CurrentAetnaPolicy 0411

Bone and Tendon Graft Substitutes and Adjuncts

This policy governs Aetna's medical necessity, coverage, and experimental/investigational determinations for bone and tendon graft substitutes and adjuncts used in orthopedic and spinal procedures, affecting providers who request coverage for these products and procedures.

Policy Summary

PayerAetna

PolicyBone and Tendon Graft Substitutes and Adjuncts

Policy CodePolicy 0411

Change TypeNo material clinical or coverage changes

Effective DateMay 4, 2000

Next Review DateApr 25, 2024

Key ActionObtain prior authorization and document that INFUSE use meets lumbar fusion criteria and approach restrictions (ALIF or lateral) when requesting coverage.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

Lumbar fusion & select tibial fracturesINFUSE covered indications

Covered for spine fusionsb-TCP status

Covered for chronic osteomyelitisAntibiotic beads

Multiple listedExperimental / investigational items

Extensive listsCoding appendix

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Coverage Criteria and Evidence-Based Positioning

Coverage Criteria and Evidence-Based Positioning — Provider Action and Documentation Guidance

Provider-action / documentation and prior authorization guidance (consolidated):

No explicit coverage criteria group present in extracted text; use the consolidated provider-action guidance above to operationalize prior authorization and documentation requirements as applicable.

Providers should confirm payer-specific prior authorization rules (Aetna prior auth portal) for all biologics, BMPs, bone void fillers, and 510(k)-cleared adjuncts prior to scheduling procedures.

When submitting requests for INFUSE or other BMPs: include device labeling, indication alignment, dose per level, surgical approach, prior conservative treatment duration, and justification if use is off‑label or pediatric (off‑label pediatric use has higher documentation and denial risk).

For 510(k)-cleared bone void fillers and adjuncts: include manufacturer 510(k) indications, intended intraoperative use, whether the defect is intrinsic to structural stability, and infection history when antibiotic carriers are proposed.

For investigational therapies (e.g., SVF, MSC products, collagen-based implants for unproven indications): anticipate investigational/not medically necessary determinations unless acting within an approved clinical trial; provide trial enrollment documentation if applicable.

Coding Appendix and Code Tables

Related CPT/HCPCS codes (partial list)mixed

0565T	Autologous cellular implant derived from adipose tissue for the treatment of osteoarthritis of the knees; tissue harvesting and cellular implant creation.
0566T	Injection of cellular implant into knee joint including ultrasound guidance, unilateral.
0841T	Digitization of glass microscope slides for pathology consultation during surgery; first tissue block, with frozen section(s), single specimen.
20690-20694	Uniplane and multiplane fixation systems.
20900	Bone graft, any donor area; minor or small (e.g., dowel or button).
20902	Bone graft, major or large.
20955	Bone graft with microvascular anastomosis; fibula.
20962	Bone graft, other than fibula, iliac crest, or metatarsal.
20974	Electrical stimulation to aid bone healing, noninvasive (nonoperative).
20975	Electrical stimulation to aid bone healing, invasive (operative).

1–10 of 20

1/2

ICD-10 codes (examples and ranges; partial list)ICD-10

M80.051-M80.059	Age-related osteoporosis with current pathological fracture, femur.
M86.18, M86.28, M86.68	Acute, subacute and other chronic osteomyelitis [spinal].
M96.0	Pseudarthrosis after fusion or arthrodesis.
Z98.1	Arthrodesis status [nonunion of prior fusion].
S72.021A - S72.023C	Femur fracture codes (examples listed).

HCPCS / product-level listingsHCPCS

HCPCS (various)	Opteform DBM; Bio DBM; Bioset; Propel DBM; Allosource femoral head bone graft; Optium allograft; Beta tri-calcium phosphate (b-TCP); AttraX Putty; Prime DBM HD; Kore Fiber; InterGro DBM; OsteoAMP and others (covered if selection criteria are met).
HCPCS not covered list (various)	AlloStem; Arthrex biopaste (BioCartilage); ChronOS bone graft substitute; Cortiva Acellular Dermal Matrix; EmCell; i-Factor; Vivigen; Avive tendon wrap; and other products explicitly listed as not covered for indications in the CPB.

PRP / related CPT codesCPT

0232T	Injection(s), platelet rich plasma, any tissue, including image guidance, harvesting and preparation when performed.
0481T	Injection(s), autologous white blood cell concentrate (autologous protein solution), any site, including image guidance, harvesting and preparation, when performed.

Covered HCPCS codes if selection criteria are metHCPCSCovered

P9020	Platelet rich plasma, each unit.
S9055	Procuren or other growth factor preparation to promote wound healing.

Allograft for spinal fusion CPT codes (covered if criteria met)CPTCovered

20930	Allograft for spine surgery only; morselized.
20931	Allograft for spine surgery only; structural.

Bone void filler HCPCS codes (covered if criteria met)HCPCSCovered

C9359	Porous purified collagen matrix bone void filler (Integra Mozaik Osteoconductive Scaffold Putty), per 0.5 cc.
C9362	Porous purified collagen matrix bone void filler (Integra Mozaik Osteoconductive Scaffold Strip), per 0.5 cc.

Anti-microbial bone graft substitutes (HCPCS not covered)HCPCSNot Covered

C1602

Orthopedic/device/drug matrix/absorbable bone void filler, antimicrobial-eluting (implantable).

Drug-delivery device CPTsCPT

11981	Insertion, non-biodegradable drug delivery implant.
11982	Removal, non-biodegradable drug delivery implant.
11983	Removal with reinsertion, non-biodegradable drug delivery implant.
+20700	Manual preparation and insertion of drug-delivery device(s), deep (eg, subfascial) (List separately in addition to code for primary procedure).
+20701	Removal of drug-delivery device(s), deep (eg, subfascial) (List separately in addition to code for primary procedure).
+20702	Manual preparation and insertion of drug-delivery device(s), intramedullary (List separately in addition to code for primary procedure).

Mesenchymal stem cell therapy / bone marrow-related CPTs (not covered for CPB indications)CPTNot Covered

38232	Bone marrow harvesting for transplantation; autologous.
38240	Hematopoietic progenitor cell (HPC) transplantation.
38241	Hematopoietic progenitor cell (HPC) transplantation.

Xenograft CPT (covered for listed CPB indications)CPTCovered

0737T

Xenograft implantation into the articular surface.

