Oxford Health Plans > Medical and Administrative Policies > Bone or Soft Tissue Healing and Fusion Enhancement Products
Title of Policy

Bone or Soft Tissue Healing and Fusion Enhancement Products

The services described in Oxford policies are subject to the terms, conditions and limitations of the Member's contract or certificate. Unless otherwise stated, Oxford policies do not apply to Medicare Advantage enrollees. Oxford reserves the right, in its sole discretion, to modify policies as necessary without prior written notice unless otherwise required by Oxford's administrative procedures. The term Oxford includes Oxford Health Plans, LLC and all of its subsidiaries as appropriate for these policies as well as SecureHorizons and Evercare.

Certain policies may not be applicable to Self-Funded Members and certain insured products. Refer to the Member's plan of benefits or Certificate of Coverage to determine whether coverage is provided or if there are any exclusions or benefit limitations applicable to any of these policies. If there is a difference between any policy and the Memberís plan of benefits or Certificate of Coverage, the plan of benefits or Certificate of Coverage will govern.


Policy #: SURGERY 056.5 T2

Coverage Statement:

Policy is applicable to:
    Commercial plans

Note:

  • When used according to U.S. Food and Drug Administration (FDA) indications, growth factors in the form of bone morphogenetic protein-2 (BMP-2) are covered for the enhancement of bone healing and/or fusion of the lumbar spine via anterior approach when used in conjunction with a threaded titanium cage. Refer to the Treatment/Application Guidelines section of this policy for additional information regarding BMP-2 and other healing and fusion enhancement products.

Conditions of Coverage:

Benefit Type General benefits package
Referral Required
(Does not apply to non-gatekeeper products)
No
Authorization (Precertification always required for inpatient admission) Yes
Precertification with MD Review Yes1
Site(s) of Service
(If not listed, MD Review required)
Outpatient, Inpatient
Special Considerations 1Medical Director review is required for all bone healing and fusion enhancement products except for bone morphogenetic protein-2 (BMP-2) in a lumbar fusion via anterior approach when used in conjunction with a threaded titanium cage.

Description of Services/Assessment/Background Information:

Bone is the most commonly transplanted solid tissue in the world. Bone grafts can be harvested from the patient (autograft), obtained from bone banks (cadaver allograft), or composed of synthetic material. An autograft, also referred to as autogenic or autologous bone, is the gold standard for spinal fusion and is typically surgically obtained from the posterior iliac crest. In the United States, autologous bone is used for more than half of these bone grafts. Bone may be grafted to repair traumatic injury, replace periodontal bone loss, aid in the fusion of spinal vertebrae, or used for other bone repair or remodeling.

Allografts, also referred to as allogenic bone, give less consistent clinical results than autografts, and there is an increased risk of disease transmission and immunogenic response. Demineralized bone (DMB) is another type of allograft. It is produced through a process that involves the decalcification of cortical bone. This substantially decreases the structural strength, but the resulting product is more osteoinductive than ordinary allograft. Synthetic bone grafts are composed of materials such as ceramic, tricalcium phosphate, and collagen.

Bone morphogenetic protein (BMP): The most common method of spinal fusion involves the transplantation of bone from the iliac crest to the spine as an autologous graft. Since autologous grafting subjects patients to a second surgical procedure, there has been considerable interest in finding other materials for grafting or other means of achieving spinal fusion. Recombinant human bone morphogenetic proteins, a type of growth factor, have been developed and studied as possible alternatives or adjuncts to autologous bone graft (autografts). Several BMP products have been identified, and some are manufactured using recombinant deoxyribonucleic (DNA) technology.

The INFUSE® Bone Graft is the first commercially available BMP-2 product. It is used with the LT-CAGE (TM) Lumbar Tapered Fusion Device. In this procedure, a titanium cage is surgically implanted between vertebrae for the purpose of maintaining spacing and stabilizing the region to be fused. The cage is filled with a collagen sponge soaked with recombinant human bone morphogenetic protein. This serves as a scaffold for the formation of new bone. No other source of bone is required.

OP-1® which consists of rhBMP-7 and bovine collagen, is mixed with carboxymethylcellulose and saline to form a putty (OP-1 Putty). OP-1 received U.S. Food and Drug Administration (FDA) Humanitarian Device Exemption (HDE) approval.

Platelet-Rich Plasma: The addition of platelet-rich plasma (PRP), also known as autologous platelet-derived growth factors, AGF Gel, or platelet gel, to bone grafts has been investigated for a variety of orthopedic indications, including lumbar spinal fusion and oral and maxillofacial surgery. PRP is produced from the patient's own blood at the time of surgery, and usually mixed with bone graft material and sprayed directly onto prepared bone surfaces. PRP is utilized in combination with cancellous bone grafts as a source of platelet-derived growth factor (PDGF). It is present in normally healing fractures and stimulates osteogenic activity in vitro. The goal of using PRP is to accelerate graft incorporation, to enhance bone density, and to promote bone healing.

Bone Void Filler: Bone void filler is a synthetic product proposed to fill in and promote healing of gaps in the skeletal system. Synthetic bone grafts have been developed as another safe, readily available, less expensive alternative. Used alone, these products do not have osteoinductive properties however they may serve as extenders of osteoinductive bone graft materials. Vitoss® Scaffold Synthetic Cancellous Bone Void Filler is an approved beta-tricalcium phosphate product. Vitoss has a high porosity which allows rapid penetration of blood and blood products, thus facilitating migration of osteoblasts, as well as bone and blood vessel ingrowth.

