Bone morphogenic protein-2 signaling in human disc degeneration and correlation to the Pfirrmann MRI grading system.

BACKGROUND CONTEXT: Back and neck pain secondary to disc degeneration is a major public health burden. There is a need for therapeutic treatments to restore intervertebral disc (IVD) composition and function. PURPOSE: To quantify ALK3, BMP-2, pSMAD1/5/8 and MMP-13 expression in IVD specimens collected from patients undergoing surgery for disc degeneration, to correlate ALK3, BMP-2, pSMAD1/5/8 and MMP-13 expression in IVD specimens to the 5-level Pfirrmann MRI grading system, and to compare ALK3, BMP-2, pSMAD1/5/8 and MMP-13 expression between cervical and lumbar degenerative disc specimens. STUDY DESIGN: An immunohistochemical study assessing ALK3, BMP-2, pSMAD1/5/8, and MMP-13 expression levels in human control and degenerative IVD specimens. METHODS: Human IVD specimens were collected from surgical patients who underwent discectomy and interbody fusion at our institution between 1/2015 and 8/2017. Each patient underwent MRI prior to surgery. The degree of disc degeneration was measured according to the 5-level Pfirrmann MRI grading system. Patients were categorized into either the 1) control group (Pfirrmann grades I-II) or 2) degenerative group (Pfirrmann grades III-V). Histology slides of the collected IVD specimens were prepared and immunohistochemical staining was performed to assess ALK3, BMP-2, pSMAD1/5/8, and MMP-13 expression levels in the control and degenerative specimens. Expression levels were also correlated to the Pfirrmann criteria. Lastly, the degenerative specimens were stratified according to their vertebral level and expression levels between the degenerative lumbar and cervical discs were compared. RESULTS: Fifty-two patients were enrolled; however, 2 control and 2 degenerative patients were excluded due to incomplete data sets. Of the remaining 48 patients, there were 12 control and 36 degenerative specimens. Degenerative specimens had increased expression levels of BMP-2 (p=.0006) and pSMAD1/5/8 (p<.0001). Pfirrmann grade 3 (p=.0365) and grade 4 (p=.0008) discs had significantly higher BMP-2 expression as compared to grade 2 discs. Pfirrmann grade 4 discs had higher pSMAD1/5/8 expression as compared to grade 2 discs (p<.0001). There were no differences in ALK3 or MMP-13 expression between the control and degenerative discs (p>.05). Stratifying the degenerative specimens according to their vertebral level showed no significant differences in expression levels between the lumbar and cervical discs (p>.05). CONCLUSIONS: BMP-2 and pSMAD1/5/8 signaling activity was significantly upregulated in the human degenerative specimens, while ALK3 and MMP-13 expression were not significantly changed. The expression levels of BMP-2 and pSMAD1/5/8 correlate positively with the degree of disc degeneration measured according to the Pfirrmann MRI grading system. CLINICAL SIGNIFICANCE: BMP-SMAD signaling represents a promising therapeutic target to restore IVD composition and function in the setting of disc degeneration.

Role of oxidative metabolism in osseointegration during spinal fusion.

Spinal fusion is a commonly performed orthopedic surgery. Autologous bone graft obtained from the iliac crest is frequently employed to perform spinal fusion. Osteogenic bone marrow stromal (a.k.a. mesenchymal stem) cells (BMSCs) are believed to be responsible for new bone formation and development of the bridging bone during spinal fusion, as these cells are located in both the graft and at the site of fusion. Our previous work revealed the importance of mitochondrial oxidative metabolism in osteogenic differentiation of BMSCs. Our objective here was to determine the impact of BMSC oxidative metabolism on osseointegration of the graft during spinal fusion. The first part of the study was focused on correlating oxidative metabolism in bone graft BMSCs to radiographic outcomes of spinal fusion in human patients. The second part of the study was focused on mechanistically proving the role of BMSC oxidative metabolism in osseointegration during spinal fusion using a genetic mouse model. Patients' iliac crest-derived graft BMSCs were identified by surface markers. Mitochondrial oxidative function was detected in BMSCs with the potentiometric probe, CMXRos. Spinal fusion radiographic outcomes, determined by the Lenke grade, were correlated to CMXRos signal in BMSCs. A genetic model of high oxidative metabolism, cyclophilin D knockout (CypD KO), was used to perform spinal fusion in mice. Graft osseointegration in mice was assessed with micro-computed tomography. Our study revealed that higher CMXRos signal in patients' BMSCs correlated with a higher Lenke grade. Mice with higher oxidative metabolism (CypD KO) had greater mineralization of the spinal fusion bridge, as compared to the control mice. We therefore conclude that higher oxidative metabolism in BMSCs correlates with better spinal fusion outcomes in both human patients and in a mouse model. Altogether, our study suggests that promoting oxidative metabolism in osteogenic cells could improve spinal fusion outcomes for patients.

