Orthobiologics are biologic devices or products used in orthopedic surgery to augment or enhance bone formation. The use of orthobiologics in pediatric orthopedics is less frequent than in other orthopedic subspecialties, mainly due to the naturally abundant healing potential and bone formation in children compared with adults. However, orthobiologics are used in certain situations in pediatric orthopedics, particularly in spine and foot surgery. Other uses have been reported in conjunction with specific procedures involving the tibia and pelvis. The use of bioabsorable implants to stabilize children’s fractures is an emerging concept but has limited supporting data.
Key points
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Use of orthobiologics in pediatric orthopedics is less frequent than in other orthopedic subspecialties.
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Allograft is effective in a variety of pediatric spinal deformity conditions in enhancing bony arthrodesis while avoiding morbidity of autograft harvest.
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Structural allograft can be used safely in foot deformity reconstruction.
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Recombinant BMP may be successful in enhancing healing of congenital pseudarthrosis of the tibia.
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The use of bioabsorable implants to stabilize children’s fractures is an emerging concept.
Introduction
The types of biologic devices or products used in orthopedics to enhance or augment bone formation can be grouped broadly into 3 categories: osteoinductive, osteoconductive, and osteogenic. Osteoinductive products encourage the host site to develop cells that form bone. Osteoconductive products are inert scaffolds that serve as a framework on which the host can produce bone. Osteogenic products are capable of independently producing bone-forming cells.
In adult orthopedics, reports of the use of orthobiologics are numerous, especially in the fields of orthopedic trauma, adult spine surgery, and foot and ankle surgery. However, reports on the use of biologics in pediatric orthopedics are less common. This may be due to the greater healing potential and more predictable bone formation in children compared with adults. Furthermore, children have fewer known comorbidities associated with deficiencies in bone healing in adults, including cigarette smoking, diabetes, and cardiovascular disease.
In pediatric orthopedics, most clinical applications of orthobiologics involve osteoconductive materials. These products are usually autograft substitutes, used in either a structural or augmentative fashion. A major benefit to the use of autograft substitutes is the elimination of the morbidity of an autograft harvest. Limited reports exist regarding the use of osteoinductive substances, such as bone morphogenic proteins, in pediatric orthopedic patients. The clinical applications of osteogenic substances in pediatric orthopedics is limited primarily to injection of autologous bone marrow aspirate to treat unicameral bone cysts or to stimulate bone formation in other lytic benign tumorous conditions. To date, the use of other osteogenic substances, such as platelet-rich plasma, has undergone little formal evaluation in pediatric orthopedic patients.
Introduction
The types of biologic devices or products used in orthopedics to enhance or augment bone formation can be grouped broadly into 3 categories: osteoinductive, osteoconductive, and osteogenic. Osteoinductive products encourage the host site to develop cells that form bone. Osteoconductive products are inert scaffolds that serve as a framework on which the host can produce bone. Osteogenic products are capable of independently producing bone-forming cells.
In adult orthopedics, reports of the use of orthobiologics are numerous, especially in the fields of orthopedic trauma, adult spine surgery, and foot and ankle surgery. However, reports on the use of biologics in pediatric orthopedics are less common. This may be due to the greater healing potential and more predictable bone formation in children compared with adults. Furthermore, children have fewer known comorbidities associated with deficiencies in bone healing in adults, including cigarette smoking, diabetes, and cardiovascular disease.
In pediatric orthopedics, most clinical applications of orthobiologics involve osteoconductive materials. These products are usually autograft substitutes, used in either a structural or augmentative fashion. A major benefit to the use of autograft substitutes is the elimination of the morbidity of an autograft harvest. Limited reports exist regarding the use of osteoinductive substances, such as bone morphogenic proteins, in pediatric orthopedic patients. The clinical applications of osteogenic substances in pediatric orthopedics is limited primarily to injection of autologous bone marrow aspirate to treat unicameral bone cysts or to stimulate bone formation in other lytic benign tumorous conditions. To date, the use of other osteogenic substances, such as platelet-rich plasma, has undergone little formal evaluation in pediatric orthopedic patients.
Spine
Scoliosis, whether adolescent, congenital, or neuromuscular, is a common condition treated by pediatric orthopedic surgeons. In patients with deformities of sufficient magnitude that demonstrate progression, or are at risk of progression, spinal fusion with instrumentation may be indicated. The goals of surgery are to obtain a solid arthrodesis, so as to prevent later curve progression, and correct the deformity to the degree that is safely possible.
Idiopathic and Neuromuscular Scoliosis
From the earliest reports, spinal fusion procedures for scoliosis were augmented with autograft, most commonly harvested from the posterior iliac crest. Autograft was considered to be essential to minimize the risks of pseudarthrosis and curve progression in the setting of uninstrumented fusions and early generation instrumentation systems. However, harvest of autogenous posterior iliac crest bone graft is not a benign procedure and can be associated with complications, including pain and/or local neuropraxia, that may be severe enough to interfere with activities of daily living. These issues have led surgeons to evaluate alternatives that would still augment the body’s natural mechanisms in generating a solid bony arthrodesis without incurring the risks of autogenous graft harvest. Orthobiologic products that have been investigated include freeze-dried allograft, synthetic ceramic bone substitutes, and allograft supplemented with bone marrow aspirate.
Following the development of modern segmental spinal instrumentation, early reports were encouraging that allograft could be used safely, with acceptable fusion rates and limited evidence of pseudarthrosis ( Fig. 1 ). Other investigators found that isolated allograft was not as successful but, by adding bone marrow aspirate, fusion rates similar to those reported with autograft could be achieved. Still others found satisfactory arthrodesis rates using a synthetic porous ceramic product. Long-term 5-year minimum follow-up on subjects treated with allograft showed a pseudarthrosis rate of 2.7% and loss of correction of 5.9%.
