Introduction

Currently, there are over 36 million people over the age of 65 years in the United States. This number is projected to increase to 71 million (nearly 20%) by 2030.¹ As the population ages there will be a similar increase in age-related diseases, such as degenerative disorders of the spine. The elderly are also living a more active lifestyle than at any other time, and thus the demand for addressing issues in this population will only increase over time. However, treating degenerative conditions of the aging spine poses particularly challenging situations to surgeons. Not only must the spinal surgeon address the spinal pathology, but these patients often have serious comorbidities that may affect the treatment options.^2,3 Therefore, patients, families, and physicians will have to weigh the additional risks of operative treatment against the benefits of reducing disabling pain and improving quality of life.

Spinal fusion is commonly considered in this population to address degeneration, deformity, and/or stabilize a decompressed segment. Although instrumentation is frequently used for initial stability, fusion is a biological event in which solid bridging bone forms between adjacent vertebrae.

Currently, iliac crest autologous bone (autograft) remains the gold standard bone graft material for achieving spinal fusion in all ages. It is an excellent choice because it is the only bone graft option that provides all of the components necessary for arthrodesis: osteoconductive matrix, osteoinductive proteins, and osteogenic cells. However, there are significant problems with using autograft including the limited supply of available bone and subjecting the patient to a secondary invasive procedure to harvest the autologous bone which is, in itself, associated with potential morbidity, such as infection, fracture, and intractable pain.^4,5 This consideration is particularly relevant for the elderly population who, because of their medical comorbidities, often have longer recovery times and more complications following surgeries of any kind. As a result, there has been significant work to develop materials to supplement or even replace iliac crest bone graft in the hope of minimizing surgical morbidities while ensuring that the treatment objectives are still achieved.

There have been few studies examining the use of biologics specifically in older patients. What has been done has focused primarily on complications as opposed to health outcomes and fusion success. Despite the limited information, older patients would intuitively seem to be an ideal target population for bone graft alternatives because of their poorer quality iliac crest bone and their higher risk for graft-associated complications. Although the roles of such biologics are still being defined, they provide an exciting adjunct or alternative treatment for spinal conditions in the aging patient population. This chapter will discuss some of these biologics designed to stimulate a successful spinal arthrodesis and their use in the elderly population.

Bone Morphogenetic Proteins

Bone morphogenetic proteins (BMPs), members of the transforming growth factor-beta superfamily, have gradually become better understood since their initial identification by Marshall Urist⁶ in the 1960s.⁷ They function by binding to the cell membrane of undifferentiated mesenchymal type of cells to promote the induction of bone formation. Although more than 12 BMPs have been identified, only a few have been explored for potential clinical use.

Two BMP molecules have been approved for use in humans. Recombinant human bone morphogenetic protein-2 (rhBMP-2) is currently approved, in conjunction with a collagen sponge and threaded intervertebral cage, for the treatment of degenerative lumbar spine disease. Recombinant human bone morphogenetic protein-7 (rhBMP-7), also referred to as osteogenic protein-1 (OP-1), currently has a humanitarian device exemption (HDE) status for posterolateral lumbar fusions in challenging fusion environments.

In a prospective, randomized trial comparing anterior lumbar interbody fusion with either rhBMP-2 implanted on a collagen sponge in a tapered fusion cage or autogenous iliac crest bone graft, there was a 94.5% fusion rate in the BMP group versus an 88.7% fusion rate in the control group, as determined radiographically.⁸ Moreover, 5.9% of the subjects in the autograft control group experienced adverse events related to their bone grafting procedures, and 32% reported persistent pain at the donor site at the time of final follow-up. Back, leg, and neurologic pain scores improved in both groups to a similar extent. Nonetheless, this procedure is less commonly considered than posterior procedures in the aged population because of the increase in complication rate and recovery time associated with anterior approaches.

Posterior lumbar fusion with BMP has significant challenges including limited surface area for healing, distractive forces, and the large gap between transverse processes needing to be bridged. Furthermore, studies have demonstrated the need for a bulking agent in posterior procedures. One recent retrospective study comparing instrumented posterolateral fusion with rhBMP-2 versus iliac crest autograft demonstrated equivalent fusion masses between the two groups at 2-year follow-up.⁹ Nonunion rate was 6.6% in the BMP group compared to 11.1% in the control group. No significant differences in the bulking agent used (local bone, allograft bone, demineralized bone matrix, and ceramic) were noted. Demonstrated outcomes when rhBMP-7 (OP-1) is used are comparable to those of autograft when used in uninstrumented posterolateral fusion for the treatment of degenerative spondylolisthesis.¹⁰

Recently Glassman and colleagues¹¹ reported on the utility of rhBMP-2 with an absorbable collagen sponge (ACS) compared to autograft in an elderly population (older than 60 years of age). They assessed the clinical, radiographic, and economic outcomes at 2-year follow-up for 102 patients treated by posterolateral lumbar fusion with iliac crest autograft versus rhBMP-2/ACS. They found no increased rates of complications due to the rhBMP-2 (8 of the 50 patients) in this population. In fact, there were increased perioperative complications in the autograft group (23 of the 52 patients). These complications included donor site infections, cardiac issues, pain, urinary tract infections, and neurologic deficit. Additionally, they found that the rhBMP-2 group had significantly better fusion grades on radiographic imaging and equivalent improvements in health-related quality of life outcomes for both groups.

Though BMPs provide substantial benefits in spinal arthrodesis, their use is not always without complication.¹² Potential complications include the formation of ectopic bone, hematoma and seroma formation, bone resorption and graft subsidence, antibody formation, and possible carcinogenicity. While some of the effects may be dose or carrier related, many of the applications currently considered for their use are off-label and their use has to be considered carefully. Further, the cost-to-benefit considerations remain to be elucidated.

Other Bone Graft Alternatives

Many other potential bone graft materials have also been considered for use alone or in combination with local bone to limit morbidity associated with iliac crest autograft. Some of these alternatives include allograft, demineralized bone matrix (DBM), and synthetic materials such as ceramics. While none of these bone graft alternatives possess all three factors necessary to promote osteogenesis, their utility in specific clinical situations is being studied. No matter what substance is chosen, the local and systemic environment must be hospitable to the formation of new bone, and there must be adequate blood supply, mechanical stability, and a lack of growth-inhibiting factors (e.g., nicotine, infection).