Non-psychoactive Cannabidiol Prevents Osteoporosis in an Animal Model and Increases Cell Viability, Proliferation, and Osteogenic Gene Expression in Human Skeletal Stem and Progenitor Cells.

Cannabidiol (CBD), the non-psychoactive component of the Cannabis sativa plant, is marketed as a potential therapeutic agent and has been studied for its roles in reducing inflammation and managing neuropathic pain. Some studies have reported that CB1 and CB2 receptor activation can attenuate and reverse bone loss in experimental animal models. Despite this, little is known about the impact of CBD on fracture healing. We investigated the effects of CBD in vitro using human osteoprogenitor cells and in vivo via murine femur fracture and osteoporosis models. In vitro mesenchymal stem cells were treated with increasing concentrations of crystalized pharmaceutical grade CBD or vehicle solution. Cell viability and proliferation were significantly increased in cells treated with CBD compared to vehicle control. Osteocalcin expression was also significantly higher in the CBD-treated human stem cells compared to vehicle control. In vivo the effect of CBD on bone mineral density and fracture healing in mice was examined using a two-phase experimental approach. Fluoxetine was used for pharmacologic induction of osteoporosis and surgical oophorectomy (OVX) was used for hormonal induction of osteoporosis. X-ray and microCT analysis showed that CBD prevented both fluoxetine- and OVX-induced osteoporosis. We found that while OVX resulted in delayed bone healing in control mice, CBD-pretreated mice exhibited normal bone healing. Collectively these in vitro and in vivo findings suggest that CBD exerts cell-specific effects which can be exploited to enhance bone metabolism. These findings also indicate that CBD usage in an osteoporotic population may positively impact bone morphology, warranting further research.

Bariatric Surgery Lowers Rates of Spinal Symptoms and Spinal Surgery in a Morbidly Obese Population.

STUDY DESIGN: Retrospective analysis of New York State Inpatient Database years 2004-2013. OBJECTIVE: Assess rates of spinal diagnoses and procedures before and after bariatric surgery (BS). SUMMARY OF BACKGROUND DATA: BS for morbid obesity helps address common comorbidity burdens and improves quality of life for patients. The effects of BS on spinal disorders and surgical intervention have yet to be investigated. MATERIALS AND METHODS: Patients included in analysis if they underwent BS and were seen at the hospital before and after this intervention. Spinal conditions and rates of surgery assessed before and after BS using χ 2 tests for categorical variables. Multivariable logistic regression analysis used to compare rates in BS patients to control group of nonoperative morbidly obese patients. Logistic testing controlled for comorbidities, age, biological sex. RESULTS: A total of 73,046 BS patients included (age 67.88±17.66 y, 56.1% female). For regression analysis, 299,504 nonbariatric, morbidly obese patients included (age 53.45±16.52 y, 65.6% female). Overall, rates of spinal symptoms decreased following BS (7.40%-5.14%, P <0.001). Cervical, thoracic, lumbar spine diagnoses rates dropped from 3.28% to 2.99%, 2.91% to 2.57%, and 5.39% to 3.92% (all P <0.001), respectively. Most marked reductions seen in cervical spontaneous compression fractures, cervical disc herniation, thoracic radicular pain, spontaneous lumbar compression fractures, lumbar spinal stenosis, lumbar spondylosis. Controlling for comorbidities, age and sex, obese nonbariatric patients more likely to have encounters associated with several cervical, thoracic or lumbar spinal diagnoses and procedures, especially for cervical spontaneous compression fracture, radicular pain, lumbar spondylosis, lumbar spinal stenosis, posterior procedures. BS significantly lowered comorbidity burden for many specific factors. CONCLUSIONS: BS lowered rates of documented spinal disorders and procedures in a morbidly obese population. These findings provide evidence of additional health benefits following BS, including reduction in health care encounters for spinal disorders and rates of surgical intervention.

Tethered Cord Syndrome in the United States Cluster Analysis of Presenting Anomalies and Associated.