Clinical Evidence:

Bone morphogenetic protein (BPM): Resnick et al. (2005) published guidelines for the performance of fusion procedures for degenerative disease of the lumbar spine regarding bone graft extenders and substitutes. The guideline states that the use of autologous bone or rhBMP-2 bone graft substitute is recommended in the setting of an anterior lumbar interbody fusion (ALIF) in conjunction with a threaded titanium cage.

In a systematic review and analysis of randomized controlled trials by Garrison et al. (2007), the clinical effectiveness of BMP for the treatment of spinal fusions and the healing of fractures was compared with the current standards of care. All selected trials were found to have several methodological weaknesses, including insufficient sample size, such that the statistical power to detect a moderate effect was low. This review found that there was evidence that BMP-2 is more effective than autogenous bone graft for radiographic fusion in patients with single-level degenerative disc disease. No significant difference was found when BMP-7 was compared with autograft for degenerative spondylolisthesis with spinal stenosis and spondylolysis. The use of BMP was associated with reduced operating time, improvement in clinical outcomes and a shorter hospital stay as compared with autograft. The proportion of secondary interventions tended to be lower in the BMP group than the control, but not of statistical significance. The authors concluded that the available evidence indicates that rhBMP-2 may promote healing in patients undergoing single-level lumbar spinal fusion, and may result in higher rates of fusion compared with autogenous bone graft.

In 2003, Burkus et al. conducted a prospective randomized study on 42 patients to investigate the radiographic progress of single-level anterior lumbar interbody fusion using cylindrical interbody fusion cages. The patients were randomly divided into two groups. The investigational group underwent interbody fusion using two tapered cylindrical fusion cages (LT-CAGE) and rhBMP-2 on an absorbable collagen sponge, and a control group underwent the procedure, receiving the devices and autogenous iliac crest bone graft. Plain radiographs and computed tomographic scans were used to evaluate the pattern of osteoinduction in the interbody space and the progression of fusion 6, 12, and 24 months after surgery. All the patients in the investigational group showed radiographic evidence of osteoinduction in the interbody cages 6 months after surgery with density in the cages increasing an average of 142 Hounsfield units. At 12 months, the increase had reached 228.7 Hounsfield units. New bone formation occurred in the disc space outside the cages by 6 months in 18 of the patients in the investigational group (18/22; 82%) and by 24 months, all the investigational patients showed new formation outside the cages. In the autograft control group, the density in the cages increased an average of 42 Hounsfield units, and 10 patients (10/20; 50%) showed evidence of bone formation outside the cages. The authors concluded that the use of rhBMP-2 is a promising method for facilitating anterior intervertebral spinal fusion in patients who have undergone anterior lumbar fusion surgery.

In another study by Burkus et al. (2006), a multicenter, randomized trial on 131 patients comparing healing and fusion rates after anterior lumbar interbody fusion (ALIF) with either autograft of rhBMP-2 was conducted. Patients with lumbar spondylosis who were undergoing single-level ALIF with allograft dowels were randomly assigned to either rhBMP-2 (79 patients)as the investigational group or autologous bone graft (52 patients)as the control group. Plain radiographs and computed tomography scans were used to evaluate fusion. At 12 and 24 months, all of the investigational patients had radiographic evidence of new bone formation and incorporation of the allografts into the adjacent vertebral endplates. Radiographic evidence of fusion was documented in 89% of patients in the control group at 12 months. This percentage declined to 81.5% at 24 months with 10% of the patients in the autograft group showing incomplete healing and 11% having no healing of the allograft dowels. On CT scan, 14 (18%) of the patients in the BMP group developed a transient, localized area of bone remodeling within the vertebral body adjacent to the allograft dowel; this disappeared by 24 months.

Singh et al., 2006, compared the use of iliac crest bone graft (ICBG) with INFUSE BMP in 41 patients vs. ICBG alone for lumbar spinal fusion. At 2-year follow-up, the ICBG with INFUSE BMP group achieved an overall fusion rate of 97%. The ICBG alone group achieved a 77% fusion rate. Glassman et al. 2005 randomized patients with single level lumbar degenerative disease in a study of lumbar spine fusion using ICBG (n=36) vs. BMP (n=38). The results of 74 patients at 1-year follow-up were analyzed. Of the ICBG group, 66% achieved grade 4 or 5 fusion and of the BMP group, 89% achieved 4 or 5 fusion.

The intent of using rhBMP-2 in a study by Pradhan et al., 2006, (n=36) was to try to improve fusion rates that were being observed in anterior lumbar interbody fusion (ALIF) using stand-alone femoral ring allografts as the interbody fusion device. These initial procedures (n=27) served as the historical controls and were followed by 9 procedures in which rhBMP-2 rather than autologous ICBG was used to fill the femoral ring allografts. The authors assume that the tight fit of the allograft that was achieved intraoperatively was lost during the resorptive phase of fusion. The attempt to prevent this with rhBMP-2 failed; there was actually a trend toward less successful fusion in the latter 9 patients. The authors cite the role of BMP-mediated signals in osteoclastic bone resorption as a reason and conclude that the use of rhBMP-2 does not preclude the need for instrumentation for additional stabilization.

