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01.12.2015 | Research article | Ausgabe 1/2015 Open Access

Journal of Orthopaedic Surgery and Research 1/2015

Bone augmentation using a new injectable bone graft substitute by combining calcium phosphate and bisphosphonate as composite—an animal model

Journal of Orthopaedic Surgery and Research > Ausgabe 1/2015
Carsten W. Schlickewei, Georg Laaff, Anne Andresen, Till O. Klatte, Johannes M. Rueger, Johannes Ruesing, Matthias Epple, Wolfgang Lehmann
Wichtige Hinweise

Competing interests

The authors declare that they have no competing interests.

Authors’ contributions

All authors have made contributions to the current work. The manuscript was written by CWS and critically revised by ME, JMR, and WL. The design of the study was done by EM, WL, GL, and CWS. The bone grafts were produced by JR and supervised by ME. Surgery, postoperative care, and radiological controls were performed by CWS and GL. Histology was carried out by AA and TOK. The final data was interpreted by all authors. All authors read and approved the final manuscript.



The aim of this study was to create a new injectable bone graft substitute by combining the features of calcium phosphate and bisphosphonate as a composite bone graft to support bone healing and to evaluate the effect of alendronate to the bone healing process in an animal model.

Material and method

In this study, 24 New Zealand white rabbits were randomly divided into two groups: a calcium phosphate alendronate group and a calcium phosphate control group. A defect was created at the proximal medial tibia and filled with the new created injectable bone graft substitute calcium phosphate alendronate or with calcium phosphate. Healing process was documented by fluoroscopy. To evaluate the potential of the bone graft substitute, the proximal tibia was harvested 2, 4, and 12 weeks after operation. Histomorphological analysis was focused on the evaluation of the dynamic bone parameters using the Osteomeasure system.


Radiologically, the bone graft materials were equally absorbed. No fracture was documented. The bones healed normally. After 2 weeks, the histological analysis showed an increased new bone formation for both materials. The osteoid volume per bone volume (OV/BV) was significantly higher for the calcium phosphate group. After 4 weeks, the results were almost equal. The trabecular thickness (Tb.Th) increased in comparison to week 2 in both groups with a slight advantage for the calcium phosphate group. The total mass of the bone graft (KEM.Ar) and the bone graft substitute surface density (KEM.Pm) were consistently decreasing. After 12 weeks, the new bone volume per tissue volume (BV/TV) was still constantly growing. Both bone grafts show a good integration. New bone was formed on the surface of both bone grafts. The calcium phosphate as well as the calcium phosphate alendronate paste had been enclosed by the bone. The trabecular thickness was higher in both groups compared to the first time point.


Calcium phosphate proved its good potential as a bone graft substitute. Initially, the diagrams seem to show a tendency that alendronate improves the known properties of calcium phosphate as a bone graft substitute. The composite graft induced a good and constant new bone formation. Not only the graft was incorporated into the bone but also a new bone was formed on its surface. But we could not prove a significant difference between the grafts. Both implants proved their function as a bone graft substitute, but the bisphosphonate alendronate does not support the bone healing process sufficiently that the known properties of calcium phosphate as a bone graft substitute were improved in the sense of a composite graft. In this study, alendronate used as a bone graft in a healthy bony environment did not influence the bone healing process in a positive or negative way.
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