Clinical UM Guideline

 

Subject: Bone Graft Substitutes
Guideline #:  CG-SURG-45 Publish Date:    12/27/2017
Status: Reviewed Last Review Date:    11/02/2017

Description

This document addresses the use of bone graft substitutes for all indications, with the exception of dental conditions or procedures.

Note: The use of recombinant human bone morphogenetic (rhBMP) protein is not addressed in this document. rhBMP is a synthetic product, and should not be confused with naturally occurring BMPs, which may be present in autologous and allogeneic bone graft materials. For information regarding rhBMP, please refer to:

Note: This document addresses the use of bone graft substitutes that involve endogenous MSCs.  For information regarding the use of bone graft substitutes that include added or exogenous mesenchymal stem cells (including but not limited to AlloStem®, Cellentra™ VCBM, Osteocel® Plus, Trinity® Evolution™) please see:

Note: For other information regarding bone growth stimulation or the use of bone marrow aspirate concentrates, platelet derived growth factors, please see:

Clinical Indications

Medically Necessary:

The use of bone graft substitutes containing demineralized bone matrix (DBM), including but not limited to the following products, is considered medically necessary when used as a bone graft extender, or when autograft is not available:

Not Medically Necessary:

The above mentioned DBM-containing bone graft substitutes are considered not medically necessary when used for all other indications not addressed above.

The use of bone graft substitutes composed of substances other than DBM (for example, beta tricalcium phosphate [β-TCP], bioactive glass, crystaline hydroxyapatite, etc.), including but not limited to the following products, is considered not medically necessary for all indications:

Coding

The following codes for treatments and procedures applicable to this guideline are included below for informational purposes. Inclusion or exclusion of a procedure, diagnosis or device code(s) does not constitute or imply member coverage or provider reimbursement policy. Please refer to the member's contract benefits in effect at the time of service to determine coverage or non-coverage of these services as it applies to an individual member.

CPT

 

20930

Allograft, morselized, or placement of osteopromotive material, for spine surgery only

20999

Unlisted procedure, musculoskeletal system, general

 

 

HCPCS

 

C9359

Porous purified collagen matrix bone void filler (Integra Mozaik Osteoconductive Scaffold Putty, Integra OS Osteoconductive Scaffold Putty), per 0.5 cc

C9362

Porous purified collagen matrix bone void filler (Integra Mozaik Osteoconductive Scaffold Strip), per 0.5 cc

 

 

ICD-10 Diagnosis

 

 

All diagnoses

Discussion/General Information

The use of bone graft substitutes has been widely accepted as the standard of care for many orthopedic conditions, including spinal fusions surgery and degenerative orthopedic conditions when the use of autologous bone graft material is unavailable, or when there is insufficient autograft to meet the needs of the surgical procedure. Such products are usually made from allogeneic bone, but may also be made from non-organic substances such as β-TCP, calcium sulfate, hydroxyapatite, or xenographic bone, or any combination of these materials. The purpose of such materials is to provide a scaffold into which new bone forming cells can migrate and proliferate to create new autologous bone.

Autologous Bone Grafts

The use of autologous bone grafts (autografts) remains the current “gold standard” bone graft material. The use of bone autografts is believed to provide an optimal combination of matrix or scaffold, growth factors, and osteoprogenitor cell properties (Bostrom, 2005; Zwingenberger, 2012). However, the harvest of autografts may be associated with donor site pain and morbidity, and in some procedures where large amounts of graft are needed, sufficient quantities of autologous bone may not be available. In such circumstances, conventional allografts, processed allograft products, or synthetic bone graft products have been used. While these types of products have been helpful in allowing surgical procedures to be done in the absence of sufficient autograft, they may be associated with decreased efficacy and safety of autograft.

Demineralized (decalcified) Bone Matrix

In the 1960s, Marshall Urist demonstrated that demineralized (decalcified) bone matrix (DBM) did have the capability of inducing new bone formation (Urist, 1968). Furthermore, DBM has been shown to be less antigenic than frozen allograft, and to provide growth factors such as native bone morphogenetic proteins. Despite the paucity of clear clinical evidence supporting the use of DBM as a bone graft extender, its use has become the standard of care when there is no or insufficient autologous bone graft to meet the needs of the procedure. Other circumstances may include when the use of autologous grafts is unsuitable, as in the case with individuals with osteoporosis.

