title: Synergistic effects of bisphosphonate and calcium phosphate nanoparticles on peri-implant bone responses in osteoporotic rats.
abstract: The prevalence of osteoporosis will increase within the next decades due to the aging world population, which can affect the bone healing response to dental and orthopedic implants. Consequently, local drug targeting of peri-implant bone has been proposed as a strategy for the enhancement of bone-implant integration in osteoporotic conditions. In the present study, an established in-vivo femoral condyle implantation model in osteoporotic and healthy bone is used to analyze the osteogenic capacity of titanium implants coated with bisphosphonate (BP)-loaded calcium phosphate nanoparticles (nCaP) under compromised medical conditions. After 4 weeks of implantation, peri-implant bone volume (%BV; by μCT) and bone area (%BA; by histomorphometry) were significantly increased within a distance of 500 μm from implant surfaces functionalized with BP compared to control implants in osteoporotic and healthy conditions. Interestingly, the deposition of nCaP/BP coatings onto implant surfaces increased both peri-implant bone contact (%BIC) and volume (%BV) compared to the deposition of nCaP or BP coatings individually, in osteoporotic and healthy conditions. The results of real-time PCR revealed similar osteogenic gene expression levels to all implant surfaces at 4-weeks post-implantation. In conclusion, simultaneous targeting of bone formation (by nCaP) and bone resorption (by BP) using nCaP/BP surface coatings represents an effective strategy for synergistically improvement of bone-implant integration, especially in osteoporotic conditions.
authors.affiliation: Department of Biomaterials, Radboud umc, Nijmegen, The Netherlands; Department of Periodontics and Community Dentistry, College of Dentistry, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Hamdan S
authors.initials: HS
authors.lastname: Alghamdi
authors.affiliation: Department of Biomaterials, Radboud umc, Nijmegen, The Netherlands.
authors.forename: Ruggero
authors.initials: R
authors.lastname: Bosco
authors.affiliation: Department of Biomaterials, Radboud umc, Nijmegen, The Netherlands.
authors.forename: Sanne K
authors.initials: SK
authors.lastname: Both
authors.affiliation: Institute of Science and Technology for Ceramics (ISTEC), National Research Council (CNR), Via Granarolo 64, 48018 Faenza, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Iafisco
authors.affiliation: Department of Biomaterials, Radboud umc, Nijmegen, The Netherlands.
authors.forename: Sander C G
authors.initials: SC
authors.lastname: Leeuwenburgh
authors.affiliation: Department of Biomaterials, Radboud umc, Nijmegen, The Netherlands.
authors.forename: John A
authors.initials: JA
authors.lastname: Jansen
authors.affiliation: Department of Biomaterials, Radboud umc, Nijmegen, The Netherlands. Electronic address: Jeroen.vandenBeucken@radboudumc.nl.
authors.forename: Jeroen J J P
authors.initials: JJ
authors.lastname: van den Beucken
mesh_terms: D000818:Animals; D001862:Bone Resorption / Q000188:drug therapy; D001842:Bone and Bones / Q000187:drug effects* / Q000378:metabolism; D002130:Calcium Phosphates / Q000737:chemistry / Q000494:pharmacology*; D020099:Coated Materials, Biocompatible / Q000737:chemistry / Q000494:pharmacology; D004164:Diphosphonates / Q000737:chemistry / Q000494:pharmacology*; D004195:Disease Models, Animal; D004357:Drug Synergism; D008297:Male; D053758:Nanoparticles / Q000737:chemistry*; D010012:Osteogenesis / Q000187:drug effects; D010024:Osteoporosis / Q000628:therapy; D019736:Prostheses and Implants; D051381:Rats; D017208:Rats, Wistar; D013499:Surface Properties; D014025:Titanium / Q000737:chemistry
chemical_list: D002130:Calcium Phosphates; D020099:Coated Materials, Biocompatible; D004164:Diphosphonates; C020243:calcium phosphate; D014025:Titanium
keywords: Bisphosphonate; Bone healing; Calcium phosphate; Implants; Osteoporosis