Bisphosphonates inhibit surface‐mediated osteogenesis

Abstract

Bisphosphonates (BPs) target osteoclasts, slowing bone resorption thus providing rationale to support osseointegration. However, BPs may negatively affect osteoblasts, impairing peri‐implant bone formation. The goal of this study was to assess the effects BPs have on surface‐mediated osteogenesis of osteoblasts. MG63 cells were cultured on 15‐mm grade 2 titanium disks: smooth, hydrophobic‐microrough, or hydrophilic‐microrough (Institut Straumann AG, Basel, Switzerland). Tissue culture polystyrene (TCPS) was used as a control. At confluence, cells were treated with 0, 10−8, 10−7, and 10−6 M of alendronate, zoledronate, or ibandronate for 24 hr. Sprague Dawley rats were also treated with 1 μg/kg/day ibandronate or phosphate‐buffered saline control for 5 weeks. Calvarial osteoblasts (rat osteoblasts [rOBs]) were isolated, characterized, and cultured on surfaces. Osteogenic markers in the media were quantified using ELISAs. BP treatment reduced osteocalcin, osteoprotegerin, osteopontin, bone morphogenetic protein‐2, prostaglandin E2, transforming growth factor β1, interleukin 10, and vascular endothelial growth factor in MG63 cells. The effect was more robust on rough surfaces, and higher concentrations of BPs stunted production to TCPS/PT levels. Ibandronate conditioned rOBs produced less osteogenic markers similar to direct BP treatment. These results suggest that BP exposure jeopardizes the pro‐osteogenic response osteoblasts have to microstructured surfaces. Their effects persist in vivo and negatively condition osteoblast response in vitro. Clinically, BPs could compromise osseointegration.

Osseointegration and Remodeling of Mineralized Bone Graft Are Negatively Impacted by Prior Treatment with Bisphosphonates

“…Block allograft remained largely unremodeled upon histologic and radiographic examination (see Appendix Supplemental Figure 2 and Supplemental Table 2). These findings support our hypothesis that mineralized bone allograft from donors treated with oral bisphosphonates will have different osteogenic and osteoconductive properties compared with donors with no history of oral bisphosphonate use, consistent with previous work that found that bisphosphonates inhibit surfacemediated osteogenesis 23 . Following surgical injury and implantation of the allogeneic block, the osteoblasts were exposed to a surface covered with bisphosphonate trapped in the mineralized matrix, producing a measurable gap observed both by micro-CT and histologically.…”

Berbamine inhibits RANKL- and M-CSF-mediated osteoclastogenesis and alleviates ovariectomy-induced bone loss

“…For example, bisphosphonate drugs are used clinically as antiresorptive drugs that inhibit osteoclastic bone resorption by disrupting intracellular signaling and inducing apoptosis of osteoclasts ( Rogers et al, 2011 ). Recent studies have reported that bisphosphonates reduce bone formation by inhibiting surface-mediated osteogenesis and impairing the onset of bone formation after resorption ( Lotz et al, 2020 ; Jensen et al, 2021 ). Therefore, we also investigated the effect of BBM on osteoblast differentiation and bone formation, and we did not observe a significant difference between the BBM treatment group and the control group, suggesting that BBM may effectively suppress osteoclast differentiation and bone resorption without affecting osteogenesis.…”

Testosterone Enanthate: An In Vitro Study of the Effects Triggered in MG-63 Cells

“…In this regard, we are aware that being an osteosarcoma-derived cell line, MG-63 cells do not represent the best model for studying differentiation. However, in the past, substantial and relevant literature used this [ 25 , 26 ] or other similar models [ 21 ] to assess osteogenic properties of biomaterials and other substances, thus justifying their use also in this study.…”