Other Bone Graft Substitutes

A variety of synthetic bone graft substitutes are under development. The majority incorporate ceramics, including calcium sulfates, hydroxyapatite, and tricalcium phosphate, either alone or in combination. Some of these products have incorporated carrier-beds of collagen or biodegradable polymers, antibacterials, bone morphogenetic proteins, and growth factors (platelet-derived growth factor, insulin-like growth factor, vascular endothelial and fibroblast growth factors), and concentrated bone marrow aspirate.

A number of products have been reviewed by the U.S. Food and Drug Administration (FDA) or are currently under investigation as an alternative to standard bone graft substitutes. There are several different types of bone graft substitutes available, to which a variety of other substance agents have been applied. Each of these products undergoes its own manufacturing process and has its own method of action. Currently, the available evidence addressing these products is scarce and of limited value. Summarized below, is the most rigorous available evidence for those products with clinical outcomes data found in the peer-reviewed published literature.

Actifuse

Actifuse is a silicate-substituted calcium phosphate product designed to be combined with autologous bone marrow aspirate (BMA). It was cleared through the FDA 510k process in 2007. At this time, the only peer-reviewed published study involving the use of Actifuse is a small case series study involving 21 subjects with idiopathic scoliosis who were treated with posterior instrumented fusion and followed for 24 months (Lerner, 2013). The authors reported that no adverse effects related to the study material had been observed. No evidence of implant failure was noted, and formation of an increasingly densifying ‘fusion mass’ was visible, as assessed by conventional radiography. Data regarding pain and quality of life were also presented, but the study lacked a comparator group. This study presents very limited evidence upon which to base judgment of the safety and efficacy of Actifuse. Another larger case series study was reported by Jenis (2010) evaluating the clinical and radiographic effectiveness of Actifuse in 42 subjects undergoing posterolateral instrumented lumbar fusion with 10 cc of Actifuse with 10 mL of BMA for 1- or 2-level lumbar degenerative disorders. The study follow-up period was 24 months. Of these 39 subjects, 15 underwent 2-level and 27 underwent single-level fusion procedures with 57 levels operated on in total. Visual analog scale measurements were used to evaluate pain scores. The average back pain scores as measured improved from 5.6 ± 2.5 preoperative to 2.1 ± 2.5 at follow-up (p<0.05) and leg pain improved from 5.8 ± 2.5 to 1.4 ± 1.9 (p<0.05). At 6 months, 35% of levels had fusion as measured by CT scan, which increased to 76.2% and 76.5% at 12 and 24 months, respectively. No evidence of ectopic bone formation or osteolysis was noted. The authors concluded that fusion rates for Actifuse-treated subjects were comparable to historical autograft controls. Further research is warranted in the form of large randomized controlled studies.

Amplex

Amplex is a product made from beta tricalcium phosphate (β-TCP) combined with B2A, a synthetic peptide designed to augment osteodifferentiation. It does not currently have approval or clearance from the FDA for marketing in the U.S. Currently, the only evidence available in the peer-reviewed published literature addressing the use of this product was an article by Glazebrook (2013). In this prospective randomized trial, 24 subjects underwent ankle and hindfoot arthrodesis. Subjects were randomized in a 1:1 fashion to receive treatment with either autologous bone graft as a control or Amplex. All participants were followed for 12 months. The authors reported that radiographic fusion success rates were similar in both groups (100% in the Amplex group vs. 92% autograft, no p-values provided). It was stated that there appeared to be radiographic stability in the Amplex group, whereas in the autograft group there may have been deterioration in radiographic outcome. No objective data were provided to support this observation. Both the Amplex group and the autograft group are reported to have had improvements in the pain and disability scores as measured by the Ankle Osteoarthritis Scale (AOS). However, no statistical analysis of this data is provided. Graft harvest-site pain affected only autograft-treated subjects. There were no adverse events attributed to the graft material in either the Amplex or autograft group. However, in the Amplex group at 6 months, the radiologist noted that 1 subject had subchondral cysts with anterior lucency. It is difficult to assess the impact of this in such a small short-term study. Overall, the evidence available addressing the safety and efficacy of Amplex is insufficient. No descriptive statistics are provided in this study to allow objective evaluation of the observed outcomes. Further research is warranted in the form of large randomized controlled trials.

