A Mechanistic and Preclinical Assessment of BioRestore Bioactive Glass as a Synthetic Bone Graft Extender and Substitute for Osteoinduction and Spine Fusion.

STUDY DESIGN: Preclinical animal study. OBJECTIVE: Evaluate the osteoinductivity and bone regenerative capacity of BioRestore bioactive glass. SUMMARY OF BACKGROUND DATA: BioRestore is a Food and Drug Administration (FDA)-approved bone void filler that has not yet been evaluated as a bone graft extender or substitute for spine fusion. METHODS: In vitro and in vivo methods were used to compare BioRestore with other biomaterials for the capacity to promote osteodifferentiation and spinal fusion. The materials evaluated (1) absorbable collagen sponge (ACS), (2) allograft, (3) BioRestore, (4) Human Demineralized Bone Matrix (DBM), and (5) MasterGraft. For in vitro studies, rat bone marrow-derived stem cells (BMSC) were cultured on the materials in either standard or osteogenic media (SM, OM), followed by quantification of osteogenic marker genes (Runx2, Osx, Alpl, Bglap, Spp1) and alkaline phosphatase (ALP) activity. Sixty female Fischer rats underwent L4-5 posterolateral fusion (PLF) with placement of 1 of 5 implants: (1) ICBG from syngeneic rats; (2) ICBG+BioRestore; (3) BioRestore alone; (4) ICBG+Allograft; or (5) ICBG+MasterGraft. Spines were harvested 8 weeks postoperatively and evaluated for bone formation and fusion via radiography, blinded manual palpation, microCT, and histology. RESULTS: After culture for 1 week, BioRestore promoted similar expression levels of Runx2 and Osx to cells grown on DBM. At the 2-week timepoint, the relative ALP activity for BioRestore-OM was significantly higher (P<0.001) than that of ACS-OM and DBM-OM (P<0.01) and statistically equivalent to cells grown on allograft-OM. In vivo, radiographic and microCT evaluation showed some degree of bridging bone formation in all groups tested, with the exception of BioRestore alone, which did not produce successful fusions. CONCLUSIONS: This study demonstrates the capacity of BioRestore to promote osteoinductivity in vitro. In vivo, BioRestore performed similarly to commercially available bone graft extender materials but was incapable of producing fusion as a bone graft substitute. LEVEL OF EVIDENCE: Level V.

Sex-based Difference in Response to Recombinant Human Bone Morphogenetic Protein-2 in a Rat Posterolateral Fusion Model.

STUDY DESIGN: This was a preclinical study. OBJECTIVE: Evaluate sex-dependent differences in the bone healing response to recombinant human bone morphogenetic protein-2 (rhBMP-2) in a rat posterolateral spinal fusion model. SUMMARY OF BACKGROUND DATA: Minimal and conflicting data exist concerning potential sex-dependent differences in rhBMP-2-mediated bone regeneration in the context of spinal fusion. MATERIALS AND METHODS: Forty-eight female and male Sprague-Dawley rats (N=24/group), underwent L4-L5 posterolateral fusion with bilateral placement of an absorbable collagen sponge, each loaded with 5 µg of bone morphogenetic protein-2 (10 µg/animal). At eight weeks postoperative, 10 specimens of each sex were tested in flexion-extension with quantification of range of motion and stiffness. The remaining specimens were evaluated for new bone growth and successful fusion via radiography, blinded manual palpation and microcomputed tomography (microCT). Laboratory microCT quantified bone microarchitecture, and synchrotron microCT examined bone microstructure at the 1 µm level. RESULTS: Manual palpation scores differed significantly between sexes, with mean fusion scores of 2.4±0.4 in females versus 3.1±0.6 in males ( P <0.001). Biomechanical stiffness did not differ between sexes, but range of motion was significantly greater and more variable for females versus males (3.7±5.6° vs. 0.27±0.15°, P <0.005, respectively). Laboratory microCT showed significantly smaller volumes of fusion masses in females versus males (262±87 vs. 732±238 mm 3 , respectively, P <0.001) but significantly higher bone volume fraction (0.27±0.08 vs. 0.12±0.05, respectively, P <0.001). Mean trabecular thickness was not different, but trabecular number was significantly greater in females (3.1±0.5 vs. 1.5±0.4 mm -1 , respectively, P <0.001). Synchrotron microCT showed fine bone structures developing in both sexes at the eight-week time point. CONCLUSIONS: This study demonstrates sex-dependent differences in bone regeneration induced by rhBMP-2. Further investigation is needed to uncover the extent of and mechanisms underlying these sex differences, particularly at different doses of rhBMP-2.

Resource utilization for non-operative cervical radiculopathy: Management by surgeons versus non-surgeons.

