Aminobisphosphonate Stimulates Bone Regeneration and Enforces Consolidation of Titanium Implant into a New Rat Caudal Vertebrae Model

Abstract

Bisphosphonates are widely used as therapeutic agents in bone disorders including cancer metastasis due to their osteoclast inhibitory effect. Recent data shows that bisphosphonates may also induce bone-building by stimulating osteoblast activity. Clinical observations, however, have revealed that bisphosphonates may cause necrosis in the oral cavity which questions their usefulness in bone regeneration during the consolidation of inorganic implants. Here we report the investigation of bone neogenesis following chronic amine bisphosphonate (Zometa) treatment in a novel experimental model, using the rat tail vertebra as a support. This method involves (1) implantation of titan screw into the tail vertebrae, (2) systemic bisphosphonate treatment and (3) quantitative biophysical measurements which mirrors consolidation of implant, i.e. strength of fixation and changes in newly formed bone architecture using micro Computer Tomograph (micro-CT). The degree of fixation of titan implants (osseointegration) increased by 36% on the effect of Zometa and the structure of newly formed bone became robust. The mass of new bone increased 3.1-fold at 6 weeks of regeneration, as compared to controls. Thus, Zometa, a potent aminobisphosphonate used in therapy of cancer metastases, osteoporosis and bone marrow transplantation, significantly increased bone neogenesis and enforced osseointegration of titan implants as measured quantitatively in the rat tail vertebra. Our data support the usefulness of aminobisphosphonates in the rehabilitation of bone loss as well as in improvement osseointegration of implants. We emphasise that this novel method may open up new possibilities for screening the effects of local and systemic treatments.

Early Healing of Hydroxyapatite‐Coated Implants in Grafted Bone of Zoledronic Acid–Treated Osteoporotic Rabbits

“…(Original magnification ·4.) [30][31][32] Although the above studies support the beneficial effects of bisphosphonates on new bone formation and implant fixation in both osteoporotic and normal native bones, the potential benefits of bisphosphonates on osseointegration of implants in osteoporotic bone with autogenous bone grafting are less reported. In a previous study by the present authors, 20 it was confirmed that ZA could promote osseointegration and fixation of implants in grafted autogenous bone in osteoporotic rabbits after 3 months of treatment.…”

“…Furthermore, a number of studies have demonstrated that bisphosphonates may exert beneficial effects on normal bones as they do on osteoporotic bones. Both new bone formation and implant osseointegration were strengthened by either systemic administration or local immobilization of bisphosphonates in normal animals 30‐32 …”

The influence of alendronate on osseointegration of nanotreated dental implants in New Zealand rabbits

“…On the other hand, ALN does not impair mineralization and seems to preserve or even improve microarchitecture (Owens et al 1997; Rodan 1998; Carbonare et al 2005). The use of bis in joint arthroplasty, which is a current topic of interest, suggests that bis influences the early stages of implant integration positively and may optimize the long‐term survival of the implant (Frenkel et al 2001; Venesmaa et al 2001; Soininvaara et al 2002; Jensen et al 2007; Blazsek et al 2009; Landesberg et al 2009).…”

“…Only one experiment (Chacon et al 2006) has studied the effect of systemic administration of ALN on dental implant osseointegration in non‐osteoporotic rabbits, but the conclusions were based only on torque removal values. The latest research (Blazsek et al 2009) investigating bone neogenesis around an implant inserted into a rat tail vertebra following chronic aminobisphosphonate treatment showed positive results.…”

Purification and processing of blood-forming tissue units, the haematons, in searching for mammalian stem cell niches

“…The X-ray scatter generated on the surface of the samples was subtracted using beam hardening correction algorithm at the level of 60% (Skyscan, Kontic, Belgium). For reconstruction of 3D images we used the cone-beam volumetric algorithm (Feldkamp) 53 . 2| Cut the skin first from the pubis along the sternum and then the wall of abdomen using scissors and forceps, then fix the skin aside by pins.…”