Augment

Augment is a product composed of β-TCP and recombinant human platelet-derived growth factor BB (rhPDGF-BB). It does not currently have approval or clearance from the FDA for marketing in the U.S. An article by DiGiovanni (2011) is currently the only evidence available in the peer-reviewed published literature addressing the use of this product. In this randomized controlled trial (RCT), 20 adult subjects requiring ankle and hindfoot arthrodesis were randomized in a 2:1 fashion to receive treatment with either Augment or autologous bone graft, respectively, and followed for a minimum of 9 months. At 36 weeks, 77% (10/13) of the Augment subjects and 50% (3/6) of the autologous bone graft subjects had fused based on radiographic criteria. Two non-unions were reported to have occurred in the Augment group (9%, 2/14). Healing rates based on 12 week CT scanning (50% osseous bridging) were 69% (9/13) in the Augment group and 60% (3/5) in the autologous bone graft group. There were no device related serious adverse events in this study. This study was very small and no comparative statistics have been provided for intergroup comparisons. Further investigation into the safety and efficacy of this product is warranted.

HEALOS

HEALOS is a product composed of Type I bovine collagen and hydroxyapatite that becomes osteoinductive when mixed with bone marrow aspirate. It received FDA 510K clearance in 2001. There are currently only three peer-reviewed published studies addressing the use of HEALOS in clinical practice. The largest of these was a case control study involving 50 subjects undergoing lumbar spinal fusion who received treatment with HEALOS (Neen, 2006). Several surgical approaches were included in the study. These subjects were compared to 50 historical controls that had undergone treatment with autograft and who were matched for age, sex, and operative approach. For posterolateral fusions, the authors reported equivalent radiologic fusion rates for the two groups, with no significant difference in subjective or objective clinical outcomes. For interbody fusions, radiologic fusion rates were significantly lower for the HEALOS group but clinical outcomes for both groups were similar. No lasting adverse events were reported in the HEALOS group, compared with persistent donor site complications in 14% of the autograft group.

A second study conducted by Kitchel (2006) involved 25 subjects undergoing one-level posterior lumbar interbody fusion and instrumented posterolateral lumbar fusion, serving as self-controls. In each subject, HEALOS was used on one side of the posterolateral fusion, with iliac crest autograft on the contralateral side. The authors reported a fusion rate of 84% (21/25) for the control side and 80% (20/25) for HEALOS side. The interbody fusion rate was 92% (23/25). Mean Oswestry Disability Index (ODI) scores decreased 57.2% at 12 months and 55.6% at 24 months, compared with baseline. However, the data describing the interbody fusion rate and ODI measures are not particularly helpful in separating out the effects of HEALOS from the control treatment.

A study by Ploumis (2010) reported the results of a small nonrandomized trial of 28 subjects who had received treatment for degenerative lumbar scoliosis with a combination of HEALOS, BMA and local autograft (n=12) or a combination of local autograft and allograft (n=16). Subjects were followed for a minimum of 2 years. The results at 2 years indicated that both groups had similar significant (p>0.05) results in terms of pain, physical function, and fusion rates. Radiographic fusion was achieved in all but two cases, one in each group. Subjects in the allograft group showed evidence of fusion earlier than those in the HEALOS group (p<0.05). No toxicity from the HEALOS graft was recorded. This small study indicates that there is little to no benefit to the use of HEALOS in this subject pool. Additional investigation is needed to fully evaluate the safety and efficacy of HEALOS.

