Reference Citation Analysis: Find an Article, Find a Category, Find a Journal, Find a Scholar

For: Rihn JA, Makda J, Hong J, Patel R, Hilibrand AS, Anderson DG, Vaccaro AR, Albert TJ. The use of RhBMP-2 in single-level transforaminal lumbar interbody fusion: a clinical and radiographic analysis. Eur Spine J. 2009;18:1629-1636. [PMID: 19475434 DOI: 10.1007/s00586-009-1046-1] [Citation(s) in RCA: 60] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [What about the content of this article? (0)] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/28/2008] [Revised: 02/16/2009] [Accepted: 05/12/2009] [Indexed: 12/18/2022]

For:	Rihn JA, Makda J, Hong J, Patel R, Hilibrand AS, Anderson DG, Vaccaro AR, Albert TJ. The use of RhBMP-2 in single-level transforaminal lumbar interbody fusion: a clinical and radiographic analysis. Eur Spine J. 2009;18:1629-1636. [PMID: 19475434 DOI: 10.1007/s00586-009-1046-1] [Citation(s) in RCA: 60] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [What about the content of this article? (0)] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/28/2008] [Revised: 02/16/2009] [Accepted: 05/12/2009] [Indexed: 12/18/2022]

Number

Cited by Other Article(s)

Sgustav C, Lacheta L, Stöckle U, Akgün D, Geisel D, Park HU, Marth A, Kim S. Clinical and magnetic resonance imaging outcome after proximal hamstring tendon repair at mean 3 years follow-up. Arch Orthop Trauma Surg 2025;145:130. [PMID: 39812698 PMCID: PMC11735579 DOI: 10.1007/s00402-024-05684-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/17/2023] [Accepted: 10/08/2024] [Indexed: 01/16/2025]

Abstract

PURPOSE

The purpose of this study was to assess clinical and radiological outcome in patients after proximal hamstring tendon repair. We hypothesized that there is a significant correlation among subjective clinical outcome and interlimb asymmetries in muscle strength, fatty infiltration, and hamstring volume.

METHODS

This retrospective monocentric case series included patients with surgical repair after proximal hamstring tendon rupture. Clinical outcome was assessed utilizing: Healthy Days Core Module (CDC HRQOL-4), numeric pain rating scale (NRS), modified Harris Hip Score (mHHS), Tegner Activity Scale (TAS), return to pre-injury activity level (RTPA), and patient satisfaction score. Postoperative hamstring strength was measured using a handheld dynamometer and radiological outcome was determined by postoperative magnetic resonance imaging (MRI).

RESULTS

Twenty-seven patients with a mean age of 51.2 (± 12.6) years were available for follow-up at a mean of 41.11 (± 18.4) months. Patients state a mean of 10.6 (± 11.5) days in the unhealthy days (UHD) index and 88.9% show "good health" in the simple summary score (SSS). Mean subjective outcome scores were as follows: NRS 1.1 (± 2.4), mHHS 90.3 (± 14.8) and TAS 5.7 (± 2.2). A total of 59.3% RTPA and 88.9% state to be somewhat or very satisfied with their surgery. Mean interlimb strength ratio was 0.88 (± 0.21). MRI demonstrated a fully restored muscle-tendon unit, significantly greater fatty infiltration in the injured hamstrings (p = 0.009, d = 0.558), and a mean interlimb hamstring volume ratio of 0.94 (± 0.11). With respect to the 10% benchmark, patients had no significant asymmetries in muscle strength (p = 0.677, d = 0.084) or hamstring volume (p = 0.102, d = - 0.34). Correlation analysis revealed moderate correlation among asymmetries in strength and volume (p = 0.073, r = 0.373). In patients with the operated side inferior to the healthy side (n = 15), there was strong correlation among asymmetries in strength and volume (p = 0.002, r = 0.725). Statistically significant correlation was found between interlimb muscle volume atrophy and increase in fatty infiltration (p = 0.015, r = 0.481).

CONCLUSION

Proximal hamstring repair results in good clinical outcome with satisfactory recovery of hamstring strength and volume. Interlimb asymmetries, in terms of muscle strength, fatty infiltration, and hamstring volume do not correlate with clinical outcome.

STUDY TYPE

Retrospective cohort study; Level of evidence, 3.

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Kim SH, Park Y, Shin JW, Ha JW, Choi HM, Kim HS, Moon SH, Suk KS, Park SY, Lee BH, Kwon JW. Accelerated fusion dynamics by recombinant human bone morphogenetic protein-2 following transforaminal lumbar interbody fusion, particularly in osteoporotic conditions. Spine J 2024;24:2078-2085. [PMID: 38909911 DOI: 10.1016/j.spinee.2024.06.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/21/2024] [Revised: 06/11/2024] [Accepted: 06/13/2024] [Indexed: 06/25/2024]

Abstract

BACKGROUND CONTEXT

Early fusion is crucial in interbody procedures to minimize mechanical complications resulting from delayed union, especially for patients with osteoporosis. Bone morphogenetic proteins (BMPs) are used in spinal fusion procedures; however, limited evaluation exists regarding time-to-fusion for BMP use, particularly in patients with osteoporosis.

PURPOSE

To evaluate the difference in time-to-fusion after single-level transforaminal lumbar interbody fusion (TLIF) surgery between recombinant human bone morphogenetic protein-2 (rhBMP-2) usage and nonusage groups according to bone density.

STUDY DESIGN

Retrospective single-center cohort study.

PATIENT SAMPLE

This study enrolled 132 patients (mean age, 65.25±8.66; male patients, 40.9%) who underwent single-level TLIF for degenerative disorders between February 2012 and December 2021, with pre- and postoperative computed tomography (CT).

OUTCOME MEASURE

The interbody fusion mass and bone graft status on postoperative CT scans was obtained annually, and time-to-fusion was recorded for each patient.

METHODS

The patients were divided into 2 groups based on rhBMP-2 use during the interbody fusion procedure. Patients were further divided into osteoporosis, osteopenia, and normal groups based on preoperative L1 vertebral body attenuation values, using cutoffs of 90 and 120 Hounsfield units. It was strictly defined that fusion is considered complete when a trabecular bone bridge was formed, and therefore, the time-to-fusion was measured in years. Time-to-fusion was statistically compared between BMP group and non-BMP groups, followed by further comparison according to bone density.

RESULTS

The time-to-fusion differed significantly between BMP and non-BMP groups, with half of the patients achieving fusion within 2.5 years in the BMP group compared with 4 years in the non-BMP group (p<.001). The fusion rate varied based on bone density, with the maximum difference observed in the osteoporosis group, when half of the patients achieved fusion within 3 years in the BMP group compared to 5 years in the non-BMP group (p<.001). Subgroup analysis was conducted, revealing no significant associations between time-to-fusion and factors known to influence the fusion process, including age, gender, medical history, smoking and alcohol use, and medication history, except for rh-BMP2 use and bone density.

CONCLUSIONS

RhBMP-2 usage significantly reduced time-to-fusion in single-level TLIF, especially in patients with osteoporosis.

LEVEL OF EVIDENCE

Level III.

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Song H, Edwards C, Curto R, Perez A, Cruess C, Schell A, Park J. Does Epidural Corticosteroid Application During Spinal Surgery Reduce Postoperative Pain?: An Adjunct to Multimodal Analgesia. Clin Spine Surg 2024;37:E354-E363. [PMID: 38446588 PMCID: PMC11421561 DOI: 10.1097/bsd.0000000000001586] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/04/2023] [Accepted: 01/22/2024] [Indexed: 03/08/2024]

Abstract

STUDY DESIGN

A prospective, randomized, placebo-controlled, double-blinded study.

OBJECTIVE

To examine the effect of intraoperative epidural administration of Depo-Medrol on postoperative back pain and radiculitis symptoms in patients undergoing Transforaminal Lumbar Interbody Fusion (TLIF).

SUMMARY OF BACKGROUND DATA

Postoperative pain is commonly experienced by patients undergoing spinal fusion surgery. Adequate management of intense pain is necessary to encourage early ambulation, increase patient satisfaction, and limit opioid consumption. Intraoperative steroid application has been shown to improve postoperative pain in patients undergoing lumbar decompression surgeries. There have been no studies examining the effect of epidural steroids on both back pain and radicular pain in patients undergoing TLIF.

METHOD

In all, 151 patients underwent TLIF surgery using rh-BMP2 with 3 surgeons at a single institution. Of those, 116 remained in the study and were included in the final analysis. Based on a 1:1 randomization, a collagen sponge saturated with either Saline (1 cc) or Depo-Medrol (40 mg/1 cc) was placed at the annulotomy site on the TLIF level. Follow-up occurred on postoperative days 1, 2, 3, 7, and postoperative months 1, 2, and 3. Lumbar radiculopathy was measured by a modified symptom- and laterality-specific Visual Analog Scale (VAS) regarding the severity of back pain and common radiculopathy symptoms.

RESULTS

The patients who received Depo-Medrol, compared with those who received saline, experienced significantly less back pain on postoperative days 1, 2, 3, and 7 ( P <0.05). There was no significant difference in back pain beyond day 7. Radiculopathy-related symptoms such as leg pain, numbness, tingling, stiffness, and weakness tended to be reduced in the steroid group at most time points.

CONCLUSION

This study provides Level 1 evidence that intraoperative application of Depo-Medrol during a TLIF surgery with rh-BMP2 significantly reduces back pain for the first week after TLIF surgery. The use of epidural Depo-Medrol may be a useful adjunct to multimodal analgesia for pain relief in the postoperative period.

