Impact of clinical fractures on health-related quality of life is dependent on time of assessment since fracture: results from the FREEDOM-trial

Summary In the Fracture Reduction Evaluation of Denosumab in Osteoporosis Every 6 Months (FREEDOM) study, women with incident clinical fractures reported significant declines in health-related quality of life (HRQoL). The largest declines were observed when the assessment was <3 months post fracture. The largest impact of incident clinical fractures was on physical function, and that of incident clinical vertebral fractures was on back pain. Introduction In the FREEDOM trial, denosumab significantly reduced the risk of new vertebral, hip, and nonvertebral fractures. We evaluated the effect of denosumab on HRQoL and the association between incident clinical fractures and HRQoL. Methods The FREEDOM trial enrolled 7,868 women aged 60-90 years with a total hip and/or lumbar spine BMD T-score <2.5 and not <4.0 at either site. Women were randomized to receive denosumab 60 mg or placebo every 6 months, in addition to daily calcium and vitamin D. HRQoL was assessed with the Osteoporosis Assessment Questionnaire-Short Version (OPAQ-SV) at baseline and every 6 months for 36 months. The OPAQ-SV assesses physical function, emotional status, and back pain. Higher scores indicate better health status. Results No statistically significant differences in mean change in HRQoL from baseline to end of study were found when comparing treatment groups. Compared with women without any incident fractures during the study, women with incident clinical fractures reported significant declines in physical function (-4.0 vs. -0.5) and emotional status (-5.0 vs. -0.8) at month 36 (P<0.001 for both). Importantly, time-dependent covariate analyses demonstrated that the largest declines were observed when the assessment was <3 months post fracture. The largest impact of incident clinical fractures was on physical function, and that of incident clinical vertebral fractures was on back pain. Conclusions These findings not only demonstrate that incident clinical fractures impact HRQoL but also contribute new information regarding the impact of these fracture events on HRQoL over time. © The Author(s) 2011

Chronic stress induced duration dependent alterations in immune system and their reversibility in rats

The objective was to find out whether severity of stress effects on immunity increases with duration of exposure and recovery depends on duration of exposure. Adult male rats (n = 30) were subjected to restraint (1 h) followed by forced swimming exercise (15 min) after a gap of 4 h daily for 2, 4 and 8 weeks and allowed to recover for 6 weeks after each exposure period. Exposure of rats to stress resulted in duration dependent significant decreases in leukocyte count, phagocytic indices of neutrophils, number of bone marrow stem cells and serum levels of IL-12 and increases in apoptotic index of peripheral blood mononuclear cells and serum levels of IL-10. The alterations in counts of neutrophils, total immunoglobulin content, phagocytic index, apoptotic index of peripheral blood mononuclear cells and serum levels of IL-10 returned to control levels in recovery group rats of 2 and 4 weeks exposure but not in that of 8 weeks exposure. However, alterations in number and apoptotic index of bone marrow stem cells returned to control levels in 2, 4 and 8 weeks stress recovery groups. The results for the first time reveal that increase in duration of exposure results in more severe damage in immune system and that shorter the exposure period, faster the recovery. In addition, in vitro study for the first time showed that corticosterone causes apoptosis of peripheral blood mononuclear cells and bone marrow stem cells in dose dependent manner. Hence death of leukocytes and their stem cells is the major cause of stress induced immune dysfunction