Humana Bone Graft Substitutes Form

Description

Bone grafts may be used in the treatment of delayed fracture unions, in spinal fusions, to bridge major bone defects or fill cavities created by tumor removal, cysts or other causes. Bone graft material may come from a number of sources: autograft (the individual’s own bones), allograft (a bone bank), demineralized bone matrix or bone graft substitutes, such as synthetic materials, ceramics (bone void fillers), collagen composites, composite cement materials, bone morphogenetic protein or recombinant human bone morphogenetic protein.

Autograft

Autograft is considered the gold standard for bone grafting and is taken directly from the individual. The usual site for an autograft harvest is the posterior iliac crest. When autograft material is of an insufficient volume, of poor quality or cannot be used for any other reason, another type of material must be used for the bone graft.

In the context of this policy, blood products (including platelets) and bone marrow aspirate (including mesenchymal stem cells) are NOT considered autograft materials.

Allograft

Allograft is obtained from cadaveric bone and/or tissue from a bone bank and may be used alone or in combination with another material. Even when used alone, allograft must be processed to decrease the likelihood of disease transmission and immunogenic response.

In the context of this policy, amniotic membrane/placental membrane, blood products (including platelets) and bone marrow aspirate (including mesenchymal stem cells) are NOT considered allograft materials.

Bone Morphogenetic Proteins and Recombinant Human Bone Morphogenetic Proteins

Bone morphogenetic proteins (BMP) are naturally occurring proteins found in human bone and play an active role in bone formation. There are currently fourteen BMPs that have been identified. In addition to the fourteen BMPs, there are several recombinant human bone morphogenetic proteins (rhBMPs). Currently there are only two which have been developed for use: rhBMP-2 and rhBMP-7 (it should be noted, however, that rhBMP-7 is no longer marketed or available in the United States).

rhBMPs serve as alternatives or adjuncts to autologous bone grafts (autografts). They are intended to promote bone formation and enhance fracture healing and may be used in spinal fusion surgery for degenerative disease to promote bone growth that results in fusion. These proteins may also be used for an individual who has up to grade I spondylolisthesis. rhBMPs have been proven safe in L2 (second lumbar vertebra) through S1 (sacral) levels of the spine. Severe life threatening complications have been associated with cervical spine use. Another major application of bone grafting with rhBMP is for bone repair, especially for treatment of delayed union of tibial fractures. rhBMP also plays a role in cartilage formation and repair of other musculoskeletal tissues.

The rhBMP needs to stay in the region of repair to influence skeletal formation (healing). In order for this to happen, the rhBMPs must be utilized with a suitable carrier.

One of the most common carriers is a collagen sponge.

Ceramics/Bone Void Fillers

Ceramics are synthetically produced bone void fillers. As a conductive technology, ceramics are synthetic materials resulting from heating up chemically formed compounds that consequently bond together. There are many different methods to produce ceramics and numerous chemical compounds that can be combined, including calcium phosphate, calcium sulfate-calcium composite, beta tricalcium phosphate or nanocrystalline hydroxyapatite. (Refer to Coverage Limitations section regarding beta tricalcium phosphate and nanocrystalline hydroxyapatite)

Demineralized Bone Matrix

Demineralized bone matrix (DBM) is a type of allograft that is produced by acid extraction of allograft bone, known as decalcification. Based on manufacturing techniques, DBM may be a freeze-dried powder, granules, gel, putty or strips.

Combination Bone Graft Substitutes

A newer practice in bone graft substitutes is the combination of different materials to produce a completely different product, with the theory that each different property working together will aid in the healing and grafting process.

This classification (combination bone graft substitutes) does not refer to the practice of combining autograft or allograft bone with a bone void filler or DBM, but rather combining different bone graft substitute products. (Refer to Coverage Limitations section)

Coverage Determination

Humana members may be eligible under the Plan for the following bone graft materials/bone graft substitute products, when criteria are met AND utilized according to the FDA-approved marketing label indications effective on the date of service:

• Autograft
  • Enhancement of bone healing
• Allograft
  • Enhancement of bone healing

Bone Graft Substitutes Effective Date: 01/01/2024

Revision Date: 01/01/2024

Review Date: 03/01/2023

Policy Number: HUM-0479-018

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BONE GRAFT MATERIALS/SUBSTITUTE PRODUCTS

Calcium Sulfate-Calcium Composite Ceramics/Bone Void Fillers Examples include, but may not be limited to:

• Altapore
• Altapore Shape
• Calcigen S
• InterSep
• OsteoSet
• OsteoVation QWIK
• Pro-Dense
• Stimulan

Demineralized Bone Matrix (DBM) Examples include, but may not be limited to:

• 3D ProFuse
• 3-Demin
• Accell Connexus
• Accell EVO3c
• Accell Total Bone Matrix
• AlloFlex Plus
• AlloFuse
• Allomatrix
• AlloSync
• AlphaGraft DBM
• Apex
• Ballast
• BIO DBM
• BioAdapt DBM
• BioReady DBM Putty
• BioReady DBM Putty with Chips
• BioSet DBM
• Conform (Cube, Flex, Sheet)

CRITERIA/INDICATIONS FOR COVERAGE

Enhancement of bone healing

Bone Graft Substitutes Effective Date: 01/01/2024

Revision Date: 01/01/2024

Review Date: 03/01/2023

Policy Number: HUM-0479-018

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BONE GRAFT MATERIALS/SUBSTITUTE PRODUCTS

Criteria/Indications For Coverage:

• Following stabilization with intramedullary nail fixation; AND
• No infection in the affected limb; AND
• Skeletally mature (at least 18 years of age or radiographic evidence of epiphyseal closure).

Recombinant Human Bone Morphogenetic Proteins (rhBMP)

INFUSE Bone Graft/LT-CAGE Lumbar Tapered Fusion Device (with titanium cage) (rhBMP-2)

This product may ONLY be approved when used with 1 of the 8 cages approved for use with INFUSE by the FDA.

• Absence of contraindications; AND
• ONLY for a SINGLE-LEVEL lumbar fusion surgery when lumbar fusion criteria are met (for information regarding coverage determination/limitations, please refer to Spinal Fusion Surgery Medical Coverage Policy); AND
• Used in combination with 1 of the following:
  • Single level fusion, L5-S1 vertebra, via an OLIF approach; OR
  • INTER FIX RP Threaded Fusion Device — single level lumbar fusion, via an open anterior approach; OR
  • INTER FIX Threaded Fusion Device – single level lumbar fusion, via an open anterior approach.

Bone Graft Substitutes Effective Date: 01/01/2024

Revision Date: 01/01/2024

Review Date: 03/01/2023

Policy Number: HUM-0479-018

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Coverage Limitations

Humana members may NOT be eligible under the Plan for the use of INFUSE Bone Graft (rhBMP-2) and/or INFUSE Bone Graft/LT-CAGE Lumbar Tapered Fusion Device (rhBMP-2) for any other indication not listed in the Coverage Determination section, which includes, but may not be limited to:

• Cervical spinal fusion; OR
• Combined with a carrier other than collagen or with a fusion device other than a cage; OR
• Craniofacial applications including sinus augmentation and/or alveolar ridge augmentation; OR
• Multilevel lumbar fusion, regardless of surgical approach; OR
• Nonanterior or nonoblique lateral interbody fusion approaches to lumbar fusion; OR
• Primary treatment of closed tibial fractures.

Bone Graft Substitutes Effective Date: 01/01/2024

Revision Date: 01/01/2024

Review Date: 03/01/2023

Policy Number: HUM-0479-018

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• Thoracic spinal fusion; OR
• Treatment of delayed union or nonunion of tibial fracture as part of a planned, staged reconstruction; OR
• Use of INFUSE Bone Graft/LT-CAGE Lumbar Tampered Fusion Device (rhBMP-2) with non-FDA approved spinal cages

These are considered experimental/investigational as they are not identified as widely used and generally accepted for any other proposed uses as reported in nationally recognized peer-reviewed medical literature published in the English language.

Contraindications to the use of INFUSE Bone Graft (rhBMP-2) and/or INFUSE Bone Graft/LT-CAGE Lumbar Tapered Fusion Device include the following:

• Active infection at the operative site; OR
• Active malignancy; OR
• Compartment syndrome of the affected limb; OR
• Inadequate neurovascular status; OR
• Known hypersensitivity to bovine Type I collagen, rhBMP-2 or other components of the formulation; OR
• Pregnancy; OR
• Skeletally immature (18 years of age or younger, or have no radiographic evidence of epiphyseal closure); OR
• Utilization in the vicinity of a resected or extant tumor

Bone Graft Substitutes Effective Date: 01/01/2024

Revision Date: 01/01/2024

Review Date: 03/01/2023

Policy Number: HUM-0479-018

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This is considered experimental/investigational as it is not identified as widely used and generally accepted for the proposed use as reported in nationally recognized peer-reviewed medical literature published in the English language.