PURPOSE: Tethered cord syndrome (TCS) is an occult spinal dysraphism that includes low lying conus, tight filum terminale, lipomeningomyelocele, split cord malformations, dermal sinus tracts, and dermoids. This congenital disorder has been associated with musculoskeletal, neurological, and gastrointestinal abnormalities. This study presents a retrospective review of the prospectively collected data of TCS patients and their concurrent diagnoses or associated anomalies. METHODS: The National Inpatient Sample (NIS) database from 2003 to 2012 was used for data collection. Hospital- and year-adjusted weights allowed for accurate assessment of the incidence of TCS, as well as cardiac and gastrointestinal (GI) and genitourinary (GU) anomalies. K-means clustering analysis was run to discover patterns of concurrent cardiac, GI, GU, and other system anomalies in TCS patients. RESULTS: A total of 13,470 discharges with a diagnosis of TCS were identified in the NIS database, and at least one additional anomaly was identified in 40.7% of TCS patients. The most common secondary anomalies by system were: spine (24.48%), cardiac (6.27%), and urinary (5.37%). For patients with multiple anomalies, the most common combinations were GI and cardiac (4.55%), urinary and GI (4.26%), and urinary and cardiac (4.19%). The most common spinal association was spina bifida (13.65%). The most common neurological or musculoskeletal anomaly was any VACTERL association (13.45%). The top relation in GI and GU anomalies was cervix and female genitalia anomalies (69.1%). The most common specific anomalies were spina bifida, large intestine atresia, Rubenstein-Taybi syndrome, and atrial and ventral septal defects. CONCLUSION: This study provides a nationwide prospective on congenital anomalies and concurrent conditions present in tethered cord syndrome patients in the United States and demonstrates that 40.7% of TCS patients have at least one associated anomaly. The most common congenital anomalies studied were spina bifida, urogenital with or without cardiac septal defects, and cystourethral anomaly or cystic kidney disease with or without large intestinal atresia.

Ossification of the Posterior Longitudinal Ligament in Cervical Spine Cases Trends in Surgical Treatments and Outcomes in the US from 2005 to 2013.

BACKGROUND: Ossification of the posterior longitudinal ligament (OPLL) is characterized by ectopic bone formation within the ligament and can elicit cervical spinal canal stenosis. Surgical treatment for OPLL is debated in the literature. This study examined nationwide data to estimate the prevalence of cervical OPLL (C-OPLL) and investigated trends in surgical treatment and outcomes. METHODS: A retrospective cross-sectional study was conducted of the National Inpatient Sample (NIS) database for patients with a diagnosis code for C-OPLL (ICD-9-CM 723.7) from 2005 to 2013. NIS supplied hospital- and yearadjusted weights allowed for accurate assessment of prevalence. Descriptive statistics assessed patient demographics, comorbidities, surgical factors, and complications. Trends were analyzed using chi-squared, ANOVA, and independent sample t-tests. RESULTS: A total of 4,601 C-OPLL discharges were identified (56.7 years, 43% female). The prevalence of C-OPLL has increased from 0.7/100,000 in 2005 to 2.1/100,000 in 2013. Among hospitalized C-OPLL patients, 89.1% underwent surgery, with 62.1% undergoing an anterior-only (A) approach, 21.5% posterior-only (P), and 16.4% combined (AP). Rates of anterior- and decompression-only surgeries have declined since 2005, from 67.5% to 44.4% and 21.6% to 14.8%, respectively (p < 0.001 for both). Corpectomy rates have dramatically increased, from 3.6% to 27.2% (p < 0.001). Overall complication rates have increased 2.5% since 2005 (p < 0.001) with higher rates of dysphagia (0.7%) and dural tears (5.6%) associated with A-only surgeries (p < 0.001 for both). The overall mortality rate was 0.8%, with P surgery associated with the highest rate, 1.6% (p = 0.002). CONCLUSIONS: The rate of hospitalization for C-OPLL has increased over the last decade as have morbidity rates for C-OPLL discharges. Anterior-only surgeries were associated with higher complication rates. Surgical rates have remained constantsince 2005, butrates of anterior-only and decompression-only procedures have decreased in favor of posterior-only and combined-approach surgeries.

Bariatric Surgery Population at Significantly Increased Risk of Spinal Disorders and Surgical Intervention Compared With Morbidly Obese Patients.

