim, Soohyun P.; Frey, Julie L.; Li, Zhu
- Proceedings of the National Academy of Sciences, Vol. 114, Issue 52
Application of anti-Sclerostin therapy in non-osteoporosis disease models
journal, March 2017
- Jacobsen, Christina M.
- Bone, Vol. 96