title: Strontium-containing apatite/polylactide composites enhance bone formation in osteopenic rabbits.
abstract: Strontium (Sr) has been shown to favor bone formation and is used clinically to treat osteoporosis. We have previously reported that Sr addition in apatite/polylactide composites could enhance the BMP-induced bone formation around implants at ectopic site in healthy animals. In this study we aimed to investigate the effectiveness of Sr addition on the local bone formation in osteoporosis. Apatite/polylactide composite granules with different Sr content were loaded with equal amount of rhBMP-2 and implanted intramuscularly in healthy rabbits (Con) and rabbits that received bilateral ovariectomy and daily injection of glucocorticoid (OP) for 12 weeks. The potential effect of Sr on the final volume of BMP-induced bone in both groups was investigated histologically and histomorphometrically. The de novo bone formed in OP implants was significantly less than in Con group when the implants contained no Sr, indicating that the BMP-induced osteogenesis was impaired in OP animals. Sr substitution as low as 0.5 mol% in apatite increased the bone volume in OP implants to levels comparable to that in the Con group, indicating a positive effect of Sr addition on the local bone formation in OP animals. In addition, more adipose tissue formed in parallel with the appearance of cartilage tissue in OP implants, suggesting that the differentiation potential of stem cell in OP animals may have shifted towards adipogenesis and chondrogenesis. From these results, we conclude that the use of Sr addition to enhance the bone growth surrounding implants in osteoporosis merits further study.
  
  
  CONCLUSIONS
  The impaired bone healing capacity of osteoporotic patients might result in poor osteointegration and surgical failure in case implants are placed. In this study we aimed to enhance the bone formation around implants under such scenario by adding strontium as the stimulus. Different from other studies, the samples were loaded with rhBMP-2 and implanted at an ectopic site (spinal muscles of New Zealand rabbits) to exclude the influence of conductive bone repair. The results showed that the addition of strontium could enhance the BMP-2-induced bone formation on implants in osteopenic rabbits to levels comparable to that in healthy rabbits. Secondarily, we observed more adipose tissue and cartilage tissue in osteopenic implants, suggesting the role of adipogenesis and chondrogenesis in osteopenia/osteoporosis.
authors.affiliation: Xpand Biotechnology BV, Prof. Bronkhorstlaan 10, Bld 48, 3723MB Bilthoven, The Netherlands; MIRA Institute, University of Twente, Drienerlolaan 5, 7522 NB Enschede, The Netherlands.
authors.forename: Xiaoman
authors.initials: X
authors.lastname: Luo
authors.affiliation: Xpand Biotechnology BV, Prof. Bronkhorstlaan 10, Bld 48, 3723MB Bilthoven, The Netherlands.
authors.forename: Davide
authors.initials: D
authors.lastname: Barbieri
authors.affiliation: MIRA Institute, University of Twente, Drienerlolaan 5, 7522 NB Enschede, The Netherlands.
authors.forename: Rongquan
authors.initials: R
authors.lastname: Duan
authors.affiliation: Xpand Biotechnology BV, Prof. Bronkhorstlaan 10, Bld 48, 3723MB Bilthoven, The Netherlands; MIRA Institute, University of Twente, Drienerlolaan 5, 7522 NB Enschede, The Netherlands; College of Physical Science and Technology, Sichuan University, Wangjiang Road 29, 610064 Chengdu, China. Electronic address: h.yuan@utwente.nl.
authors.forename: Huipin
authors.initials: H
authors.lastname: Yuan
authors.affiliation: Xpand Biotechnology BV, Prof. Bronkhorstlaan 10, Bld 48, 3723MB Bilthoven, The Netherlands; MIRA Institute, University of Twente, Drienerlolaan 5, 7522 NB Enschede, The Netherlands; School of Engineering and Materials Science, Queen Mary University of London, Mile End Rd, London E1 4NS, UK.
authors.forename: Joost D
authors.initials: JD
authors.lastname: Bruijn
mesh_terms: D000818:Animals; D001031:Apatites / Q000737:chemistry*; D001851:Bone Diseases, Metabolic / Q000188:drug therapy* / Q000473:pathology* / Q000503:physiopathology; D005260:Female; D053769:Nanocapsules / Q000008:administration & dosage / Q000737:chemistry; D053761:Nanocomposites / Q000008:administration & dosage* / Q000737:chemistry; D010012:Osteogenesis / Q000187:drug effects; D011091:Polyesters / Q000737:chemistry*; D011817:Rabbits; D013324:Strontium / Q000008:administration & dosage* / Q000737:chemistry; D016896:Treatment Outcome
chemical_list: D001031:Apatites; D053769:Nanocapsules; D011091:Polyesters; C033616:poly(lactide); D013324:Strontium
keywords: Adipocytes; Bone formation; Cartilage; Composites; Osteoporosis; Strontium