Humana members may NOT be eligible under the Plan for use of any of the following bone graft substitute products for ANY indication:

MATERIALS/SUBSTITUTE PRODUCT

(NOT COVERED FOR ANY INDICATION)

• Augment (including, but not limited to, Augment Injectable) - Comprised of beta tricalcium phosphate and recombinant human platelet derived growth factor (rhPDGF). Proposed as an alternative to autograft in arthrodesis of the ankle and/or hindfoot.
• Autologous Blood Product Injection (red blood cells [RBC], white blood cells [WBC], whole blood) including, but not limited to, nSTRIDE Autologous Protein Solution (APS) - Blood is withdrawn from an individual, and the desired component is extracted; it is then either injected into a joint (proposed as a treatment for osteoarthritis) or injured tendon, or is mixed with/combined with a bone graft substitute product. (For information regarding coverage determination/limitations for the use of autologous blood injection for plantar fasciitis,
• Beta Tricalcium Phosphate Bone Void Fillers Examples include, but may not be limited - A synthetically produced bone graft material/substitute; falls under the broad category ceramics/bone void fillers.
• to: e Allogran-R e BoneSync e ChronOS e Collage - Proposed for use as a bone graft substitute or bone graft extender to fill in and promote healing of bone voids or gaps in the skeletal system.

Bone Graft Substitutes Effective Date: 01/01/2024

Revision Date: 01/01/2024

Review Date: 03/01/2023

Policy Number: HUM-0479-018

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Refer to Medical and Pharmacy Coverage Policies to verify that this is the current version before utilizing.

BONE GRAFT MATERIALS/SUBSTITUTE PRODUCT

PURPORTED USE (NOT COVERED FOR ANY INDICATION)

• Integra Mozaik
• IsoTis Mozaik
• Matriform SI
• OSferion
• OsteoStrux
• OsSatura TCP
• OsteoVation B-TCP
• Vitoss Bioactive Glass

Examples include, but may not be limited to:

• Bi-Ostetic Bioactive Glass
• BioSphere Flex
• BioSphere Putty
• BonAlive
• FIBERGRAFT BG Morsels
• FIBERGRAFT BG Putty
• Interface NovaBone Morsels
• OssiMend
• PURbridge Signal Bioactive Fibers
• Signify Bioactive
• Tornado Bioactive
• Vitoss BA
• Vitoss BiModal

Unlike window or household glass, bioactive glass has a different chemical composition (calcium-phosphorus-sodium-silicate) and is reactive to extracellular fluids and therefore bonds to bone. Due to this reaction, it is purported that the glass will release substances that are biocompatible and activate a mechanism that promotes new bone growth. Over time, the glass dissolves completely and is replaced by bone tissue.

Proposed for use in bony voids or gaps of the skeletal system (posterolateral spine, extremities and pelvis).

• Bone Marrow Aspirate (BMA)

Mixing an individual's bone marrow aspirate with the bone graft substitute, rather than blood or autologous bone; or

NOT COVERED for ANY orthopedic applications including, but may not be limited to:

• As an adjunct to a spinal fusion; OR
• Bone cysts; OR
• Degenerative disc disease; OR
• Nonunion fractures;

Bone Graft Substitutes Effective Date: 01/01/2024

Revision Date: 01/01/2024

Review Date: 03/01/2023

Policy Number: HUM-0479-018

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• Orthopedic applications not covered when used as:
• Osteoarthritis; OR
• Repair or regeneration of musculoskeletal tissue (including intervertebral disc); OR
• When mixed with any bone graft substitute

Cell-Based Substitutes

Examples include, but may not be limited to:

• AmnioFix
• Amniovo
• Arthrex Amnion Matrix & Viscous
• Bio4 Viable Bone Matrix
• BioDFactor
• BioDFence
• BioDRestore
• BioD Dry Flex
• Cygnus ENHANCE Amnion
• NuCel
• Osteocel Plus
• Osteocel Pro
• OsteoVive Plus
• PalinGen
• Regenexx
• ReNu
• Stravix
• Trinity Elite
• Trinity Evolution
• ViaCell

ASPIRATE, MEMBRANE or PLACENTAL MEMBRANE; these products are also referred to as cell-based substitutes.

Bone Graft Substitutes Effective Date: 01/01/2024

Revision Date: 01/01/2024

Review Date: 03/01/2023

Policy Number: HUM-0479-018

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Humana's documents are updated regularly online. When printed, the version of this document becomes uncontrolled. Do not rely on printed copies for the most up-to-date version.

Refer to Medical and Pharmacy Coverage Policies to verify that this is the current version before utilizing.

MATERIALS/SUBSTITUTE PRODUCT

(NOT COVERED FOR ANY INDICATION)

• Combination Bone Graft Substitute
  • Beta tricalcium phosphate combined with bioactive glass
• e Vitoss BA2X
  • Proposed for use in orthopedic surgery for filling osteochondral defects.
• Combination Bone Graft Substitute
  • Beta tricalcium phosphate combined with bioactive glass and hydroxyapatite
• Examples include, but may not be limited to: e SignaFuse Bioactive Bone Graft Putty e SignaFuse Bioactive Bone
  • Graft Strip Proposed for use in bony voids or gaps of the skeletal system (posterolateral spine, extremities and pelvis).
• Substitute e genex
  • calcium sulfate Proposed for use in bony voids and defects that are not intrinsic to structural stability.
• Combination Bone Graft
  • Beta tricalcium phosphate combined with
  • be limited to: e Amplify e AttraX Putty/Scaffold e Bi-Ostetic e Bicera Eclipse Granules/Putty MagnetOs Mastergraft (granules, strip or putty)
    • phosphate) Proposed for use in bony voids or gaps of the skeletal system (posterolateral spine, extremities and pelvis).
• Osteon

Bone Graft Substitutes Effective Date: 01/01/2024

Revision Date: 01/01/2024

Review Date: 03/01/2023

Policy Number: HUM-0479-018

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Humana's documents are updated regularly online. When printed, the version of this document becomes uncontrolled. Do not rely on printed copies for the most up-to-date version.

Refer to Medical and Pharmacy Coverage Policies to verify that this is the current version before utilizing.

MATERIALS/SUBSTITUTE PRODUCT

(NOT COVERED FOR ANY INDICATION)

• Combination Bone Graft Substitute
  • Beta tricalcium phosphate combined with magnesium oxide
• e@ OSTEOREVIVE
  • Proposed for bony voids or defects of the extremities, posterolateral spine, and pelvis that are not intrinsic to the stability of the bony structure.
• Combination Bone Graft Substitute
  • Bioactive glass combined with carbonate apatite
  • anorganic bone mineral and Type 1 collagen
• Examples include, but may not be limited to: e BoneSync BioActive e Contour BA e Opus BA Bioactive strip e OssiMend Bioactive e VIA Mend
  • Proposed for use in bony voids or gaps of the skeletal system (extremities, pelvis and spine).
• Substitutes Examples include, but may not be limited to e Kinex Bioactive e Kinex Plus Bioactive
  • and collagen Proposed for use in bony voids or gaps of the skeletal system (extremities, pelvis and spine).
• Combination Bone Graft Substitute
  • Calcium phosphate combined with hyaluronic acid
• e Tactoset
  • Proposed for filling bone voids or defects of the skeletal system (extremities and pelvis), which are not intrinsic to the stability of the bone, created during surgery or resulting from traumatic injury.
• Combination Bone Graft Substitute
  • Combination polymer (PLGA) with hyaluronic acid

Bone Graft Substitutes Effective Date: 01/01/2024

Revision Date: 01/01/2024

Review Date: 03/01/2023

Policy Number: HUM-0479-018

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Refer to Medical and Pharmacy Coverage Policies to verify that this is the current version before utilizing.

