Ovariectomy-Induced Osteoporosis Does Not Impact Fusion Rates in a Recombinant Human Bone Morphogenetic Protein-2-Dependent Rat Posterolateral Arthrodesis Model

Jason H. Ghodasra, Michael S. Nickoli, Sohaib Z. Hashmi, John T. Nelson, Marco Mendoza, Joseph D. Nicolas, Sharath S. Bellary, Kevin Sonn, Amruta Ashtekar, Christian J. Park, Jacob Babu, Chawon Yun, Anjan Ghosh, Abhishek Kannan, Stuart R Stock, Wellington K Hsu, Erin L Hsu*

*Corresponding author for this work

Research output: Contribution to journalArticle

4 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)60-68
Number of pages9
JournalGlobal Spine Journal
Volume6
Issue number1
DOIs
StatePublished - Mar 26 2015

Fingerprint

Arthrodesis
Ovariectomy
Osteoporosis
Spinal Fusion
Bone and Bones
Estrogens
Palpation
Osteocalcin
Alkaline Phosphatase
Tomography
Bone Substitutes
Phytoestrogens
Pseudarthrosis
Porifera
Osteogenesis
Sprague Dawley Rats
recombinant human bone morphogenetic protein-2
Intercellular Signaling Peptides and Proteins
Collagen
Diet

Keywords

  • osteoporosis
  • pseudarthrosis
  • rats
  • rhBMP-2
  • spinal fusion

ASJC Scopus subject areas

  • Surgery
  • Orthopedics and Sports Medicine
  • Clinical Neurology

Cite this

Ghodasra, Jason H. ; Nickoli, Michael S. ; Hashmi, Sohaib Z. ; Nelson, John T. ; Mendoza, Marco ; Nicolas, Joseph D. ; Bellary, Sharath S. ; Sonn, Kevin ; Ashtekar, Amruta ; Park, Christian J. ; Babu, Jacob ; Yun, Chawon ; Ghosh, Anjan ; Kannan, Abhishek ; Stock, Stuart R ; Hsu, Wellington K ; Hsu, Erin L. / Ovariectomy-Induced Osteoporosis Does Not Impact Fusion Rates in a Recombinant Human Bone Morphogenetic Protein-2-Dependent Rat Posterolateral Arthrodesis Model. In: Global Spine Journal. 2015 ; Vol. 6, No. 1. pp. 60-68.
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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.",
keywords = "osteoporosis, pseudarthrosis, rats, rhBMP-2, spinal fusion",
author = "Ghodasra, {Jason H.} and Nickoli, {Michael S.} and Hashmi, {Sohaib Z.} and Nelson, {John T.} and Marco Mendoza and Nicolas, {Joseph D.} and Bellary, {Sharath S.} and Kevin Sonn and Amruta Ashtekar and Park, {Christian J.} and Jacob Babu and Chawon Yun and Anjan Ghosh and Abhishek Kannan and Stock, {Stuart R} and Hsu, {Wellington K} and Hsu, {Erin L}",
year = "2015",
month = "3",
day = "26",
doi = "10.1055/s-0035-1556582",
language = "English (US)",
volume = "6",
pages = "60--68",
journal = "Global Spine Journal",
issn = "2192-5682",
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number = "1",

}

Ghodasra, JH, Nickoli, MS, Hashmi, SZ, Nelson, JT, Mendoza, M, Nicolas, JD, Bellary, SS, Sonn, K, Ashtekar, A, Park, CJ, Babu, J, Yun, C, Ghosh, A, Kannan, A, Stock, SR, Hsu, WK & Hsu, EL 2015, 'Ovariectomy-Induced Osteoporosis Does Not Impact Fusion Rates in a Recombinant Human Bone Morphogenetic Protein-2-Dependent Rat Posterolateral Arthrodesis Model', Global Spine Journal, vol. 6, no. 1, pp. 60-68. https://doi.org/10.1055/s-0035-1556582

Ovariectomy-Induced Osteoporosis Does Not Impact Fusion Rates in a Recombinant Human Bone Morphogenetic Protein-2-Dependent Rat Posterolateral Arthrodesis Model. / Ghodasra, Jason H.; Nickoli, Michael S.; Hashmi, Sohaib Z.; Nelson, John T.; Mendoza, Marco; Nicolas, Joseph D.; Bellary, Sharath S.; Sonn, Kevin; Ashtekar, Amruta; Park, Christian J.; Babu, Jacob; Yun, Chawon; Ghosh, Anjan; Kannan, Abhishek; Stock, Stuart R; Hsu, Wellington K; Hsu, Erin L.

In: Global Spine Journal, Vol. 6, No. 1, 26.03.2015, p. 60-68.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Ovariectomy-Induced Osteoporosis Does Not Impact Fusion Rates in a Recombinant Human Bone Morphogenetic Protein-2-Dependent Rat Posterolateral Arthrodesis Model

AU - Ghodasra, Jason H.

AU - Nickoli, Michael S.

AU - Hashmi, Sohaib Z.

AU - Nelson, John T.

AU - Mendoza, Marco

AU - Nicolas, Joseph D.

AU - Bellary, Sharath S.

AU - Sonn, Kevin

AU - Ashtekar, Amruta

AU - Park, Christian J.

AU - Babu, Jacob

AU - Yun, Chawon

AU - Ghosh, Anjan

AU - Kannan, Abhishek

AU - Stock, Stuart R

AU - Hsu, Wellington K

AU - Hsu, Erin L

PY - 2015/3/26

Y1 - 2015/3/26

N2 - 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.

AB - 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.

KW - osteoporosis

KW - pseudarthrosis

KW - rats

KW - rhBMP-2

KW - spinal fusion

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