Carnosol suppresses RANKL-induced osteoclastogenesis and attenuates titanium particles-induced osteolysis.

Osteolysis is a common medical condition characterized by excessive activity of osteoclasts and bone resorption, leading to severe poor quality of life. It is essential to identify the medications that can effectively suppress the excessive differentiation and function of osteoclasts to prevent and reduce the osteolytic conditions. It has been reported that Carnosol (Car), isolated from rosemary and salvia, has anti-inflammatory, antioxidative, and anticancer effects, but its activity on osteolysis has not been determined. In this study, we found that Car has a strong inhibitory effect on the receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast differentiation dose-dependently without any observable cytotoxicity. Moreover, Car can inhibit the RANKL-induced osteoclastogenesis and resorptive function via suppressing NFATc1, which is a result of affecting MAPK, NF-κB and Ca2+ signaling pathways. Moreover, the particle-induced osteolysis mouse model confirmed that Car could be effective for the treatment of bone loss in vivo. Taken together, by suppressing the formation and function of RANKL-induced osteoclast, Car, may be a therapeutic supplementary in the prevention or the treatment of osteolysis.

Risk Factor Analysis of the Incidence of Subsequent Adjacent Vertebral Fracture After Lumbar Spinal Fusion Surgery with Instrumentation.

OBJECTIVE: This study aimed to evaluate the risk factors for adjacent vertebral compression fractures after lumbar spinal fusion with instrumentation. METHODS: A total of 669 patients who received lumbar instrumented spinal fusion between January 2012 and December 2015 were divided into 2 groups according to whether the adjacent vertebral body was fractured. The covariates recorded were age, sex, bone mineral density, and the number of fixed segments. The anatomic variables were pelvic incidence angle (PI), preoperative lumbar lordosis angle (Pre-LL), postoperative lumbar lordosis angle (Post-LL), Pre-LL minus Post-LL (Loss of LL), postoperative pelvic tilt (Post-PT), postoperative sacral slope, Pre-PI-LL mismatch (Pre-PI minus Pre-LL), and Post-PI-LL mismatch (Post-PI minus Post-LL). A 1-way analysis of variance (ANOVA) was performed with the aforementioned parameters, and binary logistic regression analysis was used to determine the relative risk factors. RESULTS: The 669 patients were followed-up for a mean of 2.7 ± 1.1 years (range, 2-4 years). Twenty-seven patients demonstrated fractures in the adjacent vertebral body after surgery. Analysis by 1-way ANOVA demonstrated that age, PI, Pre-LL, Post-LL, Loss of LL, Post-PI-LL mismatch, Post-PT, and osteoporosis were potential risk factors (all parameters, P < 0.001). Furthermore, binary logistic regression analysis showed that a large Loss of LL, osteoporosis, and old age were also risk factors for adjacent vertebral compression fractures. CONCLUSIONS: A greater Loss of LL, osteoporosis, and advanced age may be risk factors for fractures in the adjacent vertebral body of the fixed segment after lumbar fusion fixation.

Novel Surgical Strategy for Treating Osteoporotic Vertebral Fractures with Cord Compression.

OBJECTIVES: Treatment for osteoporotic vertebral fracture (OVF) with cord compression is challenging and it usually requires surgical interventions to decompress nerves and restore spinal sequences. To describe a novel surgical strategy for treating OVFs with cord compression. METHODS: This is a single-center retrospective analysis. The inclusion criteria were Frankel grade C-E, single level T10 -L2 . Between January 2008 and December 2016, a total of 56 OVF patients (47 females and nine males, with an average age of 72 years (66-88 years), comprising of eight grade C, 23 grade D, and 25 grade E patients) were enrolled. The treatment algorithm included preoperative evaluation by MRI, extension CT, and radiography to classify the OVFs as type 1.1 (reducible, stable; n = 13), type1.2 (reducible, unstable; n = 16), type 2 (irreducible; n = 19) or type 2M (modifier; n = 8). Vertebroplasty (VP)/kyphoplasty (KP) was applied in type 1.1. VP/KP with posterior fixation and posterolateral fusion was applied in type 1.2. And additional laminectomy/osteotomy was used in type 2, except in a modifier group (2M) where same procedure as applied for type 1.2 was used. VAS, ODI, Cobb angle, Frankel functional grade, and complications were recorded. RESULTS: Thirteen cases were classified as type 1.1, 16 cases as type 1.2, 19 cases as type 2, and eight cases as type 2M. The follow-up period was 38.9 months (range, 24-108 months). All patients were followed-up in at least 24 months, in which time four patients died, two patients were lost at the last follow-up, and 50 patients completed the full study. The total VAS and ODI improved from 8 (7, 9) and 75.5% (67.2%, 80.0%) preoperatively to 2 (1, 3) and 31% (24.0%, 37.0%) on conclusion, respectively (P < 0.01). The local kyphotic angle was corrected from 22.3° (17.1°, 33. 8°) preoperatively to 10.4° (6.4°, 15.3°) on conclusion (P < 0.01). Twenty-three patients had achieved neurological recovery on conclusion (42E, 8D, P < 0.01). Asymptotic cement leakage was observed in 17/56 cases (30.4%), 6/56 in the affected vertebra (10.7%), and 24/330 in the screw trajectory (7.3%). At 2 years postoperatively, 11 new VFs had occurred in nine patients (16.1%), including VFs in nine adjacent segments that all occurred within 1 year after surgery. No cement migration or implant failure was noted. CONCLUSION: The novel surgical strategy for treating OVFs with cord compression consists of the most tailored and least invasive treatment for each patient. The positive mid- and long-term clinical and radiological outcomes observed could represent a step forward in devising the proposed algorithm.