Long-term glucocorticoid use leads to glucocorticoid-induced osteoporosis (GIOP) and fractures which require proper management. Little is known about the "real-world," long-term costs and effectiveness of anti-osteoporotic treatments. A retrospective analysis of data from the 1996-2004 Medical Expenditure Panel Survey was conducted to evaluate the "real-world" outcomes. Markov modeling with Monte Carlo simulations was used to yield long-term estimates of these outcomes. A total of 5,461 subjects met the study criteria for long-term glucocorticoid users (LTGS, average prednisone-equivalent dose=11.0 mg/day, average length=237 days), which represents 2.3% of the non-institutional U.S. population. The study subjects tended to be middle-aged (49.7 years old), female (61.4%) and white (86.2%). Overall 22.4% of LTGS users reported use of any anti-osteoporotic agent. Hormone replacement therapy (HRT) was the most frequently used in women followed by bisphosphonates, while bisphosphonates and calcitonin were used by men. Analyses of variance indicated some significant differences in characteristics of LTGS users among treatment groups which suggest a selection bias. Female LTGS users had higher prevalence rates (6.8%) of osteoporosis than males (1.0%), but the prevalence rates of osteoporotic fractures were similar (3.0%). The logistic regression analyses indicated that the use of oral glucocorticoid tablets does not significantly change the odds of osteoporotic fractures in study subjects (relative risk (RR)=1.146, 95% confidence interval (CI) 0.901-1.458 for subjects in the WELL state; RR=0.55, 95% CI 0.188-1.621 for subjects in the GIOP state; RR=1.241, 95% CI 0.532-2.893 for subjects in the GIFX state). The estimated 10-year and lifetime incremental cost per osteoporotic fracture avoided are $27,253-$35,692 (10-year) and $84,942-$91,075 (lifetime) in hypothetical female glucocorticoid users. HRT is the most cost-effective option for hypothetical females except that calcitonin is preferred for 65-year-old females receiving lifetime treatments. When HRT is excluded, calcitonin is the next most cost-effective option except that raloxifene is preferred for 30- and 50-year-old females receiving 10-year treatments. Calcitonin is the most cost-effective option for male glucocorticoid users. Bisphosphonates are less cost-effective which may be due to selection bias. Anti-osteoporotic treatments are recommended for all long-term glucocorticoid users, but the preferred option depends on gender, age, length of treatments and budgets.

While the stress response represents an example of allostasis that enables the organism to cope with environmental and psychosocial challenges, its chronic activation imposes an allostatic load that contributes to the cumulative wear and tear of the system and induces negative mental and physical health outcomes. Nonetheless, the underlying basis of the stress-disease connection is still poorly understood and represents a gap in the knowledge that requires further research. We investigated the effects of chronic glucocorticoid stimulation in three independent human primary fibroblast lines, as an in vitro model of chronic psychosocial stress. By deploying a longitudinal, high-frequency, repeated-measures strategy across their entire lifespan, we were able to determine that chronically stressed cells present a significant increase in their total energy expenditure and that this stress-induced hypermetabolism is linked to an acceleration of their biological aging. Expanding from our results and placing emphasis on the energetic costs associated with the activation of the stress response, we proposed the “Energetic Model of Allostatic Load”. This model proposes that chronic stress causes a redirection of the energetic resources towards allostatic responses and away from growth, maintenance, and repair processes, which in turn leads to the accumulation of damage that will further contribute to the development of disease and increased risk of mortality. Finally, we highlighted new avenues to quantify allostatic load and its link to health via the integration of systemic and cellular energy expenditure measurements together with classic biomarkers, that could contribute to further advances in the stress field.

Call number: LD2668 .T4 1985 D42 / Master of Science

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