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Medical Policy

Policy Num:      02.001.027
Policy Name:    Percutaneous treatment of fracture Non-Unions or Bone Defects with Autologous Bone Marrow with Demineralized Bone Matrix (DBM)
Policy ID:          [02.001.027]  [Ar / B / M /P ]  [2.01.75]

Last Review:      April 02, 2019
Next Review:      Policy Archived
Issue:                  4:2019

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Related Policies: None

Percutaneous treatment of fracture Non-Unions or Bone Defects with Autologous Bone Marrow with Demineralized Bone Matrix (DBM)

Summary

The standard treatment of problem fractures or osseous defects has been an autologous cancellous bone graft harvested from the iliac crest. Limitations of this approach include morbidity at the graft site and the lack of adequate bone stock in some patients. Autologous bone graft is considered the gold standard because it includes components of all 3 processes considered to be essential for bone healing: osteoconductivity (i.e., a support structure), osteoinductivity (i.e., ability of graft to induce nondifferentiated stem cells to differentiate into osteoblast) and osteogenic cells.

Therefore, bone graft substitutes, used either alone or in combination are designed to reproduce these components. The extracellular bone matrix includes a wide range of bone growth factors, proteins, and other bioactive materials necessary for osteoinduction. These factors can be removed from allograft bone by using a demineralizing agent, resulting in demineralized bone matrix (DBM). Several different preparations of DBM are commercially available, including putty, gel, and paste, which can be used as an adjunct to a variety of open surgical procedures. In contrast, the Ignite™ ICS product consists of a DBM that is designed to be injectable, thus enabling percutaneous treatment. Autologous bone marrow aspirate is designed to provide marrow stromal cells and osteogenic cells, and has been investigated as a stand-alone treatment of fracture, or in conjunction with demineralized bone marrow.

The Ignite™ ICS product is specifically designed to be used in conjunction with bone marrow aspirate, and has the following labeled indication: “After the powder is mixed with autologous bone marrow aspirate, the resultant composite material can then be injected into the defect site. Ignite™ ICS is indicated only for bone voids or gaps that are not intrinsic to the stability of the bony structure. Ignite™ ICS is intended to be injected into bony voids or gaps of the skeletal system (i.e., the extremities, spine, and pelvis). These defects may be surgically created osseous defects or osseous defects created from traumatic injury to the bone.” Various different preparations of DBM are commercially available, regulated by the U.S. Food and Drug Administration (FDA) as either human tissue or cleared through the 510(k) marketing clearance process. An example of a DBM preparation that is regulated as a human tissue is Osteotech’s Grafton® and 3 preparations that have received 510(k) marketing clearance are the Wright Medical Allomatrix®, Exactech Resorbable Bone Paste, and DBX® from the Musculoskeletal Transplant Foundation. Bone morphogenetic protein (BMP) is another bone graft alternative and consists of a bioengineered equivalent of 1 of the components of bone matrix. Various BMP preparations have been FDA approved through the more rigorous PMA process, which does require evidence of clinical efficacy. BMP is discussed in MPRM Policy No.7.01.100.

Objective

The objective of this review is to compare the use of bone marrow aspirate with or without demineralized bone matrix.

policy Statements

The percutaneous treatment of fracture non-unions of bone defects with the use of bone marrow aspirate with or without demineralized bone matrix is considered investigational.

Policy Guidelines

There are no specific CPT codes for the above procedure and no specific coding for the BMP products. If autologous bone marrow aspirate is used, the CPT code 38220 will be used for the aspiration procedure.

Benefit Application

BlueCard/National Account Issues

There are no specific CPT codes for the above procedure and no specific coding for the BMP products. If autologous bone marrow aspirate is used, the CPT code 38220 will be used for the aspiration procedure.

Background

In adults, boen is constantly being remodeled, first being torn down (bone resorption) and then being rebuilt (bone formation) [1,2]. The resorption and reformation of bone is important for repair of microfractures and to allow modification of structure in response to stress and other biomechanical forces. Bone formation is normally tightly coupled to bone resorption, so that bone mass does not change. Bone diseases occur when formation and resorption are uncoupled.

