Female Sprague-Dawley rats were subjected to bilateral ovariectomy (OVX) or sham surgery (control). Groups of ovariectomized (OVX) and control rats were injected daily with low, medium, or high doses of 17 beta-estradiol (10, 25, or 50 micrograms/kg BW, respectively). An additional group of OVX and control rats was injected daily with vehicle alone. All rats were killed 35 days after OVX, and their proximal tibiae were processed undecalcified for quantitative bone histomorphometry. Trabecular bone volume was markedly reduced in vehicle-treated OVX rats relative to that in control rats (12.1% vs. 26.7%). This bone loss was associated with a 2-fold increase in osteoclast surface and a 4-fold increase in osteoblast surface. The bone formation rate, studied with fluorochrome labeling, was also significantly elevated in vehicle-treated OVX rats (0.111 vs. 0.026 micron3/micron2.day). In contrast, treatment of OVX rats with the three doses of estradiol resulted in normalization of tibial trabecular bone volume and a decline in histomorphometric indices of bone resorption and formation. Our results indicate that estrogen treatment provides complete protection against osteopenia in OVX rats. The protective mechanism involves estrogenic suppression of bone turnover. These findings are consistent with the skeletal effects of estrogen therapy in postmenopausal women.

Objective The aim of this study was to determine the association between participation in organized sports programs and employment in adults with chronic spinal cord injury. Design This is a cross-sectional study of 149 adults with chronic spinal cord injury. Motor level and completeness of injury were confirmed by physical examination. Information related to demographics, employment, level of education, body mass index, duration of injury, participation in individually planned exercise, and participation in organized sports was obtained using a standardized questionnaire. Multivariable logistic regression analyses were used to assess factors associated with employment. Results In univariate analyses, employment was associated with younger age (P = 0.001) and a higher level of education (P = 0.01), whereas obesity decreased the likelihood of employment (P = 0.04). Participation in organized sports approached significance (P = 0.06). In the multivariable analysis and after adjusting for age, education, and body mass index, participation in organized sports was significantly associated with employment (odds ratio, 2.4; P = 0.04). Sex, duration of injury, wheelchair use, and participation in individually planned exercise were not significantly associated with employment (P = 0.16–0.94). Conclusions In the adults with chronic spinal cord injury, participation in organized sports was positively associated with employment. Further studies are necessary to determine the causative nature of this association and how various factors related to sports participation may contribute.

Adipose tissue is a major regulator of bone metabolism and in the general population obesity is associated with greater bone mineral density (BMD). However, bone-fat interactions are multifactorial, and may involve pathways that influence both bone formation and resorption with competing effects on the skeleton. One such pathway involves adipocyte production of adipokines that regulate bone metabolism. In this study we determined the association between BMD, walking status, and circulating adipokines (adiponectin and leptin) in 149 men with chronic spinal cord injury (SCI). Although adipokine levels did not vary significantly based on walking status, there was a significant inverse association between adiponectin and BMD in wheelchair users independent of body composition. We found no association between adiponectin and BMD in the walkers and no association between leptin and BMD in either group. These findings suggest that for subjects with chronic SCI, walking may mitigate the effect of adiponectin mediated bone loss. For wheelchair users, adipose-derived adiponectin may contribute to SCI-induced osteoporosis because the osteoprotective benefits of obesity appear to require mechanical loading during ambulation.

