Off-Label Use in Orthopaedic Surgery

Benjamin C. Taylor, MD; Jacob J. Triplet, DO; Taleed El-Sabawi, MS, JD

Disclosures

J Am Acad Orthop Surg. 2019;27(17):e767-e774. 

In This Article

Clinical Experiences

Pediatrics

Off-label use is more prevalent in pediatrics.[11,17] Most commonly, adult orthopedic devices are modified for off-label application in pediatrics.[10] Off-label use of common prescription drugs, including antibiotics, anticonvulsants, and antihistamines, is also common in the pediatric population.[9,10]

Orthopedic implants are quite frequently used off-label because pediatric-specific indications for many implants remain rare.[11,17] The lack of pediatric-specific implants can be attributed to the historic lack of pediatric orthopedic implant trials and concerns about liability.[11] Although the US Congress has recognized the significant lack of pediatric implant development with passage of the Pediatric Medical Safety Act in 2007, there remains many specific instances where the off-label use of another implant remains a generally accepted medical standard.[12]

Because of the smaller size of children and the presence of growth plates, many adult implants have to be modified or used in a drastically different manner than in the individuals these were designed and FDA approved for. Most adult-approved orthopedic implants can be successfully used in pediatric patients, but this use requires improvisation or creativity of the surgeon to implement a successful surgical tactic with the available implant(s). Examples of this include the use of implants designed for different bones, that is, tibial nails used for femur fractures[22] or implantation of devices in a manner different than described by the manufacturer, that is, screws stopping short of physes to minimize the risk of growth disturbances.[23]

In orthopedics, FDA approval is lacking for biological agents, with little to no data available on safety of use in this population. The most commonly described biologic adjunct in children appears to be recombinant human bone morphogenetic proteins (rhBMP)-2, although some very limited data also exist on rhBMP-7 use.[8,24,25] The small case series currently in print in regard to rhBMP use in children note a small complication rate, no noticeable increase in the incidence of malignancy, but conflicting results reported regarding the effect of these two biochemical agents on bone healing or fusion.[8,24,25]

Trauma

The field of orthopedic trauma and the wide array of injury presentations often necessitate a creative and novel approach to fixation of injuries, and this approach may result in off-label use of implants or biologics in an effort to treat the patient in the best possible fashion. Commonly, fracture-related implants can be used on areas of the body or bones the implant has not been designed or tested for[26] (Figure 1). Rapid technological advancement or adaptation of technology may make difficult regulatory review or may result in a nonapproved technology to become the standard of care without any effort placed into regulatory paperwork by the manufacturer(s). One such example of this would be use of polymethylmethacrylate as a temporary bone void filler with the induced membrane technique[27] (Figure 2).

Figure 1.

A, A stainless steel mesh plate approved by the FDA for use in the foot on a comminuted patella fracture. B, A titanium rib plate used in an off-label manner for a fracture-dislocation of the costovertebral joint.

Figure 2.

A, Polymethylmethacrylate used in an off-label manner in an induced membrane (Masquelet) technique case. B, Off-label use of trabecular metal cones designed and approved for arthroplasty in a patient with bone loss.

Bone morphogenetic proteins (BMP; ie, rhBMP) are often used off-label in orthopedics. Currently, rhBMP has two FDA-approved indications; rhBMP-2 is approved for use with anterior lumbar fusion with certain interbody devices and acute open tibial shaft fractures treated with an intramedullary nail, whereas rhBMP-7 is approved for use in long bone nonunions.[28,29] However, both of these products have been used in the trauma setting in an off-label manner, for both acute fractures and nonunion/malunion cases.[28,29] Subsequent published reports regarding the use of these biologics reveal conflicting results, with some authors noting an improvement in union rate, whereas others are unable to show any improvement despite the additional cost.[30–32]

Joints/Reconstruction

Implants for joint reconstruction are often relatively similar among different manufacturers, and these implants are generally used for their FDA indication. Although arthroplasty implants are most commonly placed in this manner, there are some notable exceptions to this, including total hip arthroplasty as a treatment method for acute femoral head, femoral neck, or acetabular fractures.[32,33] Although not formally approved for implantation in a patient with an acute fracture and often without preexisting degenerative changes, multiple published analyses have discussed the clinical, radiographic, and financial outcomes of this nonapproved indication.[32–35]

Moreover, Malcom et al[16] showed a 70% growth in off-label total hip and knee arthroplasty in the United States between 2000 and 2010. Obesity is an important risk factor for the mechanical failure of total joint arthroplasty. Several manufacturers list obesity as a contraindication for implantation, whereas several others merely note a caution or warning in their approval paperwork.[36] This can carry medicolegal ramifications because surgeons can be blamed for not providing adequate informed consent preoperatively if they are knowingly implanting these devices against published recommendations, or possibly even if the surgeon is unaware of the status of that particular implant. The incidence of implantation in the face of these formal contraindications or written warnings regarding obesity appears to be nearly 15% of all total hip and knee arthroplasty procedures.[36]

Upper Extremity

Similar to lower extremity arthroplasty and reconstruction, upper extremity reconstructive options can also be performed in an off-label manner. In particular, treatment of wrist degenerative changes in the younger patient is one area with many different published reports using non–FDA-approved implants. For example, off-label use of midcarpal hemiarthroplasty as a motion-preserving modality for radiocarpal arthritis has been shown to have benefit in young active patients with a maintained distal carpal row sustaining significant arthritis.[10] Another off-label treatment of radiocarpal arthritis reported includes implantation of meniscal allograft as an interposition after proximal row carpectomy[37] (Figure 3).

Figure 3.

The use of a lateral meniscal allograft as an interposition in a young patient with posttraumatic wrist arthritis.

Treatment of elbow arthritis with total elbow arthroplasty (TEA) is well described and has undergone formal FDA approval. But many TEA manufacturers do not have acute, nonpathologic fractures listed in their FDA approval, and therefore, use of TEA for elderly patients with osteoporotic or nonreconstructable fractures may be off-label, depending on the manufacturer used. In addition, reports of elbow hemiarthroplasty, with replacement of the humeral side only, have been increasing of late, and the use of only part of the FDA-approved implant would also technically be an off-label use of the device.[38]

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