The protocols followed by the other four studies of lumbar fusion involved a posterolateral or posterior lumbar interbody fusion (PLIF) approach, neither of which is included in the FDA approval of INFUSE (Boden et al., 2002; Haid et al., 2004; Glassman et al., 2005; Singh et al., 2006). In Boden et al. (n=25), rhBMP-2 was used with or without an internal fixation device, the Texas Scottish Rite Hospital pedicle screw instrumentation (TSRH), and compared with AICBG in conjunction with TSRH. The rhBMP carrier was not collagen but rather granules of hydroxyapatite/tricalcium phosphate (HA/TCP). At 1-year follow-up, there was fusion in 100% of each investigational arm and in only 40% of the control group. The very small number of patients (n=5) in the control group precluded a reliable estimate of fusion success rate. Pain and disability were considered secondary outcomes in this study. However, the rhBMP-2-alone group had consistently and substantially superior clinical outcomes than either the rhBMP-2 with TSRH- or AICBG with TSRH-group. These measures included the Oswestry Low Back Pain Disability Questionnaire score, back and leg pain, the SF-36 Physical Component Summary, and patient assessment of whether the outcome was good/excellent. The authors did not see a clear explanation for the difference in clinical outcomes between the two investigational groups. They speculated that this had to do with the more extensive retraction and prolonged operative time necessitated by internal fixation. There were a few adverse events in the two investigational arms and none in the control group, but again, the size of the control group limits conclusions about safety differences.

Haid et al., 2004, studied single-level posterior lumbar interbody fusion in 67 patients. Patients were randomly assigned to one of two groups: 34 patients received rhBMP-2 on a collagen sponge carrier and 33 patients received an autogenous iliac crest bone graft. The mean operative time and blood loss for the two groups were not significantly different. At 24 months follow-up, the group receiving rhBMP-2 had a fusion rate of 92.3%; the group receiving autogenous iliac crest bone graft had a fusion rate of 77.8%. No significant differences were found in the mean Oswestry Disability Index, back and leg pain scores and physical components of the SF-36. Two adverse events related to the harvesting of the iliac crest graft occurred in two patients.

Glassman et al., 2007, reviewed the outcomes of 91 patients two years after treatment with INFUSE BMP for posterolateral spine fusion. The overall group had a mean of 4.38 computed tomographic (CT) fusion grade and a 6.6% nonunion rate. Primary one-level fusion cases (n=48) had a mean of 4.42 CT fusion grade and a 4.2% nonunion rate. Primary multilevel fusions (n=27) had a mean of 4.65 CT fusion grade. No nonunions were detected. A comparison group of 35 primary one-level patients treated with fusion using iliac crest bone graft had a mean CT fusion grade of 4.35 and a nonunion rate of 11.4%.

Glassman et al. (2008) conducted a prospective randomized controlled trial of rhBMP-2/ACS (Infuse bone graft) versus iliac crest bone graft (ICBG) for posterolateral lumbar spine fusion in patients over 60 years of age. Patients were randomized to rhBMP-2/ACS (n = 50) or ICBG (n = 52). Two-year postoperative improvement in Oswestry Disability Index averaged 15.8 in the rhBMP-2/ACS group and 13.0 in the ICBG group. Mean improvement in Short Form-36 physical component score was 6.6 in the rhBMP-2/ACS group and 7.5 in the ICBG group. There were 20 complications in the ICBG group and 8 complications in the rhBMP-2/ACS group. Sixteen ICBG and 10 rhBMP-2/ACS patients required additional treatment for persistent back or leg symptoms. Two rhBMP-2/ACS patients had revision procedures, 1 for nonunion. Eight patients in the ICBG group had revision procedures, 5 for nonunion. Mean fusion grade on computed tomography scan was significantly better in the rhBMP-2/ACS (4.3) compared with the ICBG group (3.8). The investigators concluded that RhBMP-2/ACS is a viable ICBG replacement in older patients in terms of safety, clinical efficacy, and cost-effectiveness.

Three studies evaluating the use of BMP-2 in patients with tibial fractures were assessed. Govender et al., 2002, conducted a multicenter randomized controlled trial (called BESST trial) involving 49 centers in 11 countries. The study group consisted of 450 patients with open tibial fractures. Both treatment groups underwent standard primary treatment (intramedullary nail fixation). The trial compared the addition of an rhBMP-2 implant (rhBMP-2 on collagen sponge) at two different concentrations with standard treatment alone. The patients with rhBMP implants were substantially less likely to require secondary intervention, and a statistically significant dose-response relationship between rhBMP-2 concentration and prevention of secondary intervention was demonstrated. The difference in frequency of secondary intervention, however, did not meet the authors' a priori definition of clinical significance. rhBMP-2 implants also reduced the invasiveness of procedures, promoted faster healing, and resulted in greater overall treatment success. Adverse events were less frequent in patients who received the rhBMP-2 implants; differences in infection were observed only among patients with severe-grade fractures.

Swiontkowski et al., 2006, combined results from the randomized controlled trial reported by Govender et al., 2002, with a smaller trial (n=60) in U.S. centers only. The U.S. study followed a design identical to that of the BESTT trial. Raw data from the two studies were combined for subgroup analyses: (1) severe (Gustilo-Anderson type IIIA-IIIB) fractures and (2) reamed nailing. The first subgroup analysis revealed a greater effect of rhBMP-2 on both prevention of secondary procedure and on infection rates for severe fracture than in the earlier study group with a range of fracture types. The confounding effect of reamed nailing was reinforced in the second subgroup analysis, with outcomes only modestly and nonsignificantly superior in the rhBMP-2 treatment group compared with standard treatment in an analysis restricted to patients who underwent reamed nailing.

