Finding the evidence: spinal pseudoarthrosis
Question 5: What are the reported risk factors with the use of the various FDA/EMEA
approved orthobiologics?
Case 1 clarification
The patient is treated with revision intramedullary nailing and OP-1 with allograft.
Finding the evidence
• PubMed (www.ncbi.nlm.nih.gov/pubmed/): “rhBMP-2 complications,” “OP-1 complications”
C H A P T E R 1 3 Orthobiologics
• There is a need for more randomized studies, particu- larly in the upper extremity, to elucidate the safety and efficacy of OP-1 before expanded use can be recommended.
• In patients at risk for continued nonunion after revision, and when ICBG is not a reasonable option, then the use of either OP-1 or rhBMP-2 can be recommended, in light of the lack of other alternatives
Conclusion
The evidence regarding the use of orthobiologics is slowly evolving. Currently, the expanding use of these products is reflected in an increasing number of case reports and series that evaluate the treatment of nonunions in areas of the body for which the product has not been tested. Long-term follow-up and larger-scale randomized trials will need to be conducted to confirm the safety and efficacy of these procedures, as well as the cost benefits when compared to current practice standards.
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The two approved BMPs are members of the TGF-β family, and part of the mechanism of action is through stimulation of the inflammatory process. Crawford et al.
reviewed rhBMP-2 use in posterior cervical fusion proce- dures and found an increased rate of wound complica- tions, although the number only approached significance (p = 0.113).164 They proposed that this finding was related to a local inflammatory reaction induced by rhBMP-2. It is not surprising that there are several reports of postop- erative swelling associated with its use.155,165–167 Sheilds et al. reported a 18.5% complication rate related to postop- erative swelling after ACDF with INFUSE® graft.165 This included 15 (8.6%) patients with hematoma, 8 of whom required a return to the operating room for evacuation. A similar review of 234 patients found a clinically signifi- cant increase in the rate of swelling, with only a 3.6% rate seen in the patients treated with autograft or allograft alone.167
Summary of recommendations
• With regards to the use of orthobiologics to stimulate fracture healing, the current evidence does not support treating elderly patients with fractures differently than any other group of patients
• Diabetic patients deserve special attention with regards to management of lower extremity fractures, with particu- lar attention to wound care, peripheral vascular disease, peripheral neuropathy, and renal disease
• The prevalence of endocrine abnormalities, as well as the need to treat these conditions regardless of their effect on bone healing, should alert the treating physician to recog- nize patients at risk early in the treatment of fractures
• For HIV-infected patients, the available evidence sug- gests a trend that Gustilo–Anderson type II and III frac- tures are at an increased risk of infection and possibly nonunion
• Obesity alone is not an indication for the use of an ortho- biologic agent
• The physician should counsel patients on smoking ces- sation and reducing or eliminating other risky behavior such as drug and alcohol abuse, as these interventions will promote the overall health of the patient and will likely decrease the risk of complications in those treated both operatively and nonoperatively
• Use of rhBMP-2 in open fractures can only be recom- mended in high-energy open tibia fractures treated with nails; there is no data in other long bones or with other modes of fracture stabilization
• Cost analysis supports the use of rhBMP-2 as a potential cost-saving measure in lumbar fusion
• The use of OP-1 as a standard treatment is not warranted at this time
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