Summary We explored the association between adiponectin levels and bone strength in paralyzed men with spinal cord injury. We found that bone strength was inversely associated with circulating adiponectin levels. Thus, strength estimates and adiponectin levels may improve fracture risk prediction and detection of response to osteogenic therapies following spinal cord injury. Purpose Previous research has demonstrated an inverse relationship between circulating adiponectin and bone mineral density, suggesting that adiponectin may be used as a biomarker for bone health. However, this relationship may reflect indirect effects on bone metabolism via adipose-mediated mechanical pathways rather than the direct effects of adipokines on bone metabolism. Thus, we explored the association between circulating adiponectin levels and bone strength in 27 men with spinal cord injury. Methods Plasma adiponectin levels were quantified by ELISA assay. Axial stiffness and maximal load to fracture of the distal femur were quantified via finite element analysis using reconstructed 3D models of volumetric CT scans. We also collected information on timing, location, and cause of previous fractures. Results Axial stiffness and maximal load were inversely associated with circulating adiponectin levels (R2=0.44, p= 0.01; R2=0.58, p=0.05) after adjusting for injury duration and lower extremity lean mass. In individuals with post-SCI osteoporotic fractures, distal femur stiffness (p=0.01) and maximal load (p=0.005) were lower, and adiponectin was higher (p=0.04) than those with no fracture history. Conclusions Based on these findings, strength estimates may improve fracture risk prediction and detection of response to osteogenic therapies following spinal cord injury. Furthermore, our findings suggest that circulating adiponectin may indeed be a feasible biomarker for bone health and osteoporotic fracture risk in paralyzed individuals with spinal cord injury.

It is hard to overestimate the influence of the endocannabinoid signaling (ECS) system on central nervous system (CNS) function. In the 40 years since cannabinoids were found to trigger specific cell signaling cascades, studies of the ECS system continue to cause amazement, surprise, and confusion! CB1 cannabinoid receptors are expressed widely in the CNS and regulate cell-cell communication via effects on the release of both neurotransmitters and gliotransmitters. CB2 cannabinoid receptors are difficult to detect in the CNS but seem to "punch above their weight" as compounds targeting these receptors have significant effects on inflammatory state and behavior. Positive and negative allosteric modulators for both receptors have been identified and examined in preclinical studies. Concentrations of the endocannabinoid ligands, N-arachidonoylethanolamine and 2-arachidonoylglycerol (2-AG), are regulated by a combination of enzymatic synthesis and degradation and inhibitors of these processes are available and making their way into clinical trials. Importantly, ECS regulates many essential brain functions, including regulation of reward, anxiety, inflammation, motor control, and cellular development. While the field is on the cusp of preclinical discoveries providing impactful clinical and therapeutic insights into many CNS disorders, there is still much to be learned about this remarkable and versatile modulatory system.

Objectives:The laparoscopic-assisted gastrostomy tube placement (LAP) has increasingly become the preferred method for placing gastrostomy tubes in infants and children. The goal of this retrospective review was to examine our institutional experiences with our transition from the percutaneous endoscopic gastrostomy (PEG) procedure to LAP technique.Methods:All patients undergoing primary PEG or LAP gastrostomy at Boston Children's Hospital between January 2010 and June 2015 were identified. The primary aim was to compare complication rates within the first 6 months after tube placement; differences in total hospital procedural costs, hospital resource utilization, and postoperative gastroesophageal reflux disease were examined.Results:Nine hundred and eighty-seven patients (442 PEG and 545 LAP gastrostomy tubes) were included. No differences in total complications within 6 months were seen. Patients undergoing PEG placement had more gastrostomy-related complications (PEG 30 [6.7%] vs LAP 13 [2.4%], P = 0.0007) and cellulitis (PEG 23 [5.1%] vs LAP 2 [0.4%], P = 0.03) within the first week of placement. Patients undergoing LAP procedures had more granulation tissue episodes (PEG 19 [4.4%] vs LAP 107 [19.8%], P = 0.005). No differences in emergency room visits, hospital readmissions, or postoperative gastroesophageal reflux disease were seen, although transition to a gastrojejunal tube was higher in patients undergoing LAP procedure (PEG 20 patients [4.6%] vs LAP 51 patients [9.5%], P = 0.0008).Conclusions:Total complications were similar between patients undergoing PEG versus LAP gastrostomy tube placement. Patients with the PEG procedure had more complications within the first week of placement versus patients with the LAP procedure had more granulation skin complications.

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