Cause-specific survival continues to decline up to 30 years after diagnosis in ACC of the head and neck. In the interval between 10 and 30 years after diagnosis, patients are nearly as likely to die of ACC as from all competing causes combined. Certain clinicopathological factors are associated with decreased survival. There is no evidence of increased survival in patients receiving adjuvant RT.

Bone loss is a consequence of exposure to high-dose radio-therapy. While damage to bone vasculature and reduced proliferation of bone-forming osteoblasts has been implicated in this process, the effect of radiation on the number and activity of bone-resorbing osteoclasts has not been characterized. In this study, we exposed mice to a whole-body dose of 2 Gy of X rays to quantify the early effects of radiation on osteoclasts and bone structural properties. Female C57BL/6 mice (13 weeks old) were divided into two groups: irradiated and nonirradiated controls. Animals were killed humanely 3 days after radiation exposure. Analysis of serum chemistry revealed a 14% increase in the concentration of tartrate resistant acid phosphatase (TRAP)-5b, a marker of osteoclast activity, in irradiated mice (P < 0.05). Osteoclast number (+44%; P < 0.05) and osteoclast surface (+213%; P < 0.001) were elevated in TRAP-stained histological sections of tibial metaphyses. No significant change was observed in osteoblast surface or osteocalcin concentration or in trabecular microarchitecture (i.e. bone volume fraction) as measured through microcomputed tomography (P > 0.05). This study provides definitive, quantitative evidence of an early, radiation-induced increase in osteoclast activity and number. Osteoclastic bone resorption may represent a contributor to bone atrophy observed after therapeutic irradiation.

Connexin 43 (Cx43) is the most abundant gap junction protein in bone and has been demonstrated as an integral component of skeletal homeostasis. In the present study, we sought to further refine the role of Cx43 in the response to mechanical unloading by subjecting skeletally mature mice with a bone-specific deletion of Cx43 (cKO) to three weeks of mechanical unloading via hindlimb suspension (HLS). The HLS model was selected to recapitulate the effects of skeletal unloading due to prolonged bed rest, reduced activity associated with aging, and spaceflight microgravity. At baseline, the cortical bone of cKO mice displayed an osteopenic phenotype, with expanded cortices, decreased cortical thickness, decreased bone mineral density, and increased porosity. There was no baseline trabecular phenotype. Following three weeks of HLS, wild-type (WT) mice experienced substantial declines in trabecular bone volume fraction, connectivity density, trabecular thickness, and trabecular tissue mineral density. These deleterious effects were attenuated in cKO mice. Conversely, there was a similar and significant amount of cortical bone loss in both WT and cKO. Interestingly, mechanical testing revealed a greater loss of strength and rigidity for cKO during HLS. Analysis of double-label quantitative histomorphometry data demonstrated a substantial decrease in bone formation rate, mineralizing surface, and mineral apposition rate at both the periosteal and endocortical surfaces of the femur following unloading of WT mice. This suppression of bone formation was not observed in cKO mice, where parameters were maintained at baseline levels. Taken together, the results of the present study indicate that Cx43 deficiency desensitizes bone to the effects of mechanical unloading, and that this may be due to an inability of mechanosensing osteocytes to effectively communicate the unloading state to osteoblasts to suppress bone formation. Cx43 may represent a novel therapeutic target for investigation as a countermeasure for age-related and unloading-induced bone loss.

Previous research has indicated a high prevalence of childhood sexual abuse (CSA) among men who have sex with men (MSM) in the United States, and has suggested that CSA history is a risk factor for HIV infection in MSM. We conducted a systematic review to identify, synthesize, meta-analyze, and critique the current state of relevant literature. Systematic review methodology was utilized to identify 12 studies that compared MSM with a history of CSA to MSM without a history of CSA on HIV risk indicators including HIV serostatus, sexually transmitted infections (STIs), sexual behaviors, and illicit drug use. Overall, 27.3% (n = 4,263) of the MSM in all included studies (n = 15,622) reported a CSA history. Across the studies that used probabilistic sampling (n = 8,240), the estimated prevalence of CSA was 21.8% (n = 1,800). Meta-analysis indicated that MSM with CSA history were more likely to be HIV positive [odds ratio (OR) = 1.54; 95% confidence interval (CI) = 1.22-1.95)] and to engage in recent unprotected anal intercourse (OR = 1.85, 95% CI = 1.36-2.51). Studies also indicated that MSM with a history of CSA were more likely to report frequent casual male partners, substance use, and sex while under the influence of alcohol or other drugs. Trends across studies indicated a need for interventions to assess CSA history and address effects of CSA on sexual risk behavior of MSM. Inconsistencies across studies indicated a need to reach consensus among researchers and providers in defining CSA.