Four small trials (total n=88) comparing OP-1 Implant, OP-1 Putty, or OP-1 Putty plus autologous ICBG (intervention groups) with autologous ICBG alone or with local autograft plus a ceramic bone substitute (control groups) showed OP-1 to be safe; however they failed to provide strong evidence of the superiority of OP-1 (Vaccaro et al., 2005a, Kanayama et al., 2006, Vaccaro et al., 2005b, Johnsson et al., 2002). All four protocols were different, and none was consistent with the FDAs HDE for OP-1 Putty. High loss to follow-up or other methodological weaknesses were present.

Vaccaro et al. (2008) conducted a prospective, randomized, controlled, multicenter clinical pilot study of 36 patients undergoing decompressive laminectomy and single-level uninstrumented fusion for degenerative spondylolisthesis and symptomatic spinal stenosis. The patients were randomized in a 2:1 fashion to receive either OP-1 Putty (24 patients) or autogenous iliac crest bone graft (12 patients). At the 48-month time point, complete radiographic and clinical data were available for 22 of 36 patients (16 OP-1 putty and 6 autograft) and 25 of 36 patients (18 OP-1 putty and 7 autograft). Radiographic evidence of a solid arthrodesis was present in 11 of 16 OP-1 putty patients (68.8%) and 3 of 6 autograft patients (50%). Clinically successful outcomes, defined as at least a 20% improvement in preoperative Oswestry scores, were experienced by 14 of 19 OP-1 putty patients (73.7%) and 4 of 7 autograft patients (57.1%). The investigators concluded that despite the challenges associated with obtaining a solid uninstrumented fusion in patients with degenerative spondylolisthesis, the rates of radiographic fusion, clinical improvement, and overall success associated with the use of OP-1 putty were at least comparable to that of the autograft controls for at least 48 months after surgery.

Two randomized controlled trials evaluating rhBMP-7 as an aid to promoting bone repair in tibial fracture with nonunion (Friedlaender et al., 2001) or fresh tibial fracture (Maniscalco et al., 2002) were identified. Friedlaender et al., 2001, (n=122) followed a protocol consistent with the humanitarian device exemption (HDE) for OP-1 Implant. The inclusion criteria included nonunion of a tibial fracture at 9 months following injury. The patients underwent intramedullary (IM) fixation and were randomized to rhBMP-7 in a collagen carrier or fresh bone autograft. At 9-month follow-up (after treatment of nonunion), the clinical success, physician satisfaction, and bone bridging were slightly better in the control group, but there was a greater incidence of osteomyelitis in the control group. The clinical success rate at 2 years was 82% of patients in each group, nearly as high as at the 9-month follow-up. Substantial loss to follow-up at 2 years limits long-term conclusions.

Smucker et al. (2006) examined off-label use of BMP-2 to determine if BMP-2 is associated with an increased incidence of clinically relevant post-operative prevertebral swelling problems in patients undergoing anterior cervical fusions. A total of 234 consecutive patients (aged 12 - 82 years) undergoing anterior cervical fusion with and without BMP-2 over a 2-year period at one institution comprised the study population. The incidence of clinically relevant prevertebral swelling was calculated. The populations were compared and statistical significance was determined. A total of 234 patients met the study criteria, 69 of whom underwent anterior cervical spine fusions using BMP-2; 27.5 % of those patients in the BMP-2 group had a clinically significant swelling event versus only 3.6 % of patients in the non-BMP-2 group. This difference was statistically significant (p < 0.0001) and remained so after controlling for other significant predictors of swelling. The authors concluded that off-label use of BMP-2 in the anterior cervical spine is associated with an increased rate of clinically relevant swelling events.

Platelet-Rich Plasma: Only clinical trials utilizing autologous platelet-rich plasma (PRP) and study populations consisting of at least 5 patients were selected for detailed review. In an earlier review, several clinical trials studying the use of PRP for bone grafting were identified in the peer-reviewed literature, with six meeting the criteria for review. Five were studies of dental surgeries, including one randomized controlled trial, one randomized 'split-mouth' study, and three reports of case series. A single retrospective review of the use of PRP for lumbar spinal fusion was analyzed. Study population sizes ranged from 5 to 88 patients. Follow-up times ranged from 6 months to 2 years. Results of these studies suggest that PRP as an adjunct to bone grafting may enhance graft maturation and promote bone healing. However, only one study (Marx et al.,1998) provided a randomized comparison of outcomes with and without PRP.

In a literature search at a later date, several new studies were identified. Two studies were case series of 5 and 19 patients. Authors of both observed benefits from the use of autologous platelet gel in terms of stable hemostasis, reduced infections, shorter hospital stays, and improved osteoblastic reaction and reconstruction of bone structure (Giannini et al., 2004, Franchini et al., 2005). However, both were uncontrolled.

Two studies were controlled. Carreon et al., 2005, reviewed 76 consecutive patients who underwent lumbar fusion with autologous iliac crest bone graft mixed with autologous growth factor from platelet gel. The investigators randomly selected a control group from patients who underwent lumbar fusion with autologous bone graft alone. Groups were matched for age, sex, smoking history and the number of levels fused. The Fisher exact test was used to compare fusion rates. The difference in the nonunion rate in the two groups was not statistically significant, leading the authors to conclude that platelet gel failed to enhance fusion rates in this setting. Castro, 2004, compared 22 consecutive patients who received activated growth factor platelet gel and lumbar interbody fusion with 62 patients who had lumbar interbody fusion alone. Differences in results 34 months post procedure in the first group and 41 months post procedure in the second group were not statistically significant. The author concluded the theoretical benefits of platelet gel were not clinically realized.

