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Sclerostin Antibody Increases Callus Size and Strength but does not Improve Fracture Union in a Challenged Open Rat Fracture Model
Open fractures remain a challenge in orthopedics. Current strategies to intervene are often inadequate, particularly in severe fractures or when treatment is delayed. Sclerostin is a negative regulator of bone growth and sclerostin-neutralizing antibodies (Scl-Ab) can increase bone mass and strength...
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| Published in: | Calcified tissue international 2017-08, Vol.101 (2), p.217-228 |
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| container_title | Calcified tissue international |
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| creator | Morse, Alyson McDonald, Michelle M. Schindeler, Aaron Peacock, Lauren Mikulec, Kathy Cheng, Tegan L. Liu, Min Ke, Hua Zhu Little, David G. |
| description | Open fractures remain a challenge in orthopedics. Current strategies to intervene are often inadequate, particularly in severe fractures or when treatment is delayed. Sclerostin is a negative regulator of bone growth and sclerostin-neutralizing antibodies (Scl-Ab) can increase bone mass and strength. The application of these antibodies to improve orthopedic repair has shown varied results, and may be dependent on the location and severity of the bony injury. We examined Scl-Ab treatment within an established rat osteotomy model with periosteal stripping analogous to open fracture repair. In one study, Scl-Ab was given 25 mg/kg bi-weekly, either from the time of fracture or from 3 weeks post-fracture up to an end-point of 12 weeks. A second study treated only delayed union open fractures that did not show radiographic union by week 6 post-fracture. Outcome measures included radiographic union, microCT analysis of bone volume and architecture, and histology. In the first study, Scl-Ab given from either 0 or 3 weeks significantly improved callus bone volume (+52%,
p
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| doi_str_mv | 10.1007/s00223-017-0275-2 |
| format | article |
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p
< 0.05 and +58%,
p
< 0.01) at 12 weeks, as well as strength (+48%,
p
< 0.05 and +70%,
p
< 0.05). Despite these improvements, union rate was not changed. In the second study treating only established delayed fractures, bony callus volume was similarly increased by Scl-Ab treatment; however, this did not translate to increased biomechanical strength or union improvement. Sclerostin antibody treatment has limited effects on the healing of challenging open fractures with periosteal stripping, but shows the greatest benefits on callus size and strength with earlier intervention.</description><identifier>ISSN: 0171-967X</identifier><identifier>EISSN: 1432-0827</identifier><identifier>DOI: 10.1007/s00223-017-0275-2</identifier><identifier>PMID: 28391431</identifier><language>eng</language><publisher>New York: Springer US</publisher><subject>Animals ; Antibodies ; Antibodies - pharmacology ; Biochemistry ; Biomechanical Phenomena - drug effects ; Biomedical and Life Sciences ; Bone Density - drug effects ; Bone growth ; Bone mass ; Bone Morphogenetic Proteins - immunology ; Bones ; Bony Callus - pathology ; Callus ; Cell Biology ; Cellular biology ; Computed tomography ; Disease Models, Animal ; Endocrinology ; Femoral Fractures - drug therapy ; Femoral Fractures - pathology ; Femur - drug effects ; Femur - pathology ; Fracture Healing - drug effects ; Fractures ; Genetic Markers - immunology ; Immunoglobulins ; Life Sciences ; Male ; Original Research ; Orthopedics ; Osteogenesis - drug effects ; Osteotomy ; Osteotomy - methods ; Rats ; Rodents ; SOST protein</subject><ispartof>Calcified tissue international, 2017-08, Vol.101 (2), p.217-228</ispartof><rights>Springer Science+Business Media New York 2017</rights><rights>Calcified Tissue International is a copyright of Springer, 2017.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c372t-4dedcf58ee057b63ff996db0c0673d0fe68883de08217010110c2b470ae28eef3</citedby><cites>FETCH-LOGICAL-c372t-4dedcf58ee057b63ff996db0c0673d0fe68883de08217010110c2b470ae28eef3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28391431$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Morse, Alyson</creatorcontrib><creatorcontrib>McDonald, Michelle M.</creatorcontrib><creatorcontrib>Schindeler, Aaron</creatorcontrib><creatorcontrib>Peacock, Lauren</creatorcontrib><creatorcontrib>Mikulec, Kathy</creatorcontrib><creatorcontrib>Cheng, Tegan L.</creatorcontrib><creatorcontrib>Liu, Min</creatorcontrib><creatorcontrib>Ke, Hua Zhu</creatorcontrib><creatorcontrib>Little, David G.