One of the foremost concerns regarding allograft use is the potential for infection. Although some data exist that demonstrates increased rates of surgical site infections following use of allograft, other reports refute this claim. In 2 separate prospective randomized trials of spinal fusion in idiopathic scoliosis subjects, synthetic ceramic was found to produce equal rates of fusion, with no increase rate of infection. To date, no similar studies exist that compare allograft with autograft.
Additional considerations regarding risk of infection in pediatric spine surgery concern the addition of antibiotics to any graft substance. The addition of gentamicin to bone graft has been shown to decrease rates of postoperative surgical site infection in cerebral palsy patients undergoing spinal fusion with unit rod instrumentation. No further data exist regarding indications for antibiotic use in children undergoing spinal fusion surgery. The choice of antibiotic, as well as dose and location of use (either in the local wound bed or within a graft substance), must be tailored to each clinical situation. In a consensus statement regarding best practice guidelines in pediatric spine surgery, addition of antibiotic within the surgical site was recommended in high risk cases.
Other Spine
The use of allograft has been reported in other spine applications besides idiopathic and neuromuscular scoliosis. Traditionally, allograft use has been discouraged in the cervical spine due to historical studies reporting near universal failure. In 2015, Reintjes and colleagues published a meta-analysis that assessed the use of allograft and autograft in association with pediatric patients undergoing posterior cervical fusion or occipitocervical fusion. They found a statistically higher fusion rate with use of autograft and in fusions that included the occiput. However, the investigators noted a wide variability in fixation systems and the use of other osteoinductive agents. To date, there are no studies that compare long-term fusion rates between allograft and autograft using comparable implant and instrumentation systems.
Although autograft is still recommended at the occipitocervical junction, more recent data show that allograft can be used successfully in the pediatric subaxial cervical spine. Murphy and colleagues reported on 26 subjects who underwent rigid segmental spinal instrumentation and allograft or autograft for a variety of conditions and disorders in the subaxial cervical spine. When compared with allograft, autograft subjects had similar rates of fusion with acceptable rates of complications. Given the ability to avoid donor site morbidity, the investigators recommended consideration of allograft in cases of subaxial pediatric cervical spine fusion with rigid segmental spinal instrumentation. In a review of 107 subjects with congenital spine deformity, Hedequist and colleagues reported a 97% union rate when using freeze-dried corticocancellous graft and instrumentation, with few complications.
There has been increasing information regarding the use of bone morphogenetic protein (BMP) in pediatric spinal deformity patients. To date, the use of BMP in pediatric patients is considered off-label for all indications by the US Food and Drug Administration. There have been concerns regarding increased complication rates in adult spinal fusion patients. In 2013, Carragee and colleagues reported an increased risk of new cancer in adult patients undergoing lumbar spinal arthrodesis procedures using BMP. However, since that time, further large cohorts of adult patients undergoing lumbar arthrodesis showed no evidence of increased cancer risk with utilization of BMP.
Reports of BMP use in pediatric spinal fusion procedures have become more frequent. Rocque and colleagues reviewed information on 4658 pediatric spinal fusion subjects available through a private payer database. Of these, 93.1% underwent a thoracolumbar fusion and BMP was used in 37.6% of all spinal fusion subjects in this cohort. The investigators found no difference in acute complications between the BMP and non-BMP groups. In 2015, Sayama and colleagues reviewed 57 consecutive posterior spinal fusion subjects treated with BMP with a minimum of 24 months follow-up. They found no new cases of cancer or spread of any existing malignancies in this subject group.
Most recently, Garg and colleagues performed a retrospective review of 312 subjects from 5 medical centers who underwent BMP application as part of an orthopedic procedure from 2000 to 2013. Of the 312 subjects, 228 (73%) underwent a spinal fusion procedure. In subjects treated with BMP, 22% were noted to have had a major or minor complication. Infection and implant failures were the most common major complication.
Overall, it seems that there is some role for the use of BMP application in pediatric spinal surgery, particularly in the face of deformity or nonunion. Complication rates are similar in patients with and without BMP utilization, at least in the short term, and the concern about increased cancer risk has not been shown in pediatric patients to date. However, significant questions remain as to the indications and patient population that will be best served by the use of this specific orthobiologic agent in pediatric spinal patients.
Foot and ankle
Foot reconstructions in patients with symptomatic planovalgus or cavovarus feet that fail nonoperative management are common in many pediatric orthopedic practices. In many of these procedures, bone graft is required to obtain and maintain the position of the newly corrected foot. As in other areas in orthopedics, structural autograft is the gold standard, due to strength, nonimmunogenicity, and ease of incorporation. However, as noted previously, iliac crest autograft harvest and utilization is not without potential complications.
Fresh frozen structural allograft has been used most commonly, and studied most frequently, in pediatric foot and ankle procedures, particularly in the management of pes planovalgus deformity with calcaneal lengthening osteotomy. In his original report detailing lateral column lengthening with a modified Evans osteotomy, Mosca used tricortical iliac allograft in 13 of 20 subjects, with an acceptable rate of complications and avoidance of donor site morbidity ( Fig. 2 ). In a larger follow-up series of 161 children who had foot reconstruction, with the use of 182 allografts and 63 autografts, Vining and colleagues reported similar rates of incorporation between allograft and autograft. All cases of allograft failure were attributed to technical error, rather than graft type. Furthermore, these investigators found that when accounting for iliac crest operating room harvest time, as well as surgeon fees for graft harvest, use of allograft resulted in a savings of approximately 25% per case. Other investigators have also reported successful use of structural allograft in pediatric foot reconstruction surgery, with acceptable rates of complications.
