Abstract
Introduction: Recombinant human bone morphogenetic protein-2 (rhBMP-2) (Infuse) has been shown to cause osteolysis rather than accelerated fusion in some series. This paper reports two cases of vertebral osteolysis in patients undergoing anterior cervical corpectomy with stabilization using titanium prosthesis where rhBMP-7 (OP1) has been used in high concentration.
Methods: Case series and review of literature.
Results: OP1 was used in 23 patients undergoing anterior cervical surgery. Each case had at least two CT scans during the first twelve months of follow-up. The two cases of osteolysis were identified amongst a subgroup of 8 patients undergoing anterior cervical corporectomy and reconstruction using a titanium rod and buttress implant. The first case was a 71 year old man who underwent C4-T1 corpectomy for spondylotic cord compression and the second case was a 62 year old man who underwent C3-T1 corpectomy for spondylotic cord compression. In both cases a bottle of OP1 (3.5mg) was mixed with 5mls of carboxy-methyl-cellulose/tri-calcium phosphate (CMC/TCP) putty, approximately half of which was then applied to the ends of the titanium rod and buttress prosthesis and compressed between the buttress end and the vertebral endplate, and some residual OP1-containing putty was placed at the sides of each buttress.
CT scans performed at 3 months postoperative in case 1 and 3.5 months postoperatively in case 2 demonstrated osteolysis in the vertebral bodies adjacent to the implant. In both cases however, CT scans performed 12 months post-operatively showed that the osteolytic cysts were beginning to resolve and fusion at the bone-titanium junction may have begun. No other cases of cystic osteolysis were found amongst other anterior cervical cases or 115 posterior lumbar interbody fusion (PLIF) cases similarly followed-up with serial CT scans. The concentration of rhBMP-7 used in a subgroup of 8 corpectomy cases undergoing anterior cervical corporectomy and reconstruction using a titanium rod and buttress implant was at least twice the concentration used in other anterior cervical cases and approximately one quarter to one fifth the concentration used in lumbar interbody PLIF cages.
Discussion: These are the first reported cases of osteolysis associated with the use of BMP-7.
Osteolysis has been described in association with the use of rhBMP-2. Following these reports, the manufacturers of rhBMP-2 have advised surgeons strongly not to use more than the (recently) recommended dose, despite there being no published evidence that osteolysis is dose-related. Similar recommendations have not been made regarding the use of BMP-7 (OP1).
The concentration of BMP-7 (OP1) which led to osteolysis in these cases was much greater than used elsewhere in the spine, where OP1 (3.5mg) is usually mixed with 10–15 mls of finely-milled autograft. This suggests that the concentration achieved by mixing 3.5 mg of OP1 with 5 mls of CMC/TPC putty may increase the risk of osteolysis when inserted into the anterior cervical spine.
Correspondence should be addressed to Dr Owen Williamson, Editorial Secretary, Spine Society of Australia, 25 Erin Street, Richmond, Victoria 3121, Australia.
