title: Local drug delivery for enhancing fracture healing in osteoporotic bone.
abstract: Fragility fractures can cause significant morbidity and mortality in patients with osteoporosis and inflict a considerable medical and socioeconomic burden. Moreover, treatment of an osteoporotic fracture is challenging due to the decreased strength of the surrounding bone and suboptimal healing capacity, predisposing both to fixation failure and non-union. Whereas a systemic osteoporosis treatment acts slowly, local release of osteogenic agents in osteoporotic fracture would act rapidly to increase bone strength and quality, as well as to reduce the bone healing period and prevent development of a problematic non-union. The identification of agents with potential to stimulate bone formation and improve implant fixation strength in osteoporotic bone has raised hope for the fast augmentation of osteoporotic fractures. Stimulation of bone formation by local delivery of growth factors is an approach already in clinical use for the treatment of non-unions, and could be utilized for osteoporotic fractures as well. Small molecules have also gained ground as stable and inexpensive compounds to enhance bone formation and tackle osteoporosis. The aim of this paper is to present the state of the art on local drug delivery in osteoporotic fractures. Advantages, disadvantages and underlying molecular mechanisms of different active species for local bone healing in osteoporotic bone are discussed. This review also identifies promising new candidate molecules and innovative approaches for the local drug delivery in osteoporotic bone.
authors.affiliation: AO Research Institute Davos, Clavadelerstrasse 8, 7270 Davos Platz, Switzerland. Electronic address: laura.kylloenen@aofoundation.org.
authors.forename: Laura
authors.initials: L
authors.lastname: Kyllönen
authors.affiliation: AO Research Institute Davos, Clavadelerstrasse 8, 7270 Davos Platz, Switzerland.
authors.forename: Matteo
authors.initials: M
authors.lastname: D'Este
authors.affiliation: AO Research Institute Davos, Clavadelerstrasse 8, 7270 Davos Platz, Switzerland.
authors.forename: Mauro
authors.initials: M
authors.lastname: Alini
authors.affiliation: AO Research Institute Davos, Clavadelerstrasse 8, 7270 Davos Platz, Switzerland.
authors.forename: David
authors.initials: D
authors.lastname: Eglin
mesh_terms: D055396:Bone Morphogenetic Protein 2 / Q000008:administration & dosage* / Q000737:chemistry; D004343:Drug Implants / Q000008:administration & dosage* / Q000138:chemical synthesis; D016222:Fibroblast Growth Factor 2 / Q000008:administration & dosage* / Q000737:chemistry; D017102:Fracture Healing / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D053769:Nanocapsules / Q000008:administration & dosage / Q000737:chemistry* / Q000648:ultrastructure; D058866:Osteoporotic Fractures / Q000188:drug therapy* / Q000503:physiopathology*
chemical_list: C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; D004343:Drug Implants; D053769:Nanocapsules; D016222:Fibroblast Growth Factor 2
keywords: Drug delivery; Growth factors; Osteoporotic fracture; Small molecules