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Cheers GM, Weimer LP, Neuerburg C, Arnholdt J, Gilbert F, Thorwächter C, Holzapfel BM, Mayer-Wagner S, Laubach M. Advances in implants and bone graft types for lumbar spinal fusion surgery. Biomater Sci 2024;12:4875-4902. [PMID: 39190323 DOI: 10.1039/d4bm00848k] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/28/2024]

Abstract

The increasing prevalence of spinal disorders worldwide necessitates advanced treatments, particularly interbody fusion for severe cases that are unresponsive to non-surgical interventions. This procedure, especially 360° lumbar interbody fusion, employs an interbody cage, pedicle screw-and-rod instrumentation, and autologous bone graft (ABG) to enhance spinal stability and promote fusion. Despite significant advancements, a persistent 10% incidence of non-union continues to result in compromised patient outcomes and escalated healthcare costs. Innovations in lumbar stabilisation seek to mimic the properties of natural bone, with evolving implant materials like titanium (Ti) and polyetheretherketone (PEEK) and their composites offering new prospects. Additionally, biomimetic cages featuring precisely engineered porosities and interconnectivity have gained traction, as they enhance osteogenic differentiation, support osteogenesis, and alleviate stress-shielding. However, the limitations of ABG, such as harvesting morbidities and limited fusion capacity, have spurred the exploration of sophisticated solutions involving advanced bone graft substitutes. Currently, demineralised bone matrix and ceramics are in clinical use, forming the basis for future investigations into novel bone graft substitutes. Bioglass, a promising newcomer, is under investigation despite its observed rapid absorption and the potential for foreign body reactions in preclinical studies. Its clinical applicability remains under scrutiny, with ongoing research addressing challenges related to burst release and appropriate dosing. Conversely, the well-documented favourable osteogenic potential of growth factors remains encouraging, with current efforts focused on modulating their release dynamics to minimise complications. In this evidence-based narrative review, we provide a comprehensive overview of the evolving landscape of non-degradable spinal implants and bone graft substitutes, emphasising their applications in lumbar spinal fusion surgery. We highlight the necessity for continued research to improve clinical outcomes and enhance patient well-being.

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Affiliation(s)

Giles Michael Cheers Department of Orthopaedics and Trauma Surgery, Musculoskeletal University Center Munich (MUM), LMU University Hospital, LMU Munich, Marchioninistraße 15, 81377 Munich, Germany.
Lucas Philipp Weimer Department of Orthopaedics and Trauma Surgery, Musculoskeletal University Center Munich (MUM), LMU University Hospital, LMU Munich, Marchioninistraße 15, 81377 Munich, Germany.
Carl Neuerburg Department of Orthopaedics and Trauma Surgery, Musculoskeletal University Center Munich (MUM), LMU University Hospital, LMU Munich, Marchioninistraße 15, 81377 Munich, Germany.
Jörg Arnholdt Department of Orthopaedics and Trauma Surgery, Musculoskeletal University Center Munich (MUM), LMU University Hospital, LMU Munich, Marchioninistraße 15, 81377 Munich, Germany.
Fabian Gilbert Department of Orthopaedics and Trauma Surgery, Musculoskeletal University Center Munich (MUM), LMU University Hospital, LMU Munich, Marchioninistraße 15, 81377 Munich, Germany.
Christoph Thorwächter Department of Orthopaedics and Trauma Surgery, Musculoskeletal University Center Munich (MUM), LMU University Hospital, LMU Munich, Marchioninistraße 15, 81377 Munich, Germany.
Boris Michael Holzapfel Department of Orthopaedics and Trauma Surgery, Musculoskeletal University Center Munich (MUM), LMU University Hospital, LMU Munich, Marchioninistraße 15, 81377 Munich, Germany.
Susanne Mayer-Wagner Department of Orthopaedics and Trauma Surgery, Musculoskeletal University Center Munich (MUM), LMU University Hospital, LMU Munich, Marchioninistraße 15, 81377 Munich, Germany.
Markus Laubach Department of Orthopaedics and Trauma Surgery, Musculoskeletal University Center Munich (MUM), LMU University Hospital, LMU Munich, Marchioninistraße 15, 81377 Munich, Germany. Australian Research Council (ARC) Training Centre for Multiscale 3D Imaging, Modelling and Manufacturing (M3D Innovation), Queensland University of Technology, Brisbane, QLD 4000, Australia

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Son JI, Lee YS, Ko MJ, Wui SH, Park SW. Effect of Mixture of Recombinant Human Bone Morphogenic Protein-2 and Demineralized Bone Matrix in Lateral Lumbar Interbody Fusion. J Korean Neurosurg Soc 2024;67:354-363. [PMID: 37850225 PMCID: PMC11079555 DOI: 10.3340/jkns.2023.0136] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2023] [Revised: 09/21/2023] [Accepted: 10/11/2023] [Indexed: 10/19/2023] Open

Abstract

OBJECTIVE

This study aims to determine the optimal dose of recombinant-human bone morphogenic protein-2 (rhBMP-2) for successful bone fusion in minimally invasive lateral lumbar interbody fusion (MIS LLIF). Previous studies show that rhBMP is an effective alternative to autologous iliac crest bone graft, but the optimal dose remains uncertain. The study analyzes the fusion rates associated with different rhBMP doses to provide a recommendation for the optimal dose in MIS LLIF.

METHODS

Ninety-three patients underwent MIS LLIF using demineralized bone matrix (DBM) or a mixture of rhBMP-2 and DBM as fusion material. The group was divided into the following three groups according to the rhBMP-2 usage : group A, only DBM was used (n=27); group B, 1 mg of rhBMP-2 per 5 mL of DBM paste (n=41); and group C, 2 mg of rhBMP-2 per 5 mL of DBM paste (n=25). Demographic data, clinical outcomes, postoperative complication and fusion were assessed.

RESULTS

At 12 months post-surgery, the overall fusion rate was 92.3% according to Bridwell fusion grading system. Groups B and C, who received rhBMP-2, had significantly higher fusion rates than group A, who received only DBM. However, there was no significant increase in fusion rate when the rhBMP-2 dosage was increased from group B to group C. The groups B and C showed significant improvement in back pain and Oswestry disability index compared to the group A. The incidence of screw loosening was decreased in groups B and C, but there was no significant difference in the occurrence of other complications.

CONCLUSION

Usage of rhBMP-2 in LLIF surgery leads to early and increased final fusion rates, which can result in faster pain relief and return to daily activities for patients. The benefits of using rhBMP-2 were not significantly different between the groups that received 1 mg/5 mL and 2 mg/5 mL of rhBMP-2. Therefore, it is recommended to use 1 mg of rhBMP-2 with 5 mL of DBM, taking both economic and clinical aspects into consideration.

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Kim E, Brennan M, Margabandu P, Oska N, Cielito Robles M, Rademacher A, Telemi E, Mansour T, Chang VW. Bone Grafting Options for Single-Level TLIF: So Many Options, What Is the Evidence? Int J Spine Surg 2023;17:S53-S60. [PMID: 38124018 PMCID: PMC10753332 DOI: 10.14444/8561] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2023] [Revised: 09/08/2023] [Accepted: 10/31/2023] [Indexed: 12/23/2023] Open

Abstract

BACKGROUND

This review seeks to investigate the clinically relevant bone graft materials in single-level transforaminal lumbar interbody fusion (TLIF) procedures as defined by (1) primary outcomes (ie, fusion rates and complication rates) and (2) patient-reported outcomes (ie, visual analog scale [VAS] and Oswestry disability index [ODI]). Because of the advantages in stimulating bone growth, autologous bone grafts such as the iliac crest bone graft (ICBG) have been the gold standard. Numerous alternatives to ICBG have been introduced. Understanding the risks and benefits of bone graft options is vital to optimizing patient care.

METHODS

A PubMed search was performed for all clinical studies published between January 2008 and March 2023 that referenced the single-level TLIF procedure as well as one of the following grafts: autograft, allograft, bone morphogenetic protein (BMP), demineralized bone matrix, or mesenchymal stem cells (MSCs). Case studies and reports were excluded.

RESULTS

Twenty-eight studies met the inclusion criteria. Studies from the PubMed search demonstrated similarly high fusion rates across nearly all graft materials, the lone exception being MSCs, which showed lower fusion rates. ICBG grafts experienced higher rates of postoperative graft site pain. The BMP graft material had high rates of radiculitis, heterogeneous ossification, and vertebral osteolysis. Patients saw an overall improvement in VAS and ODI scores with all graft materials.

CONCLUSION

Local autografts and ICBG have been the most studied. Fusion rates during single-level TLIF were similar across all graft materials except MSCs. Patient-reported pain levels improved after TLIF surgery regardless of the type of grafts used. While BMP implants have shown promising benefits, they have introduced a new array of complications not normally seen in ICBG implants. The study is limited by the lack of evidence of certain graft materials as well as nonuniformity in metrics evaluating the efficacy of graft materials.

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Keum BR, Kim HJ, Kim GH, Chang DG. Osteobiologies for Spinal Fusion from Biological Mechanisms to Clinical Applications: A Narrative Review. Int J Mol Sci 2023;24:17365. [PMID: 38139194 PMCID: PMC10743675 DOI: 10.3390/ijms242417365] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2023] [Revised: 12/01/2023] [Accepted: 12/03/2023] [Indexed: 12/24/2023] Open

Gonzalez GA, Porto G, Tecce E, Oghli YS, Miao J, O'Leary M, Chadid DP, Vo M, Harrop J. Advances in diagnosis and management of atypical spinal infections: A comprehensive review. NORTH AMERICAN SPINE SOCIETY JOURNAL 2023;16:100282. [PMID: 37915965 PMCID: PMC10616400 DOI: 10.1016/j.xnsj.2023.100282] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/30/2023] [Revised: 07/28/2023] [Accepted: 09/24/2023] [Indexed: 11/03/2023]

Park S, Jeong YH, Ha BJ, Yoo BS, Kim SH, Lee CK, Yi S, Ha Y, Kim KN, Shin DA. Fusion rate of Escherichia coli-derived recombinant human bone morphogenetic protein-2 compared with local bone autograft in posterior lumbar interbody fusion for degenerative lumbar disorders. Spine J 2023;23:1877-1885. [PMID: 37516282 DOI: 10.1016/j.spinee.2023.07.017] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2023] [Revised: 07/16/2023] [Accepted: 07/18/2023] [Indexed: 07/31/2023]

Abstract

BACKGROUND CONTEXT

The use of recombinant human bone morphogenetic proteins-2 (rhBMP-2) for spinal fusion has been reported to be effective. However, most studies have focused on posterolateral and anterior lumbar interbody fusion, and few have investigated posterior lumbar interbody fusion (PLIF).

