O

What do we mean by "Osteostimulation"?

Osteostimulation is  defined as an active stimulation of osteoblast proliferation and differentiation, as evidenced during in vitro studies by increased levels of DNA synthesis and of the osteoblast markers "osteocalcin" and " alkaline phosphatase". Through an ionic exchange PerioGlas first acts as a scaffolding around and through which new bone forms. In vivo studies have demonstrated that this osteostimulative property results in stimulation and acceleration of new bone formation in an osseous defect *.

Synthetic bone graft materials are typically defined as osteoconductive. Simply defined, osteoconductive means that a material provides a scaffolding on which bone cells can migrate and proliferate. The common histological observation would be (in the case of particulate graft material) bone growth beginning at the interface with healthy host bone, and extending gradually inward over time toward the center of the defect.

Osteostimulative, by contrast, means that the material supports a higher level of osteoblast expression and activity than seen with materials that are merely osteoconductive. The corresponding histological observation is bone growth in a grafted defect occurring not just at the margins, but throughout the site concurrently.

The term osteoinductive is used to describe materials such as autograft and allograft bone. These materials also support a high level of osteoblast activity in a graft defect like that described for osteostimulation. However, osteoinductive materials are also capable of inducing bone growth and stimulating osteoblast activity in the absence of host bone. The classic experiment to demonstrate this is implantation and bone growth intra-muscularly.

Bioglass® bone graft materials, can clearly be called osteostimulative, and have been demonstrated as such in many studies. At a cellular level it has been shown to offer a surface that is osteoblast friendly, allowing the cells to attach and proliferate on its surface (as with other common biomaterials, like hydroxyapatite (HA) or titanium)(1). More than that, however, it clearly supports a higher level of osteoblastic activity and expression far beyond what one sees with more bioinert materials like HA or titanium.

On a clinical level, in-vivo studies show a different pattern of new bone formation than has been seen with materials like HA(2). Growth is observed throughout the graft site, working outward from each individual particle, not just inward from the host-bone margins.

 What is the data to support this claim?

In Vitro Evidence:

It is broadly accepted that certain biochemical assays relating to alkaline phosphatase activity (APA) are legitimate indicators of osteoblastic expression and osteogenic activity in general (3).

In a study by Vrouwenvelder et al. the authors compared osteoblast activity on the surface of Bioglass® (sold under the brand names of PerioGlas®, NovaBone® and NovaBone-C/M®) with three well characterized biomaterials: hydroxyapatite (HA), titanium (Ti) and stainless steel (SS).(1) In the experiment, fetal rat osteoblasts were cultured on polished disks of the materials. Cultures were evaluated biochemically to determine APA as an indicator of relative osteogenic activity. The authors observed significantly greater (p=.0001) APA levels for Bioglass® (NovaBone™) at 6 days and again at 8 days. At the 8 day time period, levels for Bioglass® were nearly 3x those for the other materials:

In Vivo Evidence:

Oonishi et al. compared Bioglass® particulate to hydroxyapatite (HA) in an animal model.(2) The model involved a 6 mm (diameter) critical sized defect in rabbit femurs.

The authors found that, histological, bone formation with the Bioglass® was much greater and occurred much faster than with the HA. More strikingly, perhaps, is that they observed visible bone formation throughout the Bioglass®-filled defects after only 2 weeks, while the HA filled defects were observed to be only beginning to grow in from the margin. At six weeks, essentially all of the Bioglass® particles were surrounded by new bone, while the HA defects never reached this extent within the 12 week study duration. The authors concluded that this effect was a novel one for a synthetic material and amounted to more than just osteoconduction.

References:
1. Vrouwenvelder WCA et al. J Biomed Mater Res, 1993, Vol. 27, pp. 465 475
2. Oonishi H et al. Clinical Orthopedics, Jan. 1997, pp. 316-325
3. Principles Of Bone Biology, Bilezikian JP, Raisz LG, Rodan GA editors, Academic Press, San Diego, CA 1996. pg 1232

 * The supporting data has only been demonstrated in animals and not established in humans.