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Bone physiology and therapeutics in chronic critical illness

Modern medical practices allow patients to survive acute insults and be sustained by machinery and medicines for extended periods of time. We define chronic critical illness as a later stage of prolonged critical illness that requires tracheotomy. These patients have persistent elevations of inflammatory cytokines, diminished hypothalamic–pituitary function, hypercatabolism, immobilization, and malnutrition. The measurement of bone turnover markers reveals markedly enhanced osteoclastic bone resorption that is uncoupled from osteoblastic bone formation. We review the mechanisms by which these factors contribute to the metabolic bone disease of chronic critical illness and suggest potential therapeutics.