Share this article on:

Abstract 28: Intraperitoneally Administered PEGylated NELL-1 Treatment for Osteoporosis, in Mice

Plastic and Reconstructive Surgery - Global Open: April 2016 - Volume 4 - Issue 4S - p 48
doi: 10.1097/01.GOX.0000488960.47279.b5
PRS PSRC Podium Proofs 2016

This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially.

Michael D. Uyeda, MD

From the University of California, Los Angeles, Los Angeles, Calif.

PURPOSE: Osteoporosis affects more than 200 million people worldwide. Current antiresorptive treatments have significant limitations because of systemic side effects. NELL-1 is a potent cytokine with combined proosteogenic and antiosteoclastic effects. Previous systemic administration studies using PEGylated NELL-1(NELL-PEG) showed increased bone quality and quantity in healthy mice given 1.25 mg/kg intravenously every 7 days. This study aims to reduce NELL-PEG injection frequency to 14 days while using more patient-friendly intraperitoneal (IP) administration route to recover bone in OVX-induced osteoporotic mice.

METHODS: Three-month-old female BALB/c mice underwent ovariectomy (OVX; n = 10) or Sham operation (n = 10). Osteoporosis induction was confirmed using dual-energy x-ray absorptiometry and ex vivo micro computed tomography (CT) scans. Twelve 5-week-post-OVX BALB/c mice underwent NELL-PEG treatment every 2 weeks with dosages of (1) 5 mg/kg IP or (2) 10 mg/kg IP and harvested at 8 weeks. Serum was analyzed at 0, 4, and 8 weeks. Dynamic BMD was measured by dual-energy x-ray absorptiometry. Ex vivo micro CT, colony-forming unit assay, and histology were performed after harvest.

RESULTS: Ovariectomy was confirmed by decreased BMD (7%) and BV/TV (39.3%). Systemic NELL-PEG at 10 mg/kg IP increased BMD in distal femur (13%), proximal tibia (14%), and lumbar vertebrae (15%). Micro CT data showed the same trend in BMD, BV/TV, and trabecular structures. Colony-forming unit assay confirmed greater osteogenesis in bone marrow stem cells flushed from 10 mg/kg delivery than 5 mg/kg group, and histology confirmed increased bone formation in both treatment groups.

CONCLUSIONS: Systemic NELL-PEG therapy regenerates bone in osteoporotic mice when administered at 10 mg/kg dosage via IP administration every 2 weeks. Systemic NELL-PEG may be applied to improve overall bone architecture and potentially enhance postsurgical craniofacial and alveolar bone healing.

© 2016 American Society of Plastic Surgeons