Two studies compared bone healing using iliac bone grafts mixed with PRP vs. iliac bone grafts alone. Al-Sukhun et al., 2007, used PRP for reconstruction of the mandible in ten patients. Thor et al., 2005, used PRP for reconstruction of the maxilla in 19 patients. In both studies, statistically significant bone healing was demonstrated by the use of iliac bone grafts mixed with PRP.

Bibbo et al., 2005, studied autologous platelet concentrate to assist bone healing in foot and ankle surgery in 62 high-risk patients who underwent 123 procedures. Overall, a 94% union rate was achieved at a mean of 41 days. There was no control group for comparison.

Piemontese et al. (2008) conducted a randomized, double-masked, clinical trial to compare platelet-rich plasma (PRP) combined with a demineralized freeze-dried bone allograft (DFDBA) to DFDBA mixed with a saline solution in the treatment of human intrabony defects in 60 patients. Thirty patients each were randomly assigned to the test group (PRP + DFDBA) or the control group (DFDBA + saline). The investigators concluded that treatment with a combination of PRP and DFDBA led to a significantly greater clinical improvement in intrabony periodontal defects compared to DFDBA with saline. No statistically significant differences were observed in the hard tissue response between the two treatment groups, which confirmed that PRP had no effect on hard tissue fill or gain in new hard tissue formation.

Schaaf et al. (2008) conducted a randomized controlled study to evaluate that effectiveness of platelet-rich plasma (PRP). Fifty-three patients who underwent osteoplastic bone grafting for sinus floor elevation were included. The intervention group was treated with defined concentrations of PRP in addition to transplanted bone. Bone biopsies did not indicate superiority of any of the treatments in terms of bone volume. The investigators concluded that topical use of PRP did not improve maxillary bone volume either clinically relevant or statistically significant compared to that in conventionally treated patients. The use of PRP to support bone regeneration cannot be recommended as a standard method for maxillary augmentation.

Bone Void Filler: Four small prospective studies showed that beta tricalcium phosphate (b-TCP), a bone void filler, was at least as effective as an allograft when used as an autograft extender in surgery for 94 patients with idiopathic scoliosis or reported positive, noncomparison results using b-TCP as an extender in 47 patients with a lumbar fusion. These general results apply to fusion successes, but one study reported positive functional results as well. The two studies comparing b-TCP with allografts in scoliosis surgery combined one of these two extenders with an autograft in each patient group. One study showed little between-group differences in degree of scoliosis improvement, operative time, blood loss, or hospital length of stay (Muschik, 2001). The other study reported fusion success for all patients in both groups but better maintenance of correction in the b-TCP group (Le Huec, 1997). Of the two noncomparison studies involving lumbar fusion, one simply reported that there was fusion success at all treated levels within 6 months (Linovitz and Peppers, 2002). The other reported high (84% to 96%) 1-year fusion success rates (Epstein, 2006).

Four small studies (n=143) provided limited but positive evidence of the safety and efficacy of b-TCP for filling bone voids created by surgical excision of lesions, its superiority over hydroxyapatite (HA) in promoting healing, its ability to prevent postoperative pain in autogenous iliac crest bone graft (ICBG) sites, or its usefulness as a filler when an autograft was obtained from adjacent vertebral bodies in lumbar fusion. The strongest study in this group was a small (n=30) RCT that provided data on pain outcomes (Resnick, 2005). Following cervical discectomy or cervical corpectomy with the use of autogenous ICBG, patients were randomized to either b-TCP or standard treatment for promotion of bone hemostasis at the autogenous ICBG site. Patients were blinded to their treatment assignment and reported pain according to multiple measures. Strong differences were observed at six weeks, but the differences were considerably diminished at 3 months. Furthermore, the 3-month differences did not meet the authors' a priori definition of clinical significance.

Arlet et al., 2006, also used b-TCP to backfill the autograft site in lumbar fusion surgery. In this protocol, the autograft was harvested from an adjacent vertebral body instead of the iliac crest. The overall procedure was successful both radiographically and clinically. However, the contribution of b-TCP to these results cannot be assessed, because there was no control or comparison group. There were no complications attributable to b-TCP; thus, adverse effects associated with autogenous ICBG were avoided without the introduction of new adverse effects. Moreover, use of b-TCP was found not to require special precautions during insertion of posterior pedicle screw fixation in addition to anterior interbody fusion. By contrast, the authors relate that in their experience use of machined cortical allograft, an alternative bone void filler, required careful pedicle screw positioning to avoid extrusion of graft.

McConnell et al., 2003, randomized 29 patients to coralline hydroxyapatite vs. autograft for cervical interbody fusion. There was no significant difference in clinical outcome or fusion rates between the two groups. However, graft fragmentation occurred in 89% of the coralline hydroxyapatite grafts and 11% of the autografts. One patient in the coralline hydroxyapatite group required revision surgery for graft failure. Follow-up time was not stated in the abstract.

Epstein (2008) assessed fusion rates and outcomes in 60 geriatric patients undergoing multilevel lumbar laminectomies and 1- to 2-level noninstrumented fusions using B-TCP/autograft. Odom's criteria and Short-Form 36 (SF-36) outcomes were studied 2 years postoperatively. Pseudarthrosis was documented in nine (15%) patients. Two years postoperatively, Odom's criteria revealed 28 excellent, 23 good, 5 fair, and 4 poor results, whereas SF-36 data revealed improvement on 6 of 8 Health Scales in all patients.