INTRODUCTION: Obesity is associated with acceleration of musculoskeletal degenerative diseases and functional impairment secondary to spinal disorders. Bariatric surgery (BS) is an increasingly common treatment for severe obesity but can affect bone and mineral metabolism. The effect of BS on degenerative spinal disorders is yet to be fully described. The aim of our study was to analyze changes in bariatric patients' risk for spinal degenerative diseases and spinal surgery. METHODS: Retrospective analysis of the prospectively collected New York State Inpatient Database (NYSID) years (2004-2013) using patient linkage codes. The incidence of degenerative spinal diagnoses and spinal surgery was queried using International Classification of Diseases, Ninth Revision (ICD)-9 codes for morbidly obese patients (ICD-9 278.01) with and without a history of BS. The incidence of degenerative spinal diagnoses and spinal surgery was determined using χ tests for independence. Logistic testing controlled for age, sex, and comorbidity burden. RESULTS: A total of 18,176 patients were identified in the NYSID database with a history of BS and 146,252 patients were identified as morbidly obese without a history of BS. BS patients have a significantly higher rate of spinal diagnoses than morbidly obese patients without BS (19.3% vs. 8.1%, P<0.001). Bariatric patients were more likely to have spinal diagnoses and procedures than nonbariatric obese patients (P<0.001). This was mostly observed in lumbar spinal stenosis (5.0%), cervical disk herniation (3.3%), lumbar disk degeneration (3.4%), lumbar spondylolisthesis (2.9%), lumbar spondylosis (1.9%), and cervical spondylosis with myelopathy (2.0%). Spine procedure rates are higher for bariatric patients than nonbariatric overall (25.6% vs. 2.3, P<0.001) and for fusions and decompressions (P<0.001). When controlling for age, sex, and comorbidities (and diagnosis rate with regards to procedure rates), these results persist, with BS patients having a higher likelihood of spinal diagnoses and procedures. In addition, bariatric patients had a lower comorbidity burden than morbidly obese patients without a history of BS. CONCLUSIONS: Morbidly obese BS patients have a dramatically higher incidence of spinal diagnoses and procedures, relative to morbidly obese patients without BS. Further study is necessary to determine if there is a pathophysiological mechanism underlying this higher risk of spinal disease and intervention in bariatric patients, and the effect of BS on these rates following treatment. LEVEL OF EVIDENCE: Level III.

Incidence of Acute, Progressive, and Delayed Proximal Junctional Kyphosis Over an 8-Year Period in Adult Spinal Deformity Patients.

BACKGROUND: Proximal junctional kyphosis (PJK) is a common radiographic complication of adult spinal deformity (ASD) corrective surgery. Although previous literature has reported a 5 to 61% incidence of PJK, these studies are limited by small sample sizes and short-term follow-up. OBJECTIVE: To assess the incidence of PJK utilizing a high-powered ASD database. METHODS: Retrospective review of a prospective multicenter ASD database. Operative ASD patients > 18 yr old from 2009 to 2017 were included. PJK was defined as ≥ 10° for the sagittal Cobb angle between the inferior upper instrumented vertebra (UIV) endplate and the superior endplate of the UIV + 2. Chi-square analysis and post hoc testing assessed annual and overall incidence of acute (6-wk follow-up [f/u]), progressive (increase in degree of PJK from 6 wk to 1 yr), and delayed (1-yr, 2-yr, and 3-yr f/u) PJK development. RESULTS: A total of 1005 patients were included (age: 59.3; 73.5% F; body mass index: 27.99). Overall PJK incidence was 69.4%. Overall incidence of acute PJK was 48.0%. Annual incidence of acute PJK has decreased from 53.7% in 2012 to 31.6% in 2017 (P = .038). Overall incidence of progressive PJK was 35.0%, with stable rates observed from 2009 to 2016 (P = .297). Overall incidence of 1-yr-delayed PJK was 9.3%. Annual incidence of 1-yr-delayed PJK has decreased from 9.2% in 2009 to 3.2% in 2016 (P < .001). Overall incidence of 2-yr-delayed PJK development was 4.3%. Annual incidence of 2-yr-delayed PJK has decreased from 7.3% in 2009 to 0.9% in 2015 (P < .05). Overall incidence of 3-yr-delayed PJK was 1.8%, with stable rates observed from 2009 to 2014 (P = .594). CONCLUSION: Although progressive PJK has remained a challenge for physicians over time, significantly lower incidences of acute and delayed PJK in recent years may indicate improving operative decision-making and management strategies.

