Pearls:
The perfect storm for arthrodesis is a combination of osteoinductive, osteogenic, and osteoconductive components.
Recombinant BMP2 can be used as an osteoinductive agent and has been shown to improve fusion rates in various spinal fusion procedures..
The literature regarding the use of BMP2 in spinal fusion is a bit messy at the moment, but a few highlights are that is that it provides for effective fusion without harvesting bone from the iliac crest
Clinical Scenario:
A 63 year old female is undergoing posterior decompression and fusion for degenerative spondylolysthesis of L4 on L5 causing several months of leg pain and, recently, leg weakness. The spinous processes and lamina were harvested and preserved for use as autograft material. As graft material is packed into the construct, the attending asks:
Attending: What is BMP?
Me: BMP is an osteoinductive agent used to improve bony growth after surgery.
Attending: True. Sorry, I was unclear. What does BMP stand for?
Me: [cannot stop thinking brain natriuritic peptide, but fully aware that the patient is not in heart failure] ... Bone... uhhh.
Resident: [trying to get to closure faster because its 7pm] it's "bone morphogenetic protein." Do you know the two other properties of grafting materials that promote bone growth?
Me: [back on terra firma] Yes, you need an osteogenic material and an osteoconductive material?
Resident: Great. Is there anything that you worry about with BMP?
Me: I'm afraid I do not know.
Resident: Some studies have shown that there is a risk for radiculitis and ectopic bone growth in certain kind of fusions. You can also just fail to fuse, even with the BMP. At yoru level of training, just remember that like most things that we do, BMP is not completely benign.
Details
First some definitions:
Osteogenic: material that provides osteogenic cells (i.e. osteoblast, osteoclasts, and their progenitor cells).
Osteoinductive: material that stimulates bone production by promoting differentiation of osteogenic cells.
Osteoconductive: material that provides a structure along which new bone can grow.
Bone healing is a collaborative project between osteoblasts and osteoclasts. Generally, osteoblasts lay down bone and osteoclasts break it down. Osteoblasts activate osteoclast precursors via the RANK/RANK ligand interaction. This interaction is inhibited by osteoprotegerin, a decoy receptor for RANK ligand produced by osteoblasts. Unbalanced activity of these cells is pathological. Variations of this balance are well illustrated in the lytic, mixed, and sclerotic phases of Paget's Disease of Bone.
A few other nuggets about bone healing while I have my notes open:
Bony healing requires some amount of force to be born by the bony callus, but movement prevents bony healing. This has several implications. First, it motivates the goals of instrumentation as immobilization, stabilization, and decompression rather than unburdening of weight from the instrumented spinal segments. Second, it motivates the need for patients to walk after surgery - unloaded bony callus will be resorbed.
Parathyroid hormone transiently increases bone deposition by activation of osteoblasts but chronically induces bone resorption (and thereby increase in serum calcium) as those activated osteoblasts release cytokines to activate osteoclasts.
Steroids induce bone resorption by promoting osteoclastogenesis via upregulation of RANK and downregulation of OPG as well as suppression of osteoblast activity.
Estrogen promotes the production of osteoprotegerin. Decreases in estrogen levels contribute to loss of bony mass after menopause.
Regarding BMP specifically, the point raised my resident regarding its complications is an important one. Although BMP is very effective for promoting fusion without the need for iliac crest bone harvesting - even improving results in smokers - it is associated with rare but potentially severe complications. This topic is deserving of a much more thorough literature review, but if you wish to approach with appropriate medical student caution, check out this paper. Particularly terrifying is the rapid deterioration associated with seroma formation in the cervical spine!
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