Table 1.
Summary of mechanism, efficacy, and unsolved challenges of therapeutics for the enhancement of spinal fusion. BMPs: Bone morphogenetic proteins; MSC: Mesenchymal stem cell; DBM: Demineralized bone matrix; BMA: Bone marrow aspirate; PRP: Platelet-rich plasma.
| Therapeutics | Mechanism | Efficacy | Unsolved challenges |
|---|---|---|---|
| Osteobiologics | |||
| BMPs | Stimulate osteogenic differentiation of MSCs (osteoinduction) and new bone formation [16] | Superior effect in combination with autograft bone | Dosage and safety concerns, lack of slow-release carrier |
| Other Growth Factors | NELL-1: Induce MSCs expansion and new bone formation [35] Activin A: Stimulate osteogenic differentiation of MSCs and new bone formation [36] |
Some have shown efficacy in animal models | Lack of clinical data in human |
| Biological Factor-containing Bone Expanders | |||
| DBM | Offer osteoconductive and osteoinductive capacities [39] | Non-inferior to autograft bone | Lack of mechanical strength and osteoinductive capacity |
| BMA | Offer osteoinductive capacity with cytokines and growth factors secreted by cells [40] | Non-inferior to autograft bone | Intraoperative leakage and lack of mechanical strength |
| PRP | Offer osteoinductive capacities with growth factors [43] | More than five times of concentration as it is in the peripheral blood to take effect | Inconsistent concentration among samples |
| Systemic Therapies | |||
| Bisphosphonates | Inhibit osteolysis and increase bone density [47] | Do not impede the spinal fusion | Low grade of evidence |
| Teriparatide | Stimulate bone formation [[49], [50]] | Correlated with a higher spinal fusion rate | Lack of evidence for routine use |
| Denosumab | Inhibit osteolysis and increase bone density [54] | Correlated with a higher spinal fusion rate | Lack of evidence for routine use |
| Romosozumab | Dual effect | No reports | Unknow efficacy |
| Other Therapies | |||
| Cell and Gene Therapies | |||
| Stem Cells | Facilitate spinal fusion with their osteogenic properties [56] | Not convincing in spinal fusion | GMP facility needed |
| Gene Therapy | Provide a vector expressing growth factors [62] | Provide expression of osteoinductive proteins | Adverse reactions are common |
| Controlled-release Formulation and Carriers | |||
| New Formulations | Controlled release of osteoinductive molecules [63] | Presently not well developed in spinal fusion | Adjustment of releasing profile and sterile |
| Potential Carriers | Controlled release of osteoinductive molecules provide instant mechanical strength [66] | Presently not well developed in spinal fusions, especially for macro-molecules | Optimization of releasing profile and stable combination with the molecule of interest |