Osteocel Plus

Eastlack and others (2014) published the results of a large case series study involving 182 subjects undergoing anterior cervical discectomy and fusion using Osteocel Plus in a polyetheretherketone cage and anterior plating at one or two consecutive levels. Overall 249 levels were treated. Results for subjective measures included significant improvements (p<0.05) up to 24 months including scores on the neck disability index, visual analogue scale neck, visual analogue scale arm, SF-12 physical component score, and SF-12 mental component score. In subjects treated at a single level with a minimum of 24 month follow-up, solid bridging was reported in 92% (79/86) of levels. A range of motion of less than 3° was reported in 95% of levels in this group. In subjects with multiple level procedures, 87% (157/180) of levels achieved solid bridging and 92% (148/161) had a range of motion of less than 3° at 24 months. No revision procedures for pseudarthrosis were reported.

Another case series study has been published involving 40 subjects undergoing extreme lateral interbody fusion with Osteocel Plus at a total of 61 levels (Tohmeh, 2012). The authors reported no complications. At the 12 month follow-up, 35 (87.5%) evaluable subjects had an average ODI improvement of 41%, lower back pain improved 55%, and leg pain improved 43.3%. Satisfaction was reported at 12 months, with 92% reporting "very" or "somewhat" satisfied, and 86% being either "very" or "somewhat likely" to choose to undergo the procedure again. Complete fusion was observed in 90.2% (55/61) of levels. Incomplete fusion occurred in 5 levels, with complete ossification occurring in the cage, but complete trabecular bridging had not yet occurred.

Osteofil

Epstein (2007) reported on a case series study of 140 subjects undergoing multilevel laminectomies with one-level (n=95) and two-level (n=45) instrumented posterolateral fusions with both autograft and Osteofil. The extent of postoperative fusion was evaluated via blinded independent radiologists at 3, 6, and 12 months. The authors reported that at 1 year comparably improved outcomes were observed for both the one-level and two-level fusion groups on 6 of 8 Health Scales of the SF-36 health survey tool. Two dimensional (2D) CT studies documented one-level fusion an average of 5.2 months postoperatively in 92.6% (88/95) of subjects, whereas dynamic x-rays confirmed fusion in 98% (33/98). Pseudarthrosis/instability was reported for 2 one-level fusion subjects. Both required a second surgery at an average of 8 months postoperatively. In subjects with two-level procedures, 2D-CT documented fusion at an average of 6.1 months postoperatively in 91.2% (41/45) of subjects. Dynamic x-rays confirmed fusion in 96% (43/45) of subjects in this group. For 2 subjects undergoing two-level fusions, both 2D-CT and dynamic x-rays documented pseudarthrosis/instability. Both required secondary fusion an average of 10 months postoperatively.

Trinity Evolution

Musante (2016) reported the results of a retrospective case series study involving 43 subjects who underwent 47 posterolateral lumbar arthrodeses. The authors reported that at the 12 month end point the fusion rate based on radiographic evidence was 90.7% for all subjects, and 89.4% for all surgical levels. The incidence of bridging bone was not significantly different between two levels treated (85.7% for L3-L4 and 87.5% for L4-L5). Three subjects did not meet the fused criteria but were asymptomatic. No significant differences were noted between subgroups, including stratification by BMI, diabetes status, smokers, gender and age. Statistically significant improvements were reported in both leg and back pain outcomes after surgery (p<0.0001) at every time point. No adverse events related to the use of Trinity Evolution were reported. While no data were presented regarding historical controls, the authors concluded that, “Fusion rates using TE were higher than or comparable to fusion rates with autologous iliac crest bone graft that have been reported in the recent literature for posterolateral fusion procedures.”

References

Peer Reviewed Publications:

