Vertebral Implantation of NELL-1 Enhances Bone Formation in an Osteoporotic Sheep Model.
Vertebral compression fractures related to osteoporosis greatly afflict the aging population. One of the most commonly used therapy today is balloon kyphoplasty. However, this treatment is far from ideal and is associated with significant side effects. NELL-1, an osteoinductive factor that possesses both pro-osteogenic and anti-osteoclastic properties, is a promising candidate for an alternative to current treatment modalities. This study utilizes the pro-osteogenic properties of recombinant human NELL-1 (rhNELL-1) in lumbar spine vertebral defect model in osteoporotic sheep.



Osteoporosis was induced through ovariectomy, dietary depletion of calcium and vitamin D, and steroid administration. After osteoporotic induction, lumbar vertebral body defect creation was performed. Sheep were randomly implanted with the control vehicle, comprised of hyaluronic acid (HA) with hydroxyapatite-coated β-tricalcium phosphate (β-TCP), or the treatment material of rhNELL-1 protein lyophilized onto β-TCP mixed with HA. Analysis of lumbar spine defect healing was performed by radiographic, histologic, and computer-simulated biomechanical testing.



rhNELL-1 treatment significantly increased lumbar spine bone formation, as determined by bone mineral density, % bone volume, and mean cortical width as assessed by micro-computed tomography. Histological analysis revealed a significant increase in bone area and osteoblast number and decrease in osteoclast number around the implant site. Computer-simulated biomechanical analysis of trabecular bone demonstrated that rhNELL-1-treatment resulted in a significantly more stress-resistant composition.



Our findings suggest rhNELL-1-based vertebral implantation successfully improved cortical and cancellous bone regeneration in the lumbar spine of osteoporotic sheep. rhNELL-1-based bone graft substitutes represent a potential new local therapy.
1 Departments of Surgery and Orthopaedic Surgery, Orthopaedic Hospital Research Center, UCLA and Orthopedic Hospital , Los Angeles, California.|2 Division of Growth and Development and Section of Orthodontics, Dental and Craniofacial Research Institute, School of Dentistry, University of California , Los Angeles, Los Angeles, California.|3 Department of Pathology and Laboratory Medicine, University of California , Los Angeles, Los Angeles, California.
Aaron W
AW
James
2 Division of Growth and Development and Section of Orthodontics, Dental and Craniofacial Research Institute, School of Dentistry, University of California , Los Angeles, Los Angeles, California.
Michael
M
Chiang
2 Division of Growth and Development and Section of Orthodontics, Dental and Craniofacial Research Institute, School of Dentistry, University of California , Los Angeles, Los Angeles, California.
Greg
G
Asatrian
1 Departments of Surgery and Orthopaedic Surgery, Orthopaedic Hospital Research Center, UCLA and Orthopedic Hospital , Los Angeles, California.|2 Division of Growth and Development and Section of Orthodontics, Dental and Craniofacial Research Institute, School of Dentistry, University of California , Los Angeles, Los Angeles, California.
Jia
J
Shen
2 Division of Growth and Development and Section of Orthodontics, Dental and Craniofacial Research Institute, School of Dentistry, University of California , Los Angeles, Los Angeles, California.
Raghav
R
Goyal
2 Division of Growth and Development and Section of Orthodontics, Dental and Craniofacial Research Institute, School of Dentistry, University of California , Los Angeles, Los Angeles, California.
Choon G
CG
Chung
1 Departments of Surgery and Orthopaedic Surgery, Orthopaedic Hospital Research Center, UCLA and Orthopedic Hospital , Los Angeles, California.|2 Division of Growth and Development and Section of Orthodontics, Dental and Craniofacial Research Institute, School of Dentistry, University of California , Los Angeles, Los Angeles, California.
Le
L
Chang
1 Departments of Surgery and Orthopaedic Surgery, Orthopaedic Hospital Research Center, UCLA and Orthopedic Hospital , Los Angeles, California.|2 Division of Growth and Development and Section of Orthodontics, Dental and Craniofacial Research Institute, School of Dentistry, University of California , Los Angeles, Los Angeles, California.
Swati
S
Shrestha
4 Department of Veterinary Sciences, Colorado State University , Fort Collins, Colorado.
A Simon
AS
Turner
4 Department of Veterinary Sciences, Colorado State University , Fort Collins, Colorado.
Howard B
HB
Seim
1 Departments of Surgery and Orthopaedic Surgery, Orthopaedic Hospital Research Center, UCLA and Orthopedic Hospital , Los Angeles, California.|2 Division of Growth and Development and Section of Orthodontics, Dental and Craniofacial Research Institute, School of Dentistry, University of California , Los Angeles, Los Angeles, California.
Xinli
X
Zhang
5 Departments of Bioengineering and Material Sciences, University of California , Los Angeles, Los Angeles, California.
Benjamin M
BM
Wu
1 Departments of Surgery and Orthopaedic Surgery, Orthopaedic Hospital Research Center, UCLA and Orthopedic Hospital , Los Angeles, California.|2 Division of Growth and Development and Section of Orthodontics, Dental and Craniofacial Research Institute, School of Dentistry, University of California , Los Angeles, Los Angeles, California.
Kang
K
Ting
1 Departments of Surgery and Orthopaedic Surgery, Orthopaedic Hospital Research Center, UCLA and Orthopedic Hospital , Los Angeles, California.|6 Division of Plastic and Reconstructive Surgery, Department of Surgery, David Geffen School of Medicine, University of California , Los Angeles, Los Angeles, California.
Chia
C
Soo
D015502:Absorptiometry, Photon; D000818:Animals; D001696:Biomechanical Phenomena; D015519:Bone Density / Q000187:drug effects; D002135:Calcium-Binding Proteins; D002452:Cell Count; D004195:Disease Models, Animal; D020342:Finite Element Analysis; D006801:Humans; D020007:Implants, Experimental; D008159:Lumbar Vertebrae / Q000000981:diagnostic imaging / Q000187:drug effects / Q000473:pathology* / Q000503:physiopathology; D009419:Nerve Tissue Proteins / Q000494:pharmacology*; D010006:Osteoblasts / Q000187:drug effects / Q000473:pathology; D010010:Osteoclasts / Q000187:drug effects / Q000473:pathology; D010012:Osteogenesis / Q000187:drug effects*; D010024:Osteoporosis / Q000000981:diagnostic imaging / Q000473:pathology* / Q000503:physiopathology / Q000628:therapy; D012756:Sheep; D055114:X-Ray Microtomography
D002135:Calcium-Binding Proteins; C104144:NELL1 protein, human; D009419:Nerve Tissue Proteins