Spine surgeons are familiar with the pitfalls associated with thoracolumbar fusion in osteoporotic patients, namely screw loosening, cage subsidence, fracture, and pseudarthrosis. Given the increasing rate of spinal fusion in elderly patients, surgeons are encountering osteoporotic bone more frequently. Bisphosphonates and teriparatide are the most commonly used medications to treat osteoporosis. However, animal models have raised questions about bisphosphonates potentially interfering with bone healing and spinal fusion. On the other hand, teriparatide has been consistently shown to improve spinal fusion in animal models. In order to better clarify the literature on this topic, Dr. Buerba and colleagues performed a meta-analysis looking at the effect of bisphosphates and teriparatide on fusion rate, screw loosening, fracture, and patient reported outcomes. They identified 9 comparative studies, including 3 RCTs, 4 prospective cohort studies, and 2 retrospective cohort studies. Four compared bisphosphonates to controls and demonstrated trends towards increased fusion rate (OR = 2.2. p = 0.09) and lower screw loosening rate (OR = 0.45, p = 0.19) for the bisphosphonate group. Only one study compared teriparatide to a control group, and this showed higher fusion rates and lower screw loosening in the teriparatide group. In two studies comparing bisphosphonates to teriparatide, the teriparatide group had a significantly higher fusion rate (OR = 2.3, p < 0.0001) and trend towards lower rate of screw loosening (OR = 0.37, p = 0.09). Compared to controls, bisphosphonates were associated with a lower fracture rate at the fused or adjacent levels (OR = 0.18, p = 0.0007). Patient reported outcomes were generally not different between the groups.
The authors have done a nice job quantitatively summarizing a heterogeneous literature on this topic. This heterogeneity is also what makes interpreting the results difficult, as treatment duration, dose, type of bisphosphonate, and definition of osteoporosis varied across studies. Bisphosphates work on a complex pathway in which osteoclast inhibition can effect both bone resorption and formation, and we do not have a clear understanding of the effect of specific drug type, duration of use, or dosage on spinal fusion. The effect of teriparatide seems more straightforward, though duration of treatment remains variable across studies. There was also a heterogeneity of surgeries included in the studies, ranging from one level fusions for degenerative spondylolisthesis to long thoracolumbar fusions for deformity. Despite this being a meta-analysis, due to the different comparisons across studies (i.e. bisphosphonate or teriparatide vs. control, bisphosphonate vs. teriparatide), the actual number of patients in each comparison was relatively low and limited the study's power. Despite these limitations, the study does allow some big picture conclusions. The most important is likely that bisphosphonates due not seem to impair fusion, so it may be better to continue these medications in osteoporotic patients rather than stop them prior to fusion. Additionally, teriparatide seems to be favored over bisphosphonates if a new agent is going to be started peri-operatively. Based on the available literature, teriparatide appears to be indicated for osteoporotic patients undergoing spinal fusion. Future studies are needed to define when to start the medication pre-operatively, optimal dosage, and duration of treatment.
Please read Dr. Buerba's article on this topic in the September 1 issue. Does this change how you view the role of bisphosphonates and teriparatide in thoracolumbar spinal fusion? Let us know by leaving a comment on The Spine Blog.
Adam Pearson, MD, MS
Associate Web Editor