PURPOSE

This study aimed to determine the effectiveness and safety of the delivery of Escherichia coli-derived rhBMP-2 (E.BMP-2) with hydroxyapatite (HA) and β-tricalcium phosphate (β-TCP) poloxamer hydrogel composite carriers for PLIF.

STUDY DESIGN

A retrospective study.

PATIENT SAMPLE

Patients who underwent 1 to 3 levels of PLIF for lumbar degenerative disc disorders between 2015 and 2020 with a follow-up of ≥1 year were enrolled. In total, 254 patients (357 levels) were included in the analysis. The evaluation was performed at each segment level. In the E.BMP-2 group, 160 patients (221 levels) received autologous local bone with E.BMP-2 (maximum 0.5 mg/level), and in the control group, 94 patients (136 levels) received only local bone graft.

OUTCOME MEASURES

The primary outcome of this study was to compare the X-ray and CT fusion rates between the two groups. Secondary outcomes included analysis of the patients' clinical outcomes and postoperative complications on CT scans.

METHODS

Clinical evaluations were performed using a visual analog scale for back pain, the Oswestry Disability Index for disability, and physical and mental component summaries of the Short Form 36-Item Form Health Survey to assess functional effects and quality of life. The fusion was evaluated using radiography and CT. On radiography, solid fusion was defined when the difference between extension and flexion was less than 5°. On CT, solid fusion was defined when the upper and lower vertebral bodies were connected by the trabecular bone (bone bridge formation). In addition, complications such as osteolysis, cage subsidence, and screw loosening were investigated using CT.

RESULTS

All clinical results for low back pain, disability, and quality of life in both groups were excellent and showed statistically significant improvements compared with baseline (p<.0001). According to the X-ray evaluations, fusion was achieved in 92.31% (204/221) of the patients in the E.BMP-2 group and 82.35% (112/136) of the patients in the control group (p=.0041). According to the CT evaluations, the fusion rates were 93.21% (206/221) and 88.24% (120/136) in the E.BMP-2 and control groups (p=.1048), respectively. Except for screw loosening, which had a significantly higher incidence in the control group (p=.0014), the rates of most postoperative complications were not significantly different between the groups.

CONCLUSIONS

This study demonstrated that the adjunctive use of a low dose of E.BMP-2 with HA and β-TCP hydrogel can effectively promote bone fusion, making it a promising option for patients with limited autograft availability or compromised bone quality in PLIF.

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Affiliation(s)

Sangman Park Department of Neurosurgery, Spine and Spinal Cord Institute, Severance Hospital, Yonsei University College of Medicine, 50-1, Yonsei-ro, Seodaemun-gu, Seoul, Republic of Korea
Yeong Ha Jeong Department of Neurosurgery, Spine and Spinal Cord Institute, Severance Hospital, Yonsei University College of Medicine, 50-1, Yonsei-ro, Seodaemun-gu, Seoul, Republic of Korea
Byeong Jin Ha Department of Neurosurgery, Spine and Spinal Cord Institute, Severance Hospital, Yonsei University College of Medicine, 50-1, Yonsei-ro, Seodaemun-gu, Seoul, Republic of Korea
Beom Seok Yoo Department of Neurosurgery, Spine and Spinal Cord Institute, Severance Hospital, Yonsei University College of Medicine, 50-1, Yonsei-ro, Seodaemun-gu, Seoul, Republic of Korea
Soo-Heon Kim Department of Neurosurgery, Spine and Spinal Cord Institute, Severance Hospital, Yonsei University College of Medicine, 50-1, Yonsei-ro, Seodaemun-gu, Seoul, Republic of Korea
Chang Kyu Lee Department of Neurosurgery, Spine and Spinal Cord Institute, Severance Hospital, Yonsei University College of Medicine, 50-1, Yonsei-ro, Seodaemun-gu, Seoul, Republic of Korea
Seong Yi Department of Neurosurgery, Spine and Spinal Cord Institute, Severance Hospital, Yonsei University College of Medicine, 50-1, Yonsei-ro, Seodaemun-gu, Seoul, Republic of Korea
Yoon Ha Department of Neurosurgery, Spine and Spinal Cord Institute, Severance Hospital, Yonsei University College of Medicine, 50-1, Yonsei-ro, Seodaemun-gu, Seoul, Republic of Korea
Keung Nyun Kim Department of Neurosurgery, Spine and Spinal Cord Institute, Severance Hospital, Yonsei University College of Medicine, 50-1, Yonsei-ro, Seodaemun-gu, Seoul, Republic of Korea
Dong Ah Shin Department of Neurosurgery, Spine and Spinal Cord Institute, Severance Hospital, Yonsei University College of Medicine, 50-1, Yonsei-ro, Seodaemun-gu, Seoul, Republic of Korea.

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Takayama T, Imamura K, Yamano S. Growth Factor Delivery Using a Collagen Membrane for Bone Tissue Regeneration. Biomolecules 2023;13:biom13050809. [PMID: 37238679 DOI: 10.3390/biom13050809] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2023] [Revised: 05/01/2023] [Accepted: 05/08/2023] [Indexed: 05/28/2023] Open

Bi Z, Shi X, Liao S, Li X, Sun C, Liu J. Strategies of immobilizing BMP-2 with 3D-printed scaffolds to improve osteogenesis. Regen Med 2023;18:425-441. [PMID: 37125508 DOI: 10.2217/rme-2022-0222] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/02/2023] Open

Abd El Maksoud WM, Abbas KS, Bawahab MA, Rayzah F, Alkorbi SM, Alfaifi AG, Alqahtani AN, Alahmari AF, Alotaibi TB. Prevalence of Obstructed Defecation among Patients Who Underwent Hemorrhoidectomy and Correlation between Preoperative Constipation Score and Postoperative Patients' Satisfaction: A Prospective Study in Two Centers. Healthcare (Basel) 2023;11:healthcare11050759. [PMID: 36900764 PMCID: PMC10001578 DOI: 10.3390/healthcare11050759] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2022] [Revised: 02/05/2023] [Accepted: 03/03/2023] [Indexed: 03/08/2023] Open

Abstract

BACKGROUND AND OBJECTIVES

obstructed defecation syndrome (ODS) is a common but underestimated condition that may affect the outcomes after hemorrhoidectomy. Therefore, the aim of this study was to determine the prevalence of obstructed defecation syndrome (ODS) among patients who underwent hemorrhoidectomy and to assess the correlation between preoperative constipation score and postoperative patients' satisfaction.

MATERIALS AND METHODS

This prospective study included adult patients who underwent hemorrhoidectomy for 3rd and 4th-grade hemorrhoidal diseases. All participant patients underwent an assessment of functional OD severity by the Agachan-Wexner Constipation Scoring System. All patients were subjected to conventional hemorrhoidectomy. At 6 months postoperatively, patients were assessed again for their constipation score and postoperative patients' satisfaction.

RESULTS

The study included 120 patients (62 males and 58 females) with a mean age of 38.7 ± 12.1 years. About one-quarter of patients (24.2%) had obstructed defecation (constipation score ≥12). ODS (constipation score ≥12) was found to be significantly more among older patients, female patients, especially those with multiple pregnancies and multiple labors, and those with perineal descent. The postoperative constipation score (5.6 ± 3.3 mean ± SD) showed significant improvement (p = 0.001) compared to (9.3 ± 3.9 mean ± SD) preoperatively. Postoperative patients' satisfaction (mean 12.3 ± 3.0) at 6 months had a negative correlation with preoperative total constipation score (r = -0.035, p = 0.702).

CONCLUSIONS

The prevalence of obstructed defecation among patients with hemorrhoids was higher than reported among the general population. High preoperative constipation scores had a negative correlation with postoperative patients' satisfaction. Routine preoperative measurement of ODS can allow the detection of this particular group of patients who require a more physical and psychological evaluation, in addition to special preoperative counseling.

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Jiang F, Qi X, Wu X, Lin S, Shi J, Zhang W, Jiang X. Regulating macrophage-MSC interaction to optimize BMP-2-induced osteogenesis in the local microenvironment. Bioact Mater 2023;25:307-318. [PMID: 36844362 PMCID: PMC9947106 DOI: 10.1016/j.bioactmat.2023.02.001] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2022] [Revised: 02/01/2023] [Accepted: 02/01/2023] [Indexed: 02/12/2023] Open

Affiliation(s)

Fei Jiang Department of Prosthodontics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, No.639, Zhizaoju Road, Shanghai, 200011, China College of Stomatology, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai Engineering Research Center of Advanced Dental Technology and Materials, No.639, Zhizaoju Road, Shanghai, 200011, China Jiangsu Key Laboratory of Oral Diseases, Jiangsu Province Engineering Research Center of Stomatological Translational Medicine, Nanjing Medical University, No. 140, Han Zhong Road, Nanjing, 210029, China Department of General Dentistry, Affiliated Hospital of Stomatology, Nanjing Medical University, No. 136, Han Zhong Road, Nanjing, 210029, China
Xuanyu Qi Department of Prosthodontics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, No.639, Zhizaoju Road, Shanghai, 200011, China College of Stomatology, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai Engineering Research Center of Advanced Dental Technology and Materials, No.639, Zhizaoju Road, Shanghai, 200011, China
Xiaolin Wu Department of Prosthodontics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, No.639, Zhizaoju Road, Shanghai, 200011, China College of Stomatology, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai Engineering Research Center of Advanced Dental Technology and Materials, No.639, Zhizaoju Road, Shanghai, 200011, China
Sihan Lin Department of Prosthodontics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, No.639, Zhizaoju Road, Shanghai, 200011, China College of Stomatology, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai Engineering Research Center of Advanced Dental Technology and Materials, No.639, Zhizaoju Road, Shanghai, 200011, China
Junfeng Shi Department of Prosthodontics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, No.639, Zhizaoju Road, Shanghai, 200011, China College of Stomatology, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai Engineering Research Center of Advanced Dental Technology and Materials, No.639, Zhizaoju Road, Shanghai, 200011, China
Wenjie Zhang Department of Prosthodontics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, No.639, Zhizaoju Road, Shanghai, 200011, China College of Stomatology, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai Engineering Research Center of Advanced Dental Technology and Materials, No.639, Zhizaoju Road, Shanghai, 200011, China
Xinquan Jiang Department of Prosthodontics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, No.639, Zhizaoju Road, Shanghai, 200011, China College of Stomatology, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai Engineering Research Center of Advanced Dental Technology and Materials, No.639, Zhizaoju Road, Shanghai, 200011, China Corresponding author. Department of Prosthodontics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, No.639, Zhizaoju Road, Shanghai, 200011, China.