Subchondroplasty CPT (not covered for indications listed)CPTNot Covered

0707T

Injection(s), bone substitute material (eg, calcium phosphate) into subchondral bone defect, including imaging guidance and arthroscopic assistance.

Allograft HCPCS (covered if selection criteria are met)HCPCSCovered

C1762

Connective tissue, human (includes fascia lata).

No codes listed in this excerptmixed

No codes listed

Codes referenced in these excerptsmixed

No codes listed

No codes listed in this excerptmixed

No codes listed

INFUSE application window for tibial shaft fractures (clinical key-value)

Clinical windowINFUSE must be applied within 14 days after the initial tibial shaft fracture

Patient populationSkeletally mature persons with acute, open tibial shaft fractures

Stabilization requirementFracture stabilized with intramedullary nail fixation after appropriate wound management

Coverage stanceMedically necessary for indicated tibial shaft fractures when all criteria met

Prior Authorization, Documentation, and Billing Guidance

Documentation Required

INFUSE for tibial shaft fractures — document intramedullary fixation and application within 14 days

Submit documentation that INFUSE use for tibial shaft fractures occurred within 14 days of the initial fracture and that fracture stabilization with intramedullary nail fixation and appropriate wound management were performed.

Timing (within 14 days) and fixation method are explicit policy requirements for INFUSE tibial shaft fracture coverage.

Prior Authorization

Prior auth: INFUSE must match FDA‑labeled indications and policy criteria

Use INFUSE Bone Graft only in accordance with FDA‑labeled single‑level anterior/lateral lumbar interbody fusion indications and the policy’s stated criteria; prior authorization reviewers will expect device‑label concordant documentation.

INFUSE is FDA‑approved for single‑level ALIF (L4–S1) after ≥6 months nonoperative treatment; coverage follows device labeling and policy criteria.

Background and Scope

Scope: This Clinical Policy Bulletin defines Aetna’s determinations regarding medical necessity and investigational status for a broad range of bone and tendon graft substitutes and adjuncts used in orthopedic and spinal procedures. The policy identifies specific products and classes that are medically necessary when policy criteria are met (for example, INFUSE for specified lumbar ALIF/ lateral fusion approaches and certain acute open tibial shaft fractures when applied within 14 days of fracture), as well as numerous devices and biologics considered experimental and investigational (not medically necessary) due to insufficient evidence. The policy consolidates evidence summaries, device‑specific indications, coding guidance, and documentation/prior authorization considerations to guide clinical and coverage decision‑making.

Definitions and Product Glossary

INFUSE Bone Graft (BMP-2) — definition/key value

DefinitionINFUSE Bone Graft = recombinant human bone morphogenetic protein-2 (rhBMP-2) delivered on a collagen absorbable sponge

FDA-approved useApproved for single-level anterior lumbar interbody fusion (ALIF) for symptomatic degenerative disc disease L4–S1 per device labeling

Policy coverageConsidered medically necessary for lumbar ALIF/ lateral approaches in skeletally mature patients who meet CPB 0743 criteria and for specified acute open tibial shaft fractures when applied within 14 days

b-TCP (beta tri-calcium phosphate) — definition/key value

Definitionb-TCP (beta-tricalcium phosphate) = a synthetic calcium phosphate ceramic used as an osteoconductive bone void filler and graft extender

Clinical role

Policy Summary

PayerAetna

PolicyBone and Tendon Graft Substitutes and Adjuncts

Policy CodePolicy 0411

Change TypeNo material clinical or coverage changes

Effective DateMay 4, 2000

Next Review DateApr 25, 2024

Key ActionObtain prior authorization and document that INFUSE use meets lumbar fusion criteria and approach restrictions (ALIF or lateral) when requesting coverage.

SourceLink

On This Page

Nonoperative treatment duration before INFUSE (>= 6 months)

Required conservative management before lumbar INFUSE (per device labeling)>= 6 months of nonoperative treatment for single-level ALIF indications

ScopeApplies to FDA-approved single-level anterior lumbar interbody fusion (L4–S1) use of INFUSE

Policy alignmentCoverage for lumbar fusion should align with device labeling and CPB 0743 criteria

Tear thickness threshold commonly reported (~50%)

Common imaging thresholdPartial-thickness rotator cuff tears commonly analyzed using a ~50% tear-thickness threshold

Context of useUsed as inclusion/analysis threshold in studies of bio-inductive implants for PTRCTs

Implication for selection~50% thickness can be used to define clinically meaningful partial-thickness tears in trial inclusion

Off‑label uses are considered investigational and may be denied.

Documentation Required

Verify prior authorization for 510(k)‑cleared grafts/adjuncts; supply device labeling

Several grafts and adjunct devices have 510(k) clearances with specific intended uses; verify prior authorization and provide device labeling/indication when requesting coverage.

Examples include PRP preparation devices (510(k)), Restore SIS for rotator cuff soft tissue reinforcement, and MIIG/Integra Mozaik OS putty for surgically treated osseous defects.
Document manufacturer/FDA intended use when submitting authorization requests.

Prior Authorization

Recommend prior auth for bone void fillers proposed for nonunion/delayed healing

Prior authorization is recommended when bone void fillers or novel graft substitutes are proposed for delayed union/nonunion or large volumetric defects because evidence is limited and outcomes variable.

Provide prior treatment history, duration of nonunion, infection history, and rationale for substitute versus autograft in authorization documentation.
Products cleared for surgically treated osseous defects may not be supported for nonunion therapy.

Documentation Required

Support clinical use of biologics and synthetics with evidence — supply during authorization

When requesting coverage for biologics or synthetic substitutes, include clinical evidence and rationale demonstrating expected benefit given mixed or limited fusion/outcome data.

OP‑1, calcium phosphate/β‑TCP compounds, and novel cellular products require documented indication and supporting evidence for coverage consideration.

Prior Authorization

Prior auth expectation: cellular bone matrices — provide comparative evidence

Prior authorization for cellular bone matrices (e.g., Osteocel Plus) should request supporting clinical evidence because randomized controlled trial data of effectiveness versus autograft are lacking.

Expect payers to request comparative data and intended use when cellular bone matrices are proposed as alternatives to autograft.