FDA approval of Norian SRS™ was based on multicenter clinical studies sponsored by the manufacturers, involving 161 patients with simple wrist fractures who were treated with the product; 162 control patients were treated conventionally with casts or other fixation devices for six to eight weeks. Patients were followed for one year. Results demonstrated that the new product was similar in effectiveness to the conventional treatments in healing the fracture. The rate of complications was about the same at the end of one year. However, certain patients who received this product lost more bone length than patients treated conventionally. There are several published studies in the peer-reviewed medical literature on the use of Norian SRS for wrist fracture surgery. The use of Norian SRS for calcaneous fractures is an off-label use in the US.

U.S. Food and Drug Administration (FDA):

Growth factor-mediated spinal fusion systems are regulated by the FDA as Class III devices. The InFUSE Bone Graft/LT-CAGE Lumbar Tapered Fusion Device (Medtronic Sofamor Danek Inc.) device is indicated for spinal fusion procedures in skeletally mature patients with degenerative disc disease at one level from L4-S1, where the patient has had at least 6 months of non-operative treatment. These patients may also have up to Grade I spondylolisthesis at the involved level. Patients receiving the The InFUSE Bone Graft/LT-CAGE are to be implanted via an anterior open or a laparoscopic approach. See the following Web site for more information: http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfTopic/pma/pma.cfm?num=P000058. Accessed February 2009.

The INFUSE® Bone Graft device to be used along with an intermedullary nail (IM nail) to help heal fractures of the lower leg bone (tibia) received FDA approval April 30, 2007.

According to the manufacturer, the InFUSE™ Bone Graft/ LT-CAGE™ Lumbar Tapered Fusion Device is contraindicated for patients with a known hypersensitivity to recombinant human bone morphogenetic protein-2, bovine Type I collagen or to other components of the formulation. This device should not be used in the vicinity of a resected or extant tumor, in patients who are skeletally immature, or in patients with an active infection at the operative site or with an allergy to titanium or titanium alloy. Moreover, the safety and effectiveness of this device during pregnancy or nursing has not been established. See the following Web site for more information: http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfTopic/pma/pma.cfm?num=P000058. Accessed February 2009.

Additional information may be obtained from the U.S. Food and Drug Administration [Website] - Center for Devices and Radiological Health (CDRH) under product code NEK at: http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfPCD/classification.cfm?ID=4035. Accessed February 2009.

On July 1, 2008, the FDA issued a Public Health Notification regarding life-threatening complications associated with recombinant human Bone Morphogenetic Protein (rhBMP) when used in the cervical spine. There have been several reports of complications, occurring between 2 and 14 days post-op, such as swelling of neck and throat tissue, resulting in compression of the airway and/or neurological structures in the neck; difficulty swallowing, breathing or speaking; and severe dysphagia following cervical spine fusion with rhBMP due to the anatomical proximity of the cervical spine to airway structures in the body. Safety and effectiveness of rhBMP in the cervical spine have not been demonstrated and these products are not approved by FDA for this use. See the following Web site for more information: (Use product code NEK) http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfRL/rl.cfm. Accessed February 2009. Additional information is available from the U.S. Food and Drug Administration [Website] - 2008 Safety Alerts for Drugs, Biologics, Medical Devices, and Dietary Supplements available at: http://www.fda.gov/cdrh/safety/070108-rhbmp.html. Accessed February 2009.

OP-1® Putty (Stryker Biotech) received a Humanitarian Device Exemption (HDE) (H020008) on April 7, 2004, for application to lumbar fusion. See the following Web site for more information: http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfHDE/HDEInformation.cfm. Accessed February 2009.

The FDA has issued 510(k) approvals for the following platelet concentration systems for preparation of platelet-poor plasma and PRP (platelet concentrate) from a small sample of blood. SmartPReP™ Centrifuge System (Harvest(TM) Technologies Corp) May 28, 1999. ACCESS™ System (Interpore Cross Intl Inc.) March 26, 2002. PCCS™ Platelet Concentrate Separation Kit (3i [Implant Innovations Inc.] July 12, 2002. Magellan™ Autologous Platelet Separator System (Medtronic Perfusion Systems.) August 12, 2002.

The FDA issued 510(k) approvals for the following devices for use in the delivery of allograft, autograft, or synthetic bone graft materials to an orthopedic surgical site. In addition, they are designed to facilitate premixing of bone graft materials with intravenous fluids, blood, plasma, PRP, bone marrow, or other specific blood component(s), as deemed necessary by the clinical use requirements. SmartJet Bone Grafting Liquid Applicator (Harvest™ Technologies Corp.) July 3, 2001. Symphony Graft Delivery System (DePuy AcroMed, Inc., a Johnson & Johnson Co.) November 14, 2001. Graft Delivery System (Osseous Technologies, Inc., a Division of Biomet Orthopedics, Inc.) July 1, 2002.

Additional information regarding graft delivery systems may be obtained from the U.S. Food and Drug Administration [Website] - Center for Devices and Radiological Health (CDRH) under product code FMF at: http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfRL/listing.cfm. Accessed February 2009.

The FDA has published standards for the preparation of PRP. These standards state that PRP shall be prepared from blood collected by a single uninterrupted venipuncture with minimal damage to and manipulation of the donor's tissue. The plasma shall be separated from the red blood cells by centrifugation within 4 hours after completion of the phlebotomy or within the time frame specified in the directions for use for the blood collecting, processing, and storage system. The time and speed of the centrifugation shall have been shown to produce a product with at least 250,000 platelets per microliter. The plasma shall be stored at a temperature between 20 degrees C and 24 degrees C immediately after filling the final container. A gentle and continuous agitation of the product shall be maintained throughout the storage period, if stored at a temperature of 20 degrees C to 24 degrees C. See the following Web site for more information: http://www.cfsan.fda.gov/~dms/reg-2.html. Accessed February 2009.