OBJECTIVES: To compare the estimated resource utilization for non-operative treatment of cervical radiculopathy if managed by surgeons versus non-surgeons. PATIENTS AND METHODS: A Cervical Spine Research Society-sponsored survey was administered at a national spine surgery conference to surgeons and non-surgeons, as classified above. The survey asked questions regarding resource utilization and perceived costs for the "average patient" with cervical radiculopathy managed non-operatively. Resource utilization and perceived costs were compared between surgeon and non-surgeon participants, and between private practice and academic and/or hybrid groups that combine academic and private practices. RESULTS: In total, 101 of the 125 conference attendees participated in the survey (return rate 80.8%, of which 60% were surgeons). Surgeon and non-surgeon estimates for duration of non-operative care did not differ (3.3 versus 4.2 months, p=0.071). Estimates also did not differ for estimated number of physical therapy visits (10.5 versus 10.5, p=0.983), cervical injections (1.4 versus 1.7, p=0.272), chiropractic visits (3.1 versus 3.7, p=0.583), or perceived days off from work (14.9 versus 16.3, p=0.816). The only difference identified was that surgeon estimates of the number of physician visits while providing non-operative care were lower than non-surgeon estimates (3.2 versus 4.0, p=0.018). In terms of estimated costs, surgeon and non-surgeon were mostly similar (only difference being that surgeon estimates for the total cost of physician visits per patient were lower than non-surgeon estimates ($382 versus $579, p=0.007). Surgeon estimates for the percent of their patients that go on to receive surgery within 6 months were higher than non-surgeon estimates (28.6% versus 18.8%, p=0.018). Similarly, surgeon estimates for the percent of their patients to go on to receive surgery within 2 years were higher than non-surgeon estimates (37.8% versus 24.8%, p=0.013). Academic/hybrid and private practice group resource utilization estimates and costs were also compared, and no significant differences were found in any comparisons. Additionally, no significant differences were found in these groups for duration of non-operative care, or the estimates of the percent of patients who go on to receive surgery within 6 months or two years. CONCLUSION: These data suggest that patients with cervical radiculopathy managed by surgeons and those by non-surgeons have overall similar resource utilization during a non-operative trial. This suggests that relatively similar care is provided regardless of whom initiates the non-operative trial (surgeon or non-surgeon). Although surgeons thought their patients more likely to undergo surgery following a non-operative trial, this may be a bias due to patient referral-specifically, surgeons may be more likely than non-surgeons to manage patients with more severe or longer-standing radiculopathy.

The Effect of Dynamic Versus Static Plating Systems on Fusion Rates and Complications in 1-Level and/or 2-Level Anterior Cervical Discectomy and Fusion: A Systematic Review.

STUDY DESIGN: A systematic review. OBJECTIVE: To determine the effect of plate design on fusion rates in patients undergoing a 1- and 2-level anterior cervical discectomy and fusion (ACDF). METHODS: Articles published between January 1, 2002 and January 1, 2015 were systematically reviewed to determine the fusion rate of 1- and 2-level ACDFs using either a fully constrained or semiconstrained locking plate. Additional variables that were collected included the number of levels, the type of graft/cage used, the study design, the method for determining fusion, and complications. RESULTS: Fifty-two articles and 3053 patients were included. No significant difference in the fusion rate for 1- and 2-level ACDF using a fully constrained plate (96.1%) and a semiconstrained plate (95.29%) was identified (P=0.84). No difference (P=0.85) in the total complication rate between fully constrained plates (3.20%) and semiconstrained plates (3.66%), or the rate of complications that required a revision (2.17% vs. 2.41%, P=0.82) was identified. However, semiconstrained plates had a nonsignificant increase in total dysphagia rates (odds ratio=1.660, P=0.28) and short-term dysphagia rates (odds ratio=2.349, P=0.10). CONCLUSIONS: In patients undergoing a 1- or 2-level ACDF, there is no significant difference in the fusion or complication rate between fully constrained plates and semiconstrained plates. LEVEL OF EVIDENCE: Level II-systematic review.

A Systematic Review of the Treatment of Geriatric Type II Odontoid Fractures.

BACKGROUND: Odontoid fractures are the most common cervical spine fracture in the geriatric population; however, the treatment of type II odontoid fractures in this age group is controversial. OBJECTIVE: To compare the short-term (<3 months) mortality, long-term (≥12 months) mortality, and complication rates of patients >60 years of age with a type II odontoid fracture managed either operatively or nonoperatively. METHODS: We performed a systematic review of literature published between January 1, 2000, and February 1, 2015, related to the treatment of type II odontoid fractures in patients >60 years of age. An analysis of short-term mortality, long-term mortality, and the occurrence of complications was performed. RESULTS: A total of 452 articles were identified, of which 21 articles with 1233 patients met the inclusion criteria. Short-term mortality (odds ratio, 0.43; 95% confidence interval, 0.30-0.63) and long-term mortality (odds ratio, 0.47; 95% confidence interval, 0.34-0.64) were lower in patients who underwent surgical treatment than in those who had nonsurgical treatment, and there were no significant differences in the rate of complications (odds ratio, 1.01; 95% confidence interval, 0.63-1.63). Surgical approach (posterior vs anterior) showed no significant difference in mortality or complication rate. Similarly, no difference in mortality or complication rate was identified with hard collar or a halo orthosis immobilization. CONCLUSION: The current literature suggests that well-selected patients >60 years of age undergoing surgical treatment for a type II odontoid fracture have a decreased risk of short-term and long-term mortality without an increase in the risk of complications.