MATERIALS/SUBSTITUTE PRODUCT

(NOT COVERED FOR ANY INDICATION)

• Proposed for use as a bone graft substitute in the skeletal system (extremities and pelvis) and as a bone graft extender in the spine when combined with bone autograft.
• Combination Bone Graft Substitute
  • DBM combined with bioactive glass
• Examples include, but may not be limited to:
  • NanoFUSE Bioactive Matrix
  • NanoFUSE putty, strips
  Proposed for use as a bone graft substitute in the skeletal system (extremities and pelvis) and as a bone graft extender in the posterolateral spine when combined with bone autograft.
• Combination Bone Graft Substitute Examples include, but may not be limited to:
  • Allomatrix C
  • Allomatrix Custom
  DBM combined with calcium sulfate Proposed for filling bony voids or gaps in the extremities and pelvis that are not intrinsic to the bony stability of the structure, and as an autograft extender in the spine.
• Allomatrix DR
• Substitutes Examples include, but may not be limited to:
  • InterGro DBM Plus
  • Pro-Stim Inductive
  Proposed for filling bony voids or gaps in the extremities and pelvis that are not intrinsic to the bony stability of the structure, and as an autograft extender in the spine.
• Injectable Graft
• Combination Bone Graft
  • DBM combined with hydroxyapatite and calcium carbonate
• Substitutes include, but not may be limited to:
  • StaGraft DBM Putty
  • StaGraft DBM PLUS
  Proposed for use in bone voids and gaps in the extremities or pelvis that is not intrinsic to the stability of the structure.
• Combination Bone Graft
  • DBM combined with nanocrystalline hydroxyapatite

Bone Graft Substitutes Effective Date: 01/01/2024

Revision Date: 01/01/2024

Review Date: 03/01/2023

Policy Number: HUM-0479-018

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Humana's documents are updated regularly online. When printed, the version of this document becomes uncontrolled. Do not rely on printed copies for the most up-to-date version.

Refer to Medical and Pharmacy Coverage Policies to verify that this is the current version before utilizing.

BONE GRAFT MATERIALS/SUBSTITUTE PRODUCT

PURPORTED USE (NOT COVERED FOR ANY INDICATION)

• Proposed for use as bone void fillers of the pelvis, extremities and the posterolateral spine.
• Combination Bone Graft
  • Hydroxyapatite combined with beta tricalcium
  • phosphate, bioactive glass and alpha tricalcium
  • e OsteoFlo NanoPutty
    • phosphate
  (may also be referred to as quadphasic synthetic bone graft)
• Proposed for bony voids or gaps of the skeletal system (extremities and pelvis) not intrinsic to the stability of the bony structure.
• Substitutes Examples include, but may not be limited to:
• carbonate Proposed for filling bony voids or gaps caused by
• e Pro Osteon 200R e Pro Osteon 500R
• trauma or surgery, including use in the maxillofacial and/or mandibular bone.

• Combination Bone Graft Substitute e Cerament e Cerament G
  • Hydroxyapatite combined with calcium sulfate Proposed for use in bony voids or gaps of the skeletal system (posterolateral spine, extremities and pelvis).

• Combination Bone Graft
  • Nanocrystalline hydroxycarbonoapatite
  • Examples include, but may not be limited to: e Agilon Moldable e Aglion Strip e OsteoSpan e Morpheus
    • Proposed for bony voids or gaps that are not intrinsic to the stability of the bony structure of the skeletal system (the extremities, posterolateral spine and pelvis).

• Combination Bone Graft
  • Tricalcium phosphate combined with
  • Substitute Examples include, but may not
  • hydroxyapatite

Bone Graft Substitutes Effective Date: 01/01/2024

Revision Date: 01/01/2024

Review Date: 03/01/2023

Policy Number: HUM-0479-018

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MATERIALS/SUBSTITUTE PRODUCT

(NOT COVERED FOR ANY INDICATION)

• e Current e OsteoCurrent
  • Proposed for use in bony voids or gaps of the skeletal system (posterolateral spine, extremities and pelvis).
• i-FACTOR Peptide Enhanced Bone Graft
  • Composite material consisting of a synthetic peptide (P-15) adsorbed onto calcium phosphate particles, suspended in a hydrogel carrier.
  • Proposed for single level anterior cervical spinal fusion.
• INFUSE/MASTERGRAFT (rhBMP-2)
  • Combination rhBMP-2 and Mastergraft granules (beta tricalcium phosphate and hydroxyapatite).
  • Proposed for use in posterolateral spinal fusion at two or more levels for pseudoarthrodesis.
• Nanocrystalline Hydroxyapatite Examples include, but may not be limited to:
  • e Beta-BSM Injectable e Cem-Ostetic e Gamma-BSM moldable putty e N-Force Blue e NanoBone e NanOss
  • A synthetically produced bone graft material/ substitute that is a specific type of ceramic/bone void filler. It consists of a calcium phosphate that has been subjected to additional structural process, which changes the particle size. Proposed for bony voids or gaps that are not intrinsic to the stability of bony structure.
• Platelet Rich Plasma (PRP)
  • PRP, which is harvested from an individual’s own blood, has been proposed as a treatment to accelerate healing of tendon/ligament injuries or aid in bone healing or grafting.

PRP is prepared by obtaining a small amount of the individual’s blood, which is then centrifuged to separate the platelets from the other components found in blood.

MATERIALS/SUBSTITUTE PRODUCT

(NOT COVERED FOR ANY INDICATION)

PRP is NOT covered for ANY indication including, but may not be limited to:

• Bone healing and fusion; OR
• Joint pain or repair; OR
• Ligament or tendon injuries; OR
• Osteoarthritis; OR
• Soft tissue injuries; OR
• Used in combination with ANY bone graft substitute product

Bone Graft Substitutes Effective Date: 01/01/2024
Revision Date: 01/01/2024
Review Date: 03/01/2023
Policy Number: HUM-0479-018
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Products That MUST Be Mixed With Bone Marrow Aspirate: Examples include, but may not be limited to:

• ATEC Neocore

These products must be mixed with bone marrow aspirate in order to activate their osteoconductive properties for new bone regeneration.

• CopiOs Bone Void Filler Paste
• CopiOs Bone Void Filler Sponge
• FIBERGRAFT BG Matrix
• Grafton DBF
• Ignite
• Influx
• Mastergraft Matrix EXT
• Mastergraft Strip
• PLATFORM CM
• Sorrento
• ViaSorb

Proposed for bony voids or gaps that are not intrinsic to the stability of bony structure.

Bone Graft Substitutes Effective Date: 01/01/2024
Revision Date: 01/01/2024
Review Date: 03/01/2023
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Additional information about bone grafting, degenerative disc disease, fractures, spinal fusion and spondylolisthesis may be found from the following websites:

• American Academy of Orthopaedic Surgeons
• National Library of Medicine
• North American Spine Society

Medical Alternatives

Physician consultation is advised to make an informed decision based on an individual’s health needs.

Provider Claims Codes

Bone Graft Substitutes Effective Date: 01/01/2024
Revision Date: 01/01/2024
Review Date: 03/01/2023
Policy Number: HUM-0479-018
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Refer to Medical and Pharmacy Coverage Policies to verify that this is the current version before utilizing.

Bone Graft Substitutes Effective Date: 01/01/2024
Revision Date: 01/01/2024
Review Date: 03/01/2023
Policy Number: HUM-0479-018
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Excision of bone cyst or benign tumor, wing of ilium, symphysis pubis, or greater trochanter of femur; with autograft requiring separate incision

27067. Bone Graft Substitutes Effective Date: 01/01/2024
27068. Revision Date: 01/01/2024
27069. Review Date: 03/01/2023
27070. Policy Number: HUM-0479-018
27071. Page: 23 of 47

CPT® Category III Code(s) Description Comments

• 0232T Injection(s), platelet rich plasma, any site, including image guidance, harvesting and preparation when performed Not Covered

Bone Graft Substitutes Effective Date: 01/01/2024
Revision Date: 01/01/2024
Review Date: 03/01/2023
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1. Agency for Healthcare Research and Quality (AHRQ). Technology Assessment (ARCHIVED). Bone morphogenetic protein: the state of the evidence of on-label and off-label use. https://www.ahrq.gov. Published August 6, 2010. Updated December 13, 2010. Accessed January 31, 2023.

References

Bone Graft Substitutes Effective Date: 01/01/2024
Revision Date: 01/01/2024
Review Date: 03/01/2023
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Humana's documents are updated regularly online. When printed, the version of this document becomes uncontrolled. Do not rely on printed copies for the most up-to-date version. Refer to Medical and Pharmacy Coverage Policies to verify that this is the current version before utilizing.

American Academy of Orthopaedic Surgeons (AAOS). Evidence-Based Clinical Practice Guideline. Management of glenohumeral joint osteoarthritis. https://www.aaos.org. Published March 23, 2020. Accessed February 7, 2023.

American Academy of Orthopaedic Surgeons (AAOS). Evidence-Based Clinical Practice Guideline. Management of osteoarthritis of the knee (non-arthroplasty). https://www.aaos.org. Published August 31, 2021. Accessed February 7, 2023.