Additional information regarding graft delivery systems may be obtained from the U.S. Food and Drug Administration [Website] - Center for Devices and Radiological Health (CDRH) under product code JQC at: http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfRL/listing.cfm. Accessed February 2009.

Bone Void Fillers under product code MQV include Vitoss® Scaffold Synthetic Cancellous Bone Void Filler (Orthovita Inc.) which was approved on December 14, 2000 (K032130) for use as a bone void filler for voids or gaps that are not intrinsic to the stability of the bony structure. It is indicated for use in the treatment of surgically created osseous defects or osseous defects resulting from traumatic injury to the bone. Vitoss should not be used to treat large defects that in the surgeon's opinion would fail to heal spontaneously. This product is intended to be packed into bony voids or gaps of the skeletal system (i.e., the extremities, spine, and pelvis). The bone filler product and the IMBIBE™ II Syringe (K030208) have since been combined to create the Vitoss-Filled Cartridge (K032130) approved November 3, 2003. The syringe is prefilled with Vitoss Bone Void Filler. A secondary syringe, the Meric Piston Syringe (K875196), and an adapter valve for the vacuum line in the surgical suite, are also included in the kit. The surgeon can use either the secondary syringe or the vacuum line to aspirate blood or marrow into the Vitoss-Filled Cartridge. Lastly, a mixture of b-TCP and Type 1 bovine collagen in a hydroxyapatite carrier, Vitoss® Scaffold Foam™ (K032288), was approved December 19, 2003.

Biosorb® Resorbable Bone Filler (Science for Biomaterials) was approved January 28, 2003 (K021963); and chronOS™ (Synthes-Stratec Inc.) was approved November 26, 2002 (K013072). These products are very similar to Vitoss, although less porous, and are approved for the same indications. The FDA has approved other b-TCP products as well.

Cross-Bone Bone Filler received 501(k) approval on December 17, 2007 as a bone filler and for bone reconstruction. Similar to other b-TCP, Cross Bone is a resorbable, biphasic ceramic implant composed of 60% hydroxyapatite and 40% P-tricalcium phosphate in the form of granules.

Additional information regarding b-TCP devices may be obtained from the U.S. Food and Drug Administration [Website] - Center for Devices and Radiological Health (CDRH) under product code MQV at: http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfRL/listing.cfm. Accessed February 2009.

Additional Products
ProOsteon 200™, Actifuse, PerioGlas, NovaBone and NovaBone-C/M, Grafton DBM, Plasmax, Hydroxyapatite

Policy and Rationale:

Oxford will provide coverage for bone healing and fusion enhancement products only as outlined in the Treatment/Application Guidelines section of this policy.

Treatment/Application Guidelines:

Covered Indications:

  • When used according to U.S. Food and Drug Administration (FDA) indications, growth factors, in the form of bone morphogenetic protein-2 (BMP-2), are considered medically necessary for the enhancement of bone healing and/or fusion of the lumbar spine via anterior approach when used in conjunction with a threaded titanium cage.

Non-Reimbursable Indications:

  • Use of bone morphogenetic protein-2 (BMP-2), via a posterior approach, is not considered to be medically necessary for the enhancement of bone healing and/or fusion of the lumbar spine or any other area. Posteriorlateral or posterior lumbar interbody fusion utilizing BMP2 has not received FDA approval. The use of BMP-2 via the posterior approach is investigational. There are no FDA labeling for this indications. In addition, available studies have demonstrated increased adverse events with the posterior approach.

  • Use of bone morphogenetic protein-2 (BMP-2) is not considered to be medically necessary for the enhancement of bone healing and/or fusion of the cervical spine or any other area.

  • Bone morphogenetic protein-7 (BMP-7), such as OP-1 putty, is not considered to be medically necessary for the enhancement of bone healing and/or fusion. Available studies have been limited by substantial loss of study participants at follow-up as well as short follow-up times. Additionally, use of BMP7 has not demonstrated accelerated healing and in one study better results were achieved in patients receiving traditional autograft.

  • Platelet-rich plasma is not considered to be medically necessary for the enhancement of bone healing, fusion enhancement, and injection into the tendon, joint or other soft tissue area of the body (including but not limited to achilles tendinopathy, elbow tendinosis, and lateral epicondylosis). Available clinical evidence is insufficient to conclude that the use of autologous platelet-rich plasma (PRP) in conjunction with bone grafting improves outcomes following orthopedic surgery or trauma. Although preliminary data suggest that use of PRP is safe and is associated with good outcomes when used in maxillofacial or spinal fusion procedures, only one RCT was identified, therefore, the contribution of PRP to bone fusion and graft incorporation cannot be evaluated and patient selection criteria cannot be defined.

  • Bone void fillers such as beta tricalcium phosphate (b-TCP) are not considered to be medically necessary for the enhancement of bone healing and/or fusion. Only very weak conclusions about effectiveness of bone void fillers may be drawn from studies because of small sample sizes, lack of control or comparison groups in most studies, and the absence of a formal assessment of clinical outcomes (as opposed to radiographic outcomes) in most studies. Furthermore, definitive patient selection criteria have not been established for the use of b-TCP bone void fillers.

Payment Guidelines

Coding Clarification: Most bone healing and fusion enhancement products are not represented by a specific CPT or HCPCS code. It may be necessary to use the most closely appropriate code and supplement with specific comments in the precertification documentation.

