Prognostic role of nuclear factor/IB and bone remodeling proteins in metastatic giant cell tumor of bone: A retrospective study

Giant cell tumor of bone (GCTb) represents 5% of bone tumors, and although considered benign, 5% metastasize to the lung. The expression of proteins directly or indirectly associated with osteolysis and tumor growth was studied on 163 samples of GCTb. Of these, 33 patients developed lung metastasis during follow‐up. The impact of tumor–host interaction on clinical aspects was evaluated with the aim of finding specific markers for new biological therapies, thus improving clinical management of GCTb. Protein expression was evaluated by immunohistochemical analysis on Tissue Microarray. The majority of GCTb samples from patients with metastatic disease were strongly positive to RANKL and its receptor RANK as well as to CAII and MMP‐2 and to pro‐survival proteins NFIB and c‐Fos. Kaplan–Meier analysis indicated a significant difference in metastasis free survival curves based on protein staining. Interestingly, the statistical correlation established a strong association between all variables studied with a higher τ coefficient for RANK/RANKL, RANK/NFIB, and RANKL/NFIB pairs. At multivariate analysis co‐overexpression of NFIB, RANK and RANKL significantly increased the risk of metastasis with an odds ratio of 13.59 (95%CI 4.12–44.82; p < 0.0005). In conclusion, the interconnection between matrix remodeling and tumor cell activity may identify tumor–host endpoints for new biological treatments. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:1205–1211, 2015.     

Urinary Tract Stones and Osteoporosis: Findings From the Women's Health Initiative

Kidney and bladder stones (urinary tract stones) and osteoporosis are prevalent, serious conditions for postmenopausal women. Men with kidney stones are at increased risk of osteoporosis; however, the relationship of urinary tract stones to osteoporosis in postmenopausal women has not been established. The purpose of this study was to determine whether urinary tract stones are an independent risk factor for changes in bone mineral density (BMD) and incident fractures in women in the Women's Health Initiative (WHI). Data were obtained from 150,689 women in the Observational Study and Clinical Trials of the WHI with information on urinary tract stones status: 9856 of these women reported urinary tract stones at baseline and/or incident urinary tract stones during follow‐up. Cox regression models were used to determine the association of urinary tract stones with incident fractures and linear mixed models were used to investigate the relationship of urinary tract stones with changes in BMD that occurred during WHI. Follow‐up was over an average of 8 years. Models were adjusted for demographic and clinical factors, medication use, and dietary histories. In unadjusted models there was a significant association of urinary tract stones with incident total fractures (HR 1.10; 95% CI, 1.04 to 1.17). However, in covariate adjusted analyses, urinary tract stones were not significantly related to changes in BMD at any skeletal site or to incident fractures. In conclusion, urinary tract stones in postmenopausal women are not an independent risk factor for osteoporosis. © 2015 American Society for Bone and Mineral Research.     

Short‐Term Effect of Estrogen on Human Bone Marrow Fat

Bone marrow fat, an unique component of the bone marrow cavity increases with aging and menopause and is inversely related to bone mass. Sex steroids may be involved in the regulation of bone marrow fat, because men have higher bone marrow fat than women and clinical observations have suggested that the variation in bone marrow fat fraction is greater in premenopausal compared to postmenopausal women and men. We hypothesized that the menstrual cycle and/or estrogen affects the bone marrow fat fraction. First, we measured vertebral bone marrow fat fraction with Dixon Quantitative Chemical Shift MRI (QCSI) twice a week during 1 month in 10 regularly ovulating women. The vertebral bone marrow fat fraction increased 0.02 (95% CI, 0.00 to 0.03) during the follicular phase (p = 0.033), and showed a nonsignificant decrease of 0.02 (95% CI, –0.01 to 0.04) during the luteal phase (p = 0.091). To determine the effect of estrogen on bone marrow fat, we measured vertebral bone marrow fat fraction every week for 6 consecutive weeks in 6 postmenopausal women before, during, and after 2 weeks of oral 17‐β estradiol treatment (2 mg/day). Bone marrow fat fraction decreased by 0.05 (95% CI, 0.01 to 0.09) from 0.48 (95% CI, 0.42 to 0.53) to 0.43 (95% CI, 0.34 to 0.51) during 17‐β estradiol administration (p < 0.001) and increased again after cessation. During 17‐β estradiol administration the bone formation marker procollagen type I N propeptide (P1NP) increased (p = 0.034) and the bone resorption marker C‐terminal crosslinking telopeptides of collagen type I (CTx) decreased (p < 0.001). In conclusion, we described the variation in vertebral bone marrow fat fraction among ovulating premenopausal women. And among postmenopausal women, we demonstrated that 17‐β estradiol rapidly reduces the marrow fat fraction, suggesting that 17‐β estradiol regulates bone marrow fat independent of bone mass. © 2015 American Society for Bone and Mineral Research.     

Posttraumatic Stress Symptom Trajectories Among Children Exposed to Violence

Little research has examined the developmental course of posttraumatic stress symptoms (PTSS) in children. The current study aimed to identify developmental trajectories of PTSS in childhood and to examine predictors of symptom presentation in 1,178 children from the Longitudinal Studies of Child Abuse and Neglect (LONGSCAN) studies, a consortium of studies focusing on the causes and effects of child maltreatment. Most children had a history of documented reports with Child Protective Services (CPS) and all were identified as living in high‐risk environments. Using group‐based trajectory modeling, 3 unique developmental trajectories were identified: Resilient, Clinical‐Improving (PTSS in the clinical range at baseline then declining over time), and Borderline‐Stable (chronically subclinical PTSS). Children in the Clinical‐Improving group were more likely than children in the Resilient group to have reports of physical abuse (RRR = 1.76), emotional abuse (RRR = 2.55), neglect (RRR = 1.57), and exposure to violence at home and in the community (RRR = 1.04). Children in the Borderline‐Stable group were more likely than children in the Resilient group to have a CPS history of neglect (RRR = 2.44) and exposure to violence at home and in the community (RRR = 1.04). Many children living in high‐risk environments exhibit resilience to PTSS, but exposure to witnessed violence and neglect appear to put children at chronic risk for poor adjustment. These children may require more intensive, integrated clinical services that attend to multiple adverse experiences.     

Biomechanical and clinical study of single posterior oblique cage POLIF in the treatment of degenerative diseases of the lumbar spine

Introduction

Aim of the study was to evaluate the biomechanical stability and the clinical efficacy of a lumbar interbody fusion obtained by single oblique cage implanted by a posterior approach.

Method

Through the realization of three finite element models (FEMs), the biomechanics of POLIF was compared to PLIF and TLIF. Ninety-four patients underwent interbody fusion by POLIF with instrumented posterolateral fusion. Clinical and radiographic outcomes were evaluated at regular intervals for at least 6 months.

Results

The FEMs showed no statistically significant differences in stability in compression and flexion–extension. Mean preoperative VAS score was 7.1, decreased to 2.1 at follow-up. Mean preoperative SF-12 value was 34.5 %, increased to 75.4 % at follow-up. All patients showed a good fusion rate and no hardware failure.

Discussion

POLIF associated to instrumented posterolateral fusion is a viable and safe surgical technique, which ensures a biomechanical stability similar to other surgical techniques.