3.American Academy of Orthopaedic Surgeons (AAOS). Evidence-Based Clinical Practice Guideline. Management of rotator cuff injuries. https://www.aaos.org. Published March 11, 2019.

Accessed February 7, 2023.

American Academy of Orthopaedic Surgeons (AAOS). Position Statement. Use of emerging biologic therapies. https://www.aaos.org. Published December 2017. Updated September 2020. Accessed February 7, 2023.

American Academy of Orthopaedic Surgeons (AAOS). Technology Overview. Concentrated bone marrow aspiration for knee osteoarthritis. https://www.aaos.org. Published December 3, 2021. Accessed February 7, 2023.

American Academy of Orthopaedic Surgeons (AAOS). Technology Overview. Platelet-rich plasma (PRP) for knee osteoarthritis. https://www.aaos.org. Published August 25, 2021. Accessed February 7, 2023.

7.American College of Rheumatology (ACR). 2019 American College of Rheumatology/Arthritis Foundation guideline for the management of osteoarthritis of the hand, hip, and knee. https://www.rheumatology.org. Published February 2020. Accessed February 7, 2023.

American Society of Interventional Pain Physicians (ASIPP). Bone marrow concentrate (BMC) therapy in musculoskeletal disorders: evidence-based policy position statement of American Society of Interventional Pain Physicians (ASIPP). https://asipp.org. Published March/April 2020. Accessed February 7, 2023.

Bone Graft Substitutes Effective Date: 01/01/2024
Revision Date: 01/01/2024
Review Date: 03/01/2023
Policy Number: HUM-0479-018
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Humana's documents are updated regularly online. When printed, the version of this document becomes uncontrolled. Do not rely on printed copies for the most up-to-date version. Refer to Medical and Pharmacy Coverage Policies to verify that this is the current version before utilizing.

10. American Society of Interventional Pain Physicians (ASIPP). Responsible, safe, and effective use of biologics in the management of low back pain: American Society of Interventional Pain Physicians (ASIPP) guidelines. https://asipp.org. Published 2019. Accessed February 7, 2023.

11. Chakravarthy K, Chen Y, He C, Christo P. Stem cell therapy for chronic pain management: review of uses, advances, and adverse effects. Pain Physician. 2017;20:293-305.

12. ClinicalKey. Schneider B, Hunt C, Conger A, et al. The effectiveness of intradiscal biologic treatments for discogenic low back pain: a systematic review. Spine J. 2022;22:226-237. https://www.clinicalkey.com. Accessed January 31, 2022.

13. Congress of Neurological Surgeons (CNS). Guideline update for the performance of fusion procedures for degenerative disease of the lumbar spine. Part 16: bone graft extenders and substitutes as an adjunct for lumbar fusion. https://www.cns.org. Published July 2014. Accessed February 6, 2023.

14. Dettori J, Chapman J, DeVine J, McGuire R, Junge M, Norvell D. Longer follow-up continues to reveal no increased risk of cancer with the use of recombinant human bone morphogenetic protein in spin fusion. Spine J. 2019;19:1640-1647.

15. ECRI Institute. Clinical Evidence Assessment. Allogenic mesenchymal stem cell therapy for chronic knee pain. https://www.ecri.org. Published October 15, 2019. Updated January 31, 2022. Accessed January 26, 2023.

16. ECRI Institute. Clinical Evidence Assessment. AlloSync Pure demineralized bone graft (Arthex, Inc.) for treating avascular necrosis of the hip. https://www.ecri.org. Published August 1, 2021. Accessed January 24, 2023.

17. ECRI Institute. Clinical Evidence Assessment. Amniotic tissue products for use in cervical spine surgery. https://www.ecri.org. Published November 23, 2021. Accessed January 26, 2023.

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18. ECRI Institute. Clinical Evidence Assessment.

• Arthrex Amnion Matrix (Arthrex, Inc.) for repairing rotator cuff tears. https://www.ecri.org. Published September 24, 2018. Updated January 27, 2021. Accessed January 26, 2023.
• ECRI Institute. Clinical Evidence Assessment. Augment bone graft (Wright Medical Group) for ankle or hindfoot arthrodesis. https://www.ecri.org. Published December 14, 2015. Updated February 19, 2021. Accessed January 24, 2023.
• ECRI Institute. Clinical Evidence Assessment. Autologous mesenchymal stem cell therapy for chronic knee or ankle pain from osteoarthritis. https://www.ecri.org. Published October 15, 2019. Updated January 26, 2022. Accessed January 26, 2023.
• ECRI Institute. Clinical Evidence Assessment. Bicera bone graft substitute (Wiltrom Corp. Ltd.) for filling bone defects. https://www.ecri.org. Published April 8, 2022. Accessed January 24, 2023.
• ECRI Institute. Clinical Evidence Assessment. Bio4 viable bone matrix (Osiris Therapeutics, Inc.) for lumbar fusion procedures. https://www.ecri.org. Published September 1, 2019. Updated February 16, 2022. Accessed January 24, 2023.
• ECRI Institute. Clinical Evidence Assessment. Bioactive glass bone graft substitutes for spinal fusion and long bone voids. https://www.ecri.org. Published April 13, 2022. Accessed January 24, 2023.
• ECRI Institute. Clinical Evidence Assessment. Bone marrow aspirate concentrate injection for treating knee osteoarthritis. https://www.ecri.org. Published February 22, 2022. Accessed January 26, 2023.
• ECRI Institute. Clinical Evidence Assessment. Bone marrow aspirate concentrate therapy for Achilles tendinopathy. https://www.ecri.org. Published February 15, 2022. Accessed January 24, 2023.
• Bone Graft Substitutes Effective Date: 01/01/2024 Revision Date: 01/01/2024 Review Date: 03/01/2023 Policy Number: HUM-0479-018 Page: 28 of 47 Humana's documents are updated regularly online. When printed, the version of this document becomes uncontrolled. Do not rely on printed copies for the most up-to-date version. Refer to Medical and Pharmacy Coverage Policies to verify that this is the current version before utilizing.
• ECRI Institute. Clinical Evidence Assessment. Bone marrow aspirate concentrate therapy for cervical fusion. https://www.ecri.org. Published July 19, 2022. Accessed January 24, 2023.
• ECRI Institute. Clinical Evidence Assessment. Bone marrow aspirate concentrate therapy for lumbar fusion. https://www.ecri.org. Published July 19, 2022. Accessed January 24, 2023.
• ECRI Institute. Clinical Evidence Assessment. Cellular bone allograft for cervical spine fusion. https://www.ecri.org. Published August 4, 2022. Accessed January 24, 2023.
• ECRI Institute. Clinical Evidence Assessment. Cellular bone allograft for lumbar fusion. https://www.ecri.org. Published August 4, 2022. Accessed January 24, 2023.
• ECRI Institute. Clinical Evidence Assessment. Cerament bone void filler (Bonesupport AB) for treating osteolytic bone lesions. https://www.ecri.org. Published July 7, 2021. Accessed January 24, 2023.
• ECRI Institute. Clinical Evidence Assessment. Ceramic bone graft substitutes for spinal fusion and long bone voids. https://www.ecri.org. Published April 25, 2022. Accessed January 24, 2023.
• ECRI Institute. Clinical Evidence Assessment. DBX demineralized bone matrix (Musculoskeletal Transplant Foundation) for filling bone voids. https://www.ecri.org. Published February 29, 2012. Updated December 29, 2020. Accessed January 24, 2023.
• ECRI Institute. Clinical Evidence Assessment. Demineralized bone matrix for orthopedic and spine procedures. https://www.ecri.org. Published January 7, 2022. Accessed January 24, 2023.
• ECRI Institute. Clinical Evidence Assessment. Demineralized bone matrix for spinal fusion and long bone voids. https://www.ecri.org. Published April 7, 2022.

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35. ECRI Institute. Clinical Evidence Assessment. Fibergraft BG (Prosidyan, Inc.) for filling bone voids during spinal surgery. https://www.ecri.org. Published November 1, 2020. Accessed January 24, 2023.
36. ECRI Institute. Clinical Evidence Assessment. FiberOs demineralized cortical fiber matrix (Organogenesis, Inc.) for filling bone voids. https://www.ecri.org. Published October 1, 2020. Accessed January 24, 2023.
37. ECRI Institute. Clinical Evidence Assessment. Genex bone graft substitute (Biocomposites) for filling bone defects. https://www.ecri.org. Published July 21, 2022. Accessed January 24, 2023.
38. ECRI Institute. Clinical Evidence Assessment. Grafton demineralized bone matrix (Medtronic plc.) for orthopedic procedures. https://www.ecri.org. Published September 17, 2013. Updated December 21, 2020. Accessed January 24, 2023.
39. ECRI Institute. Clinical Evidence Assessment. Human amniotic membrane grafts for preventing intradural adhesions after spine surgery. https://www.ecri.org. Published August 18, 2022. Accessed January 26, 2023.