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Palackdkharry CS, Wottrich S, Dienes E, Bydon M, Steinmetz MP, Traynelis VC. The leptomeninges as a critical organ for normal CNS development and function: First patient and public involved systematic review of arachnoiditis (chronic meningitis). PLoS One 2022;17:e0274634. [PMID: 36178925 PMCID: PMC9524710 DOI: 10.1371/journal.pone.0274634] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2022] [Accepted: 08/31/2022] [Indexed: 11/28/2022] Open

Abstract

BACKGROUND & IMPORTANCE

This patient and public-involved systematic review originally focused on arachnoiditis, a supposedly rare "iatrogenic chronic meningitis" causing permanent neurologic damage and intractable pain. We sought to prove disease existence, causation, symptoms, and inform future directions. After 63 terms for the same pathology were found, the study was renamed Diseases of the Leptomeninges (DLMs). We present results that nullify traditional clinical thinking about DLMs, answer study questions, and create a unified path forward.

METHODS

The prospective PRISMA protocol is published at Arcsology.org. We used four platforms, 10 sources, extraction software, and critical review with ≥2 researchers at each phase. All human sources to 12/6/2020 were eligible for qualitative synthesis utilizing R. Weekly updates since cutoff strengthen conclusions.

RESULTS

Included were 887/14286 sources containing 12721 DLMs patients. Pathology involves the subarachnoid space (SAS) and pia. DLMs occurred in all countries as a contributor to the top 10 causes of disability-adjusted life years lost, with communicable diseases (CDs) predominating. In the USA, the ratio of CDs to iatrogenic causes is 2.4:1, contradicting arachnoiditis literature. Spinal fusion surgery comprised 54.7% of the iatrogenic category, with rhBMP-2 resulting in 2.4x more DLMs than no use (p<0.0001). Spinal injections and neuraxial anesthesia procedures cause 1.1%, and 0.2% permanent DLMs, respectively. Syringomyelia, hydrocephalus, and arachnoid cysts are complications caused by blocked CSF flow. CNS neuron death occurs due to insufficient arterial supply from compromised vasculature and nerves traversing the SAS. Contrast MRI is currently the diagnostic test of choice. Lack of radiologist recognition is problematic.

DISCUSSION & CONCLUSION

DLMs are common. The LM clinically functions as an organ with critical CNS-sustaining roles involving the SAS-pia structure, enclosed cells, lymphatics, and biologic pathways. Cases involve all specialties. Causes are numerous, symptoms predictable, and outcomes dependent on time to treatment and extent of residual SAS damage. An international disease classification and possible treatment trials are proposed.

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Yaw Tee LY, Hunter S, Baker JF. BMP use in the surgical treatment of pyogenic spondylodiscitis: Is it safe? J Clin Neurosci 2021;95:94-98. [PMID: 34929659 DOI: 10.1016/j.jocn.2021.11.018] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2021] [Revised: 10/09/2021] [Accepted: 11/21/2021] [Indexed: 11/17/2022]

Lo WC, Tsai LW, Yang YS, Chan RWY. Understanding the Future Prospects of Synergizing Minimally Invasive Transforaminal Lumbar Interbody Fusion Surgery with Ceramics and Regenerative Cellular Therapies. Int J Mol Sci 2021;22:3638. [PMID: 33807361 PMCID: PMC8037583 DOI: 10.3390/ijms22073638] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2021] [Revised: 03/22/2021] [Accepted: 03/26/2021] [Indexed: 12/14/2022] Open

Microendoscope-Assisted Versus Open Posterior Lumbar Interbody Fusion for Lumbar Degenerative Disease: A Multicenter Retrospective Cohort Study. ACTA ACUST UNITED AC 2021;57:medicina57020150. [PMID: 33567496 PMCID: PMC7916072 DOI: 10.3390/medicina57020150] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2021] [Revised: 01/28/2021] [Accepted: 02/03/2021] [Indexed: 11/17/2022]

Son S, Yoon SH, Kim MH, Yun X. Activin A and BMP chimera (AB204) induced bone fusion in osteoporotic spine using an ovariectomized rat model. Spine J 2020;20:809-820. [PMID: 31899374 DOI: 10.1016/j.spinee.2019.12.015] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/27/2019] [Revised: 12/22/2019] [Accepted: 12/23/2019] [Indexed: 02/03/2023]

Abstract

BACKGROUND CONTEXT

Recombinant human bone morphogenic protein 2 (rhBMP2) has been used to induce bone fusion in patients with spinal fusion surgery. However, the effectiveness of rhBMP2 in the bone fusion process is limited in osteoporosis patients, and a high dose of rhBMP2 for enough bone fusion sometimes provokes side effects. Therefore, substitutes for rhBMP2 with a higher therapeutic potency are needed, and already several studies have published the effectiveness of Activin A/BMP2 chimera (AB204) in new bone formation process in vitro and in vivo.

PURPOSE

In the present study, we provide evidence that bone fusion activity of AB204 is superior to that of rhBMP2 in osteoporotic rat models.

STUDY DESIGN/SETTINGS

An in vivo animal study was carried out.

METHODS

A total of 40 Sprague-Dawley rats underwent bilateral ovariectomy. At 6 weeks after ovariectomy, a lumbar spinal bone fusion model of bilateral intertransverse process was performed. All rats were randomly divided into four groups as follows: rats receiving 5 µg of rhBMP2 (Group I), rats receiving 10 µg of rhBMP2 (Group II), rats receiving 5 µg of AB204 (Group III), and rats receiving 10 µg of AB204 (Group IV). Simple radiographs were performed at 6 and 12 weeks after bone fusion, and direct palpation, micro-CT, and immunohistochemistry (hematoxylin-eosin stain and Masson's trichrome stain) were performed at 12 weeks after bone fusion. The qualitative degree of bone fusion was assessed as manual fusion score from direct palpation, and radio-histologic fusion score from simple radiographs, micro-CT, and immunohistochemistry. Also, the quantitative degree of bone fusion was assessed using fusion bone volume by micro-CT and serum osteocalcin level as bone turnover markers.

RESULTS

The change of body weight was not different among the groups during follow-up. The qualitative degree of bone fusion assessed by direct palpation, simple radiographs, micro-CT, and histologic evaluation was significantly different among the four groups. Also, the quantitative degree of bone fusion including fusion bone volume and serum osteocalcin was significantly different among the groups. Especially, in manual fusion score, radio-histologic fusion score, and fusion bone volume, the AB204 group revealed superior results to the rhBMP2 group when using the same dose. Furthermore, even the low-dose AB204 group (Group III) showed superior results to the high-dose rhBMP2 group (Group II) in radio-histologic fusion score and fusion bone volume.

CONCLUSION

The effect of bone fusion in osteoporotic rats was significantly higher in the AB204 group than in the rhBMP2 group.

CLINICAL SIGNIFICANCE

If further organized animal studies and clinical trials are provided, AB204 may be a good substitute for rhBMP2 in osteoporotic spinal fusion surgery, as a superior osteogenesis inducer.

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Niu S, Anastasio AT, Faraj RR, Rhee JM. Evaluation of Heterotopic Ossification After Using Recombinant Human Bone Morphogenetic Protein-2 in Transforaminal Lumbar Interbody Fusion: A Computed Tomography Review of 996 Disc Levels. Global Spine J 2020;10:280-285. [PMID: 32313793 PMCID: PMC7160810 DOI: 10.1177/2192568219846074] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open

Tiffany AS, Dewey MJ, Harley BAC. Sequential sequestrations increase the incorporation and retention of multiple growth factors in mineralized collagen scaffolds. RSC Adv 2020;10:26982-26996. [PMID: 33767853 PMCID: PMC7990239 DOI: 10.1039/d0ra03872e] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open

Formica M, Vallerga D, Zanirato A, Cavagnaro L, Basso M, Divano S, Mosconi L, Quarto E, Siri G, Felli L. Fusion rate and influence of surgery-related factors in lumbar interbody arthrodesis for degenerative spine diseases: a meta-analysis and systematic review. Musculoskelet Surg 2020;104:1-15. [PMID: 31894472 DOI: 10.1007/s12306-019-00634-x] [Citation(s) in RCA: 38] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2019] [Accepted: 12/21/2019] [Indexed: 12/20/2022]

Current and Future Concepts for the Treatment of Impaired Fracture Healing. Int J Mol Sci 2019;20:ijms20225805. [PMID: 31752267 PMCID: PMC6888215 DOI: 10.3390/ijms20225805] [Citation(s) in RCA: 53] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2019] [Revised: 11/15/2019] [Accepted: 11/15/2019] [Indexed: 02/06/2023] Open

Minimally Effective Dose of Bone Morphogenetic Protein in Minimally Invasive Lumbar Interbody Fusions: Six Hundred Ninety Patients in a Dose-Finding Longitudinal Cohort Study. Spine (Phila Pa 1976) 2019;44:989-995. [PMID: 30817730 DOI: 10.1097/brs.0000000000002993] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]

The Use of Bone Morphogenetic Protein in the Intervertebral Disk Space in Minimally Invasive Transforaminal Lumbar Interbody Fusion: 10-year Experience in 688 Patients. Clin Spine Surg 2019;32:E272-E276. [PMID: 30839419 DOI: 10.1097/bsd.0000000000000800] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]

Abstract

STUDY DESIGN

Retrospective Cohort.

