Michael D. McKee, M.D., FRCSC, Associate Professor,
Division of Orthopaedics, Department of Surgery
St. Michael’s Hospital, University of Toronto
Toronto, ON

Osteoset^TM is medical grade calcium sulfate alpha hemi-hydrate in pellet form. It also is available as Osteoset-T^TM, which is a similar material impregnated with tobramycin. Calcium sulfate has been used clinically as a bone defect or bone void filler for close to 100 years. Previous studies have shown it to be biocompatible and bioresorbable, and it is associated with a good safety and efficacy profile^1,2. Recent technological developments have been incorporated into Osteoset^TM that have improved its utility for the practicing orthopaedic surgeon.
 

In the past, calcium sulphate crystals have been plagued by lack of uniformity amongst pellet size and shape. More recently, processes have been devised which control shape and size of the hemihydrate crystals, which lends a level of regularity that was not previously available. Experimentally, this seems to stabilize the resorption rate at a controlled pace, and results in a predictable biological response¹.

While calcium sulfate pellets in of themselves are not osteo-inductive or osteo-genic, they do appear, both experimentally and clinically, to be osteo-conductive^1,2,3. Osteoset^TM pellets resorb at a fairly steady rate (typically six to 12 weeks after insertion, depending on local conditions) consistent with new bone formation. New, immature or woven bone, can be seen peripherally around the area of residual calcium sulfate pellets. Experimentally, calcium sulfate has been shown to stimulate bone growth when placed in direct contact with bone or periosteum. With time, the cavity previously occupied by the calcium sulfate tends to fill with new bone at a fairly predictable (albeit slow) rate.

Figure 1: Infected tibial defect following debridement, Osteoset-T^TM insertion and flap coverage.

As the calcium sulfate pellets are resorbed, a sterile effluent is produced. Typically, this is resorbed by the body itself but if there are a large number of pellets in a subcutaneous bone such as the tibia or ulna, this can occasionally produce a sinus causing some alarm for the patient and surgeon. However, this does not represent infection, cultures of the effluent are negative and the sinus tends to resolve spontaneously with time.

At the present time, the main utility of this product is in the filling of contained voids or defects with structural integrity of the bone and reasonable soft tissue coverage. It is unclear at the present time whether OsteosetTM, in isolation, has sufficient biological stimulus to promote union in long bone nonunion when used in isolation. There is some preliminary evidence that, when used as part of a standard surgical protocol to obtain soft tissue coverage, add mechanical stability, and oppose viable bony surfaces, it may be useful in this context³.

The other major advance in the use of calcium sulfate as a bone graft substitute is the addition of a high concentration of tobramycin to the crystalline structure (Osteoset-T^TM). The majority of our experience with this product has stemmed from the use of Osteoset-T^TM for infected bony defects and infected long bone nonunion. The elution characteristics of tobramycin from calcium sulfate hemihydrate have been well studied, and an initial burst of tobramycin on day-1 produces local levels of antibiotic which are 2-10,000 times greater than the minimal inhibitory concentration (MIC) for most staphylococcal species⁴. Local levels obtained are thus tremendously higher than can be obtained through oral or intravenous administration. This is sufficient to eradicate most bacteria (a 92 percent efficacy for eliminating infection in our initial series of 25 patients³). Resistant pseudomonas species and methicillin-resistant staphylococcus aureus (MRSA) are notable exceptions to this rule. Another benefit of the Osteoset-T^TM when compared to standard therapy using antibiotic impregnated cement beads is the biocompatibility and lack of requirement for a second operation to remove beads and insert bone graft. While the Osteoset-T^TM has been shown to be extremely effective in eliminating infection and filling bony defects, its role in promoting union remains uncertain. Another major advantage of this substance is that it is relatively inexpensive compared to other bone graft substitutes.

Figure 2: Eradication of infection and solid bony healing twelve months postoperatively.

There are randomized and prospective clinical trials currently underway examining the use of Osteoset^TM and Osteoset-T^TM in a variety of clinical situations. The results of these trials will help to define and delineate the role of this material in the care of the orthopaedic patient. Osteoset^TM was approved for use by the FDA in June 1996. Both Osteoset^TM and Osteoset-T^TM are approved for clinical use in Canada.

References

1. Coetzee A.S. Regeneration of bone in the presence of calcium sulfate. Arch. Otolaryngol., 106: 405-9, 1980.
   
   
2. Kelly C.M., Wilkins R.M., Gitelis S., et al. The use of a surgical grade calcium sulfate as a bone graft substitute: results of a multicenter trial. Clin Orthop., 382: 42-50, 2001.
   
   
3. McKee M.D., Wild L.M., Schemitsch E.H., Waddell J.P. The use of antibiotic-impregnated, osteoconductive, bioabsorbable bone substitute in the treatment of infected long bone defects: Early results of a prospective trial. Journal of Orthopaedic Trauma (accepted for publication).
   
   
4. Miclau T., Dahners L.E., Lindsey R.W. In vitro pharmacokinetics of antibiotic release from locally implantable materials. J Orthop Res., 11(5): 627-632, 1993.