Rosenblat J D, Gregory J M, Carvalho A F, McIntyre R S
Department of Psychiatry, University of Toronto, 399 Bathurst Street, Toronto, ON, M5T 2S8, Canada.
Curr Mol Med. 2016;16(2):165-78. doi: 10.2174/1566524016666160126144303.
Major depressive disorder (MDD) is a pervasive chronic condition that contributes substantially to the global burden of disease and disability. Adding to the complexity of this disorder are numerous associated medical comorbidities with a bidirectional impact on morbidity and mortality. In recent years, osteoporosis has been increasingly identified as a significant comorbidity of MDD. This narrative review examines the literature to summarize key epidemiological studies and discuss postulated mechanisms of interaction. Epidemiological studies have repeatedly shown an increased co-prevalence of fractures and decreased bone mineral density (BMD) in MDD. The pathophysiological mechanism underlying this interaction is undoubtedly complex and multifactorial, and proposed pathways have varying levels of evidence from preclinical and clinical models. Conceptually, the mechanisms by which depression might influence bone metabolism can be categorized into biological, behavioral, iatrogenic, and comorbidity-related factors. Biological factors include the inflammatory-mood pathway, hypothalamic-pituitary-adrenal (HPA) axis dysregulation, metabolic dysfunction, and serotonin's direct and indirect effects on bone cells. Behavioral factors incorporate lifestyle choices typical in depressed patients, such as increased tobacco use or limited exercise. The prominent iatrogenic factor is the independent effects of anti-depressants on bone metabolism. Psychiatric and medical comorbidities common to both osteoporosis and MDD are also important to consider. Physical activity promotion, vitamin D supplementation, and routine BMD screening of MDD patients are simple interventions that might lead to improved outcomes for both conditions. An improved understanding of the underlying mechanisms may yield insights into novel prevention and treatment strategies to target osteoporosis and fractures in the MDD population.
重度抑郁症（MDD）是一种普遍存在的慢性疾病，对全球疾病负担和残疾状况有重大影响。该疾病的复杂性还在于存在众多相关的医学合并症，这些合并症对发病率和死亡率具有双向影响。近年来，骨质疏松症越来越多地被认为是MDD的一种重要合并症。这篇叙述性综述通过查阅文献，总结关键的流行病学研究，并讨论假定的相互作用机制。流行病学研究反复表明，MDD患者骨折的共患病率增加，骨矿物质密度（BMD）降低。这种相互作用背后的病理生理机制无疑是复杂且多因素的，从临床前和临床模型得出的证据表明，所提出的途径具有不同程度的证据支持。从概念上讲，抑郁症可能影响骨代谢的机制可分为生物学、行为学、医源性和合并症相关因素。生物学因素包括炎症-情绪途径、下丘脑-垂体-肾上腺（HPA）轴失调、代谢功能障碍以及血清素对骨细胞的直接和间接影响。行为因素包括抑郁症患者典型的生活方式选择，如吸烟增加或运动受限。突出的医源性因素是抗抑郁药对骨代谢的独立影响。骨质疏松症和MDD共有的精神和医学合并症也很重要，需要考虑。促进身体活动、补充维生素D以及对MDD患者进行常规BMD筛查是简单的干预措施，可能会改善这两种疾病的预后。对潜在机制的更好理解可能会为针对MDD人群的骨质疏松症和骨折的新型预防和治疗策略提供见解。
