Can Acute Galactic Cosmic Radiation-Induced Bone Loss Be Mitigated By Dietary Modulation Of Inflammatory Cytokines?

The space environment includes weightlessness and galactic cosmic radiation (GCR), both of which can have a negative impact on bone parameters. In particular, acute exposures to space-relevant doses (2 Gy or less) of simulated GCR lead to a rapid acceleration of bone resorption activity and suppression of bone forming osteoblasts, resulting in diminished bone mineral density (BMD), strength and altered microarchitecture. A key mechanism driving these changes may be a radiation-induced increase in pro-inflammatory cytokines, such as TNF-α. Consuming a diet rich in omega-3 fatty acids has been associated with attenuated reductions in bone parameters in astronauts, mice and elderly humans with corresponding reductions in circulating inflammatory cytokines. PURPOSE: To test the hypothesis thata diet high in omega-3 fatty acids will mitigate radiation-induced bone loss and reduce inflammatory cytokines in bone osteocytes and serum. METHODS: Adult (30- to 50-week-old) female Lgr5-EGFP C57BL/6 mice (n=4-6 per group) were acclimated to a corn oil/cellulose (COC) or fish oil/pectin (FOP) diet for 3 weeks. Animals were subsequently randomized to total body low dose high-energy radiation (0.1, 0.25, 0.5 Gy of 1000 MeV/n 56Fe at 25 cGy/min at Brookhaven National Lab) or non-irradiated control (sham) and euthanized 8 weeks later. MicroCT (ScanCo, Switzerland) analyses were performed to assess bone geometry and microarchitecture at the mid-shaft and distal end of the femur. Significance was assessed using an αof 0.10. RESULTS:There was a significant main effect of diet on mid-shaft femur periosteal diameter (Peri.Dm) (p=0.001) and endocortical diameter (Endo. Dm.) (p\u3c0.001). The FOP diet led to larger Peri.Dm. (p\u3c0.051 for all) and Endo.Dm. (p\u3c0.41 for all) than did the COC diet at all doses. We could not detect an impact of 56Fe on cortical area or cancellous bone volume at the distal femur. Irradiation with 0.25 and 0.5 Gy in the FOP mice showed significant increases in distal femur volumetric BMD (p=0.014, p=0.063) and trabecular thickness (p=0.058, p=0.028), as compared with sham FOP mice. CONCLUSION: Though we did not detect a significant impact of radiation on bone parameters, these early data analyses suggest some modest benefits from a diet high in omega-3 fatty acids on cortical and cancellous bone parameters

Do Implantable, Progestin Only Contraceptives Alter the Bone Response to Unloading?

Hormonal contraception is routinely used by premenopausal women, including female astronauts, to suppress reproductive function. Long-acting reversible contraceptives (LARC-progestin only) have become a common choice amongst women due to their practicality. PURPOSE: Understand the interaction of unloading and LARC on bone health. We hypothesize that the decrease in bone mineral density (BMD) and cortical thickness of the tibia associated with hindlimb unloading (HU) will be lessened by LARC implantation. METHODS: Virgin female Sprague-Dawley rats (n=26; 4-mo-old) were singly housed and randomly assigned to placebo (PL) and LARC groups, via a slow-release etonogestrel pellet (0.00 vs. 0.09 vs. 0.17 vs. 0.30ug/d) implanted under the skin. Animals were further randomized into ambulatory (AMB) and HU subgroups (n=6-7/subgroup), with HU initiated a week following pellet insertion and lasting for 6 weeks. Ex-vivo proximal tibia metaphysis (PTM) and diaphysis (PTD) were scanned with peripheral quantitative computed tomography. Univariate ANOVA was used to determine group differences, with significance accepted at p\u3c 0.05. RESULTS: Body weight at termination was not different among groups (p\u3e0.29). Soleus weights were significantly lower in HU compared to AMB animals (p0.12). Total area at the PTD was significantly different among groups (p=0.011); the LARC-HU group had a larger area than the PL-HU and LARC-AMB groups (p0.07). CONCLUSION: LARC implantation did alter the response to unloading, however, the changes were site specific. At the metaphysis the response to unloading was not altered by LARC implantation. Loss of diaphyseal total area with unloading was reduced with LARC implantation. Analyses are ongoing to further elucidate these site specific differences

12-months of increased dietary intake does not exacerbate disordered eating-related attitudes, stress, or depressive symptoms in women with exercise-associated menstrual disturbances: the REFUEL randomized controlled trial

Disordered eating-related attitudes are a leading cause of energy deficiency and menstrual disturbances in exercising women. Although treatment recommendations include psychological counseling with increases in dietary intake, a key concern is whether increased dietary intake may exacerbate negative eating behaviors. Objective: To determine the effects of a 12-month nutritional intervention on eating-related attitudes and psychological characteristics in exercising women with oligomenorrhea/amenorrhea (Oligo/Amen). Methods: Intent-to-treat analysis of the REFUEL randomized controlled trial (#NCT00392873) in 113 exercising women (age [mean±SEM]:] 21.9±0.4 yrs; BMI: 20.9±0.2 kg/m2). Women were randomized to increase energy intake 20-40% above baseline energy needs (Oligo/Amen+Cal, n=40) or maintain energy intake (Oligo/Amen Control, n=36) while maintaining their exercise behaviors. A reference group of ovulatory women (OVref, n=37) maintained diet and exercise behaviors. Body composition, eating behavior, stress, and depressive symptoms were assessed at baseline and every 3 months. Results: At baseline, the Oligo/Amen groups had higher drive for thinness, cognitive restraint, and eating disorder risk than OVref group (p Discussion: Long-term nutritional intervention consisting of modest increases in dietary intake with guidance from a registered dietician and a psychologist increases body and fat mass without increasing disordered eating-related attitudes, stress, or depressive symptoms in exercising women with Oligo/Amen.</p