Sir,
We read with interest this paper which concludes that processed
and irradiated allografts provide the same clinical results as fresh
frozen ones while increasing the safety of the grafts. This is a finding
that is well known from literature and is in compliance with our own
experience. The authors fear that processing and irradiating the grafts
may have compromised their biological and mechanical properties, and claim
that “combining autologous marrow, a rich source of autologous
osteoinductive cells and growth factors, with sterile allografts” may be
the explanation for comparably good clinical performance. However, the
comparable efficacy cannot be attributed to the addition of autologous
bone marrow.
There is no “osteoinductive cell” and there is no growth factor in
bone marrow that is able to induce bone formation. Osteoinduction is
triggered by proteins that are deposited and stored in the matrix of bone,
not in the marrow.1 When set free due to fracture, osteoclastic
resorption or demineralisation, these are able to trigger the
transformation of mesenchymal stem cells into osteoblasts that
consequently build up new bone. These progenitor cells are physiologically
recruited by released growth factors through the bloodstream. Iliac crest
bone marrow contains only 181 (70 to 401) osteoprogenitor cells among 17
million nucleated cells per cc.2 It cannot be expected that injecting
a fractional amount of them into dead bone provides a relevant advantage
in comparison with physiological recruitment from the entire body,
especially considering that their survival is very unlikely outside a
vascularised environment or sophisticated culture media. Simply injecting
marrow into an allograft cannot be considered to be creating a “living
composite”, as the authors claim, since injected bone marrow cells devoid
of blood supply or culture media are doomed to rapid cell death.
On the other hand the fear of compromise through processing seems to
be overestimated. One reference cited by the authors clearly shows that
lipid extracted bone grafts have even better osteoconductive properties
than fresh frozen ones and possess comparable mechanical properties, even
when irradiated with 25kgy.3 One reason for improved performance is the
removal of cell surface antigens eliciting an immune response. Reports of
gamma sterilisation compromising mechanical as well as osteoinductive
properties of allograft bone have covered exclusively the behaviour of
fresh frozen bone, including all allogenic marrow. The authors cite such a
reference, where fresh frozen cortical bone has been irradiated.4
However, (as the authors of the reference admit) the differences
between irradiated and non irradiated bone are negligible, as long as the
bone is dry and free from cells and fatty bone marrow inducing free
radicals during irradiation. The processed grafts used in the study group
B are supposed to be dry and free of immunogenic cells and lipids and
therefore may be estimated to show the described advantages. These should
be sufficient to compensate for eventual compromise of osteogenic features
occurring during processing.
It therefore may be estimated that the processed bone used in the
study shows comparable, if not better, biological properties than the
unprocessed one, not surprisingly leading to comparable clinical results
independent from the addition of autologous bone marrow. An additional
invasive procedure for harvesting autologous marrow is
therefore unnecessary.
H.Winkler,
Consultant Orthopaedic Surgeon,
Osteitis Center, Privatklinik Doebling,
Vienna, Austria.
1. Mizutani H, Urist MR. The nature of bone morphogenetic protein
(BMP) fractions derived from bovine bone matrix gelatin. Clin Orthop 1982;171:213-23.
2. McLain RF, Fleming JE, Boehm CA, Muschler GF. Aspiration of
osteoprogenitor cells for augmenting spinal fusion: comparison of
progenitor cell concentrations from the vertebral body and iliac crest. J
Bone Joint Surg [Am] 2005;87-A:2655-61.
3. Thorén K, Aspenberg P, Thorngren KG. Lipid extracted bank bone: bone conductive and mechanical properties. Clin Orthop 1995;311:232-46.
4. Hamer AJ, Stockley I, Elson RA. Changes in allograft bone
irradiated at different temperatures. J Bone Joint Surg [Br] 1999;81-B:342-4.