ISASS Recommendations and Coverage Criteria for Bone Graft Substitutes used in Spinal Surgery
Published by Nikki Golden / January 30, 2019
Over the past 3 decades, there has been an increased interest in bone grafting materials as these materials have become a vital part of most spinal procedures. Unlike other areas of orthopedics, spinal surgery often requires grafting procedures to induce de novo bone in an area stabilized by metal devices. When considering potential graft materials, assuming an adequate blood supply, it is important to note that a successful graft needs to have at least 2 of the following: cells, signal, and/or matrix. Cells refers to the process of osteogenesis that is deﬁned as cellular formation of new bone. These are dedicated cells in the area of the graft, such as osteoblasts or stem cells, that enter the osteoblastic lineage and ultimately form new bone. The signal, or osteoinduction, is orchestrated by bioactive molecules, primarily low-molecular-weight members of the transforming-growth-factor–b family that actively recruit mesenchymal cells, and stimulate them to differentiate into bone-forming cells for osseous repair. The matrix is the scaffolding that permits cell inﬁltration and in-growth of new host bone that is referred to as osteoconduction. The combination of these properties can either come from materials introduced to the site or those recruited from the host.
When evaluating the complex landscape of grafting materials, it is difﬁcult to compare the options as the regulatory pathways, mechanisms of action, and supportive clinical evidence of the materials vary widely. In the 1990s, demineralized bone matrix (DBM) and synthetic bone grafts became widely available. Whereas DBMs were initially classiﬁed as tissue product and not a medical device, synthetics were classiﬁed as medical devices subject to the 510(k) pathway. In 2006, the regulatory pathway signiﬁcantly changed in the United States regarding DBMs, with the Food and Drug Administration (FDA) reclassifying versions of DBMs with a non- tissue carrier to require 510(k) clearance, while leaving pure DBM versions exempt as human tissue products. Further, in 2001, the ﬁrst Class III medical device grafting material was approved by the FDA, bone morphogenetic protein (BMP)-2. In the mid- 2000s, annual sales of BMP-2 rose to approach $900 million per year, but, in response to new data and the medico-legal concerns, revenues declined to less than $450 million annually in 2017. Lastly, an area almost nonexistent a decade ago has now gained almost 10% of the market: cell-based matrices. These matrices are a broad category of materials marketed as human cell or tissue products (HCT/Ps) claimed to contain stem cells and related factors. (Note: HCT/P status requires that the market product’s mechanism of action not ‘‘be dependent on the metabolic activity of living cells.’’)
Although autologous bone grafting (ABG), most commonly from the iliac crest or local bone, is the classical standard, this guidance focuses on the alternatives to ABG. This guidance is separated into 6 major categories: (1) nonstructural allograft, (2) demineralized bone grafts, (3) cellular allografts, (4) synthetic bone grafts, (5) autologous cellular grafts, and (6) Class III, drug-device combination products (Table 1).