  1. Bae H, Zhao I, Zhu D, et al. Variability across ten production lots of a single demineralized bone matrix product. J Bone Joint Surg Am. 2010; 92(2):427-435.
  2. Cheung S, Westerheide K, Ziran B. Efficacy of contained metaphyseal and periarticular defects treated with two different demineralized bone matrix allografts. Int Orthop. 2003; 27(1):56-59.
  3. Digiovanni CW, Baumhauer J, Lin SS, et al. Prospective, randomized, multi-center feasibility trial of rhPDGF-BB versus autologous bone graft in a foot and ankle fusion model. Foot Ankle Int. 2011; 32(4):344-354.
  4. Eastlack RK, Garfin SR, Brown CR, Meyer SC. Osteocel plus cellular allograft in anterior cervical discectomy and fusion: evaluation of clinical and radiographic outcomes from a prospective multicenter study. Spine (Phila Pa 1976). 2014; 39(22):E1331-E1337.
  5. Epstein NE, Epstein JA. SF-36 outcomes and fusion rates after multilevel laminectomies and 1 and 2-level instrumented posterolateral fusions using lamina autograft and demineralized bone matrix. J Spinal Disord Tech. 2007; 20(2):139-145.
  6. Glazebrook M, Younger A, Wing K, Lalonde KA. A prospective pilot study of B2A-coated ceramic granules (Amplex) compared to autograft for ankle and hindfoot arthrodesis. Foot Ankle Int. 2013; 34(8):1055-1063.
  7. Kang J, An H, Hilibrand A, et al. Grafton and local bone have comparable outcomes to iliac crest bone in instrumented single-level lumbar fusions. Spine (Phila Pa 1976). 2012; 37(12):1083-1091.
  8. Kitchel SH. A preliminary comparative study of radiographic results using mineralized collagen and bone marrow aspirate versus autologous bone in the same patients undergoing posterior lumbar interbody fusion with instrumented posterolateral lumbar fusion. Spine J. 2006; 6(4):405-411.
  9. Lerner T, Liljenqvist U. Silicate-substituted calcium phosphate as a bone graft substitute in surgery for adolescent idiopathic scoliosis. Eur Spine J. 2013; 22 Suppl 2:S185-194.
  10. Neen D, Noyes D, Shaw M, et al. Healos and bone marrow aspirate used for lumbar spine fusion: a case controlled study comparing Healos with autograft. Spine (Phila Pa 1976). 2006; 31(18):E636-640.
  11. Musante DB, Firtha ME, Atkinson BL, et al. Clinical evaluation of an allogeneic bone matrix containing viable osteogenic cells in patients undergoing one- and two-level posterolateral lumbar arthrodesis with decompressive laminectomy. J Orthop Surg Res. 2016; 11(1):63.
  12. Ploumis A, Albert TJ, Brown Z, et al. Healos graft carrier with bone marrow aspirate instead of allograft as adjunct to local autograft for posterolateral fusion in degenerative lumbar scoliosis: a minimum 2-year follow-up study. J Neurosurg Spine. 2010; 13(2):211-215.
  13. Thordarson DB, Kuehn S. Use of demineralized bone matrix in ankle/hindfoot fusion. Foot Ankle Int. 2003; 24(7):557-560.
  14. Urist MR, Dowell TA. Inductive substratum for osteogenesis in pellets of particulate bone matrix. Clin Orthop Relat Res. 1968; 61:61-78.
  15. Wang JC, Alanay A, Mark D, et al. A comparison of commercially available demineralized bone matrix for spinal fusion. Eur Spine J. 2007; 16(8):1233-1240.
  16. Zwingenberger S, Nich C, Valladares RD, et al. Recommendations and considerations for the use of biologics in orthopedic surgery. BioDrugs. 2012; 26(4):245-256.

Government Agency, Medical Society, and Other Authoritative Publications:

  1. North American Spine Society. Allograft and Demineralized Bone Matrix for Spinal Fusion. October 2017. Available at: https://www.spine.org. Accessed on October 20, 2017.
Index

Bone graft substitute

The use of specific product names is illustrative only. It is not intended to be a recommendation of one product over another, and is not intended to represent a complete listing of all products available.

History

Status

Date

Action

Reviewed

11/02/2017

Medical Policy & Technology Assessment Committee (MPTAC) review. The document header wording updated from “Current Effective Date” to “Publish Date.” Updated Reference section.

 

03/06/2017

Revised note in Description section to clarify that CG-SURG-45 addresses bone graft products with endogenous MSCs and that bone graft products with added or exogenous with MSCs are addressed in TRANS.00035.

Revised

11/03/2016

MPTAC review. Added several products to MN list that were previously listed on TRANS.00035. Updated Reference section.

Reviewed

11/05/2015

MPTAC review. Removed ICD-9 codes from Coding section.

New

11/13/2014

MPTAC review. Initial document development.