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44. ECRI Institute. Clinical Evidence Assessment. OsteoAMP bone graft (Bioventus, LLC.) for ankle fusion. https://www.ecri.org. Published April 5, 2022. Accessed January 24, 2023.
45. ECRI Institute. Clinical Evidence Assessment. OsteoAMP bone graft (Bioventus, LLC.) for cervical spinal fusion. https://www.ecri.org. Published April 5, 2022. Accessed January 24, 2023.
46. ECRI Institute. Clinical Evidence Assessment. OsteoAMP bone graft (Bioventus, LLC.) for lumbar spine surgery. https://www.ecri.org. Published June 23, 2016. Updated April 5, 2022. Accessed January 24, 2023.
47. ECRI Institute. Clinical Evidence Assessment. OsteoXcell viable bone matrix (Aziyo Biologics, Inc.) for filling bone defects. https://www.ecri.org. Published January 13, 2023. Accessed January 24, 2023.
48. ECRI Institute. Clinical Evidence Assessment. Overview of selected bone graft substitutes for cervical fusion. https://www.ecri.org. Published November 1, 2019. Accessed January 26, 2023.

Clinical Evidence Assessment

• Platelet-rich plasma for knee osteoarthritis. https://www.ecri.org. Published December 15, 2020. Updated February 21, 2022. Accessed January 27, 2023.
• Platelet-rich plasma for nonsurgical treatment of rotator cuff injury. https://www.ecri.org. Published September 7, 2022. Accessed January 27, 2023.
• Platelet-rich plasma therapy for Achilles tendinopathy. https://www.ecri.org. Published February 8, 2022. Accessed January 27, 2023.

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• Platelet-rich plasma therapy for lateral epicondylitis. https://www.ecri.org. Published April 30, 2021. Accessed January 27, 2023.
• Platelet-rich plasma therapy for nonunion fractures. https://www.ecri.org. Published November 7, 2022. Accessed January 27, 2023.
• Platelet-rich plasma therapy for patellar tendinopathy. https://www.ecri.org. Published May 4, 2021. Accessed January 27, 2023.
• PrimaGen Advanced allograft (Zimmer Biomet) for lumbar fusion procedures. https://www.ecri.org. Published February 1, 2019. Updated February 16, 2022. Accessed January 24, 2023.
• Recombinant human bone morphogenetic protein 2 for cervical spine fusion. https://www.ecri.org. Published July 21, 2022. Accessed January 24, 2023.
• Recombinant human bone morphogenetic protein 2 for lumbar fusion. https://www.ecri.org. Published August 5, 2022. Accessed January 24, 2023.
• Tactoset injectable bone substitute (Anika Therapeutics, Inc.) for filling bone voids. https://www.ecri.org. Published April 27, 2021. Accessed January 24, 2023.
• Trinity Elite (Orthofix Medical) for lumbar fusion. https://www.ecri.org. Published January 31, 2020. Updated December 31, 2022. Accessed January 24, 2023.
• VIA Disc Allograft (Vivex Biologics, Inc.) for treating lumbar degenerative disc disease. https://www.ecri.org. Published June 28, 2021. Accessed January 24, 2023.

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• Emerging Technology Evidence Report. Autologous mesenchymal stem cells for treating knee osteoarthritis. https://www.ecri.org. Published May 20, 2013. Updated June 18, 2013. Accessed January 26, 2023.
• Evidence Report. Platelet-rich plasma injections for treating chronic tendinopathies. https://www.ecri.org. Published July 23, 2012. Accessed January 27, 2023.
• Evidence Report (ARCHIVED). Interbody cage with bone morphogenetic protein (InFUSE/LT-CAGE) for degenerative disc disease. https://www.ecri.org. Published December 31, 2004. Accessed December 5, 2014.
• Health Technology Assessment Information Service. Special Report. Osteoinductive potential of commercial demineralized bone matrix products. https://www.ecri.org.

• ECRI Institute. Health Technology Assessment Information Service. Special Report. Patient safety issues when using bone allografts in spinal surgery. https://www.ecri.org. Published September 15, 2017. Accessed January 26, 2023.
• ECRI Institute. Health Technology Forecast. Autologous and allogeneic mesenchymal stem cell therapy for treating osteoarthritis. https://www.ecri.org. Published November 2, 2012. Accessed January 27, 2023.
• ECRI Institute. Health Technology Forecast. Autologous platelet-rich plasma therapy for knee osteoarthritis. https://www.ecri.org. Published February 13, 2013. Accessed January 27, 2023.
• ECRI Institute. Hotline Response. Platelet-rich plasma to aid healing with rotator cuff surgery. https://www.ecri.org. Published July 14, 2017. Updated February 20, 2020. Accessed January 27, 2023.

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• ECRI Institute. Hotline Response (ARCHIVED). Amniotic membrane transplantation for ophthalmic surgery, wound care and orthopedic procedures. https://www.ecri.org. Published August 12, 2014. Accessed January 26, 2023.
• ECRI Institute. Hotline Response (ARCHIVED). Autologous blood injection for treating tendinopathies. https://www.ecri.org. Published February 12, 2013. Accessed January 27, 2023.
• ECRI Institute. Hotline Response (ARCHIVED). Bone substitution with bioactive glass during orthopedic surgery procedures. https://www.ecri.org. Published September 22, 2006. Updated December 28, 2015. Accessed January 26, 2023.
• ECRI Institute. Hotline Response (ARCHIVED). Calcium phosphate-based synthetic bone graft substitutes for spinal surgery. https://www.ecri.org. Published February 27, 2018. Accessed January 26, 2023.
• ECRI Institute. Hotline Response (ARCHIVED). Demineralized bone matrix for orthopedic and spine procedures. https://www.ecri.org. Published November 5, 2015. Updated May 1, 2017. Accessed January 27, 2023.
• ECRI Institute. Hotline Response (ARCHIVED). Demineralized bone matrix to aid sternal closure or sternal nonunion after open heart surgery. https://www.ecri.org. Published July 31, 2017. Accessed February 3, 2022.
• ECRI Institute. Hotline Response (ARCHIVED). Guidelines for using platelet-rich plasma in surgical procedures. https://www.ecri.org. Published November 11, 2015. Accessed January 26, 2023.
• ECRI Institute. Hotline Response (ARCHIVED). Nanocrystalline calcium phosphate/hydroxyapatite as a bone substitute for orthopedic surgery. https://www.ecri.org. Published December 19, 2012. Accessed January 27, 2023.
• ECRI Institute. Hotline Response (ARCHIVED). Orthopedic surgery uses for recombinant human bone morphogenetic protein-2. https://www.ecri.org. Published September 30, 2009. Accessed January 18, 2013.

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• ECRI Institute. Hotline Response (ARCHIVED). Platelet-rich plasma therapy for osteoarthritis and acute joint injury. https://www.ecri.org. Published November 3, 2009. Updated May 15, 2013. Accessed January 27, 2023.
• ECRI Institute. Hotline Response (ARCHIVED). Recombinant human bone morphogenetic protein-2 (Infuse bone graft) for spinal fusion. https://www.ecri.org.

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81. ECRI Institute. Hotline Response (ARCHIVED). Synthetic bone graft substitutes for orthopedic procedures. https://www.ecri.org. Published September 24, 2013. Updated December 28, 2015. Accessed January 26, 2023.
82. ECRI Institute. Hotline Response (ARCHIVED). Synthetic bone growth and bone graft products for spinal fusion procedures. https://www.ecri.org. Published February 7, 2008. Updated November 13, 2014. Accessed January 26, 2023.
83. ECRI Institute. Product Brief. ActiveBarrier and ActiveMatrix allografts (Skye Biologics, Inc.) for use in orthopedic procedures. https://www.ecri.org. Published February 1, 2020. Accessed January 26, 2023.
84. ECRI Institute. Product Brief. AmnioFill and AmnioFix allografts (MiMedx) for use in orthopedic procedures. https://www.ecri.org. Published March 9, 2020. Accessed January 26, 2023.
85. ECRI Institute. Product Brief. ArthroCell bone allograft (Arthrex, Inc.) for filling bone voids. https://www.ecri.org. Published February 11, 2020. Accessed January 24, 2023.
86. ECRI Institute. Product Brief. Bonus Triad allograft (Zimmer Biomet) for ankle fusion surgery. https://www.ecri.org. Published November 1, 2019. Accessed January 27, 2023.
87. ECRI Institute. Product Brief. Bonus Triad allograft (Zimmer Biomet) for open reduction internal fixation surgery. https://www.ecri.org. Published November 1, 2019. Accessed January 27, 2023.