</creatorcontrib><title>Sclerostin Antibody Increases Callus Size and Strength but does not Improve Fracture Union in a Challenged Open Rat Fracture Model</title><title>Calcified tissue international</title><addtitle>Calcif Tissue Int</addtitle><addtitle>Calcif Tissue Int</addtitle><description>Open fractures remain a challenge in orthopedics. Current strategies to intervene are often inadequate, particularly in severe fractures or when treatment is delayed. Sclerostin is a negative regulator of bone growth and sclerostin-neutralizing antibodies (Scl-Ab) can increase bone mass and strength. The application of these antibodies to improve orthopedic repair has shown varied results, and may be dependent on the location and severity of the bony injury. We examined Scl-Ab treatment within an established rat osteotomy model with periosteal stripping analogous to open fracture repair. In one study, Scl-Ab was given 25 mg/kg bi-weekly, either from the time of fracture or from 3 weeks post-fracture up to an end-point of 12 weeks. A second study treated only delayed union open fractures that did not show radiographic union by week 6 post-fracture. Outcome measures included radiographic union, microCT analysis of bone volume and architecture, and histology. In the first study, Scl-Ab given from either 0 or 3 weeks significantly improved callus bone volume (+52%,
p
< 0.05 and +58%,
p
< 0.01) at 12 weeks, as well as strength (+48%,
p
< 0.05 and +70%,
p
< 0.05). Despite these improvements, union rate was not changed. In the second study treating only established delayed fractures, bony callus volume was similarly increased by Scl-Ab treatment; however, this did not translate to increased biomechanical strength or union improvement. Sclerostin antibody treatment has limited effects on the healing of challenging open fractures with periosteal stripping, but shows the greatest benefits on callus size and strength with earlier intervention.</description><subject>Animals</subject><subject>Antibodies</subject><subject>Antibodies - pharmacology</subject><subject>Biochemistry</subject><subject>Biomechanical Phenomena - drug effects</subject><subject>Biomedical and Life Sciences</subject><subject>Bone Density - drug effects</subject><subject>Bone growth</subject><subject>Bone mass</subject><subject>Bone Morphogenetic Proteins - immunology</subject><subject>Bones</subject><subject>Bony Callus - pathology</subject><subject>Callus</subject><subject>Cell Biology</subject><subject>Cellular biology</subject><subject>Computed tomography</subject><subject>Disease Models, Animal</subject><subject>Endocrinology</subject><subject>Femoral Fractures - drug therapy</subject><subject>Femoral Fractures - pathology</subject><subject>Femur - drug effects</subject><subject>Femur - pathology</subject><subject>Fracture Healing - drug effects</subject><subject>Fractures</subject><subject>Genetic Markers - immunology</subject><subject>Immunoglobulins</subject><subject>Life Sciences</subject><subject>Male</subject><subject>Original Research</subject><subject>Orthopedics</subject><subject>Osteogenesis - drug effects</subject><subject>Osteotomy</subject><subject>Osteotomy - methods</subject><subject>Rats</subject><subject>Rodents</subject><subject>SOST protein</subject><issn>0171-967X</issn><issn>1432-0827</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><recordid>eNp1kU2LFDEQhoMo7rj6A7xIwIuX1krSk3Qfl8HVgZUFxwVvIZ1Uu730JGOSFtajv9xaZv1A8FSHet63Pl7Gngt4LQDMmwIgpWpAmAakWTfyAVuJVskGOmkeshU1RNNr8_mEPSnlBkC0WuvH7ER2qidQrNiPnZ8xp1KnyM9inYYUbvk2-oyuYOEbN89L4bvpO3IXA9_VjPFLvebDUnlIRMRU-XZ_yOkb8vPsfF0y8qs4pcjJ0vHNNVmQBgO_PGDkH139w31IAeen7NHo5oLP7uspuzp_-2nzvrm4fLfdnF00XhlZmzZg8OO6Q4S1GbQax77XYQAP2qgAI-qu61RAul0YECAEeDm0BhxKEo3qlL06-tKyXxcs1e6n4nGeXcS0FCu6TqtWC9kT-vIf9CYtOdJ2VvRibXoldUuUOFKeHlgyjvaQp73Lt1aAvQvIHgOylIO9C8hK0ry4d16GPYbfil-JECCPQKEWvS3_Nfq_rj8BbQqbUQ</recordid><startdate>20170801</startdate><enddate>20170801</enddate><creator>Morse, Alyson</creator><creator>McDonald, Michelle M.</creator><creator>Schindeler, Aaron</creator><creator>Peacock, Lauren</creator><creator>Mikulec, Kathy</creator><creator>Cheng, Tegan L.</creator><creator>Liu, Min</creator><creator>Ke, Hua Zhu</creator><creator>Little, David G.</creator><general>Springer US</general><general>Springer Nature B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QP</scope><scope>7RV</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB0</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope></search><sort><creationdate>20170801</creationdate><title>Sclerostin Antibody Increases Callus Size and Strength but does not Improve Fracture Union in a Challenged Open Rat Fracture Model</title><author>Morse, Alyson ; McDonald, Michelle M. ; Schindeler, Aaron ; Peacock, Lauren ; Mikulec, Kathy ; Cheng, Tegan L. ; Liu, Min ; Ke, Hua Zhu ; Little, David G.