OBJECTIVE

The objective of this study was to characterize one surgeon's experience over a 10-year period using rhBMP-2 in the disk space for minimally invasive transforaminal lumbar interbody fusion (MIS TLIF).

SUMMARY OF BACKGROUND DATA

MIS TLIF has been utilized as a technique for decreasing patients' immediate postoperative pain, decreasing blood loss, and shortened hospital stays. Effectiveness and complications of rhBMP-2's use in the disk space is limited because of its off-label status.

METHODS

Retrospective analysis of consecutive MIS TLIFs performed by senior author between 2004 and 2014. rhBMP-2 was used in the disk space in all cases. Patients were stratified based on the dose of rhBMP-2 utilized. Patients had 9 to 12 month computerized tomography scan to evaluate for bony fusion and continued follow-up for 18 months.

RESULTS

A total of 688 patients underwent a MIS TLIF. A medium kit of rhBMP-2 was utilized in 97 patients, and small kit was used in 591 patients. Fusion rate was 97.9% and this was not different between the 2 groups with 96/97 patients fusing in the medium kit group and 577/591 patients fusing in the small kit group. Five patients taken back to the operating room for symptomatic pseudoarthrosis, 4 reoperated for bony hyperostosis, and 10 radiographic pseudoarthroses that did not require reoperation. A statistically significant difference in the rate of foraminal hyperostosis was found when using a medium sized kit of rhBMP-2 was 4.12% (4/97 patients), compared with a small kit (0/591 patients, P=0.0004).

CONCLUSIONS

Utilization of rhBMP-2 in an MIS TLIF leads to high fusion rate (97.9%), with an acceptable complication profile. The development of foraminal hyperostosis is a rare complication that only affected 0.6% of patients, and seems to be a dose related complication, as this complication was eliminated when a lower dose of rhBMP-2 was utilized.

LEVEL OF EVIDENCE

Level IV.

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Sebastian AS, Wanderman NR, Currier BL, Pichelmann MA, Treder VM, Fogelson JL, Clarke MJ, Nassr AN. Prospective Evaluation of Radiculitis following Bone Morphogenetic Protein-2 Use for Transforaminal Interbody Arthrodesis in Spine Surgery. Asian Spine J 2019;13:544-555. [PMID: 30866616 PMCID: PMC6680045 DOI: 10.31616/asj.2018.0277] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/24/2018] [Accepted: 12/13/2018] [Indexed: 11/30/2022] Open

Abstract

Study Design

Prospective observational cohort study.

Purpose

This study aims to evaluate the safety and efficacy of bone morphogenetic protein-2 (BMP-2) in transforaminal lumbar interbody fusion (TLIF) with regard to postoperative radiculitis.

Overview of Literature

Bone morphogenetic protein (BMP) is being used increasingly as an alternative to iliac crest autograft in spinal arthrodesis. Recently, the use of BMP in TLIF has been examined, but concerns exist that the placement of BMP close to the nerve roots may cause postoperative radiculitis. Furthermore, prospective studies regarding the use of BMP in TLIF are lacking.

Methods

This prospective study included 77 patients. The use of BMP-2 was determined individually, and demographic and operative characteristics were recorded. Leg pain was assessed using the Visual Analog Scale (VAS) for pain and the Sciatica Bothersome Index (SBI) with several secondary outcome measures. The outcome data were collected at each follow-up visit.

Results

Among the 77 patients, 29 were administered with BMP. Postoperative leg pain significantly improved according to VAS leg and SBI scores for the entire cohort, and no clinically significant differences were observed between the BMP and control groups. The VAS back, Oswestry Disability Index, and Short-Form 36 scores also significantly improved. A significantly increased 6-month fusion rate was noted in the BMP group (82.8% vs. 55.3%), but no significant differences in fusion rate were observed at the 12- and 24-month follow-up. Heterotopic ossification was observed in seven patients: six patients and one patient in the BMP and control groups, respectively (20.7% vs. 2.1%). However, no clinical effect was observed.

Conclusions

In this prospective observational trial, the use of BMP in TLIF did not lead to significant postoperative radiculitis, as measured by VAS leg and SBI scores. Back pain and other functional outcome scores also improved, and no differences existed between the BMP and control groups. The careful use of BMP in TLIF appears to be both safe and effective.

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Tally WC, Temple HT, Subhawong TY, Ganey T. Transforaminal Lumbar Interbody Fusion With Viable Allograft: 75 Consecutive Cases at 12-Month Follow-up. Int J Spine Surg 2018;12:76-84. [PMID: 30280087 DOI: 10.14444/5013] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open

Abstract

Background

When conservative treatments fail to alleviate the discomfort of abnormal motion, spinal fusion has been shown to provide symptomatic treatment for spinal instability, stenosis, spondylolisthesis, and symptomatic degenerative disc disease. The trend and rates of fusion over the past few years have been dramatic in the United States. Accompanying that higher incidence has been the shifting from traditional open surgery to minimally invasive techniques to reduce scar tissue formation, extent of muscle stripping, and muscle retraction which all have been shown to adversely affect outcomes. Other reasons supporting the widespread transition to minimally invasive surgical (MIS) techniques include decreased postoperative pain, decreased intraoperative blood loss, shorter postoperative hospital stay, faster return to normal activity, and reduced reoperation rates. Spinal fusion procedures rely on a bony fusion substrate in addition to fixation hardware. While available grafting options include autogenous, allogeneic, and synthetic materials, recent interest in viable allograft material with living cells has drawn attention and attraction for incorporating a biologic basis for regenerative consideration. A recent viable allograft, complete with cellular and designated bone carrier (VIA Graft, Vivex Biomedical, Marietta, Georgia) has been developed. This study represents a retrospective review of a single-practice, single-surgeon evaluation of the product in 75 consecutive patients for fusion by computed tomography (CT) and radiographic evaluation at 12 months in conjunction with a MIS approach. Viable allograft was used to fill the peri-implant space, and central implant lumen was filled with a cancellous bone sponge soaked in perivertebral bone marrow. Posterolateral supplementation was attained with beta-tricalcium phosphate as a bulking agent.

Methods

A retrospective review identified patients treated for both primary and revision surgery who received VIA Graft cellular bone matrix material in minimally invasive interbody fusion (MIS-TLIF) with a minimum of 12-month follow up. The patient diagnoses included radiculopathy in all instances and varied collateral indications such as foraminal collapse, recurrent disc herniation, and spondylolisthesis to which pain and morbidity had been unresolved by conservative treatment. Adverse events including infection, revisions, and evidence of immune response were evaluated and patient comorbidities defined for the entire population of patients. Patient fusion status was assessed using thin slice CT by 2 independent radiologists separate from the surgeon. There were 75 consecutive adult patients with degenerative conditions of the lumbar spine who underwent MIS-TLIF surgery of which 40 (53%) were male and 35 (47%) were female. Mean age, height, and weight were 58 years, 170.18 cm (67 in), and 88.45 kg (195 lbs), respectively. The mean body mass index was 30. There were 16 patients (21%) who smoked and 12 (16%) with a history of diabetes. Independent blinded review of fusion was obtained by a board certified musculoskeletal radiologist and an experienced board certified orthopaedic surgeon to assess patient fusion status. Spinal segments were deemed fused if 12-month CT scans demonstrated evidence of bridging bone at the fusion site without observed motion on flexion-extension radiographs. Findings such as osteolysis around the implant or pedicle screws, extensive endplate cystic changes, or linear defects parallel to the endplates through intradiscal new bone formation were interpreted as signs of pseudarthrosis. Interobserver and intraobserver error and κ assessments were analyzed to assure agreement in the CT outcomes assessment where interpretation of κ were as follows: <0.00 = poor agreement, 0.00-0.20 = slight agreement, 0.21-0.40 = fair agreement, 0.41-0.60 = moderate agreement, 0.61-0.80 = substantial agreement, and 0.81-1.00 = almost perfect agreement. Differences were resolved by consensus amongst the observers.

Results

In total, 96% of the 75 patients with a total of 85 levels (96.5% of levels treated) achieved a fusion at 12 months. There were no perioperative or latent complications and no transfusions in all 75 patients.

Conclusions

In this population, 96% of the patients treated achieved the surgical objective in 96.5% of the levels treated.

Level of Evidence

IV.

Clinical Relevance

The high rate of fusion, the lack of secondary morbidity with autologous bone harvest, and the clinical success account for the benefits of viable allograft matrix for MIS-TLIF use.