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88. ECRI Institute. Product Brief. i-Factor peptide-enhanced bone graft (Cerapedics, Inc.) for treating cervical degenerative disc disease. https://www.ecri.org. Published October 23, 2017. Updated October 25, 2019. Accessed January 26, 2023.
89. ECRI Institute. Product Brief. Incite allograft (Spineology, Inc.) for use in spinal surgery. https://www.ecri.org. Published February 1, 2020. Accessed January 24, 2023.
90. ECRI Institute. Product Brief. Mastergraft Matrix EXT bone graft (Medtronic plc) for spinal fusion surgery. https://www.ecri.org. Published July 1, 2019. Accessed January 27, 2023.
91. ECRI Institute. Product Brief. Mastergraft Strip bone graft (Medtronic plc) for spinal fusion surgery. https://www.ecri.org. Published July 1, 2019. Accessed January 27, 2023.
92. ECRI Institute. Product Brief. NovaBone MacroPor-Si+ (NovaBone Products, LLC) for orthopedic procedures. https://www.ecri.org. Published March 1, 2020. Accessed January 24, 2023.
93. ECRI Institute. Product Brief. NuCel human amniotic allograft (Organogenesis, Inc.) for use in orthopedic procedures. https://www.ecri.org. Published February 1, 2020. Accessed January 26, 2023.
94. ECRI Institute. Product Brief. NuShield placental allograft (Organogenesis, Inc.) for use in orthopedic procedures. https://www.ecri.org. Published February 1, 2020. Accessed January 26, 2023.
95. ECRI Institute. Product Brief. Osteocel cellular allograft (NuVasive, Inc.) for spinal fusion procedures. https://www.ecri.org. Published June 17, 2019. Accessed January 26, 2023.
96. ECRI Institute. Product Brief. OsteoCrete bone void filler (Bone Solutions, Inc.) for orthopedic procedures. https://www.ecri.org. Published October 1, 2018. Accessed January 27, 2023.

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97. ECRI Institute. Product Brief. Overview of two bone graft substitutes for lumbar fusion. https://www.ecri.org. Published March 1, 2018. Accessed January 26, 2023.
98. ECRI Institute. Product Brief. Overview of two tissue products for tendon and ligament repair. https://www.ecri.org. Published February 1, 2018. Accessed January 27, 2023.
99. ECRI Institute. Product Brief. ReVive Flow Matrix (Skye Biologics, Inc.) for use in orthopedic procedures. https://www.ecri.org. Published March 1, 2020. Accessed January 26, 2023.
100. ECRI Institute. Product Brief. Trinity Elite (Orthofix International) for shoulder revision surgery. https://www.ecri.org. Published September 1, 2019. Accessed January 27, 2023.
101. ECRI Institute. Product Brief. Vitoss BA, Vitoss BA2X, and Vitoss Bimodal synthetic bone grafts (Stryker Corp.) for spinal fusion surgery. https://www.ecri.org. Published May 1, 2019. Accessed January 27, 2023.
102. ECRI Institute. Product Brief. Vitoss bone graft substitute (Stryker Corp.) for filling bone voids during spinal surgery. https://www.ecri.org. Published May 10, 2019. Accessed January 26, 2023.
103. ECRI Institute. Product Brief. ViviGen cellular bone matrix (DePuy Synthes) for ankle fusion surgery. https://www.ecri.org. Published November 1, 2019. Accessed January 27, 2023.
104. ECRI Institute. Product Brief. ViviGen cellular bone matrix (DePuy Synthes) for lumbar fusion procedures. https://www.ecri.org. Published October 1, 2018. Accessed January 27, 2023.
105. ECRI Institute. Product Brief. ViviGen cellular bone matrix (DePuy Synthes) for open reduction internal fixation surgery. https://www.ecri.org. Published November 1, 2019. Accessed January 27, 2023.

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106. ECRI Institute. Product Brief (ARCHIVED). AlloStem stem cell bone growth substitute (AlloSource) for orthopedic procedures. https://www.ecri.org. Published August 13, 2013. Accessed January 27, 2023.
107. ECRI Institute. Product Brief (ARCHIVED). BioDfactor human amniotic allograft (BioDlogics, LLC) for covering wounds and filling bone voids. https://www.ecri.org. Published February 6, 2012. Accessed November 30, 2017.
108. ECRI Institute. Product Brief (ARCHIVED). Graftjacket regenerative tissue matrix (Wright Medical Technology) to augment tendon and ligament repair. https://www.ecri.org. Published April 7, 2004. Updated February 12, 2018. Accessed January 27, 2023.
109. ECRI Institute. Product Brief (ARCHIVED). Infuse bone graft (Medtronic plc.) for anterior lumbar interbody fusion. https://www.ecri.org. Published October 6, 2017. Accessed January 26, 2023.
110. ECRI Institute. Product Brief (ARCHIVED). Infuse bone graft (Medtronic plc.) for cervical fusion procedures. https://www.ecri.org. Published March 20, 2018. Accessed January 26, 2023.
111. ECRI Institute. Product Brief (ARCHIVED). Infuse bone graft (Medtronic plc) for extreme lateral interbody lumbar fusion. https://www.ecri.org. Published August 31, 2017. Accessed January 26, 2023.
112. ECRI Institute. Product Brief (ARCHIVED). Infuse bone graft (Medtronic plc) for lumbar posterolateral fusion. https://www.ecri.org. Published August 25, 2017. Accessed January 26, 2023.
113. ECRI Institute. Product Brief (ARCHIVED). Infuse bone graft (Medtronic plc.) for transforaminal lumbar interbody fusion. https://www.ecri.org. Published October 23, 2017. Accessed January 26, 2023.
114. ECRI Institute.

     Infuse Bone Graft (Medtronic, Inc.) for use in lumbar fusion and tibial repair surgical procedures.

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     Review Date: 03/01/2023
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     https://www.ecri.org. Published March 14, 2013. Updated July 11, 2014. Accessed January 26, 2023.

     115. ECRI Institute. Product Brief (ARCHIVED). Ovation cellular repair matrix (Osiris Therapeutics, Inc.) for repairing bone during orthopedic procedures. https://www.ecri.org. Published February 6, 2012. Accessed January 26, 2023.

     116. ECRI Institute. Product Brief (ARCHIVED). Pro-Dense Injectable Regenerative Graft and Core Decompression Kit (Wright Medical Technology, Inc.) for treating avascular necrosis of the hip. https://www.ecri.org. Published November 26, 2018. Accessed January 26, 2023.

     117. ECRI Institute. Product Brief (ARCHIVED). Progenix (Medtronic, Inc.) demineralized bone matrix for orthopedic procedures. https://www.ecri.org. Published September 17, 2013. Accessed January 27, 2023.

     118. ECRI Institute. Product Brief (ARCHIVED). Puros (Zimmer Carolinas) demineralized bone matrix for orthopedic procedures. https://www.ecri.org. Published September 18, 2013. Accessed January 27, 2023.

     119. ECRI Institute. Product Brief (ARCHIVED). Stimulan Rapid Cure (Biocomposites Ltd.) bone substitute for filling voids during total joint replacement. https://www.ecri.org. Published September 27, 2018. Accessed January 26, 2023.

     120. ECRI Institute. Product Brief (ARCHIVED). Stimulan Rapid Cure (Biocomposites Ltd.) resorbable, biocompatible bone graft material. https://www.ecri.org. Published December 12, 2013. Accessed January 26, 2023.

     121. Fu R, Selph S, McDonagh M, et al. Effectiveness and harms of recombinant human bone morphogenetic protein-2 in spine fusion. Ann Intern Med. 2013;158:890-902.

     122. Guzman J, Merrill R, Kim J, et al. Bone morphogenetic protein use in spine surgery in the United States: how have we responded to the warnings? Spine J. 2017;17:1247-1254.

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     123. Hayes, Inc. Clinical Research Response (ARCHIVED). Actifuse (Baxter Healthcare) versus Biosphere (Synergy Biomedical) – product comparison. https://evidence.hayesinc.com. Published February 25, 2016. Accessed December 6, 2018.

     124. Hayes, Inc. Clinical Research Response (ARCHIVED). BioCartilage (Arthrex) for orthopedic indications. https://evidence.hayesinc.com. Published February 9, 2021. Accessed January 27, 2023.

