Complication Rates After Bone Morphogenetic Protein (BMP) Use in Orthopaedic Surgery in Children: A Concise Multicenter Retrospective Cohort Study.

BACKGROUND: The use of bone morphogenetic protein (BMP) has been associated with a number of complications in adult patients. However, this association is less established in children. The aim of this study was to evaluate the safety of BMP use in children by determining the complication rates after BMP use at multiple institutions. METHODS: In a retrospective study (2000 to 2013), the medical records of all patients who received BMP at any of the 5 institutions were reviewed. Demographic information, preoperative data, and postoperative follow-up data were collected on those patients who were under the age of 18 at the time of surgery. RESULTS: A total of 312 pediatric patients underwent surgery with BMP application during the study period. The surgical procedures consisted of 228 spinal fusions, 39 pars repairs, 33 nonunion repair, and 12 other various procedures. Overall 21% (65/312) of patients who had BMP utilized had a complication. Fifty-five percent (36/65) of patients with a complication required a revision surgery. The average follow-up was 27 months (range, 3 to 96 mo); 80% of patients had a follow-up period of >12 months. The average age at the time of surgery was 13 years (range, 1 to 17 y). Males and females were almost equally represented in the study: 143 males (46%) and 168 females (54%). Of the patients who received BMP, 9% had minor complications and 13% had major complications. Wound dehiscence without infection was the most common minor complication and occurred in 59% (16/27) of patients with minor complications. Infection and implant failures were the most frequent major complications, occurring in 38% (15/39) and 33% (13/39) of patients with major complications, respectively. Five of 312 (2%) patients had neurological injury, 3 of which were only temporary. CONCLUSIONS: This multicenter study demonstrates a relatively high rate of complications after the use of BMP in children. However, further study is needed to attribute the complications directly to the use of BMP. LEVEL OF EVIDENCE: Level IV.

Single Nucleotide Polymorphisms in Osteogenic Genes in Atrophic Delayed Fracture-Healing: A Preliminary Investigation.

UpdateThis article was updated on September 10, 2014, because of a previous error. On page 1242, in the byline, and on page 1247, in the author addresses, the academic degree for Henry J. Donahue had previously read "MD." The degree now reads "PhD." BACKGROUND: We propose that fracture-healing potential is affected by the patient's genome. This genotype is then phenotypically expressed by the patient at the time of injury. We examined the hypothesis that patients who exhibit delayed or impaired fracture-healing may have one or more single nucleotide polymorphisms (SNPs) within a series of genes related to bone formation. METHODS: We performed a population-based, case-controlled study of delayed fracture-healing. Sixty-two adults with a long-bone fracture were identified from a surgical database. Thirty-three patients had an atrophic nonunion (delayed healing), and twenty-nine displayed normal fracture-healing. These patients underwent buccal mucosal cell harvesting. SNP genotyping was performed with use of bead array technology. One hundred and forty-four SNPs (selected from HapMap) within thirty genes associated with fracture-healing were investigated. Three SNPs did not segregate in the population and were excluded from the analysis. Eight of the remaining SNPs failed the test for Hardy-Weinberg equilibrium (p value smaller than the Bonferroni-corrected level of 0.05/141 = 0.000355) and were excluded. RESULTS: Five SNPs on four genes were found to have a p value of <0.05 in the additive genetic model. Of these five significant SNPs, three had an odds ratio (OR) of >1, indicating that the presence of the allele increased the risk of nonunion. The rs2853550 SNP, which had the largest effect (OR = 5.9, p = 0.034), was on the IL1B gene, which codes for interleukin 1 beta. The rs2297514 SNP (OR = 3.98, p = 0.015) and the rs2248814 SNP (OR = 2.27, p = 0.038) were on the NOS2 gene coding for nitric oxide synthase. The remaining two SNPs had an OR of <1, indicating that the presence of the allele may be protective against nonunion. The rs3819089 SNP (OR = 0.26, p = 0.026) was on the MMP13 gene for matrix metallopeptidase 13, and the rs270393 SNP (OR = 0.30, p = 0.015) was on the BMP6 gene for bone morphogenetic protein 6. CONCLUSIONS: Variations in the IL1B and NOS2 genes may contribute to delayed fracture-healing and warrant further investigation. CLINICAL RELEVANCE: Impaired fracture union may have genetic contributions.