Prior Authorization

Consider prior auth for extensive/off‑label BMP use — document dose, levels, and rationale

Consider prior authorization for extensive or off‑label BMP use (for example, deformity fusions >8 levels); reviewers will weigh clinical rationale, dosing, levels treated, and cost versus expected benefit.

Observational data show differing re‑operation rates and costs in extensive fusion cases; include dose/level rationale in requests.

Note

i‑Factor: follow labeled use and device instructions; document per labeling

i‑Factor is labeled for single‑level cervical fusion (C3–C4 to C6–C7) in skeletally mature patients and must be used inside an allograft bone ring with supplemental anterior plate fixation per product labeling; prior authorization should reflect these device instructions.

Do not use i‑Factor where contraindications apply (infection, absence of load‑bearing support, compromised organ function, metabolic disorders, or sensitivity to components).

Note

Clinical evidence may inform prior authorization — include trial details

Clinical evidence presented in the policy may inform prior authorization decisions; when evidence is limited provide study-level data, expected outcomes, and comparator information in requests.

Include relevant trial outcomes, fusion rates, follow‑up duration, and limitations when justifying non‑standard uses.

Prior Authorization

Prior auth expectations for synthetic spinal grafts — provide comparative evidence

When proposing synthetic spinal grafts for fusion, prior authorization reviewers will expect comparative data demonstrating fusion rates and complication profiles versus autograft/allograft.

Comparative evidence for synthetic substitutes is limited and heterogeneous; document rationale and supporting data for patient‑specific coverage decisions.

Note

Prior authorization — no explicit rules in this excerpt; verify with payer

This excerpt does not state explicit prior authorization rules for other listed items; verify payer‑specific rules when billing or seeking authorization.

Absent explicit rules in the policy, follow standard Aetna prior authorization processes and cite CPB criteria where relevant.

Denial Risk

Denial risk: appendix‑listed experimental/investigational products

Use of products explicitly listed as experimental/investigational in the appendix will trigger noncoverage per the policy; expect denials for those products when used for unsupported indications.

The appendix enumerates numerous products considered not medically necessary due to insufficient evidence; providers should consult the appendix prior to use.

Documentation Required

Ceracell Ortho Foam — document intended nonstructural posterolateral use and mixing with autograft

When Ceracell Ortho Foam is used for posterolateral spine applications mixed with autograft, documentation should indicate intended nonstructural void‑filling use and mixing with autograft in accordance with its 510(k) clearance.

Document the planned mixing with autograft, the anatomic site, and that the defect is nonstructural per device clearance.

Prior Authorization

Prior authorization for appendix-listed medically necessary products — provide criteria-based justification

Products listed in the 'medically necessary when criteria are met' appendix remain subject to the policy’s coverage criteria and are likely to require prior authorization or provider justification per Aetna processes.

Even appendix 'medically necessary' products require meeting the specific clinical criteria described in the CPB for coverage.

Step Therapy

Step‑therapy and conservative sequencing — document failed standard care before investigational products

Providers should attempt standard conservative therapies and/or autograft/allograft options before using newer or investigational products; include documentation of failed standard care when requesting authorization.

OP‑1 was labeled as an alternative only when autograft is unfeasible and other treatments have failed; similar sequencing principles apply to many investigational products.

Step Therapy

Conservative‑first: document failed conservative care for rotator cuff prior to augmentation

Conservative management (rest, sling, NSAIDs, physical therapy, injections) is standard first‑line care for rotator cuff tears; document failure of conservative therapy before proposing biologic augmentation or implant use.

Policy and background emphasize conservative‑first approach prior to surgical augmentation techniques.

Step Therapy

Consider autograft or standard fixation before MSC/novel therapies — document prior attempts

Consideration should be given to autograft (iliac crest) or documented standard fixation/technique attempts prior to MSC‑based or novel graft substitutes; include documentation of prior attempts when seeking authorization.

Autograft remains the gold standard; investigational MSC or novel substitutes require justification that standard options are unsuitable or have failed.

Note

Anal fistula plug: first‑line for simple fistulas; document complexity and counsel on higher failure in Crohn’s

Anal fistula plug may be considered first‑line for simple fistulas and an alternative in selected complex fistulas, but providers must counsel patients about lower long‑term closure rates in complex/Crohn’s cases and document fistula type and prior treatments.

Pooled closure in non‑Crohn's patients is ~54%; closure rates decline over time and are lower in complex or Crohn's disease patients.
Document fistula complexity, Crohn's status, prior procedures, and expected outcomes.

Step Therapy

Preferred sequencing for fusion adjuncts in long ASD fusions — document autograft/BMP rationale

For long fusions to the sacrum in adult spinal deformity, consider autograft (ICBG) or documented use of BMP with clear dose and level rationale; include this sequencing and justification in prior authorization requests.

Observational data suggest BMP may improve fusion rates in long constructs, but safety and dosing considerations require explicit documentation.

Step Therapy

Consider alternatives before rhBMP‑2; include comparative outcomes and cost rationale

Before using rhBMP‑2 for non‑labeled or alternative indications, consider established alternatives (e.g., OsteoAMP, V‑CBA) and provide comparative evidence of expected outcomes and costs when seeking authorization.

Retrospective comparisons show alternatives may have similar fusion rates and lower supply costs; include such data if pursuing rhBMP‑2.

Step Therapy

Conservative therapy prerequisite for i‑Factor (≥6 weeks) — document failures before use

i‑Factor’s labeled use requires failure of at least 6 weeks of conservative treatment for the cervical indication; use outside labeled indications requires clinical justification in the authorization request.

Document prior conservative therapy duration and response when requesting coverage for i‑Factor outside labeled indications.

Note

No explicit step‑therapy specified — document prior treatments when requesting coverage

No step‑therapy pathways are specified in these excerpts; where none are defined, follow standard prior authorization and medical necessity review and document prior treatments.

Provide prior conservative and surgical treatment history to support requests for biologics or implants when explicit step therapy is not specified.

Step Therapy

Consider established grafts/BMPs before novel cell‑based products — document comparative rationale

Evidence supports considering established grafts (autograft, allograft, DBM) and BMPs where indicated before newer cell‑based or synthetic peptide products; provide comparative rationale if proposing newer products.

Newer cell‑based products have limited evidence; stepwise consideration of established options is advised.

