Copyright © 2008 by The Journal of Bone and Joint Surgery, Inc.
Commentary & Perspective
Commentary & Perspective by
Philip E. Blazar, MD, and Hangama C. Fayaz, MD, PhD*,
Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts
Posted June 2008
Calcium phosphate bone cement is a synthetic bone graft
substitute that is osteoconductive (but not osteoinductive) and has the
capability of filling complex three-dimensional voids. It has little tensile
strength but does provide structural support against compressive loads1.
Hence, investigators have focused largely on its use in metaphyseal fractures
(distal part of the radius, tibial plateau, calcaneus, and spine).
Bajammal et al. have performed a meta-analysis of the
effectiveness of calcium phosphate bone cement in fracture treatment. They
found that the use of calcium phosphate bone cement was associated with
decreased postoperative pain, a decreased risk of losing fracture reduction (as
compared with autograft), lower infection rates in patients with radial
fractures, and likely improved functional outcomes. The study also indicates an
improvement with regard to validated functional outcome measures (Medical
Outcome Study 36-Item Short Form [SF-36] and DASH [Disabilities of the Arm,
Shoulder and Hand]) associated with the use of calcium phosphate bone cement,
as compared with no grafting material in control groups.
The authors have performed a thorough and thought-provoking
study. The major strength of this study is the use of meta-analysis, as the
authors were able to incorporate data from fourteen randomized trials. This
allowed the authors to find statistical significance for clinically significant
variables that have not been consistently supported by individual studies (i.e.,
variables such as pain relief, loss of fracture reduction, and functional
outcome). Their review of the literature to identify trials was exhaustive, and
they even attempted to avoid the nonpublication bias of studies with negative
results by including three nonpublished studies.
The study does have some limitations. First, the fourteen
studies included in this meta-analysis are heterogeneous with respect to
multiple variables, including the anatomic site, the method of fracture repair
(open reduction and internal fixation, external fixation, percutaneous pinning,
or injectable bone cement and casting) and the control group (autograft,
allograft or no "bone graft") (References 21, 22, 25, 28). This clinical
diversity is necessary to have enough trials to complete the meta-analysis but
has the potential to be misleading. Thus, the conclusion that a reader might
draw from a positive result in this setting is that the results can be
generalized to all metaphyseal fractures, and it is not clear that this is
true.
Second, the use of unpublished studies is controversial.
Their inclusion of unpublished studies, which have not passed the peer review
process (reference 35), at a minimum risks reliance on some poorer quality
studies.
Third, while this study demonstrates that the positive
effects of calcium phosphate cement are of statistical significance, it is
unclear in which fractures these differences are clinically significant. As an
example, a meta-analysis of fractures of the distal part of the radius with a
large enough number of patients might show a significant difference in time to
union between two groups of two days, but it is unclear that two days is a
clinically significant effect size.
Fourth, the meta-analysis is highly dependent on data drawn
from studies on the distal part of the radius (six of eleven published
studies). In the time period since the patients in these studies were treated,
there has been a large change in the technology of distal radial fracture
treatment to address the issues of metaphyseal comminution with the advent of
fixed-angle plating systems. This does not change the validity of the
conclusions, but the clinical relevance of these six studies is less clear than
it was even five years ago.
Lastly, as meta-analyses are susceptible to sources of bias
that exist across multiple studies, an indication of the specific sources of
funding for these fourteen trials would be appropriate. As has recently been
published in JBJS, the presence of disclosed conflicts of interest has an
impact on the likelihood of positive results2.
While these results are encouraging for the benefits of
calcium phosphate bone cements, and the authors are to be commended for their
efforts, a need for further high-quality study on the use of these
supplementary materials remains.
*The authors did not receive any outside funding or grants in support of their research for or preparation of this work. Neither they nor a member of their immediate families received payments or other benefits or a commitment or agreement to provide such benefits from a commercial entity. No commercial entity paid or directed, or agreed to pay or direct, any benefits to any research fund, foundation, division, center, clinical practice, or other charitable or nonprofit organization with which the authors, or a member of their immediate families, are affiliated or associated.
References
1. Shors EC. Development of corralline porous ceramic graft substitutes. In: Laurencin CT, editor. Bone graft substitutes. West Conshohocken, PA: ASTM International; 2003. p 271-88.
2. Okike K, Kocher MS, Mehlman CT, Bhandari M. Conflict of interest in orthopaedic research. An association between findings and funding in scientific presentations. J Bone Joint Surg Am. 2007;89:608-13.
|