     125. Hayes, Inc. Clinical Research Response (ARCHIVED). BioD Products (BioD LLC). https://evidence.hayesinc.com. Published July 23, 2015. Accessed December 6, 2017.

     126. Hayes, Inc. Clinical Research Response (ARCHIVED). BioDFence (BioDlogics, LLC) human amniotic allograft. https://evidence.hayesinc.com. Published March 9, 2018. Accessed December 4, 2020.

     127. Hayes, Inc. Clinical Research Response (ARCHIVED). Bone void fillers – product comparison. https://evidence.hayesinc.com. Published July 6, 2018. Accessed December 4, 2020.

     128. Hayes, Inc. Clinical Research Response (ARCHIVED). Cancer risk after spinal surgery using recombinant human bone morphogenetic protein (rhBMP). https://evidence.hayesinc.com. Published March 16, 2017. Accessed December 12, 2019.

     Cellular bone matrix products – part 1 – product comparison. https://evidence.hayesinc.com. Published April 11, 2018. Accessed December 4, 2020.

     130. Hayes, Inc. Clinical Research Response (ARCHIVED). Demineralized bone matrices (bone putty) – product comparison. https://evidence.hayesinc.com. Published August 23, 2019. Accessed February 1, 2022.

     131. Hayes, Inc. Clinical Research Response (ARCHIVED). i-Factor (Cerapedics) versus Trinity Elite (Orthofix) for spinal procedures.

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     Review Date: 03/01/2023
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     https://evidence.hayesinc.com. Published May 4, 2018. Accessed December 4, 2020.

     132. Hayes, Inc. Clinical Research Response (ARCHIVED). Infuse bone graft (Medtronic) versus OsteoAMP (Bioventus LLC) for spinal indications. https://evidence.hayesinc.com. Published January 22, 2019. Accessed December 4, 2020.

     133. Hayes, Inc. Clinical Research Response (ARCHIVED). Mastergraft (Medtronic) versus Fibergraft (Johnson & Johnson) as bone void fillers in spinal surgery. https://evidence.hayesinc.com. Published October 16, 2020. Accessed January 27, 2023.

     134. Hayes, Inc. Clinical Research Response (ARCHIVED). Montage bone putty (Abyrx Inc.) for supplemental sternal fixation. https://evidence.hayesinc.com. Published July 7, 2016. Accessed December 6, 2018.

     135. Hayes, Inc. Clinical Research Response (ARCHIVED). OsteoAMP (Bioventus) vs ViviGen (DuPuy Synthes) for use in spinal procedures. https://evidence.hayesinc.com. Published January 11, 2021. Accessed January 27, 2023.

     136. Hayes, Inc. Clinical Research Response (ARCHIVED). Osteocel Pro (NuVasive, Inc.) vs Trinity Elite (Orthofix Inc.) for spinal indications. https://evidence.hayesinc.com. Published December 4, 2020. Accessed January 27, 2023.

     137. Hayes, Inc. Clinical Research Response (ARCHIVED). PalinGen amniotic tissue allografts (Amnio ReGen Solutions LLC) for orthopedic indications. https://evidence.hayesinc.com. Published December 3, 2015. Accessed December 6, 2018.

     138. Hayes, Inc. Clinical Research Response (ARCHIVED). Platelet rich plasma for spinal fusion. https://evidence.hayesinc.com. Published August 4, 2021. Accessed January 27, 2023.

     Bone Graft Substitutes Effective Date: 01/01/2024
     Revision Date: 01/01/2024
     Review Date: 03/01/2023
     Policy Number: HUM-0479-018
     Page: 41 of 47

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     139. Hayes, Inc. Clinical Research Response (ARCHIVED). Spine allografts by LESBiologics – product comparison. https://evidence.hayesinc.com. Published October 8, 2015. Accessed December 6, 2018.

     140. Hayes, Inc. Clinical Research Response (ARCHIVED). Viaflow and Viaflow C Flowable placental tissue matrices (Wright Medical) for orthopedic and podiatric indications. https://evidence.hayesinc.com. Published March 10, 2016. Accessed December 6, 2018.

     141. Hayes, Inc. Evidence Analysis Research Brief. Extracellular matrix with BioCartilage for orthopedic indications. https://evidence.hayesinc.com. Published October 27, 2022. Accessed January 27, 2023.

     142. Hayes, Inc. Evidence Analysis Research Brief. i-Factor Enhanced Peptide bone graft (Cerapedics, Inc.) for cervical discectomy and fusion. https://evidence.hayesinc.com. Published January 25, 2023. Accessed January 27, 2023.

     143. Hayes, Inc. Evidence Analysis Research Brief. i-Factor Peptide Enhanced bone graft (Cerapedics, Inc.) for lumbar surgeries. https://evidence.hayesinc.com.

     Published February 2, 2023. Accessed February 7, 2023.

     Evidence Analysis Research Brief

     • Hayes, Inc. Evidence Analysis Research Brief (ARCHIVED). Amniotic allografts for hip indications. https://evidence.hayesinc.com. Published May 12, 2020. Accessed January 27, 2023.
     • Hayes, Inc. Evidence Analysis Research Brief (ARCHIVED). Amniotic allografts for lumbar spine indications. https://evidence.hayesinc.com. Published May 7, 2020. Accessed January 27, 2023.
     • Hayes, Inc. Evidence Analysis Research Brief (ARCHIVED). Bovine collagen implants for the treatment of rotator cuff injuries. https://evidence.hayesinc.com. Published August 25, 2020. Accessed January 27, 2023.

     Bone Graft Substitutes Effective Date: 01/01/2024
     Revision Date: 01/01/2024
     Review Date: 03/01/2023
     Policy Number: HUM-0479-018
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     Evolving Evidence Review

     • Hayes, Inc. Evolving Evidence Review. Amniotic allografts for treatment of knee osteoarthritis. https://evidence.hayesinc.com. Published September 1, 2021. Accessed January 27, 2023.
     • Hayes, Inc. Health Technology Assessment. Amniotic allografts for tendon and ligament injuries. https://evidence.hayesinc.com. Published September 16, 2020. Updated September 9, 2022. Accessed January 27, 2023.
     • Hayes, Inc. Health Technology Assessment. Concentrated bone marrow aspirate for spinal surgery. https://evidence.hayesinc.com. Published May 18, 2020. Updated May 12, 2022. Accessed January 27, 2023.

     HUM-0479-018

     Page: 43 of 47

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     • HAYES, INC. Health Technology Brief (ARCHIVED). Augment bone graft (Wright Medical Group Inc.) for bone regeneration in ankle and/or hindfoot fusions. https://evidence.hayesinc.com. Published December 22, 2015. Updated December 29, 2017. Accessed January 27, 2023.
     • HAYES, INC. Health Technology Brief (ARCHIVED). Autologous bone marrow- derived mesenchymal stem cell therapy for treatment of nonunion of the lower extremity. https://evidence.hayesinc.com. Published November 20, 2014. Updated October 20, 2016. Accessed January 27, 2023.
     • HAYES, INC. Health Technology Brief (ARCHIVED). Autologous platelet-rich plasma to aid bone fusion following ankle surgery. https://evidence.hayesinc.com. Published July 25, 2007. Updated August 3, 2009. Accessed January 27, 2023.

     Comparative Effectiveness Review

     • HAYES, INC. Medical Technology Directory. Comparative effectiveness review of platelet-rich plasma for rotator cuff repairs, tendinopathies, and related conditions: a review of reviews. https://evidence.hayesinc.com. Published May 31, 2018. Updated June 30, 2022. Accessed January 27, 2023.
     • HAYES, INC. Medical Technology Directory. Comparative effectiveness review of platelet-rich plasma for treatment of conditions of the Achilles tendon and plantar fasciitis. https://evidence.hayesinc.com. Published March 1, 2018. Updated February 11, 2022. Accessed January 27, 2023.
     • HAYES, INC. Medical Technology Directory. Comparative effectiveness review of platelet-rich plasma for treatment of ligament injuries and tendinopathies of the knee: a review of reviews. https://evidence.hayesinc.com. Published December 29, 2017. Updated January 26, 2022. Accessed January 27, 2023.
     • HAYES, INC. Medical Technology Directory. Comparative effectiveness review of recombinant human bone morphogenetic protein (rhBMP) for use in spinal fusion. https://evidence.hayesinc.com. Published September 17, 2018.