Documentation Required

Healos graft extender — document attempted autograft or justification when substituting ICBG

Healos (HA+collagen) used as a graft extender has mixed evidence on fusion rates versus autograft; if substituting for iliac crest bone graft, document attempted autograft or justify why autograft is not feasible.

Some series show slower radiographic fusion with Healos+BMA compared to local iliac crest graft while clinical outcomes may be similar—document rationale when used.

Step Therapy

Step‑therapy considerations for Tactoset — attempt conservative options first; document justification

Given limited evidence for Tactoset in some indications (e.g., subchondral bone marrow edema/percutaneous fixation and inadequate support after digital amputation), consider conservative steps first and provide justification and supporting data for Tactoset use.

Where evidence is insufficient, prior authorization reviewers will expect documentation of failed conservative options and rationale for Tactoset use.

Documentation Required

Required clinical documentation for INFUSE — alignment with CPB 0743 and implantation details

Authorization requests for INFUSE must include clinical documentation demonstrating the patient is skeletally mature, meets lumbar fusion criteria per CPB 0743, and that INFUSE implantation will be via an anterior or lateral approach; for tibial shaft fractures include intramedullary nail fixation and application within 14 days of fracture.

Supply operative approach, fixation method, timing relative to fracture, and CPB 0743 concordant documentation when submitting prior authorization.

Documentation Required

Safety documentation required for off‑label BMP‑2 use — document FDA safety notices and swelling risk mitigation

When BMP‑2 is used off‑label (e.g., anterior cervical spine), include FDA safety communications and documentation of awareness of increased risk of clinically relevant pre‑vertebral swelling and related safety measures in the record.

Include documentation of informed consent addressing off‑label risks and any perioperative measures taken to mitigate swelling risk.

Documentation Required

Document device labeling/intended use for 510(k) devices when requesting coverage

For devices cleared via 510(k), document device labeling and intended use when billing or requesting authorization to ensure proposed use matches cleared indications.

Examples include Restore SIS (rotator cuff soft tissue reinforcement), Integra Mozaik OS (surgically treated osseous defects), and MIIG (injectable bone void filler).

Documentation Required

Bone void filler documentation expectations — indicate defect type, fixation, prior treatments and infection history

When bone void fillers (e.g., MIIG, Integra Mozaik OS) are used, include indication, concurrent fixation or procedure, and rationale in documentation; for nonunions include prior treatments, duration, and infection history due to variable outcomes in the literature.

Evidence lacks support for nonunion treatment with many fillers; detailed prior treatment history is essential for review.

Documentation Required

Anal fistula plug: required clinical documentation elements — complexity, Crohn’s status, prior treatments, follow‑up

For anal fistula plug studies and clinical use, document fistula complexity, Crohn's disease status, prior treatments, follow‑up assessment of closure, and any plug extrusions; these elements informed the studies cited by the policy.

Studies defined success as closure of external openings and absence of drainage/abscess; include similar follow‑up data in requests.

Documentation Required

Procedure and imaging documentation for micronized allogeneic cartilage use

When using micronized allogeneic cartilage (BioCartilage) or similar products, document indication, prior conservative management, imaging (MRI) localization of the lesion, and intraoperative technique details given limited human outcome data.

Provide MRI findings, lesion size/location, prior nonoperative therapy, and operative steps when seeking coverage or coding justification.

Documentation Required

Imaging and fusion documentation expectations — schedule and fusion definition

Radiographic fusion assessment (x‑ray and/or CT) at standard postoperative intervals (approx. 1, 3, 6, 12, 18 months) and a clear definition of fusion (bridging across endplates or to interspace disc plugs) should be provided for fusion claims and prior authorizations.

Blinded radiographic adjudication was used in comparative studies; include imaging schedule and fusion criteria in documentation.

Documentation Required

CT documentation of bone bridging — include CT results when used to guide management

In trials assessing bone bridging (e.g., Fourman ankle study), CT at 3 months was used to quantify percent bone bridging; include CT documentation if fusion timing or device removal decisions are based on CT‑assessed bridging.

Document CT‑assessed percent bridging and how it informed clinical decisions (e.g., frame removal or subsequent interventions).

Documentation Required

Typical supporting‑study documentation: radiography and PRO measures — include when available

Supporting studies commonly required radiographic fusion assessment and patient‑reported outcome measures (VAS, NDI, SF‑36, ODI) with blinded adjudication; include similar outcome measures in documentation when available.

Including PROs and blinded radiographic assessments strengthens prior authorization and coverage submissions for novel products.

Documentation Required

Device trial documentation expectations (IDE studies) — levels, PROs, CT at 12/24 months

Registry or IDE device trials (e.g., OptiMesh) required documentation of instrumented fusion level, pre‑ and post‑op validated outcome measures, and CT imaging for fusion at 12 (and 24 if not fused) months; provide similar data when requesting coverage for devices studied under IDEs.

Independent radiologist CT assessment and adjudicated adverse events were parts of IDE protocols; include equivalent imaging and outcome data where available.

Prior Authorization

Prior auth/documentation expectations for AGN1 LOEP — limited evidence; provide osteoporosis data and prior therapies

Clinical evidence supporting AGN1 LOEP is limited to a single small cohort; document patient T‑scores, prior osteoporosis treatments, and trial applicability if proposing AGN1 LOEP, and expect requests for higher‑quality evidence.

Current evidence is insufficient to establish effectiveness; ongoing trials are recruiting but AGN1 remains investigational pending RCT data.

Billing Rule

Billing/denial examples — CPT codes not covered for CPB indications (e.g., 0707T, 0547T)

Certain CPT/HCPCS codes are listed as not covered for indications in this CPB (for example, 0707T subchondroplasty and 0547T bone‑material microindentation testing); do not bill these codes for unsupported CPB indications.

0707T (subchondroplasty) is listed as not covered for indications in this CPB.
0547T (microindentation testing) is listed as not covered for indications in this CPB.

Denial Risk

CMS non‑coverage alert: autologous PRP for certain wound indications — denial risk

CMS has issued a non‑coverage decision for autologous PRP for chronic non‑healing cutaneous wounds, acute surgical wounds when PRP is applied directly to the closed incision, and dehiscent wounds; expect payer denials consistent with CMS guidance.

When proposing PRP for CMS‑noncovered indications, include clinical justification and expect denial based on CMS policy.