Applicable CPT/HCPCS Codes:

Code Description
0232T Injection(s), platelet rich plasma, any tissue, including image guidance, harvesting and preparation when performed
C9359 Porous purified collagen matrix bone void filler (Integra Mozaik Osteoconductive Scaffold Putty, Integra OS Osteoconductive Scaffold Putty), per 0.5 cc
P9020 Platelet rich plasma; each unit

Applicable CPT Codes: Apheresis

Note: The following codes are used for various indications beyond those addressed in this policy. For additional information regarding these services, including any applicable precertification requirements, refer to policy: Apheresis for Commercial Plans.

Code Description
36513 Therapeutic apheresis; for platelets
36514 Therapeutic apheresis; for plasma pheresis

Applicable ICD-9 Procedure Codes:

Code Description
84.52 Insertion of recombinant bone morphogenetic protein rhBMP
84.55 Insertion of bone void filler

Applicable CPT Codes: Surgical Reference List

Note: This list provides the surgical procedure codes with which bone healing and fusion enhancement products are most often used. This list should be used only as a guide in identifying those precertification requests which may require Medical Director review due to the possible use of bone healing and fusion enhancement products.

Code Description
22532 Arthrodesis, lateral extracavitary technique, including minimal discectomy to prepare interspace (other than for decompression); thoracic
22533 Arthrodesis, lateral extracavitary technique, including minimal discectomy to prepare interspace (other than for decompression); lumbar
22534 Arthrodesis, lateral extracavitary technique, including minimal discectomy to prepare interspace (other than for decompression); thoracic or lumbar, each additional vertebral segment (List separately in addition to code for primary procedure)
22548 Arthrodesis, anterior transoral or extraoral technique, clivus-C1-C2 (atlas-axis), with or without excision of odontoid process
22554 Arthrodesis, anterior interbody technique, including minimal discectomy to prepare interspace (other than for decompression); cervical below C2
22556 Arthrodesis, anterior interbody technique, including minimal discectomy to prepare interspace (other than for decompression); thoracic
22558 Arthrodesis, anterior interbody technique, including minimal discectomy to prepare interspace (other than for decompression); lumbar
22585 Arthrodesis, anterior interbody technique, including minimal discectomy to prepare interspace (other than for decompression); each additional interspace (List separately in addition to code for primary procedure)
22590 Arthrodesis, posterior technique, craniocervical (occiput-C2)
22595 Arthrodesis, posterior technique, atlas-axis (C1-C2)
22600 Arthrodesis, posterior or posterolateral technique, single level; cervical below C2 segment
22610 Arthrodesis, posterior or posterolateral technique, single level; thoracic (with or without lateral transverse technique)
22612 Arthrodesis, posterior or posterolateral technique, single level; lumbar (with or without lateral transverse technique)
22614 Arthrodesis, posterior or posterolateral technique, single level; each additional vertebral segment (List separately in addition to code for primary procedure)
22630 Arthrodesis, posterior interbody technique, including laminectomy and/or discectomy to prepare interspace (other than for decompression), single interspace; lumbar
22632 Arthrodesis, posterior interbody technique, including laminectomy and/or discectomy to prepare interspace (other than for decompression), single interspace; each additional interspace (List separately in addition to code for primary procedure)
22800 Arthrodesis, posterior, for spinal deformity, with or without cast; up to 6 vertebral segments
22802 Arthrodesis, posterior, for spinal deformity, with or without cast; 7 to 12 vertebral segments
22804 Arthrodesis, posterior, for spinal deformity, with or without cast; 13 or more vertebral segments
22808 Arthrodesis, anterior, for spinal deformity, with or without cast; 2 to 3 vertebral segments
22810 Arthrodesis, anterior, for spinal deformity, with or without cast; 4 to 7 vertebral segments
22812 Arthrodesis, anterior, for spinal deformity, with or without cast; 8 or more vertebral segments
22818 Kyphectomy, circumferential exposure of spine and resection of vertebral segment(s) (including body and posterior elements); single or 2 segments
22819 Kyphectomy, circumferential exposure of spine and resection of vertebral segment(s) (including body and posterior elements); 3 or more segments
22830 Exploration of spinal fusion
22840 Posterior non-segmental instrumentation (eg, Harrington rod technique, pedicle fixation across 1 interspace, atlantoaxial transarticular screw fixation, sublaminar wiring at C1, facet screw fixation) (List separately in addition to code for primary proc
22841 Internal spinal fixation by wiring of spinous processes (List separately in addition to code for primary procedure)
22842 Posterior segmental instrumentation (eg, pedicle fixation, dual rods with multiple hooks and sublaminar wires); 3 to 6 vertebral segments (List separately in addition to code for primary procedure)
22843 Posterior segmental instrumentation (eg, pedicle fixation, dual rods with multiple hooks and sublaminar wires); 7 to 12 vertebral segments (List separately in addition to code for primary procedure)
22844 Posterior segmental instrumentation (eg, pedicle fixation, dual rods with multiple hooks and sublaminar wires); 13 or more vertebral segments (List separately in addition to code for primary procedure)
22845 Anterior instrumentation; 2 to 3 vertebral segments (List separately in addition to code for primary procedure)
22846 Anterior instrumentation; 4 to 7 vertebral segments (List separately in addition to code for primary procedure)
22847 Anterior instrumentation; 8 or more vertebral segments (List separately in addition to code for primary procedure)
22849 Reinsertion of spinal fixation device

The foregoing Oxford policy has been adapted from an existing UnitedHealthcare national policy that was researched, developed and approved by the UnitedHealthcare Medical Technology Assessment Committee. [2009T0410F]

References
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Effective Date: July 1, 2010 through September 30, 2010