title: Ovariectomy-Induced Osteoporosis Does Not Impact Fusion Rates in a Recombinant Human Bone Morphogenetic Protein-2-Dependent Rat Posterolateral Arthrodesis Model.
abstract: Study Design Randomized, controlled animal study. Objective Recombinant human bone morphogenetic protein-2 (rhBMP-2) is frequently utilized as a bone graft substitute in spinal fusions to overcome the difficult healing environment in patients with osteoporosis. However, the effects of estrogen deficiency and poor bone quality on rhBMP-2 efficacy are unknown. This study sought to determine whether rhBMP-2-induced healing is affected by estrogen deficiency and poor bone quality in a stringent osteoporotic posterolateral spinal fusion model. Methods Aged female Sprague-Dawley rats underwent an ovariectomy (OVX group) or a sham procedure, and the OVX animals were fed a low-calcium, low-phytoestrogen diet. After 12 weeks, the animals underwent a posterolateral spinal fusion with 1 μg rhBMP-2 on an absorbable collagen sponge. Representative animals were sacrificed at 1 week postoperative for alkaline phosphatase (ALP) and osteocalcin serum analyses. The remaining animals underwent radiographs 2 and 4 weeks after surgery and were subsequently euthanized for fusion analysis by manual palpation, micro-computed tomography (CT) imaging, and histologic analysis. Results The ALP and osteocalcin levels were similar between the control and OVX groups. Manual palpation revealed no significant differences in the fusion scores between the control (1.42 ± 0.50) and OVX groups (1.83 ± 0.36; p = 0.07). Fusion rates were 100% in both groups. Micro-CT imaging revealed no significant difference in the quantity of new bone formation, and histologic analysis demonstrated bridging bone across the transverse processes in fused animals from both groups. Conclusions This study demonstrates that estrogen deficiency and compromised bone quality do not negatively influence spinal fusion when utilizing rhBMP-2, and the osteoinductive capacity of the growth factor is not functionally reduced under osteoporotic conditions in the rat. Although osteoporosis is a risk factor for pseudarthrosis/nonunion, rhBMP-2-induced healing was not inhibited in osteoporotic rats.
authors.affiliation: Department of Orthopaedic Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States.
authors.forename: Jason H
authors.initials: JH
authors.lastname: Ghodasra
authors.affiliation: Department of Orthopaedic Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Nickoli
authors.affiliation: Department of Orthopaedic Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States.
authors.forename: Sohaib Z
authors.initials: SZ
authors.lastname: Hashmi
authors.affiliation: Department of Orthopaedic Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States.
authors.forename: John T
authors.initials: JT
authors.lastname: Nelson
authors.affiliation: Department of Orthopaedic Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States.
authors.forename: Marco
authors.initials: M
authors.lastname: Mendoza
authors.affiliation: Department of Orthopaedic Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States.
authors.forename: Joseph D
authors.initials: JD
authors.lastname: Nicolas
authors.affiliation: Department of Orthopaedic Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States.
authors.forename: Sharath S
authors.initials: SS
authors.lastname: Bellary
authors.affiliation: Department of Orthopaedic Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States.
authors.forename: Kevin
authors.initials: K
authors.lastname: Sonn
authors.affiliation: Department of Orthopaedic Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States.
authors.forename: Amruta
authors.initials: A
authors.lastname: Ashtekar
authors.affiliation: Department of Orthopaedic Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States.
authors.forename: Christian J
authors.initials: CJ
authors.lastname: Park
authors.affiliation: Department of Orthopaedic Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States.
authors.forename: Jacob
authors.initials: J
authors.lastname: Babu
authors.affiliation: Department of Orthopaedic Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States.
authors.forename: Chawon
authors.initials: C
authors.lastname: Yun
authors.affiliation: Department of Orthopaedic Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States.
authors.forename: Anjan
authors.initials: A
authors.lastname: Ghosh
authors.affiliation: Department of Orthopaedic Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States.
authors.forename: Abhishek
authors.initials: A
authors.lastname: Kannan
authors.affiliation: Department of Materials Science and Engineering, Northwestern University Feinberg School of Medicine, Evanston, Illinois, United States.
authors.forename: Stuart R
authors.initials: SR
authors.lastname: Stock
authors.affiliation: Department of Orthopaedic Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States; Department of Neurological Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States.
authors.forename: Wellington K
authors.initials: WK
authors.lastname: Hsu
authors.affiliation: Department of Orthopaedic Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States.
authors.forename: Erin L
authors.initials: EL
authors.lastname: Hsu
keywords: osteoporosis; pseudarthrosis; rats; rhBMP-2; spinal fusion
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