Denial Risk

Bone void fillers for delayed union/nonunion — unsupported; potential denials

Use of bone void fillers for delayed union or nonunions is unsupported by sufficient evidence and may be denied when intended as treatment for delayed fracture healing or nonunion.

ECRI and other assessments concluded there is no reliable evidence to support calcium sulfate or other bone void fillers for delayed fracture healing/nonunions.

Denial Risk

AlloMatrix putty — documented high complication/infection rates; denial/documentation risk

AlloMatrix putty has been associated with high postoperative drainage and infection rates in nonunion series; providers should document infection risk and prior infection history if proposing its use and expect potential denial.

In the Ziran series, over half developed postoperative drainage and many required reoperation for deep infection.

Denial Risk

Evidence gap for cellular bone matrices — may trigger denial or request for comparative evidence

Evidence gaps for cellular bone matrices (e.g., Osteocel) may lead to denial or requests for comparative evidence when used as a replacement for standard allograft or autograft in procedures like ACDF.

Matched‑cohort data showed lower 1‑year fusion rates for Osteocel in one series (87.7% vs 94.7%), prompting requests for higher‑level evidence.

Documentation Required

Off‑label pediatric rhBMP use — documentation and denial risk

Off‑label pediatric use of rhBMP requires careful documentation; although some large administrative analyses did not show higher overall complication rates, certain infections were more common and long‑term growth/cancer risks were not assessed — expect payers to require detailed justification.

Document indications, alternative options, and informed consent addressing off‑label pediatric concerns when requesting coverage.

Note

i‑Factor contraindications — do not use when listed contraindications present

i‑Factor contraindications must be observed: do not use when acute/chronic infection is present at the operative site, load‑bearing structural support is absent, or in patients with compromised renal/hepatic function, metabolic disorders affecting healing, or known sensitivity to components.

Prior authorization or chart documentation should confirm absence of these contraindications when i‑Factor is proposed.

Documentation Required

Evidence limitations may affect coverage — provide robust supporting data

Because evidence is often limited (small samples, single‑center designs, or biased registries), coverage decisions may be affected — supply robust study details and address limitations when requesting authorization.

Clearly state study design limitations and how proposed use differs from populations in cited studies when seeking coverage for novel products.

Denial Risk

Synthetic grafts (PMMA/BOP) — higher risks reported; document comparative justification

Synthetic grafts such as PMMA and biocompatible osteoconductive polymer (BOP) have been associated with lower fusion rates and higher device‑related complications versus iliac crest bone graft in some studies; expect prior authorization scrutiny and need for comparative justification.

Document comparative fusion and complication data when proposing synthetic grafts in place of accepted grafts.

Denial Risk

SVF therapies — insufficient evidence; likely denial without strong data

Use of adipose‑derived stromal vascular fraction (SVF) cells lacks sufficient evidence for clinical indications; services based on insufficient evidence may be denied and prior authorization requests should include high‑level supporting data.

Intraoperative isolation methods and small pilot studies exist, but clinical efficacy remains unproven—expect denials without robust trial evidence.

Denial Risk

Xenograft implantation into articular surfaces — insufficient evidence; denial risk

Xenograft implantation into articular surfaces is unsupported by sufficient evidence and may be denied; do not propose xenograft articular implantation without compelling investigational trial data.

Policy explicitly lists xenograft implantation into articular surfaces as investigational.

Denial Risk

Denial risk for products listed as experimental/investigational in appendix

Use of products explicitly listed as 'experimental and investigational' in the appendix will trigger noncoverage per policy; verify the appendix before proposing a product and include comparative evidence if requesting exception.

The appendix enumerates many products considered not medically necessary; exceptions require compelling, high‑quality evidence.

Used as a bone graft extender/substitute and indicated for spinal fusions that meet CPB 0743 criteria (example: AttraX Putty)

Remodeling noteUltraporous formulations aim for greater remodeling and resorption approximating bone; remodeling kinetics vary by compound

OP-1 (BMP-7) — definition/key value

DefinitionOP-1 (BMP-7) = recombinant human osteogenic protein-1, developed as an osteoinductive implant (HUD approval for limited indication)

Clinical evidenceInduced viable new bone in human fusion trials but randomized data showed lower surgical-exploration fusion success versus controls in small trials

Regulatory/market noteApproved as a Humanitarian Use Device for limited indications; manufacturer later ceased production/removed from US market (noted in background)

INFUSE (BMP-2) — definition/key value

DefinitionINFUSE (BMP-2) = recombinant human bone morphogenetic protein-2 on a collagen sponge used as an osteoinductive adjunct

IndicationsFDA-approved for specified anterior lumbar interbody fusion devices; off-label uses include other fusion sites but may carry safety concerns (eg, cervical swelling)

Safety noteOff-label anterior cervical use is associated with increased risk of clinically relevant pre-vertebral swelling

Platelet-rich plasma (PRP) — definition/key value

DefinitionPlatelet-rich plasma (PRP) = autologous blood-derived concentrate of platelets delivering growth factors to enhance bone and soft-tissue healing

Evidence statusClinical evidence is mixed and contradictory across indications; CMS has non-coverage decisions for some PRP wound indications

Typical useUsed adjunctively with grafts in augmentation procedures (eg, sinus lift, microfracture) though benefit for routine use is not well established

Restore Orthobiologic Soft Tissue Implant (porcine SIS) — definition/key value

DefinitionRestore Orthobiologic Soft Tissue Implant = porcine small intestinal submucosa (multi-layer SIS) surgical mesh intended as a resorbable scaffold for soft-tissue reinforcement (eg, supraspinatus augmentation)

Regulatory noteCleared via FDA 510(k) with labeled intended use for soft tissue reinforcement limited to supraspinatus in rotator cuff surgery

Clinical cautionCase series report early post-op inflammatory reactions in some patients; document device labeling when used

MIIG (minimally invasive injectable graft) — definition/key value

DefinitionMIIG = a minimally invasive injectable graft (calcium sulfate paste) that cures in situ, resorbs, and is replaced by bone; used as a bone void filler

Regulatory statusCleared by FDA via 510(k) as substantially equivalent to other bone void fillers

Clinical noteIntended for surgically treated osseous defects or traumatic bone defects; evidence does not support use for delayed unions/nonunions

Demineralized bone matrix (DBM) — definition/key value

DefinitionDemineralized bone matrix (DBM) = allograft-derived grafting agents prepared from processed cadaveric bone used as graft extenders/enhancers

