METHODS: Guideline.
OBJECTIVE: To develop an international guideline (AOGO) about the use of osteobiologics in anterior cervical discectomy and fusion (ACDF) for treating degenerative spine conditions.
METHODS: The guideline development process was guided by AO Spine Knowledge Forum Degenerative (KF Degen) and followed the Guideline International Network McMaster Guideline Development Checklist. The process involved 73 participants with expertise in degenerative spine diseases and surgery from 22 countries. Fifteen systematic reviews were conducted addressing respective key topics and evidence was collected. The methodologist compiled the evidence into GRADE Evidence-to-Decision frameworks. Guideline panel members judged the outcomes and other criteria and made the final recommendations through consensus.
RESULTS: Five conditional recommendations were created. A conditional recommendation is about the use of allograft, autograft or a cage with an osteobiologic in primary ACDF surgery. Other conditional recommendations are about the use of osteobiologic for single- or multi-level ACDF, and for hybrid construct surgery. It is suggested that surgeons use other osteobiologics rather than human bone morphogenetic protein-2 (BMP-2) in common clinical situations. Surgeons are recommended to choose 1 graft over another or 1 osteobiologic over another primarily based on clinical situation, and the costs and availability of the materials.
CONCLUSIONS: This AOGO guideline is the first to provide recommendations for the use of osteobiologics in ACDF. Despite the comprehensive searches for evidence, there were few studies completed with small sample sizes and primarily as case series with inherent risks of bias. Therefore, high-quality clinical evidence is demanded to improve the guideline.

OBJECTIVE: With the advances in biological technologies over the past 20 years, a number of new therapies to promote bone healing have been introduced. Particularly in the spinal surgery field, more unprecedented biological therapeutics become available to enhance spinal fusion success rate along with advanced instrumentation approaches. Yet surgeons may not have been well informed about their safety and efficacy profiles in order to improve clinical practices. Therefore there is a need to summarize the evidence and bring the latest progress to surgeons for better clinical services for patients.
METHODS: We comprehensively reviewed the literatures in regard to the biological therapeutics for enhancement of spinal fusion published in the last two decades.
RESULTS: Autograft bone is still the gold standard for bone grafting in spinal fusion surgery due to its good osteoconductive, osteoinductive, and osteogenic abilities. Accumulating evidence suggests that adding rhBMPs in combination with autograft effectively promotes the fusion rate and improves surgical outcomes. However, the stimulating effect on spinal fusion of other growth factors, including PDGF, VEGF, TGF-beta, and FGF, is not convincing, while Nell-1 and activin A exhibited preliminary efficacy. In terms of systemic therapeutic approaches, the osteoporosis drug Teriparatide has played a positive role in promoting bone healing after spinal surgery, while new medications such as denosumab and sclerostin antibodies still need further validation. Currently, other treatment, such as controlled-release formulations and carriers, are being studied for better releasing profile and the administration convenience of the active ingredients.
CONCLUSIONS: As the world\'s population continues to grow older, the number of spinal fusion cases grows substantially due to increased surgical needs for spinal degenerative disease (SDD). Critical advancements in biological therapeutics that promote spinal fusion have brought better clinical outcomes to patients lately. With the accumulation of higher-level evidence, the safety and efficacy of present and emerging products are becoming more evident. These emerging therapeutics will shift the landscape of perioperative therapy for the enhancement of spinal fusion.