Alendronate Enhances Osteogenic Differentiation of Bone Marrow Stromal Cells: A Preliminary Study

Abstract

Alendronate inhibits osteoclastic activity. However, some studies suggest alendronate also has effects on osteoblast activity. We hypothesized alendronate would enhance osteoblastic differentiation without causing cytotoxicity of the osteoblasts. We evaluated the effect of alendronate on the osteogenic differentiation of mouse mesenchymal stem cells. D1 cells (multipotent mouse mesenchymal stem cells) were cultured in osteogenic differentiation medium for 7 days and then treated with alendronate for 2 days before being subjected to various tests using MTT assays, Alizarin Red, enzyme-linked immunosorbent assay, energy-dispersive xray spectrophotometry, reverse transcriptase-polymerase chain reaction, confocal microscopy, and flow cytometric analysis. D1 cells differentiated into osteoblasts in the presence of osteogenic differentiation medium as confirmed by positive Alizarin Red S staining, increased alkaline phosphatase activity and osteocalcin mRNA expression, a calcium peak by energy-dispersive xray spectrophotometry, and by positive immunofluorescence staining against CD44. Osteogenic differentiation was enhanced after treatment with alendronate as confirmed by Alizarin Red S staining, elevated alkaline phosphatase activity and osteocalcin mRNA expression, a greater calcium peak by energy-dispersive xray spectrophotometry, and by immunofluorescence staining against CD44 by flow cytometric analysis. These data suggest alendronate enhances osteogenic differentiation when treated with mouse mesenchymal stem cells in osteogenic differentiation medium.

Promotion of Bone Formation around Alendronate-immobilized Screw-Type Titanium Implants after Implantation into Rat Molar Tooth Sockets

“…Some researchers reported that alendronate enhanced the osteogenic differentiation of osteoblasts and bone marrow mesenchymal stem cells. 43,44) Moon et al 45) demonstrated that alendronate-immobilized titanium implant surface showed enhancement of osteoblast function as well as h and then decline gradually. McKenzie et al 48) also investigated the elution of zolendronic acid from a porous apatite-coated tantalum implant using a radio-labeling technique and claimed that the elution of zoledronic acids mainly localized in peri-implant bone, and peri-implant bone formation was strongly confined to the immediate space around the implant border.…”

The Effect of Local Delivery Doxycycline and Alendronate on Bone Repair

“…In the present study, it was hypothesized that association of the anabolic properties of alendronate (12) with the antibiotic and anti-proteolytic properties of doxycycline (29) combined with the delivery system of PLGA (30,31) would increase bone neoformation and accelerate bone repair. The null hypothesis tested was that local delivery of 10% doxycycline and 1% alendronate in PLGA would not affect the repair of experimental bone defects in rats at 7 and 15 days.…”

“…Recent investigations have shown that different classes of drugs, such as bisphosphonates, tetracyclines, and their combination, stimulate osteogenesis when their use was evaluated with regard to alveolar bone loss in periodontitis (8)(9)(10), healing of bone defects (1) and in vitro cell culture (11,12).…”

Internalization of (bis)phosphonate-modified cellulose nanocrystals by human osteoblast cells

“…Bis-phosphonates are small (molecular size \300 Da) organic pyrophosphate analogue drugs, where two phosphates are connected by a carbon atom (P-C-P) with various side chains (Lezcano et al 2014), being used in the treatment of several bone diseases, such as osteoporosis, Paget's disease, fibrous dysplasia, hypercalcemia of malignancy, heterotopic ossification, osteogenesis imperfecta, multiple myeloma (Lewiecki 2010), etc. Recent studies have reported that Alendronate (Aln), the most commonly administered bisphosphonate, enhances osteogenic differentiation of bone marrow stromal cells (Kim et al 2009), bone marrow mesenchymal stem cells (von Knoch et al 2005), and adipose-derived stem cells (Wang et al 2010). However, its fast dissolution at physiological conditions and side effects from oral administration lead to several attempts for its immobilization, as, for example, on a titanium implant surface (Moon et al 2011) or within calcium phosphate microspheres (Kim et al 2010), liposomes (Epstein et al 2008), chitosan scaffolds (Kim et al 2012), and poly (lacticco-glycolic acid) nanoparticles (Thamake et al 2012).…”