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Lykissas M, Gkiatas I. Use of recombinant human bone morphogenetic protein-2 in spine surgery. World J Orthop 2017;8:531-535. [PMID: 28808623 PMCID: PMC5534401 DOI: 10.5312/wjo.v8.i7.531] [Citation(s) in RCA: 35] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/18/2016] [Revised: 02/05/2017] [Accepted: 04/20/2017] [Indexed: 02/06/2023] Open

Kang DG, Hsu WK, Lehman RA. Complications Associated With Bone Morphogenetic Protein in the Lumbar Spine. Orthopedics 2017;40:e229-e237. [PMID: 27992640 DOI: 10.3928/01477447-20161213-06] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/19/2015] [Accepted: 05/24/2016] [Indexed: 02/03/2023]

Yin Wei CC, Haw SS, Bashir ES, Beng SL, Shanmugam R, Keong KM. Biomechanical comparison between cortical screw-rod construct versus pedicle screw-rod construct in transforaminal lumbar interbody fusion. J Orthop Surg (Hong Kong) 2017;25:2309499017690656. [PMID: 28219305 DOI: 10.1177/2309499017690656] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open

Hershman S, Jenis LG. BMP 2 usage in posterior lumbar fusion in degenerative conditions. ACTA ACUST UNITED AC 2016. [DOI: 10.1053/j.semss.2016.08.007] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]

Villavicencio AT, Burneikiene S. RhBMP-2-induced radiculitis in patients undergoing transforaminal lumbar interbody fusion: relationship to dose. Spine J 2016;16:1208-1213. [PMID: 27343729 DOI: 10.1016/j.spinee.2016.06.007] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/21/2015] [Revised: 05/02/2016] [Accepted: 06/21/2016] [Indexed: 02/03/2023]

Abstract

BACKGROUND CONTEXT

Recombinant human bone morphogenetic protein-2 (rhBMP-2) remains the primary synthetic osteoinductive material used in spinal fusion surgery today. The early inflammation reaction to rhBMP-2 manifesting with radicular symptoms has been previously reported in patients undergoing transforaminal lumbar interbody fusion (TLIF). There is a disagreement with regard to the factors affecting its occurrence and whether such symptoms are dose dependent.

PURPOSE

The purpose of this analysis was to determine the incidence of rhBMP-2-induced radiculitis and its relationship to dose.

STUDY DESIGN/SETTING

A retrospective cohort analysis was performed of the prospectively collected data.

PATIENT SAMPLE

All consecutive patients (n=204) who underwent one- or two-level TLIF and instrumented posterolateral fusion with an off-label rhBMP-2 use were included in this analysis.

OUTCOME MEASURES

The patients who developed new radicular symptoms after initial improvement postoperatively and had sterile fluid collections indicative of inflammatory process, or in the absence of any structural abnormalities that would explain these symptoms on imaging studies, were deemed to have rhBMP-2-induced radiculitis.

METHODS

Magnetic resonance imaging (MRI) scans were obtained for all patients who developed postoperative radicular symptoms. Correlations between the total rhBMP-2 dose, dose per spinal level, and incidence of radiculitis were evaluated while controlling for age, sex, number of TLIF levels, and surgeon.

RESULTS

The incidence of postoperative radiculitis was 11.3% (23 out of 204). The average total rhBMP-2 dose was 4.9 mg (range=2.1-12) and the average dose per spinal level was 3.8 mg (range=1.05-12). Logistic regression analysis did not identify any significant correlations between the rhBMP-2 doses and the incidence of radiculitis (p=.6).

CONCLUSION

The incidence of rhBMP-2-induced radiculitis in patients undergoing TLIF is quite high, but there were no dose-related correlations found. The study, however, cannot rule out a possibility that a larger variation in bone morphogenetic protein (BMP) doses could still be a factor in the development of rhBMP-2-associated radiculitis.

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Kadam A, Millhouse PW, Kepler CK, Radcliff KE, Fehlings MG, Janssen ME, Sasso RC, Benedict JJ, Vaccaro AR. Bone substitutes and expanders in Spine Surgery: A review of their fusion efficacies. Int J Spine Surg 2016;10:33. [PMID: 27909654 DOI: 10.14444/3033] [Citation(s) in RCA: 60] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022] Open

Abstract

STUDY DESIGN

A narrative review of literature.

OBJECTIVE

This manuscript intends to provide a review of clinically relevant bone substitutes and bone expanders for spinal surgery in terms of efficacy and associated clinical outcomes, as reported in contemporary spine literature.

SUMMARY OF BACKGROUND DATA

Ever since the introduction of allograft as a substitute for autologous bone in spinal surgery, a sea of literature has surfaced, evaluating both established and newly emerging fusion alternatives. An understanding of the available fusion options and an organized evidence-based approach to their use in spine surgery is essential for achieving optimal results.

METHODS

A Medline search of English language literature published through March 2016 discussing bone graft substitutes and fusion extenders was performed. All clinical studies reporting radiological and/or patient outcomes following the use of bone substitutes were reviewed under the broad categories of Allografts, Demineralized Bone Matrices (DBM), Ceramics, Bone Morphogenic proteins (BMPs), Autologous growth factors (AGFs), Stem cell products and Synthetic Peptides. These were further grouped depending on their application in lumbar and cervical spine surgeries, deformity correction or other miscellaneous procedures viz. trauma, infection or tumors; wherever data was forthcoming. Studies in animal populations and experimental in vitro studies were excluded. Primary endpoints were radiological fusion rates and successful clinical outcomes.

RESULTS

A total of 181 clinical studies were found suitable to be included in the review. More than a third of the published articles (62 studies, 34.25%) focused on BMP. Ceramics (40 studies) and Allografts (39 studies) were the other two highly published groups of bone substitutes. Highest radiographic fusion rates were observed with BMPs, followed by allograft and DBM. There were no significant differences in the reported clinical outcomes across all classes of bone substitutes.

CONCLUSIONS

There is a clear publication bias in the literature, mostly favoring BMP. Based on the available data, BMP is however associated with the highest radiographic fusion rate. Allograft is also very well corroborated in the literature. The use of DBM as a bone expander to augment autograft is supported, especially in the lumbar spine. Ceramics are also utilized as bone graft extenders and results are generally supportive, although limited. The use of autologous growth factors is not substantiated at this time. Cell matrix or stem cell-based products and the synthetic peptides have inadequate data. More comparative studies are needed to evaluate the efficacy of bone graft substitutes overall.

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Hsu WK. Recombinant Human Bone Morphogenetic Protein-2 in Spine Surgery. JBJS Rev 2016;2:01874474-201406000-00002. [PMID: 27500718 DOI: 10.2106/jbjs.rvw.m.00107] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]

Refaat M, Klineberg EO, Fong MC, Garcia TC, Leach JK, Haudenschild DR. Binding to COMP Reduces the BMP2 Dose for Spinal Fusion in a Rat Model. Spine (Phila Pa 1976) 2016;41:E829-E836. [PMID: 26679888 PMCID: PMC7054986 DOI: 10.1097/brs.0000000000001408] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]

Abstract

STUDY DESIGN

The aim of this study is to test the effect of cartilage oligomeric matrix protein (COMP) on enhancing rhBMP-2 induced spinal fusion in a prospective 8-week interventional trial of spinal fusion in rats.

OBJECTIVE

To determine whether the amount of bone morphogenetic protein-2 (BMP-2) required to achieve spinal fusion in a pre-clinical model can be reduced by the addition of COMP.

SUMMARY OF BACKGROUND DATA

BMPs are applied clinically at supraphysiological doses to promote spinal fusion by inducing osseous growth, but dose-related limitations include ectopic bone formation and local inflammatory reactions. COMP is a matricellular BMP-binding protein expressed during endochondral ossification and fracture healing. In vitro studies demonstrate enhanced activity of BMP bound to COMP. We hypothesized that BMP bound to COMP could achieve equivalent spinal fusion rates at lower doses and with fewer complications.

METHODS

Posterolateral intertransverse process spinal fusion at L4 to L5 was performed in 36 Lewis rats. COMP (10 μg) was tested with or without "low-dose" rhBMP-2 (2 μg), and the results were compared with the "low-dose" (2 μg rhBMP-2) and "high-dose" (10 μg rhBMP-2) groups. All groups utilized insoluble collagen bone matrix carrier (ICBM). Fusion was evaluated by radiology, histology, and manual palpation. BMP release kinetics were evaluated in vitro.

RESULTS

Fusion grading of microCT images demonstrated that the fusion rate with the COMP+LoBMP was statistically equivalent to HiBMP, and significantly better than LoBMP without COMP. These results were confirmed with radiographs and manual palpation. BMP release kinetics suggest that COMP increased local concentrations of BMP due to decreased growth factor retention on the scaffold.

CONCLUSION

COMP enhances BMP-induced bone formation, enabling lower doses of BMP to achieve the same level of spinal fusion. COMP may function by affecting the availability and biological presentation of BMP-2. A decrease of BMP-2 required for fusion may reduce dose-related adverse effects, surgical costs, and improve clinical outcomes.

LEVEL OF EVIDENCE

N/A.