Decreased rates of 30-day perioperative complications following ASD-corrective surgery: A modified Clavien analysis of 3300 patients from 2010 to 2014.

The Clavien-Dindo grading allows for broad comparison of perioperative surgical complications, and a temporal analysis of complications following ASD-corrective surgery. NSQIP database was utilized from 2010 to 2014 to isolate patients. Complications were stratified by Clavien complication (Cc) grade, and patients grouped by highest Cc grade: I, II, III, IV, V. Secondary analysis grouped by minor (I, II, III) and severe (IV, V). Comorbidity burden was assessed with a NSQIP-modified Charlson Comorbidity Index (CCI) and frailty was measured with a 5-factor modified frailty index (mFI). From 2010 to 2014, 2971 patients (57 yrs, 58% F) underwent surgery for ASD (3.4 ±â€¯4.1 levels; surgical approach: 46% anterior, 44% posterior, 10% combined), the rate of which increased 0.01% to 0.13. 32% suffered >1 complication. Patient breakdown by Cc grade: 0% I, 25% II, 3% III, 4% IV, 1% V. Severe Cc patients were more comorbid than minor Cc (CCI 2.8 vs 1.8), had longer operative times (394 min vs 251), and higher rates of osteotomy (29% vs 13%) and iliac fixation (16% vs 5%). Overall CCI (2.1-1.7) and perioperative complication rates (55-29%) decreased, despite increasing surgical invasiveness (2.8-4.5) and increasing frailty score (0.14 ±â€¯0.15 vs 0.16 ±â€¯0.16). Rates of Clavien grade II (39.80-22.20%) and IV (9.40-3.50%) complications also decreased, indicative of surgical improvements and effective preoperative patient selection. The decrease in CCI and increase in the modified frailty score may show that we are becoming more cognizant of discerning of comorbidities, but likely to not to have taken into account frailty, which may have an impact on future health socioeconomics.

The Influence of Body Mass Index on Achieving Age-Adjusted Alignment Goals in Adult Spinal Deformity Corrective Surgery with Full-Body Analysis at 1 Year.

BACKGROUND: The impact of obesity on global spinopelvic alignment is poorly understood. This study investigated the effect of body mass index on achieving alignment targets and compensation mechanisms after corrective surgery for adult spinal deformity (ASD). METHODS: Retrospective review of a single-center database. Inclusion: patients ≥18 years with full-body stereographic images (baseline and 1 year) and who met ASD criteria (sagittal vertical axis [SVA] >5 cm, pelvic incidence minus lumbar lordosis [PI-LL] >10°, coronal curvature >20° or pelvic tilt >20°). Patients were stratified by age (<40, 40-65, and ≥65 years) and body mass index (<25, 25-30, and >30). Postoperative alignment was compared with age-adjusted ideal values. Prevalence of patients who matched ideals and unmatched (undercorrected/overcorrected) was assessed. Health-related quality of life (HRQL) scores, alignment, and compensatory mechanisms were compared across cohorts using analysis of variance and temporally with paired t tests. RESULTS: A total of 116 patients were included (average age, 62 years; 66% female). After corrective surgery, obese and overweight patients had more residual malalignment (worse PI-LL, T1 pelvic angle, pelvic tilt, and SVA) compared with normal patients (P < 0.05). In addition, obese and overweight patients recruited more pelvic shift (obese, 62.36; overweight, 49.80; normal, 31.50) and had a higher global sagittal angle (obese, 6.51; overweight, 6.35; normal, 3.40) (P < 0.05). Obese and overweight patients showed lower overcorrection rates and higher undercorrection rates (P < 0.05). Obese patients showed worse postoperative HRQL scores (Scoliosis Research Society 22 Questionnaire, Oswestry Disability Index, visual analog scale-leg) than did overweight and normal patients (P < 0.05). Obese and overweight patients who matched age-adjusted alignment targets for SVA or PI-LL showed no HRQL improvements (P > 0.05). CONCLUSIONS: After surgery, obese patients were undercorrected, showed more residual malalignment, recruited more pelvic shift, and had a greater global sagittal angle and worse HRQL scores. The benefits from age-adjusted alignment targets seem to be less substantial for obese and overweight patients.