Clinical evidenceMany human trials report high fusion rates when DBM used as an extender/enhancer, but few high-quality RCTs compare DBM to iliac crest autograft

Policy roleConsidered medically necessary for spinal fusion and bone void filling when policy criteria are met

Demineralized Bone Matrix (DBM) — duplicate/alternate entry (inventory) — definition/key value

DefinitionDemineralized Bone Matrix (DBM) = processed allograft bone product evaluated as a graft extender/enhancer in spine fusion

Trial resultsProspective randomized and multicenter trials report comparable fusion rates to autograft in some series (eg, Grafton DBM trial: 86% vs 92% at 2 years, not significant)

Evidence gapAdditional high-level studies are needed to define specific indications and patient populations that benefit most

Bone void filler — definition/key value

DefinitionBone void filler = synthetic or processed material (eg, calcium sulfate paste, calcium phosphate, β-TCP) placed into osseous defects to be resorbed and replaced by bone

Intended useCleared 510(k) indications typically specify use for surgically treated osseous defects or traumatic bone defects, not explicitly for nonunions

Evidence cautionInsufficient evidence supports use of many bone void fillers for delayed union/nonunions; randomized trials (eg, CERTiFy) are ongoing for some products (Cerament)

Mesenchymal Stem Cells (MSCs) — definition/key value

DefinitionMesenchymal Stem Cells (MSCs) = multipotent progenitor cells from bone marrow or adipose tissue capable of differentiating into osteoblasts, chondrocytes, adipocytes

Clinical statusMSCs show preclinical promise, but clinical evidence is insufficient for most orthopedic applications (eg, spinal fusion, nonunions); bone marrow injections are medically necessary only for unicameral bone cysts

Regulatory/implementation noteProducts marketed as cellular bone matrices (CBMs) may be regulated as HCT/P and not require premarket clinical trials, contributing to evidence gaps

OP-1 (BMP-7) — definition/key value (inventory duplicate)

DefinitionOP-1 (BMP-7) = recombinant human osteogenic protein-1 used as an osteoinductive putty/matrix to promote bone formation

HUD statusApproved by FDA as a Humanitarian Use Device for limited long-bone nonunion indications; clinical trials showed viable new bone but mixed fusion success

Practical noteRandomized trials found OP-1 less effective than autograft in some settings; manufacturer ceased production and product was removed from the US market

β-TCP (beta-tricalcium phosphate) — definition/key value

Definitionβ-TCP (beta-tricalcium phosphate) = a synthetic calcium phosphate ceramic used as an osteoconductive scaffold and bone void filler

Clinical roleUsed as graft extender or void filler in spinal fusion and fracture augmentation (eg, AttraX Putty, SiCaP variants)

Evidence noteComparative studies report variable fusion rates vs rhBMP-2 (eg, rhBMP-2 96% vs β-TCP 80% in one series); high-quality RCT evidence is limited

Cellular bone matrix (CBM) / cellular allograft — definition/key value

DefinitionCellular bone matrix (CBM) / cellular allograft = allograft processed to retain endogenous viable bone-lineage cells combined with osteoconductive/inductive scaffold (examples: ViviGen, OsteoVive)

Evidence statusObservational series show promising high fusion rates in selected series, but evidence limited by retrospective designs and lack of RCTs

Regulatory noteMany CBMs are marketed under HCT/P pathways allowing commercialization without premarket clinical efficacy data, creating evidence gaps

Micronized allogeneic cartilage (BioCartilage) — definition/key value

DefinitionMicronized allogeneic cartilage (BioCartilage) = dehydrated, micronized allogeneic cartilage scaffold used to augment microfracture aiming to restore hyaline-like cartilage

Clinical evidenceHuman outcome data are limited; ongoing trials aim to define efficacy compared with standard microfracture

Procedure documentationWhen used, document indication, prior conservative management, MRI localization, and intraoperative technique due to limited outcome data

rhBMP-2 — definition/key value

DefinitionrhBMP-2 = recombinant human bone morphogenetic protein-2 (INFUSE) used as an osteoinductive adjunct in spinal fusion delivered on a collagen sponge

Safety considerationsDosing and off-label use associated with safety signals (eg, anterior cervical swelling); careful adherence to labeled indications and documentation advised

Clinical evidenceRCTs and observational data support efficacy in ALIF; comparative outcomes vary by indication and dose

Fusion (radiographic) — definition/key value

DefinitionFusion (radiographic) = radiographic evidence of bridging across endplates or bridging from endplates to interspace disc plugs on x-ray or CT

Assessment timingRadiographic assessments are typically performed at standard postoperative intervals (approx. 1, 3, 6, 12, 18 months) and may include blinded radiologist review

Use in trialsCT and x-ray criteria used as endpoints in trials (eg, CERTiFy, OptiMesh IDE) to adjudicate fusion status

ASD (Adult Spinal Deformity) — definition/key value

DefinitionASD = Adult Spinal Deformity; refers to multilevel fusion surgeries for deformity correction often involving long constructs

Clinical implicationBMP use in ASD associated with lower pseudarthrosis rates but increased odds of radiculitis/neurologic complications in meta-analyses

Dose observationAverage BMP dose studied in ASD literature was ~8.75 mg/level (noted as lower than some advised dosages)

In-situ osteogenesis (ISO) definition/key value

DefinitionIn-situ osteogenesis (ISO) = inductive conversion of mesenchymal stem cells to osteoblasts by BMP-2 resulting in de‑novo bone synthesis

Clinical exampleISO described in alveolar cleft reconstruction using rhBMP-2 on collagen sponge producing trabecular bone in most treated sites

Mechanism noteBMP-2 stimulates local progenitor cells through signaling cascades leading to new bone formation when delivered on an appropriate scaffold

P-15 (i-Factor) — definition/key value

DefinitionP-15 (i-Factor) = a synthetic 15–amino-acid peptide (cell-binding domain of type I collagen) adsorbed to an anorganic bone matrix

Product (i-Factor)i-Factor Peptide Enhanced Bone Graft is a P-15/ABM product labeled for single-level cervical fusion (C3–C4 to C6–C7) in skeletally mature patients after failure of ≥6 weeks conservative care

