Oncostatin-M enhances osteoinduction in a rabbit critical calvarial defect model.
BACKGROUND
Oncostatin-M (OSM) is a member of the interleukin-6 family of cytokines with controversial roles in bone homeostasis. Evidence supports a role in bone regulation, but the balance between healing promotion and acceleration of bone destruction is unclear. It is also uncertain as to whether these varied responses may be dose dependent or related to interactions with other growth factors within the bone microenvironment.


OBJECTIVE
To determine whether OSM enhances osteoinduction in a rabbit critical calvarial defect model and whether there is a dose response curve.


OBJECTIVE
OSM enhances osteoinduction, and there is a dose response curve favoring lower doses over higher doses.


METHODS
Controlled animal study using arms of increasing concentrations of OSM in an inactive demineralized bone matrix (DBM) carrier to assess the degree of osteoinduction through standard histomorphometric analysis and a variant of the radiodensitometry technique.


METHODS
Twenty-five skeletally mature New Zealand white rabbits were randomized into control and experimental arms. Incremental doses of OSM (30 microg, 100 microg, and 300 microg/g) in an inactivated guanidine-extracted DBM (Gu-DBM) carrier were implanted into a critically sized (13 mm) calvarial defect. Arms of carrier alone and no carrier served as controls. The animals were sacrificed at 4 weeks, and histomorphometry and radiodensitometry analyses were then performed.


RESULTS
All OSM arms showed a statistically significant increase in bone formation and bone density compared with either control arm. There was also a statistically significant increase in bone area by histomorphometry between each OSM group, showing an inverse relationship to dose. Radiodensitometry analysis confirmed a significant bone density difference when comparing experimental groups with controls and also showed a significant difference between the low dose and the higher doses of OSM. It failed to show any significance between the higher two doses when compared with each other.


CONCLUSIONS
OSM enhances osteoinduction in vivo and will close a critically sized calvarial defect in a rabbit model when delivered in a Gu-DBM carrier. There appears to be an inverse dose relationship with new bone formation.
Moxham
J Paul
JP
Department of Pediatric Otolaryngology-Head and Neck Surgery, British Columbia Children's Hospital, University of British Columbia, Vancouver, British Columbia, Canada.
D015502:Absorptiometry, Photon; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001861:Bone Regeneration / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005260:Female; D053683:Oncostatin M / Q000008:administration & dosage / Q000494:pharmacology*; D011817:Rabbits; D011897:Random Allocation; D012886:Skull / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000473:pathology*
D000970:Antineoplastic Agents; D053683:Oncostatin M