Changes in the rate of bone turnover are an important determinant of bone disease, and therefore, measurements that correlate with the rate of turnover provide important information in assessing patients with bone disease. In the past, the best way to measure bone turnover was to perform a bone biopsy after double-labeling with tetracycline [1,3]. This technique permits measurement of the rates of bone formation and bone resorption, and the fractions of bone surface at which active resorption and formation are ongoing. However, the complexity and expense of this procedure make it unsuitable for routine clinical practice.

As an alternative, several assays are currently available that measure bone turnover markers (BTMs) These assays measure collagen breakdown products and other molecules released from osteoclasts and osteoblasts during the process of bone resorption and formation. Although the development of better assays has improved the ability of BTMs to reflect the rate of bone turnover, biologic and aboratory variability have confounded their widespread use in clinical practice.

BONE REMODELING — The steps involved in bone formation and resorption are described briefly here.

Bone resorption — Bone resorption is initiated by osteoclasts, which are derived from hematopoietic stem cells [4] and have acid phosphatase anchored to their cell membranes [2,5]. Although acid phosphatase activity is present in other tissues such as the prostate gland, the two forms of the enzyme can be distinguished by the insensitivity of osteoclastic acid phosphatase to inhibition by tartrate (tartrate-resistant acid phosphatase, TRAP).

The osteoclasts attach to the bone surface and secrete acid and hydrolytic enzymes that resorb bone, releasing bone minerals and fragments of collagen. Some of the collagen is completely digested to its smallest chemical units, resulting in formation of free pyridinoline and deoxypyridinoline residues that circulate in the blood and are excreted in the urine. Some, however, is incompletely digested, resulting in formation in pyridinoline crosslinks bound to fragments of the alpha-1 and alpha-2 chains; these peptide-bound crosslinks also circulate in the blood and are excreted in the urine [5-7].

Bone formation — Bone formation is initiated by osteoblasts, which synthesize type I collagen and other proteins, such as osteocalcin, that combine extracellularly to form osteoid, the organic substrate upon which mineralization occurs [2]. The osteoblasts contain alkaline phosphatase anchored to their cell membranes. This alkaline phosphatase is functionally similar to but antigenically distinct from hepatic and placental alkaline phosphatases [8].

The synthesis of type I collagen in bone involves the intertwining of one alpha-2 and two alpha-1 polypeptide chains to form a helical structure known as procollagen, followed by cleavage of their amino-terminal and carboxy-terminal peptides to form tropocollagen (figure 1) [1]. Tropocollagen is mainly helical; the nonhelical portions at the amino and carboxy terminals are known as the N-telopeptide and C-telopeptide regions, respectively.

The side chains of three hydroxylysine residues from different tropocollagen molecules condense to form a pyridinium ring, thereby forming the pyridinoline crosslinks (PYD) that connect three different tropocollagen molecules [1,9]. A deoxypyridinoline (D-PYR) crosslink is a variant form of the pyridinoline crosslink that is formed when two hydroxylysine side chains condense with one lysine side chain [10]. Pyridinoline crosslinks also occur in many types of collagen outside of bone except for collagen in skin [10,11].

Regulatory Status

N/A

Rationale

In the treatment of fractures, an autologous bone graft is considered when a fracture nonunion is present (usually defined as a 3-month period without evidence of further fracture healing). However, the minimally invasive nature of a percutaneous approach may prompt a broadening of the patient selection criteria.

For example, on the manufacturer’s Web site for the Ignite™ ICS product, the following indications are listed (1):

· Suspect delayed union at 6–8 weeks following index procedure with no sign of callus formation

· Delayed union with well-fixed hardware

· Fresh fracture for “high risk” patients with one or more co-morbidities such as smoking, diabetes, steroid use, etc.

· Stable non-unions with no prior surgical intervention.