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James AW, LaChaud G, Shen J, Asatrian G, Nguyen V, Zhang X, Ting K, Soo C. A Review of the Clinical Side Effects of Bone Morphogenetic Protein-2. TISSUE ENGINEERING PART B-REVIEWS 2016;22:284-97. [PMID: 26857241 DOI: 10.1089/ten.teb.2015.0357] [Citation(s) in RCA: 741] [Impact Index Per Article: 82.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]

Affiliation(s)

Aaron W James 1 Department of Orthopaedic Surgery and the Orthopaedic Hospital Research Center, UCLA and Orthopaedic Hospital, University of California , Los Angeles, Los Angeles, California.,2 Section of Orthodontics, Division of Growth and Development, School of Dentistry, University of California , Los Angeles, Los Angeles, California.,3 Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California , Los Angeles, Los Angeles, California
Gregory LaChaud 1 Department of Orthopaedic Surgery and the Orthopaedic Hospital Research Center, UCLA and Orthopaedic Hospital, University of California , Los Angeles, Los Angeles, California.,2 Section of Orthodontics, Division of Growth and Development, School of Dentistry, University of California , Los Angeles, Los Angeles, California.,3 Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California , Los Angeles, Los Angeles, California
Jia Shen 2 Section of Orthodontics, Division of Growth and Development, School of Dentistry, University of California , Los Angeles, Los Angeles, California
Greg Asatrian 2 Section of Orthodontics, Division of Growth and Development, School of Dentistry, University of California , Los Angeles, Los Angeles, California
Vi Nguyen 3 Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California , Los Angeles, Los Angeles, California
Xinli Zhang 2 Section of Orthodontics, Division of Growth and Development, School of Dentistry, University of California , Los Angeles, Los Angeles, California
Kang Ting 2 Section of Orthodontics, Division of Growth and Development, School of Dentistry, University of California , Los Angeles, Los Angeles, California
Chia Soo 1 Department of Orthopaedic Surgery and the Orthopaedic Hospital Research Center, UCLA and Orthopaedic Hospital, University of California , Los Angeles, Los Angeles, California.,4 Division of Plastic and Reconstructive Surgery, Department of Surgery, David Geffen School of Medicine, University of California , Los Angeles, Los Angeles, California

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Baron EM, Mejía DM, Drazin D, Anand N. Postoperative Cyst Associated with Bone Morphogenetic Protein Use in Posterior and Transforaminal Lumbar Interbody Fusion Managed Conservatively: Report of Two Cases. Cureus 2016;8:e485. [PMID: 27014519 PMCID: PMC4786379 DOI: 10.7759/cureus.485] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022] Open

Hofstetter CP, Hofer AS, Levi AD. Exploratory meta-analysis on dose-related efficacy and morbidity of bone morphogenetic protein in spinal arthrodesis surgery. J Neurosurg Spine 2015;24:457-75. [PMID: 26613283 DOI: 10.3171/2015.4.spine141086] [Citation(s) in RCA: 43] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2023]

Abstract

OBJECT

Bone morphogenetic protein (BMP) is frequently used for spinal arthrodesis procedures in an "off-label" fashion. Whereas complications related to BMP usage are well recognized, the role of dosage is less clear. The objective of this meta-analysis was to assess dose-dependent effectiveness (i.e., bone fusion) and morbidity of BMP used in common spinal arthrodesis procedures. A quantitative exploratory meta-analysis was conducted on studies reporting fusion and complication rates following anterior cervical discectomy and fusion (ACDF), posterior cervical fusion (PCF), anterior lumbar interbody fusion (ALIF), transforaminal lumbar interbody fusion (TLIF), posterior lumbar interbody fusion (PLIF), and posterolateral lumbar fusion (PLF) supplemented with BMP.

METHODS

A literature search was performed to identify studies on BMP in spinal fusion procedures reporting fusion and/or complication rates. From the included studies, a database for each spinal fusion procedure, including patient demographic information, dose of BMP per level, and data regarding fusion rate and complication rates, was created. The incidence of fusion and complication rates was calculated and analyzed as a function of BMP dose. The methodological quality of all included studies was assessed according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Data were analyzed using a random-effects model. Event rates are shown as percentages, with a 95% CI.

RESULTS

Forty-eight articles met the inclusion criteria: ACDF (n = 7), PCF (n = 6), ALIF (n = 9), TLIF/PLIF (n = 17), and PLF (n = 9), resulting in a total of 5890 patients. In ACDF, the lowest BMP concentration analyzed (0.2-0.6 mg/level) resulted in a fusion rate similar to the highest dose (1.1-2.1 mg/level), while permitting complication rates comparable to ACDF performed without BMP. The addition of BMP to multilevel constructs significantly (p < 0.001) increased the fusion rate (98.4% [CI 95.4%-99.4%]) versus the control group fusion rate (85.8% [CI 77.4%-91.4%]). Studies on PCF were of poor quality and suggest that BMP doses of ≤ 2.1 mg/level resulted in similar fusion rates as higher doses. Use of BMP in ALIF increased fusion rates from 79.1% (CI 57.6%-91.3%) in the control cohort to 96.9% (CI 92.3%-98.8%) in the BMP-treated group (p < 0.01). The rate of complications showed a positive correlation with the BMP dose used. Use of BMP in TLIF had only a minimal impact on fusion rates (95.0% [CI 92.8%-96.5%] vs 93.0% [CI 78.1%-98.0%] in control patients). In PLF, use of ≥ 8.5 mg BMP per level led to a significant increase of fusion rate (95.2%; CI 90.1%-97.8%) compared with the control group (75.3%; CI 64.1%-84.0%, p < 0.001). BMP did not alter the rate of complications when used in PLF.

CONCLUSIONS

The BMP doses used for various spinal arthrodesis procedures differed greatly between studies. This study provides BMP dosing recommendations for the most common spine procedures.

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Terbish M, Yoo SH, Kim HJ, Yu HS, Hwang CJ, Baik HS, Cha JY. Accelerated Bone Formation in Distracted Alveolar Bone After Injection of Recombinant Human Bone Morphogenetic Protein-2. J Periodontol 2015;86:1078-86. [PMID: 25957054 DOI: 10.1902/jop.2015.140697] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]

Vavken J, Mameghani A, Vavken P, Schaeren S. Complications and cancer rates in spine fusion with recombinant human bone morphogenetic protein-2 (rhBMP-2). EUROPEAN SPINE JOURNAL : OFFICIAL PUBLICATION OF THE EUROPEAN SPINE SOCIETY, THE EUROPEAN SPINAL DEFORMITY SOCIETY, AND THE EUROPEAN SECTION OF THE CERVICAL SPINE RESEARCH SOCIETY 2015;25:3979-3989. [PMID: 25772092 DOI: 10.1007/s00586-015-3870-9] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/21/2014] [Revised: 02/05/2015] [Accepted: 03/08/2015] [Indexed: 01/20/2023]

Cuenca-López MD, Andrades JA, Gómez S, Zamora-Navas P, Guerado E, Rubio N, Blanco J, Becerra J. Evaluation of posterolateral lumbar fusion in sheep using mineral scaffolds seeded with cultured bone marrow cells. Int J Mol Sci 2014;15:23359-76. [PMID: 25522168 PMCID: PMC4284771 DOI: 10.3390/ijms151223359] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2014] [Revised: 10/25/2014] [Accepted: 11/24/2014] [Indexed: 12/29/2022] Open

Abstract

The objective of this study is to investigate the efficacy of hybrid constructs in comparison to bone grafts (autograft and allograft) for posterolateral lumbar fusion (PLF) in sheep, instrumented with transpedicular screws and bars. Hybrid constructs using cultured bone marrow (BM) mesenchymal stem cells (MSCs) have shown promising results in several bone healing models. In particular, hybrid constructs made by calcium phosphate-enriched cells have had similar fusion rates to bone autografts in posterolateral lumbar fusion in sheep. In our study, four experimental spinal fusions in two animal groups were compared in sheep: autograft and allograft (reference group), hydroxyapatite scaffold, and hydroxyapatite scaffold seeded with cultured and osteoinduced bone marrow MSCs (hybrid construct). During the last three days of culture, dexamethasone (dex) and beta-glycerophosphate (β-GP) were added to potentiate osteoinduction. The two experimental situations of each group were tested in the same spinal segment (L4–L5). Spinal fusion and bone formation were studied by clinical observation, X-ray, computed tomography (CT), histology, and histomorphometry. Lumbar fusion rates assessed by CT scan and histology were higher for autograft and allograft (70%) than for mineral scaffold alone (22%) and hybrid constructs (35%). The quantity of new bone formation was also higher for the reference group, quite similar in both (autograft and allograft). Although the hybrid scaffold group had a better fusion rate than the non-hybrid scaffold group, the histological analysis revealed no significant differences between them in terms of quantity of bone formation. The histology results suggested that mineral scaffolds were partly resorbed in an early phase, and included in callus tissues. Far from the callus area the hydroxyapatite alone did not generate bone around it, but the hybrid scaffold did. In nude mice, labeled cells were induced to differentiate in vivo and monitored by bioluminescence imaging (BLI). Although the cultured MSCs had osteogenic potential, their contribution to spinal fusion when seeded in mineral scaffolds, in the conditions disclosed here, remains uncertain probably due to callus interference with the scaffolds. At present, bone autografts are better than hybrid constructs for posterolateral lumbar fusion, but we should continue to seek better conditions for efficient tissue engineering.

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Hustedt JW, Blizzard DJ. The controversy surrounding bone morphogenetic proteins in the spine: a review of current research. THE YALE JOURNAL OF BIOLOGY AND MEDICINE 2014;87:549-61. [PMID: 25506287 PMCID: PMC4257039] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]

Hinsenkamp M, Collard JF. Growth factors in orthopaedic surgery: demineralized bone matrix versus recombinant bone morphogenetic proteins. INTERNATIONAL ORTHOPAEDICS 2014;39:137-47. [PMID: 25338109 DOI: 10.1007/s00264-014-2562-0] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/26/2014] [Accepted: 09/30/2014] [Indexed: 12/22/2022]

Kaiser MG, Groff MW, Watters WC, Ghogawala Z, Mummaneni PV, Dailey AT, Choudhri TF, Eck JC, Sharan A, Wang JC, Dhall SS, Resnick DK. Guideline update for the performance of fusion procedures for degenerative disease of the lumbar spine. Part 16: bone graft extenders and substitutes as an adjunct for lumbar fusion. J Neurosurg Spine 2014;21:106-32. [PMID: 24980593 DOI: 10.3171/2014.4.spine14325] [Citation(s) in RCA: 47] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/16/2023]

Incidence and outcome of graft resorption in anterior lumbar interbody fusion: using femoral ring allografts and recombinant human bone morphogenetic protein-2. Spine (Phila Pa 1976) 2014;39:374-80. [PMID: 24299714 DOI: 10.1097/brs.0000000000000145] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]

Abstract

STUDY DESIGN

Retrospective cohort.

OBJECTIVE

To determine the incidence of resorption after anterior lumbar interbody fusion (ALIF) and its effect on outcome.

SUMMARY OF BACKGROUND DATA

Recombinant human bone morphogenetic protein-2 (rhBMP-2) used in ALIF has been associated with a 0.5% to 82% incidence of resorption. This has been described as either a complication or part of the natural history. We postulate that early resorption (≤4 mo) in ALIF using femoral ring allograft augmented with rhBMP-2 supplemented with posterior instrumentation has no effect on outcome.