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c372t-4dedcf58ee057b63ff996db0c0673d0fe68883de08217010110c2b470ae28eef3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Animals</topic><topic>Antibodies</topic><topic>Antibodies - pharmacology</topic><topic>Biochemistry</topic><topic>Biomechanical Phenomena - drug effects</topic><topic>Biomedical and Life Sciences</topic><topic>Bone Density - drug effects</topic><topic>Bone growth</topic><topic>Bone mass</topic><topic>Bone Morphogenetic Proteins - immunology</topic><topic>Bones</topic><topic>Bony Callus - pathology</topic><topic>Callus</topic><topic>Cell Biology</topic><topic>Cellular biology</topic><topic>Computed tomography</topic><topic>Disease Models, Animal</topic><topic>Endocrinology</topic><topic>Femoral Fractures - drug therapy</topic><topic>Femoral Fractures - pathology</topic><topic>Femur - drug effects</topic><topic>Femur - pathology</topic><topic>Fracture Healing - drug effects</topic><topic>Fractures</topic><topic>Genetic Markers - immunology</topic><topic>Immunoglobulins</topic><topic>Life Sciences</topic><topic>Male</topic><topic>Original Research</topic><topic>Orthopedics</topic><topic>Osteogenesis - drug effects</topic><topic>Osteotomy</topic><topic>Osteotomy - methods</topic><topic>Rats</topic><topic>Rodents</topic><topic>SOST protein</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Morse, Alyson</creatorcontrib><creatorcontrib>McDonald, Michelle M.</creatorcontrib><creatorcontrib>Schindeler, Aaron</creatorcontrib><creatorcontrib>Peacock, Lauren</creatorcontrib><creatorcontrib>Mikulec, Kathy</creatorcontrib><creatorcontrib>Cheng, Tegan L.</creatorcontrib><creatorcontrib>Liu, Min</creatorcontrib><creatorcontrib>Ke, Hua Zhu</creatorcontrib><creatorcontrib>Little, David G.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>AUTh Library subscriptions: ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><jtitle>Calcified tissue international</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Morse, Alyson</au><au>McDonald, Michelle M.</au><au>Schindeler, Aaron</au><au>Peacock, Lauren</au><au>Mikulec, Kathy</au><au>Cheng, Tegan L.</au><au>Liu, Min</au><au>Ke, Hua Zhu</au><au>Little, David G.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Sclerostin Antibody Increases Callus Size and Strength but does not Improve Fracture Union in a Challenged Open Rat Fracture Model</atitle><jtitle>Calcified tissue international</jtitle><stitle>Calcif Tissue Int</stitle><addtitle>Calcif Tissue Int</addtitle><date>2017-08-01</date><risdate>2017</risdate><volume>101</volume><issue>2</issue><spage>217</spage><epage>228</epage><pages>217-228</pages><issn>0171-967X</issn><eissn>1432-0827</eissn><abstract>Open fractures remain a challenge in orthopedics. Current strategies to intervene are often inadequate, particularly in severe fractures or when treatment is delayed. Sclerostin is a negative regulator of bone growth and sclerostin-neutralizing antibodies (Scl-Ab) can increase bone mass and strength. The application of these antibodies to improve orthopedic repair has shown varied results, and may be dependent on the location and severity of the bony injury. We examined Scl-Ab treatment within an established rat osteotomy model with periosteal stripping analogous to open fracture repair. In one study, Scl-Ab was given 25 mg/kg bi-weekly, either from the time of fracture or from 3 weeks post-fracture up to an end-point of 12 weeks. A second study treated only delayed union open fractures that did not show radiographic union by week 6 post-fracture. Outcome measures included radiographic union, microCT analysis of bone volume and architecture, and histology. In the first study, Scl-Ab given from either 0 or 3 weeks significantly improved callus bone volume (+52%,
p
< 0.05 and +58%,
p
< 0.01) at 12 weeks, as well as strength (+48%,
p
< 0.05 and +70%,
p
< 0.05). Despite these improvements, union rate was not changed. In the second study treating only established delayed fractures, bony callus volume was similarly increased by Scl-Ab treatment; however, this did not translate to increased biomechanical strength or union improvement. Sclerostin antibody treatment has limited effects on the healing of challenging open fractures with periosteal stripping, but shows the greatest benefits on callus size and strength with earlier intervention.</abstract><cop>New York</cop><pub>Springer US</pub><pmid>28391431</pmid><doi>10.1007/s00223-017-0275-2</doi><tpages>12</tpages></addata></record> |
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| subjects | Animals Antibodies Antibodies - pharmacology Biochemistry Biomechanical Phenomena - drug effects Biomedical and Life Sciences Bone Density - drug effects Bone growth Bone mass Bone Morphogenetic Proteins - immunology Bones Bony Callus - pathology Callus Cell Biology Cellular biology Computed tomography Disease Models, Animal Endocrinology Femoral Fractures - drug therapy Femoral Fractures - pathology Femur - drug effects Femur - pathology Fracture Healing - drug effects Fractures Genetic Markers - immunology Immunoglobulins Life Sciences Male Original Research Orthopedics Osteogenesis - drug effects Osteotomy Osteotomy - methods Rats Rodents SOST protein |
| title | Sclerostin Antibody Increases Callus Size and Strength but does not Improve Fracture Union in a Challenged Open Rat Fracture Model |
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