Letters to the Editor

Issue: March 2005

DBM/calcium sulfate is efficacious

Dear Editor:

Surgeons from around the country have provided commentary in response to the publication of a paper presented at the Orthopaedic Trauma Association and in an article in the December issue of Orthopedics Today ("Calcium sulfate DBM allograft caused high rates of complications in nonunions," page 34) regarding the "lack of efficacy" of DBM/calcium sulfate-based materials for the treatment of nonunions.

It is important to note that the product in question, Allomatrix (Wright Medical Technology), was used in this study in an ill-advised application. The patient population outlined in this long-bone nonunion study is described in the abstract by Dr. Bruce Ziran as: (1) "atrophic;" (2) "previously infected;" (3) "deemed not to have biologic potential;" (4) "tumor-type resection;" (5) "tenuous soft tissue sleeve;" and (6) "compromised local vasculature."

Walter Virkus, MD, assistant professor in orthopedic surgery, Rush University Medical Center in Chicago: I was surprised by the results of Dr. Ziran's study because in my experience of more than 30 patients, there have been no significant wound complications. My only two failures were cases with large bone defects like those presented in this study. In cases where the material was used as it was intended, I have had no failures. It appears Allomatrix can achieve healing results very similar to autograft. Although more work is needed, this product has an excellent early track record.

Raffy Mirzayan, MD, clinical associate professor of orthopedic surgery at the University of Southern California: Based on personal experience, it is clear that grafting in the absence of a healthy vascular supply is unlikely to achieve any significant benefit. The ability to recruit multipotential cells with any graft material relies on a good vascular supply. It is important to prepare the nonunion site with appropriate treatment principles, such as a muscle flap, rendering the choice of graft a secondary consideration.

Daniel Horwitz, MD, director of orthopedic trauma at the University of Utah, Department of Orthopedics: I think Dr. Ziran's clinical series points out several limitations in the treatment of atrophic nonunions with poor biology and potentially poor soft tissues. The most likely explanation for the drainage problem encountered (pointed out by Dr. Ziran) is osmolarity differences and fluid shift in a poor soft tissue sleeve. For this reason the calcium sulfate products should be reserved for situations with good soft tissue coverage and perhaps no prior infection history.

What I find most impressive: More than 50% of these atrophic nonunions went on to heal, suggesting the biologic potential of the calcium sulfate materials is quite good. We are reminded that with grafting procedures, using allograft or autograft, a critical evaluation of soft tissues may ultimately be more important than which graft material is used.

J. Tracy Watson, MD, chief, division of orthopedic traumatology at St. Louis University: The authors selected the most difficult case scenarios for a bone graft substitute. Prior to any bone graft procedure, the tenets of complex nonunion management need to be strictly adhered to.

This includes conversion of an infected, atrophic, biologically dormant region into a viable biologic envelope. Repeated meticulous debridement with excision and replacement of atrophic and infected soft tissues in conjunction with free tissue transfer is often necessary. Competent wound closure with a contained defect is necessary to avoid the osmotic effects and subsequent drainage that CaSO₄ may produce. Only after these requirements are met, should the skeletal replacement portion of the reconstruction be undertaken.

The treatment failures were all patients who presented preoperatively with infection or a history of infection. This correlated highly with postoperative infection, wound drainage and ultimate material failure.

Sterile alloplastic materials don't cause infection but will certainly potentiate latent infection, especially in a marginal environment. It is difficult to expect any graft material to perform well in these situations. The authors reported a 54% success rate, which is admirable given the magnitude of the problems.

The tremendous increase in the number of bone graft substitutes, inductive/conductive factors and growth adjuvants tend to highlight their particular advantages, and we are led to believe that now we have magic in our hands. However, none of these materials will grow bone on the sidewalk. The sidewalk has no inherent osteogenic cells or osteogenic potential. A healthy biologically sound environment that provides viable cells is the most important goal when treating these very difficult patients. Anything less and it makes no difference what is implanted - it will certainly fail.

George Muschler, MD, surgeon in Cleveland Clinic's Departments of orthopedic surgery and biomedical engineering: Fracture nonunion associated with an atrophic bone response, disvascularity, prior infection and bone defects represents one of the most challenging settings and few graft materials will perform there with exceptional efficacy.

The importance of optimal debridement and optimal soft tissue coverage cannot be underestimated. But when debridement and coverage is performed well, the local population of connective tissue progenitors that are available to provide osteogenic cells needed for new bone formation can be expected to be depleted. In this setting, purely osteoconductive materials, or even osteoinductive materials alone, will likely provide limited benefit without a target cell population. In addition, these wounds, unlike many cavitary defect settings, often have thin layers for closure. The difficulty in obtaining a "water-tight closure" may limit ability to withstand the osmotic load associated with the dissolution of calcium sulfate granules. This may have contributed to the frequency of wound drainage and subsequent infection.

Ross Wilkins, MD, medical director of the Institute for Limb Preservation in Denver: The author concluded that bone graft substitute type material should be not used in these types of cases. This is really not new or important information. Basically, bone graft substitute materials in this patient population have never have been effective nor will they ever be effective for these large and compromised defects.

It is unfortunate that new, innovative products are sometimes viewed as "miracle materials" with surgeons using them occasionally in heroic-type situations. Allomatrix and products similar to Allomatrix using bone growth factors, have been a huge improvement in the armamentarium of orthopedic surgeons in modifying the local environments to enhance bone healing.

There are some important points to be made from this abstract: (1) This study emphasizes the importance of a healthy vascular bed when using inductive products to recruit multipotential bone forming cells. (2) With the advent of partial biologic control of the bone-healing environment, shortcuts are still not allowable. We must pay attention to the basic tenants of a clean, healthy bed, appropriate long-bone fixation and healthy soft tissue coverage.

Ross Wilkins, MD
Denver