Osteogenic Activity of Locally Applied Small Molecule Drugs in a Rat Femur Defect Model

Abstract

The long-term success of arthroplastic joints is dependent on the stabilization of the implant within the skeletal site. Movement of the arthroplastic implant within the bone can stimulate osteolysis, and therefore methods which promote rigid fixation or bone growth are expected to enhance implant stability and the long-term success of joint arthroplasty. In the present study, we used a simple bilateral bone defect model to analyze the osteogenic activity of three small-molecule drug implants via microcomputerized tomography (micro-CT) and histomorphometry. In this study, we show that local delivery of alendronate, but not lovastatin or omeprazole, led to significant new bone formation at the defect site. Since alendronate impedes osteoclast-development, it is theorized that alendronate treatment results in a net increase in bone formation by preventing osteoclast mediated remodeling of the newly formed bone and upregulating osteoblasts.

Does locally delivered Zoledronate influence peri-implant bone formation? – Spatio-temporal monitoring of bone remodeling in vivo

“…Local application is of particular interest in cases where existing bone needs to be preserved and augmented whilst avoiding the known side effects related to systemic administration [14,15]. Several in vivo studies have shown that a local delivery of BPs can enhance peri-implant bone density [16,17], implant fixation [18e22], and the repair of bony defects [23,24] in animal models and humans. Furthermore BPs have been shown to preserve bone allografts [25,26] as well as bone sites affected by osteonecrosis [27].…”

Local inhibition of 5-lipoxygenase enhances bone formation in a rat model

“…Histomorphometry to determine the percentages of mineralised tissue was not conducted, as a previous study showed that histomorphometry and micro-CT analyses yield similar results in this bone defect model. 18 …”

“…18 The dose of A-79175 was calculated based on percentage dosage and the scaffold mass minus PCL scaffold mass. The rats were housed in pairs, maintained in a 12-hour light dark cycle, and provided food and water ad libitum .…”

“…15,16 For this study, a unicortical bone defect model was used in rat femora, in which the defect site was filled with a polycaprolactone (PCL) scaffold containing 5-LO inhibitor or carrier. 17,18 …”

Alendronato e vitamina D: quale ruolo in ortopedia e traumatologia?

“…5) [22,23]. È stato dimostrato che alendronato aumenta significativamente il riempimento di difetti ossei sperimentali, ostacolando il riassorbimento dell'osso neoformato da parte degli osteoclasti e up-regolando l'attività osteoblastica [24]. Va precisato che i bisfosfonati possono rallentare di 8-10 giorni i processi riparativi, ma questo non giustifica l'interruzione della loro somministrazione in caso di frattura [25]: anzi, l'utilizzo di alendronato (10 mg/die) per un periodo fino a 6 mesi nel post-operatorio si è dimostrato efficace nel ridurre il riassorbimento periprotesico nelle regioni metafisarie, riducendo in tal modo il rischio di mobilizzazione dell'impianto [26].…”