Use constraintsMust be used inside an allograft bone ring with supplemental anterior plate fixation; contraindicated in presence of infection or other listed conditions

i-Factor / ABM/P-15 — definition/key value

Definitioni-Factor / ABM-P-15 = bone graft substitute consisting of P-15 peptide bound to an anorganic bone matrix to provide osteoconductive and osteoinductive properties

Clinical evidenceRandomized trials in ACDF show non-inferior fusion rates to autograft at 2 years; observational lumbar data reported favorable fusion rates in small series

ContraindicationsShould not be used with acute/chronic infection at operative site, absence of load-bearing support, compromised renal/hepatic function, metabolic disorders affecting healing, or sensitivity to components

SiCaP — definition/key value

DefinitionSiCaP = silicated calcium phosphate, a ceramic graft material evaluated as an alternative to BMP-2 in spine fusion trials

Clinical trial notePilot RCTs comparing SiCaP to BMP-2 showed comparable fusion rates at 12–24 months but were underpowered; further data needed

Intended roleUsed as an osteoconductive graft substitute in lumbar fusion settings where alternatives to BMPs are sought

Calcium sulfate antibiotic beads (CSAAB / Osteoset-T / SHPCS) — definition/key value

DefinitionCalcium sulfate antibiotic beads (CSAAB / Osteoset-T / SHPCS) = absorbable beads composed of calcium sulfate impregnated with antibiotics for local antimicrobial delivery in osteomyelitis

Clinical useUsed in conjunction with systemic IV antibiotics and surgical debridement for chronic osteomyelitis; may cause wound drainage in some cases

Evidence exampleCase series report high infection eradication rates (eg, Osteoset-T series with 100% union in tibial reconstruction but substantial wound complication rates)

45S5 Bioglass — definition/key value

Definition45S5 Bioglass = a bioactive glass ceramic used in bone graft substitutes noted for biocompatibility and bioactivity

Research noteModifications (eg, graphene nanoplatelet reinforcement) have been investigated to improve fracture toughness and wear resistance for load-bearing applications

Cellular bone allograft (CBA) — definition/key value

DefinitionCellular bone allograft (CBA) = an allograft containing viable, lineage-committed bone cells combined with an osteoconductive/inductive scaffold (eg, ViviGen, OsteoVive)

Evidence statusObservational series suggest high fusion rates in select procedures (hind-foot/ankle arthrodesis), but evidence limited by study design and lack of RCTs

Practical considerationProduct content disclosure and standardized cell metrics are needed; prospective randomized trials required for definitive assessment

Reference point indentation / impact micro-indentation — definition/key value

DefinitionReference point indentation (RPI) / impact micro-indentation (IMI) = minimally invasive in-vivo techniques that measure bone material properties (eg, BMSi) complementary to BMD

Current statusProof-of-concept and feasibility established; validation against mechanical testing is limited and results conflicting—further research needed before routine clinical use

Device examplesOsteoProbe and BioDent are devices used for RPI/IMI in research settings

Stromal vascular fraction (SVF) — definition/key value

DefinitionStromal vascular fraction (SVF) = heterogeneous cell population isolated from adipose tissue containing adipose-derived stem/stromal cells and other cells

Clinical evidenceCurrent evidence is insufficient to support SVF use for any indication; intraoperative isolation methods vary and no preferred technique established

Regulatory/practicalFurther randomized trials required to establish safety and efficacy for orthopedic/regenerative indications

Stromal vascular fraction (SVF) — duplicate inventory entry — definition/key value

Duplicate entryStromal vascular fraction (SVF) — see primary SVF definition: heterogeneous adipose-derived cell population with insufficient evidence for routine use

Isolation methodsIntraoperative cSVF and tSVF methods yield similar cell yields and viability compared with lab-based collagenase protocols in limited studies

Evidence gapNo preferred intraoperative isolation procedure designated; clinical efficacy remains unproven

Calcium phosphate cement (Quickset) — definition/key value

DefinitionCalcium phosphate cement (Quickset) = macro-porous, injectable, hardening and resorbable bone filler used for augmentation and defect filling

Evidence statusInsufficient evidence to support clinical value; biomechanical and small clinical case-series data exist but larger trials lacking

Typical useUsed for fracture reconstructions and metaphyseal void filling where temporary support and osteoconduction are desired

Cerament bone void filler (CBVF) — definition/key value

DefinitionCerament bone void filler (CBVF) = bioresorbable hydroxyapatite/calcium sulfate injectable bone void filler that can carry antibiotics (Cerament G) and act as substitute for autograft in certain defects

Intended useDesigned to fill subchondral or metaphyseal defects and act as antibiotic carrier in osteomyelitis management when used with systemic antibiotics and debridement

Evidence noteRandomized trial (CERTiFy) planned to compare CBVF vs ICBG for tibial plateau defects; single-arm and small series report promising outcomes but larger RCT data pending

Avive tendon wrap — definition/key value

DefinitionAvive tendon wrap = cryopreserved amnion/umbilical cord tissue product used as a soft-tissue wrap adjunct to tendon repairs to reduce inflammation and adhesions

Safety/evidenceRetrospective series report low wound complication and reoperation rates (eg, 124-patient series with 5.6% wound complication rate); larger comparative studies needed

Typical applicationsUsed adjacent to repaired tendons (eg, peroneal, Achilles) as an adjunct to reduce adhesion and promote healing

Cerament bone void filler (CBVF / Cerament G) — definition/key value (duplicate)

Duplicate inventoryCerament bone void filler (CBVF / Cerament G) — injectable hydroxyapatite/calcium sulfate composite; Cerament G denotes antibiotic-loaded formulation

Use caseUsed for dead-space management and local antibiotic delivery in osteomyelitis and for bone defect filling after curettage or trauma

Evidence summaryProspective randomized trial (CERTiFy) planned; case series report infection eradication in series of diabetic foot osteomyelitis

Micronized allogeneic cartilage (BioCartilage) — definition/key value

DefinitionBio-inductive collagen implant (eg, REGENETEN) = resorbable bovine type I collagen scaffold placed over the bursal surface of the rotator cuff to induce neotendon formation and increase tendon thickness

Clinical outcomesProspective single-arm studies and registries report improved PROs, increased tendon thickness, high imaging-based healing rates, and acceptable safety in many patients, but evidence level is largely Level IV

Indication nuanceUsed for augmentation in partial- and full-thickness rotator cuff repairs, with trials often including tears around ~50% thickness for PTRCTs

