Teriparatide Enhancement of Lumbar Fusion: Bone Enhancement Versus Cost, Convenience, and Risk of Cancer: Commentary on an article by Shigeto Ebata, MD, PhD, et al.: "Role of Weekly Teriparatide Administration in Osseous Union Enhancement within Six Months After Posterior or Transforaminal Lumbar Interbody Fusion for Osteoporosis-Associated Lumbar Degenerative Disorders. A Multicenter, Prospective Randomized Study".

Abstract

Commentary The article by Ebata et al. contains several interesting and important points. However, the encouraging aspects of the study must be tempered by its short follow-up duration as well as the cost and potential for serious side-effects with the use of teriparatide. Those of us who perform spinal fusion surgery are interested in options that will stimulate healing, optimize the percentage of solid fusions, and improve patient outcomes. We are particularly looking for enhancements for challenging clinical situations, such as osteoporosis, where the quality of osseous fusion, the subsidence of implants, and screw pullout have been concerns. Teriparatide holds appeal as an intervention to address these issues, as teriparatide has been generally shown to improve bone mineral density and reduce fracture rates when compared with bisphosphonates in postmenopausal osteoporosis1,2. It is also germane that bisphosphonates have been shown to improve bone formation in osteoporotic patients who undergo posterior lumbar interbody fusion (PLIF)3. Thus, a logical research question is whether teriparatide would further enhance fusion following PLIF or TLIF (transforaminal lumbar interbody fusion)? While the short-term follow-up of 6 months in the present study limits the conclusions that can be drawn, it is encouraging that enhanced bone formation was seen within this short time frame. Fusion enhancement then leads us to look at whether teriparatide is likely to be generally applicable in day-to-day patient care. The limitations in the clinical scenario tend to be cost, convenience, and side-effects and/or complications. Teriparatide is clearly more expensive than other medications for osteoporosis. The estimated cost of daily subcutaneous injection is approximately $560 (USD) per month4 compared with $10 to $20 for the use of bisphosphonates5. One of the interesting aspects of the study by Ebata et al. is the efficacy of treatment involving the administration of a weekly dose of teriparatide compared with a daily regimen, as was studied by other authors investigating treatment following lumbar posterolateral fusion6. Weekly dosing would clearly be substantially cheaper than daily. In terms of patient convenience, a weekly dosing regimen would also have important implications, as the route of administration, subcutaneous injection, is somewhat invasive. Considering side-effects and/or complications, the potential inducement of cancer, particularly osteosarcoma, has been the primary concern with teriparatide. This has translated to a recommendation that teriparatide be used for a maximum 2-year time frame7,8. Osteosarcoma has been observed in small-animal studies involving rats at doses 3 to 60 times the standard prescription for humans7,8. However, the post-market surveillance funded by Eli Lilly but overseen by the U.S. Food and Drug Administration has not identified any cases of osteosarcoma7,8. To substantiate the encouraging early enhancement of healing, longer-term follow-up is needed. A treatment effect seen with a once-weekly dose (as opposed to the traditional daily dosing) suggests that additional investigation is necessary to further define the dose-response curve for teriparatide. Surgeons should be aware of the concern regarding the inducement of osteosarcoma with teriparatide treatment, even though this appears to be a relatively low risk. Similarly, the relatively high cost and the inconvenience of teriparatide administration by subcutaneous injection remain issues to be considered when evaluating treatment options.