Trends and Characteristics of Spine Research From 2006 to 2015: A Review of Spine Articles in a High Impact General Orthopedic Journal.

STUDY DESIGN: Literature review. OBJECTIVE: To determine characteristics and trends in published spine research over a recent decade in a high impact, general orthopedic surgery journal. SUMMARY OF BACKGROUND DATA: Recent trends in published spine research in a high-impact orthopedic surgery journal are unknown. Such knowledge could guide future research in the field. METHODS: A comprehensive literature review of clinical and basic science spine articles published in The Journal of Bone & Joint Surgery from 2006 to 2015 was conducted. Articles were assessed for: title, year of publication, authorship, academic degrees of the authors, number of citations, institution of origin, and spine topic. Clinical articles were evaluated for: sex and race/ethnicity of the human subjects, level of evidence, and inclusion of patient-reported outcome measures (PROMs). Basic science articles were evaluated for: type of study (animal, cadaver, cell-based), sex of the animals, cadavers or cells studied (male, female, or male and female), and presence of sex-based reporting (defined as reporting of results by sex). RESULTS: A total of 203 spine articles were evaluated from the 10-year study period. At least 35 validated or nonvalidated patient-reported outcome measures were utilized in clinical spine research. The most commonly reported PROMs were the Oswestry Disability Index (24.4%), Short Form-36 Health Survey (23.7%), and Visual Analog Scale for Pain (19.3%). The average level of evidence improved from 3.25 in 2006 to 2.60 in 2015. Only 13.2% of clinical spine articles reported the race/ethnicity of the subjects. CONCLUSION: A consensus regarding validated PROMs in spine research would be valuable. From 2006 to 2015, the level of evidence of spine articles in The Journal of Bone & Joint Surgery improved. Accurate and complete reporting of patient demographics is an area for improvement in spine research in light of studies demonstrating sex and race/ethnicity-related differences in clinical outcome after spine surgery. LEVEL OF EVIDENCE: 5.

Rupture of Giant Anterior Sacral Meningocele in a Patient with Marfan Syndrome: Diagnosis and Management.

BACKGROUND: Marfan syndrome is a genetic disorder that results in the weakening of connective tissues. Dural ectasia has been defined as a feature of Marfan syndrome and is present in up to 92% of patients. Rarely, dural ectasia can erode through the sacrum expanding into an anterior sacral meningocele. CASE DESCRIPTION: Information for this case report was gathered from patient notes and imaging from the patient chart. This is a case of a 46-year-old woman who presented with urinary incontinence, early satiety, and back pain in the setting of a known anterior sacral meningocele. Before operative management, the anterior sacral meningocele ruptured with the patient presenting signs and symptoms of intracranial hypotension. Conservative management did not alleviate the pain. She was ultimately managed with posterior sacroplasty followed by anterior sacral meningocele resection and placement of a lumboperitoneal shunt. The patient did not have reaccumulation of the meningocele or recurrent symptoms at the latest follow-up. CONCLUSIONS: The progression of dural ectasia in Marfan syndrome to an anterior sacral meningocele is uncommon. It is important to identify the characteristics associated with an expanding dural ectasia as this patient's symptoms progressed over time and the meningocele grew large. Given its rarity, there are no guidelines in place regarding size at which repair of an anterior sacral meningocele should occur prophylactically. It is important to review these cases in order continue to learn about progression, management, and outcomes of patients with an anterior sacral meningocele.

What Factors Influence Compliance With Sequential Compression Devices in an Orthopaedic Unit: A Quality Assurance Observational Study.

The purpose of this study was to determine the compliance rate with sequential suppression devices (SCDs) of patients admitted to an orthopaedic unit of a level I trauma center. A quality assurance observational study was conducted over a 4-week period (June/July 2015). Three observations were performed per 24-hour period (0700, 1300, 1900 hours). ``Full SCD compliance'' was defined as the SCD ordered, on and functioning properly at the time of observation. Of the 1356 observations in 109 patients, 434 (32%) were fully compliant with SCD prophylaxis. SCD compliance in trauma patients was higher (21%) as compared with elective surgical patients (10%) (p < .0001). Morning observations had the highest compliance rate (38.3%), whereas the afternoon (23.5%) and evening observations (33.1%) had less compliance rates (p < .0001). There was a significantly higher compliance rate on weekdays (33.9%) as compared with weekends (28%) (p < .03). The overall low compliance level (32%) indicates compliance challenges and not the modality of the prophylaxis as the cause (Journal of Surgical Orthopaedic Advances 27(4):307-311, 2018).