Bio-inductive implant (REGENETEN) — definition/key value

DefinitionBio-inductive implant (REGENETEN) = resorbable bovine collagen implant intended to induce tendon remodeling and increase tendon thickness when used as augmentation in rotator cuff repairs

Evidence statusRegistry and single-arm studies report improvements in PROs and imaging healing rates; randomized comparative trials are needed to establish added clinical benefit

Practical pointDocument tear size, prior conservative management, and imaging when used given heterogeneity of published cohorts

AttraX Putty / β-TCP — definition/key value

DefinitionAttraX Putty / β-TCP = ceramic-based bone graft substitute (biphasic calcium-phosphate or β-TCP) used as a bone graft extender or stand-alone material in fusion procedures

Clinical evidenceIntra-patient RCT showed variable fusion performance with AttraX putty (fusion rates and overall fusion variable); other series report fusion rates around 71% in some cohorts

RoleUsed as graft extender or substitute where avoidance of autograft harvest is desired; evidence mixed and device selection should consider comparative data

Solum IV — definition/key value

DefinitionSolum IV = resorbable porous calcium phosphate (predominantly hydroxyapatite) bone void filler combined with a porcine gelatin-based carrier to form a moldable osteoconductive scaffold

Intended useDesigned to be hydrated and mixed with bone marrow aspirate to create a moldable implant conforming to defect geometry

Evidence statusPreclinical and limited clinical data described; further studies required to define comparative effectiveness

Healos — definition/key value

DefinitionHealos = hydroxyapatite-collagen composite (HA+collagen) sponge graft carrier intended to be used with bone marrow aspirate or autograft as a graft extender in spinal fusion

Evidence summaryComparative and retrospective studies show variable radiographic fusion rates versus iliac crest autograft; clinical outcomes may be similar though fusion timing can differ

Practical considerationDocument rationale and prior autograft attempts when substituting for ICBG due to mixed evidence

Solum IV — duplicate inventory entry — definition/key value

Duplicate inventorySolum IV — see Solum IV definition: resorbable porous calcium phosphate with porcine gelatin carrier used as moldable osteoconductive scaffold

Regulatory noteSubstantially equivalent to other bioactive graft materials; further clinical data needed for broad adoption

Healos (HA+collagen sponge) — definition/key value (duplicate)

Duplicate inventoryHealos (HA+collagen sponge) — see Healos definition: hydroxyapatite-collagen carrier used with BMA or autograft as graft extender

Evidence noteSome studies report slower radiographic fusion but comparable clinical outcomes; use when donor-site morbidity avoidance is prioritized

Subchondroplasty — definition/key value

DefinitionSubchondroplasty = minimally invasive procedure involving intra‑osseous injection of bone substitute materials (commonly calcium phosphate) into bone marrow lesions associated with osteoarthritis

Clinical evidenceSystematic reviews and case series report short-term improvements in pain and function but highlight low-quality evidence and need for RCTs and longer follow-up

Safety/contraindicationsContraindicated or cautioned in skeletally immature patients due to potential physeal injury; conversion to TKA reported in some series (12.5–30%)

OptiMesh — definition/key value

DefinitionOptiMesh = conformable porous polyester mesh pouch device filled in‑situ with bone graft to achieve a large interbody fusion footprint via a small portal

Clinical trial resultsIDE single-arm trial reported high CT-assessed fusion rates (97.9% at 12 months; 99% at 24 months) and sustained clinical improvements in ~96 patients, but evidence is single-arm

Use contextIntended for instrumented lumbar interbody fusion to expand graft footprint with minimally invasive insertion

Ceracell Ortho Foam — definition/key value

DefinitionCeracell Ortho Foam = a 510(k)-cleared resorbable device intended to fill nonstructural bony voids (eg, posterolateral spine) to be mixed with autograft bone

Intended usePer 510(k), to fill bony voids or gaps that are not intrinsic to stability; in posterolateral spine to be mixed with autograft

EvidenceLimited clinical evidence regarding effectiveness for cervical instrumentation or other structural uses

Signafuse — definition/key value

DefinitionSignafuse = synthetic bioactive bone graft composed of bioglass and a biphasic mineral (60% hydroxyapatite, 40% β‑TCP) available in putty and strip formats for spinal fusion

Intended roleDesigned to support spinal fusion and new bone formation as a synthetic alternative to autograft/allograft

Evidence statusClinical evidence limited; product described in background with need for further comparative studies

Signafuse bioactive bone graft — definition/key value (duplicate)

Duplicate inventorySignafuse bioactive bone graft — synthetic graft of bioglass + biphasic mineral (60% HA / 40% β‑TCP) in putty/strip formats intended for spinal fusion

Evidence noteFurther comparative clinical trials needed to establish effectiveness relative to autograft/allograft

SurGenTec ViMax viable fiber allograft — definition/key value

DefinitionSurGenTec ViMax viable fiber allograft = human‑origin viable fiber allograft containing numerous cells including mesenchymal stem cells

Evidence statusLack of robust clinical evidence regarding effectiveness; considered investigational in many indications

Regulatory/precautionProducts with viable cells marketed with limited high-level clinical data; prospective randomized trials needed

Tactoset Injectable Bone Substitute — definition/key value

DefinitionTactoset Injectable Bone Substitute = synthetic, biocompatible injectable bone graft substitute that hardens to poorly crystalline hydroxyapatite for filling nonstructural bone voids

IndicationsIndicated for filling bone voids/defects of extremities and pelvis not intrinsic to structural stability; used in percutaneous skeletal fixation for subchondral bone marrow edema techniques

Evidence cautionInsufficient evidence to support use after digital amputation; limited data for some indications (eg, SBME) and further studies needed

OSSURE LOEP (AGN1) — definition/key value

DefinitionOSSURE LOEP (AGN1) = Local Osteo-Enhancement Procedure using an injected triphasic resorbable implant (calcium sulfate, brushite, β‑TCP) intended to augment osteoporotic proximal femur strength

Clinical evidenceEvidence limited to small prospective cohorts (eg, n=12) with increases in femoral neck aBMD and estimated strength; risk of bias and small sample sizes limit conclusions

Policy stanceCurrent evidence insufficient to establish effectiveness for prevention/treatment of osteoporotic hip fractures; ongoing RCTs registered