METHODS

Institutional review board-approved retrospective 60 chart cohort study of ALIF using femoral ring allograft-augmented rhBMP-2 supplemented with posterior instrumentation from May 5, 2005, to April 6, 2010. Two groups were based upon the presence or absence of early graft resorption (≤4 mo). Patients were seen prior to surgery and postoperatively until 29 ± 20 months (last visit). Follow-up visual analogue scale pain scores and radiographical evidence of fusion were measured and compared between the 2 groups.

RESULTS

Sixty patients, 27 females and 33 males had follow-up for 29 ± 20 months. Group 1 (33 patients, 45 levels) and group 2 (27 patients, 36 levels) were identical in age (P = 0.62), sex distribution (P = 0.43), preoperative pain score (P = 0.63), and in the rhBMP-2 dose per level (P = 0.77). There were no significant group differences in postoperative visual analogue scale scores but a trend to higher fusion rate in group 1 was seen (P = 0.07) at 6 months. There was a 40% incidence of early resorption with no significant differences in visual analogue scale scores or fusion rate between both groups.

CONCLUSION

There is a 40% incidence of early resorption (≤4 mo) that had no significant effect on pain score or fusion rate. Resorption should be considered part of the fusion process and not necessarily a complication.

LEVEL OF EVIDENCE

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Does recombinant human bone morphogenetic protein-2 use in adult spinal deformity increase complications and are complications associated with location of rhBMP-2 use? A prospective, multicenter study of 279 consecutive patients. Spine (Phila Pa 1976) 2014;39:233-42. [PMID: 24477081 DOI: 10.1097/brs.0000000000000104] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]

Abstract

STUDY DESIGN

Multicenter, prospective analysis of consecutive patients with adult spinal deformity (ASD).

OBJECTIVE

Evaluate complications associated with recombinant human bone morphogenetic protein-2 (rhBMP-2) use in ASD.

SUMMARY OF BACKGROUND DATA

Off-label rhBMP-2 use is common; however, underreporting of rhBMP-2 associated complications has been recently scrutinized.

METHODS

Patients with ASD consecutively enrolled into a prospective, multicenter database were evaluated for type and timing of acute perioperative complications.

INCLUSION CRITERIA

age 18 years and older, ASD, spinal arthrodesis of more than 4 levels, and 3 or more months of follow-up. Patients were divided into those receiving rhBMP-2 (BMP) or no rhBMP-2 (NOBMP). BMP divided into location of use: posterior (PBMP), interbody (IBMP), and interbody + posterior spine (I + PBMP). Correlations between acute perioperative complications and rhBMP-2 use including total dose, dose/level, and location of use were evaluated.

RESULTS

A total of 279 patients (mean age: 57 yr; mean spinal levels fused: 12.0; and mean follow-up: 28.8 mo) met inclusion criteria. BMP (n = 172; average posterior dose = 2.5 mg/level, average interbody dose = 5 mg/level) had similar age, smoking history, previous spine surgery, total spinal levels fused, estimated blood loss, and duration of hospital stay as NOBMP (n = 107; P > 0.05). BMP had greater Charlson Comorbidity Index (1.9 vs. 1.2), greater scoliosis (43° vs. 38°), longer operative time (488.2 vs. 414.6 min), more osteotomies per patient (4.0 vs. 1.6), and greater percentage of anteroposterior fusion (APSF; 20.9% vs. 8.4%) than NOBMP, respectively (P < 0.05). BMP had more total complications per patient (1.4 vs. 0.6) and more minor complications per patient (0.9 vs. 0.2) than NOBMP, respectively (P < 0.05). NOBMP had more complications requiring surgery per patient than BMP (0.3 vs. 0.2; P < 0.05). Major, neurological, wound, and infectious complications were similar for NOBMP, BMP, PBMP, IBMP, and I + PBMP (P > 0.05). Multivariate analysis demonstrated small to nonexistent correlations between rhBMP-2 use and complications.

CONCLUSION

RhBMP-2 use and location of rhBMP-2 use in ASD surgery, at reported doses, do not increase acute major, neurological, or wound complications. Research is needed for higher rhBMP-2 dosing and long-term follow-up.

LEVEL OF EVIDENCE

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Effectiveness and safety of recombinant human bone morphogenetic protein-2 versus local bone graft in primary lumbar interbody fusions. Spine (Phila Pa 1976) 2014;39:164-71. [PMID: 24153173 DOI: 10.1097/brs.0000000000000089] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]

Abstract

STUDY DESIGN

Retrospective cohort study.

OBJECTIVE

To compare clinical outcomes, fusion rates, and rates of complications in posterior lumbar interbody fusions (PLIFs) and transforaminal lumbar interbody fusion procedures with either recombinant human bone morphogenetic protein-2 (rhBMP-2) and local bone graft (LBG) or LBG alone used as graft material.

SUMMARY OF BACKGROUND DATA

rhBMP-2 is often used in PLIF and transforaminal lumbar interbody fusion procedures, but is associated with complications. Furthermore, recent evidence suggests that using LBG may be sufficient to induce fusion.

METHODS

All patients who underwent primary interbody fusions under a single surgeon were identified from the surgeon's records. In November 2008, the surgeon changed from routinely using LBG to using LBG and rhBMP-2 routinely, limiting selection bias. A retrospective review of prospectively collected data preoperatively and up to 12 months postoperatively was performed. Data collected included visual analogue scale, pain scores for back and leg, Oswestry Disability Index scores, Short-Form 36 (SF-36), standing lumbar radiographs, and clinical notes.

RESULTS

Seventy-seven patients met the study criteria and 70 consented to be part of the study. Fifty-one were treated with rhBMP-2 and 19 with LBG. At 12-month follow-up, no significant differences were seen in visual analogue scale score, Oswestry Disability Index score, or SF-36 scores. A total of 89.5% of the LBG group and 94.1% of the rhBMP-2 group went on to show radiographical evidence of fusion by 12-month follow-up (P = 0.61). The rhMBP-2 group had a higher complication rate (41.2% vs. 10.5%, incidence rate ratio = 3.91, P = 0.05).

CONCLUSION

In comparison we found no difference in clinical outcomes, comparable rates of fusion and a significant increase in complication rates with rhBMP-2. Using rhBMP-2 may unnecessarily increase the risk of complication in routine PLIF and transforaminal lumbar interbody fusion procedures.

LEVEL OF EVIDENCE

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Girasole G, Muro G, Mintz A, Chertoff J. Transforaminal lumbar interbody fusion rates in patients using a novel titanium implant and demineralized cancellous allograft bone sponge. Int J Spine Surg 2013;7:e95-e100. [PMID: 25580378 PMCID: PMC4288454 DOI: 10.1016/j.ijsp.2013.08.001] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/15/2023] Open

BMP-2 induced early bone formation in spine fusion using rat ovariectomy osteoporosis model. Spine J 2013;13:1273-80. [PMID: 23953506 DOI: 10.1016/j.spinee.2013.06.010] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/27/2012] [Revised: 03/21/2013] [Accepted: 06/01/2013] [Indexed: 02/03/2023]

Abstract

BACKGROUND CONTEXT

Bone morphogenetic proteins (BMPs) enhance bone formation. Numerous animal studies have established that BMPs can augment spinal fusion. However, there is a lack of data on the effect of BMP-2 on spinal fusion in the osteoporotic spine.

PURPOSE

To investigate whether recombinant human BMP-2 (rhBMP-2) enhances spine fusion in an ovariectomized rat model.

STUDY DESIGN

In vivo animal study.

METHODS

Female Sprague-Dawley rats (n=60) were ovariectomized or sham operated and randomized into three groups: Sham (sham operated+fusion), ovariectomy (OVX) (OVX+fusion), and BMP (OVX+fusion+BMP-2). Six weeks after ovariectomy, unilateral lumbar spine fusion was performed using autologous iliac bone with/without rhBMP-2 delivered on a collagen matrix. For each group, gene expression and histology were evaluated at 3 and 6 weeks after fusion, and bone parameters were measured by microcomputed tomography at 3, 6, 9, and 12 weeks.

RESULTS

Real-time reverse-transcription polymerase chain reaction at 3 weeks showed markedly increased expression of osteoblast-related markers (namely alkaline phosphatase, osteocalcin, Runx2, Smad1, and Smad5) in the BMP group compared with the other groups (p=.0005, .0005, .003, .009 and .012, respectively). Although the Sham and OVX groups showed both sparse and compacted bones between transverse processes at 6 weeks, the BMP group had a significantly larger bone mass within the fusion bed at 3 weeks and later. All rats in the BMP group had bridging bone at 3 weeks; at 12 weeks, bridging bones in the Sham and OVX groups were about 50% and 25%, respectively, of that in the BMP group.

CONCLUSIONS

Recombinant human BMP-2 enhances spinal fusion in OVX rats and acts during early bone formation. Therapeutic BMP-2 may therefore improve the outcome of spinal fusion in the osteoporotic patient.

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Zarrinkalam MR, Schultz CG, Ardern DW, Vernon-Roberts B, Moore RJ. Recombinant human bone morphogenetic protein-type 2 (rhBMP-2) enhances local bone formation in the lumbar spine of osteoporotic sheep. J Orthop Res 2013;31:1390-7. [PMID: 23737220 DOI: 10.1002/jor.22387] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/19/2012] [Accepted: 04/25/2013] [Indexed: 02/04/2023]

Heida K, Ebraheim M, Siddiqui S, Liu J. Effects on clinical outcomes of grafts and spacers used in transforaminal lumbar interbody fusion: a critical review. Orthop Surg 2013;5:13-7. [PMID: 23420741 DOI: 10.1111/os.12026] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/02/2012] [Accepted: 10/09/2012] [Indexed: 12/19/2022] Open