It has been almost 40 years since Marshall Urist’s
seminal observations on the bone induction principle were first
published, yet we have not seen the common use of bone morphogenetic proteins
(BMPs) in our patients. I believe that two obstacles have delayed
this translation: (1) underestimation of the need for a higher concentration
or dose of BMPS in primates compared with lower animals and rodents; and
(2) difficulty finding a suitable carrier and delivery system to
adequately immobilize the growth factor(s), promote vascular ingrowth
with new bone induction, and ultimately resorb without undue inflammation. Clinical
trials are underway with promising results that may overcome both
obstacles.
Some important questions remain to be answered. Will the dose
of growth factor have to be adjusted on the basis of the characteristics
of the patients (smoking, diabetes, medications, and so on)? Will
a consistent (near 100%) success rate be achievable in
humans as it is in animals? Will the results justify the cost of this
technology?
Lastly, the issue of design of future clinical trials deserves consideration.
It is imperative that the design allow us to distinguish bone formation
resulting through osteoinduction (BMPs) from bone formation that
may be spontaneous or from some other iatrogenic manipulation (e.g., reaming,
intramedullary nailing, or fracture/nonunion site surgical preparation).
In addition, if BMPs are used in conjunction with local bone or
autogenous iliac crest bone, the evidence will still be required
to show a result better than that with identical control patients
lacking only the active BMP agent. Failure to adhere to this type
of strict design risks dissemination of BMP products that may not
be optimized for dose and carrier and may not have the efficacy expected
by those who use them.