A literature search based on the MEDLINE database did not identify any controlled trials comparing the standard treatment of autologous bone graft to treatment with autologous bone marrow aspirate used either alone or in conjunction with demineralized bone matrix (DBM). The published literature, including citations from the 1990s, consisted primarily of single institution case series with heterogeneous groups of patients. In 1995, Connolly published a retrospective review of the use of bone marrow aspirate used either alone or in combination with DBM in 100 cases (2). The author states that the results were at least equivalent to autologous grafting, but did not provide detailed results or statistical analysis. Skoff reported on a prospective case series of 19 patients with a localized skeletal defect requiring bone grafting. (3) The patients were treated with cancellous cubes of allograft bone that were combined with autologous bone marrow aspirate. The composite graft was implanted through a stab incision over the skeletal defect. A total of 100% of patients achieved clinical healing.

In 2003 Wilkins and colleagues reported on a prospective study of 66 patients with stiff non-unions (i.e., no gross motion) who were treated with a percutaneous administration of a mixture of autologous bone marrow and DBM. (4) A total of 88% of patients achieved union at 8.1 months. Finally, Goel and colleagues reported on a prospective case series of 20 patients with tibial non-unions who received a percutaneous bone marrow injection alone. The authors reported a 75% union rate. (5) In summary, published data are inadequate to permit scientific conclusions. 2006-2007 Update A search of the MEDLINE database for the period of September 2005 through December 2006 did not identify any evidence that would alter the previous conclusion. One study with 60 patients reported the clinical healing rate along with the number and concentration of progenitor cells that were transplanted for the treatment of nonunion. (6) The investigators found a significant relation between bone union and the number of progenitor cells that had been aspirated and concentrated prior to treatment. The development of appropriate graft materials is evolving; randomized controlled trials comparing outcomes of percutaneous injection of bone marrow aspirate with bone grafts are lacking. 2008 Update A search of the MEDLINE database was performed for the period of January 2007 through April 2008. The search identified 1 randomized trial from the multicenter Simple Bone Cyst Trial Group. (7) This study compared percutaneous bone marrow with methylprednisolone injection for the treatment of bone cysts in 90 children. At 2-year follow-up, 23% of the cysts in the bone marrow group (87% follow-up) had healed, compared with 42% in the steroid group (84% follow-up); the odds ratio was 4.9. There was no difference between the two groups in pain function, or adverse events. Subsequent fracture was associated with cyst healing at 2 years. Based on the available evidence, percutaneous treatment of bone cysts with bone marrow has not been shown to be as beneficial as the established alternative. This treatment is considered to be investigational.

Population Reference No. 1 

Individuals with problem fractures or osseous defects treted with Autologous bone marrow aspirate

Population Reference No. 2 

Individuals with problem fractures or osseous defects treated with Autologous bone marrow aspirate + demineralized bone matrix

Supplemental Information

N/A

Practice Guidelines and Position Statements

N/A

Medicare National Coverage

N/A

References

1. www.wmt.com

2. Connolly JF. Injectable bone marrow preparations to stimulate osteogenic repair. Clin Orthop Rel Res 1995; (313):8-18.

3. Skoff HD. Bone marrow/allograft component therapy. A clinical trial. Am J Orthop 1995; 24(1):40-7. 4. Wilkins RM, Chimenti BT, Rifkin RM. Percutaneous treatment of long bone nonunions: the use of autologous bone marrow and allograft bone matrix. Orthopedics 2003; 26(5 suppl):s549-54.

5. Goel A, Sangwan SS, Siwach RC et al. Percutaneous bone marrow grafting for the treatment of tibial non-union. Injury 2005; 36(1):203-6.

6. Hernigou P, Poignard A, Beaujean F et al. Percutaneous autologous bone-marrow grafting for nonunions. Influence of the number and concentration of progenitor cells. J Bone Joint Surg Am 2005; 87(7):1430-7.

Codes

Appplicable Modifiers

N/A

Policy History