     Page: 43 of 47

     • Updated October 11, 2022. Accessed January 27, 2023.
     • Hayes, Inc. Medical Technology Directory. Comparative effectiveness review of stem cell therapy for joint pain. Published July 12, 2018. Updated August 17, 2022. Accessed January 27, 2023.
     • Hayes, Inc. Medical Technology Directory. Platelet-rich plasma for hip osteoarthritis. Published June 14, 2019. Updated June 22, 2022. Accessed January 27, 2023.
     • Hayes, Inc. Medical Technology Directory (ARCHIVED). Autologous stem cell therapy for treatment of avascular necrosis of the hip. Published December 17, 2015. Updated December 19, 2019. Accessed January 27, 2023.
     • Hayes, Inc. Medical Technology Directory (ARCHIVED). Beta-tricalcium phosphate bone void filler. Published September 25, 2006. Updated August 2, 2010. Accessed January 27, 2023.
     • Hayes, Inc. Medical Technology Directory (ARCHIVED). Comparative effectiveness review of platelet-rich plasma for knee osteoarthritis: a review of reviews. Published November 9, 2017. Updated January 11, 2022. Accessed January 27, 2023.
     • Hayes, Inc. Medical Technology Directory (ARCHIVED). Comparative effectiveness review of platelet-rich plasma for treatment of lateral epicondylitis: a review of reviews. Published December 8, 2017. Updated January 11, 2022. Accessed January 27, 2023.

     Bone Graft Substitutes Effective Date: 01/01/2024
     Revision Date: 01/01/2024
     Review Date: 03/01/2023
     Policy Number: HUM-0479-018
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     163. Hayes, Inc. Medical Technology Directory (ARCHIVED). Recombinant human bone morphogenetic protein for use in tibia repair. Published September 12, 2011. Updated July 30, 2015. Accessed January 30, 2023.
     164. Hayes, Inc. Prognosis Overview (ARCHIVED). AMPLIFY recombinant human bone morphogenetic protein (rhBMP-2) matrix. Published March 11, 2011. Accessed January 30, 2023.
     165. Hayes, Inc. Search & Summary (ARCHIVED). Actifuse (ApaTech) silicate substituted synthetic bone graft. Published January 25, 2011. Accessed January 18, 2013.
     166. Hayes, Inc. Search & Summary (ARCHIVED). Platelet-rich plasma injections for hamstring tendon injuries. Published July 10, 2014. Accessed November 20, 2015.
     167. Hayes, Inc. Search & Summary (ARCHIVED). Trinity Evolution bone allograft (Orthofix Holdings Inc.). Published February 27, 2014. Accessed November 20, 2015.

     Interventional Society for the Advancement of Spine Surgery (ISASS). ISASS recommendations and coverage criteria for bone graft substitutes used in spinal surgery. Published January 30, 2019. Accessed February 6, 2023.

     Khan T, Pearce K, McAnany S, Peters C, Gupta M, Zebala L. Comparison of transforaminal lumbar interbody fusion outcomes in patients receiving rhBMP-2 versus autograft. Spine J. 2018;18:439-446.

     McAnany S, Ahn J, Elboghdady I, et al. Mesenchymal stem cell allograft as a fusion adjunct in one- and two-level anterior cervical discectomy and fusion: a matched cohort analysis. Spine J. 2016;16:163-167.

     MCG Health. Platelet-rich plasma. 26th edition. Accessed December 20, 2022.

     Bone Graft Substitutes Effective Date: 01/01/2024
     Revision Date: 01/01/2024
     Review Date: 03/01/2023
     Policy Number: HUM-0479-018
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     172. Moore M, Deckey D, Pollock J, Smith J, Tokish J, Neal M. The effect of amniotic tissue on spinal interventions: a systematic review. Int J Spine Surg. 2022;0:1-11. https://www.ijssurgery.com. Accessed November 18, 2022.
     173. North American Spine Society (NASS). Coverage Policy Recommendations. Allograft and demineralized bone matrix for spinal fusion. https://www.spine.org. Published October 2017. Accessed February 6, 2023.
     174. North American Spine Society (NASS). Coverage Policy Recommendations. Recombinant human bone morphogenetic protein (rhBMP-2). https://www.spine.org. Published May 2014. Accessed February 6, 2023.
     175. North American Spine Society (NASS). Evidence-Based Clinical Guidelines for Multidisciplinary Spine Care. Diagnosis and treatment of degenerative lumbar spondylolisthesis. https://www.spine.org. Published 2008. Updated 2014. Accessed February 6, 2023.
     176. North American Spine Society (NASS). Evidence-Based Clinical Guidelines for Multidisciplinary Spine Care. Diagnosis and treatment of low back pain. https://www.spine.org. Published 2020. Accessed February 6, 2023.
     177. Sanapati J, Manchikanti L, Atluris S, et al. Do regenerative medicine therapies provide long-term relief in chronic low back pain: a systematic review and meta-analysis. Pain Physician. 2018;21:515-540.
     178. UpToDate, Inc. Achilles tendinopathy and tendon rupture. https://www.uptodate.com. Updated December 2022. Accessed January 31, 2023.
     179. UpToDate, Inc. Basic principles of bone grafts and bone substitutes. https://www.uptodate.ocm [Note: There may be a typo in the original URL here]. Updated December 2022. Accessed January 31, 2023.
     180. UpToDate, Inc. Biologic therapies for tendon and muscle injury. https://www.uptodate.com. Updated December 2022. Accessed January 31, 2023.
     181. UpToDate, Inc. Elbow tendinopathy (tennis and golf elbow).https://www.uptodate.com. Updated December 2022. Accessed January 31, 2023.
     182. UpToDate, Inc. General principles of definitive fracture management. https://www.uptodate.com. Updated December 2022. Accessed January 31, 2023.
     183. UpToDate, Inc. General principles of fracture management: bone healing and fracture description. https://www.uptodate.com. Updated December 2022. Accessed January 31, 2023.
     184. UpToDate, Inc. Hamstring muscle and tendon injuries. https://www.uptodate.com. Updated December 2022. Accessed January 31, 2023.
     185. UpToDate, Inc. Investigational approaches to the management of osteoarthritis. https://www.uptodate.com. Updated December 2022. Accessed January 31, 2023.
     186. UpToDate, Inc. Management of knee osteoarthritis. https://www.uptodate.com. Updated December 2022. Accessed January 31, 2023.
     187. UpToDate, Inc. Overview of the management of overuse (persistent) tendinopathy. https://www.uptodate.com. Updated December 2022. Accessed January 31, 2023.
     188. UpToDate, Inc. Subacute and chronic low back pain: surgical treatment. https://www.uptodate.com. Updated December 2022. Accessed January 31, 2023.
     189. US Department of Veteran Affairs (VA). VA/DoD Clinical Practice Guideline. Diagnosis and treatment of low back pain. https://www.va.gov. Published February 2022. Accessed February 6, 2023.

     Bone Graft Substitutes Effective Date: 01/01/2024
     Revision Date: 01/01/2024
     Review Date: 03/01/2023
     Policy Number: HUM-0479-018
     Page: 46 of 47
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     Revision Date: 01/01/2024
     Review Date: 03/01/2023
     Policy Number: HUM-0479-018
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     190. US Department of Veteran Affairs (VA). VA/DoD Clinical Practice Guideline. Nonsurgical management of hip and knee osteoarthritis. https://www.va.gov. Published July 2020. Accessed February 6, 2023.
     191. US Food & Drug Administration (FDA). 510(k) summary: KINEX Bioactive. https://www.fda.gov. Published August 15, 2013. Accessed December 21, 2016.
     192. US Food & Drug Administration (FDA). 510(k) summary: NanoFUSE. https://www.fda.gov. Published February 16, 2017. Accessed March 8, 2017.
     193. US Food & Drug Administration (FDA). 510(k) summary: Signify Bioactive. https://www.fda.gov. Published December 24, 2013. Accessed December 21, 2016.
     194. US Food & Drug Administration (FDA). Premarket approval application (PMA): Augment Bone Graft. https://www.fda.gov. Published September 1, 2015. Accessed January 6, 2016.
     195. US Food & Drug Administration (FDA). Safety Communications. Use of bone graft substitutes containing recombinant proteins or synthetic peptides in patients under age 18. https://www.fda.gov. Published January 21, 2015. Accessed December 28, 2015.
     196. US Food & Drug Administration (FDA). Summary of safety and effectiveness data: INFUSE Bone Graft. https://www.fda.gov. Published April 30, 2004. Accessed February 1, 2013.
     197. US Food & Drug Administration (FDA). Summary of safety and effectiveness data: INFUSE Bone Graft/LT-CAGE Lumbar Tapered Fusion Device. https://www.fda.gov. Published July 2, 2002. Accessed February 1, 2013.
     198. Zhao L, Kaye AD, Abd-Elsayed A. Stem cells for the treatment of knee osteoarthritis: a comprehensive review. Pain Physician. 2018;21:299-241.