Depression and Bone Metabolism

Williams, Lana J.; Pasco, Julie A.; Jacka, Felice N.; Henry, Margaret J.; Dodd, Seetal; Berk, Michael

doi:10.1159/000162297

Cited by 53 publications

(29 citation statements)

References 297 publications

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“…First, as depression itself has been shown to be a risk factor of osteoporosis [19–22], incomplete elimination of the impact of disease severity (or other potential confounders) during the matching process could affect our findings, especially in our cohort with depression diagnoses. Another limitation comes from our assessment of medication exposure.…”

Section: Discussionmentioning

confidence: 99%

Serotonin–Norepinephrine Reuptake Inhibitor and Selective Serotonin Reuptake Inhibitor Use and Risk of Fractures: A New-User Cohort Study Among US Adults Aged 50 Years and Older

et al. 2015

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Background Antidepressants may increase the risk of fractures by disrupting sensory-motor function, thereby increasing the risk of falls, and by decreasing bone mineral density and consequently increasing the fall- or impact-related risk of fracture. Selective serotonin reuptake inhibitor (SSRI) antidepressants appear to increase fracture risk relative to no treatment, while less is known about the effect of serotonin-norepinephrine reuptake inhibitor (SNRI) antidepressants, despite SNRIs being prescribed with increasing frequency. No prior study has directly examined how fracture risk differs among patients initiating SNRIs versus those initiating SSRIs. Objective The objective of this study was to assess the effect of SNRI vs. SSRI initiation on fracture rates. Data source Data came from a PharMetrics claims database, 1998–2010, which is comprised of commercial health plan information obtained from managed care plans throughout the US. Methods We constructed a cohort of patients aged 50 years or older initiating either of the two drug classes (SSRI, N=335,146; SNRI, N=61,612). Standardized mortality weighting and Cox proportional hazards regression were used to estimate hazard ratios for fractures by antidepressant class. Results In weighted analyses, the fracture rates were approximately equal in SNRI and SSRI initiators: hazard ratios for the first one and five-year periods following initiation were, respectively, 1.11 (95% CI: 0.92–1.36) and 1.06 (95% CI: 0.90–1.26). For the sub-group of patients with depression who initiated on either SNRIs or SSRIs, those initiating SNRIs had a modestly, but not significantly elevated fracture risk, compared with those who initiated on SSRIs, hazard ratio = 1.31 (95% CI: 0.95–1.79). Conclusions We found no evidence that initiating SNRIs rather than SSRIs materially influenced fracture risk among a cohort of middle-aged and older adults.

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Section: Discussionmentioning

confidence: 99%

Serotonin–Norepinephrine Reuptake Inhibitor and Selective Serotonin Reuptake Inhibitor Use and Risk of Fractures: A New-User Cohort Study Among US Adults Aged 50 Years and Older

et al. 2015

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“…Increased hypothalamic-pituitary-adrenal (HPA) axis activity and stress hormone levels are known to affect metabolism, causing alterations in visceral adiposity and insulin sensitivity. Chronic stress also affects bone turnover, leading to "lowturnover" osteoporosis (12,13,56,61). Involuntary forms of exercise such as swimming and forced treadmill running increase serum biomarkers of stress in rats (15), and even voluntary wheel running has been shown to increase corticosterone secretion (7, 21).…”

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confidence: 99%

Short-term voluntary exercise in the rat causes bone modeling without initiating a physiological stress response

Rosa¹,

Firth²,

Blair³

et al. 2010

American Journal of Physiology-Regulatory, Integrative and Comp

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research has revealed a neuroendocrine connection between the skeleton and metabolism. Exercise alters both bone modeling and energy balance and may be useful in further developing our understanding of this complex interplay. However, research in this field requires an animal model of exercise that does not cause a physiological stress response in the exercised subjects. In this study, we develop a model of short-term voluntary exercise in the female rat that causes bone modeling without causing stress. Rats were randomly assigned to one of three age-matched groups: control, tower climbing, and squat exercise (rising to an erect bipedal stance). Exercise for 21 days resulted in bone modeling as assessed by peripheral quantitative computed tomography. Fecal corticosterone output was used to assess physiological stress at three time points during the study (preexercise, early exercise, and late in the exercise period). There were no differences in fecal corticosterone levels between groups or time points. This model of voluntary exercise in the rat will be useful for future studies of the influence of exercise on the relationship between skeletal and metabolic health and may be appropriate for investigation of the developmental origins of those effects. computed tomography; corticosterone; exercise; metabolism; stress RECENT ADVANCES IN OUR UNDERSTANDING of the dynamic relationship between body structure and metabolism have revealed a neuroendocrine connection between bone remodeling and energy balance, with both bone and fat acting as endocrine organs (14). The osteoblast-specific protein osteocalcin regulates glucose handling through effects on insulin secretion and sensitivity (33). This action is in turn mediated by the adipokine leptin, which inhibits insulin secretion through direct effects on pancreatic ␤-cells (18) and through inhibition of osteocalcin activity (25). The interplay between bone and metabolism has recently been further elucidated by the discovery that the Forkhead family transcription factor FoxO1, a key regulator of insulin handling in multiple tissues, also acts within the osteoblast to control osteocalcin expression and bioactivity (46).Exercise stimulates modeling of the musculoskeletal system (19, 55, 65), alters metabolism (40), and enhances brain function (17), and thus exercise provides an excellent means of exploring the neuroendocrine connection between bone, fat, and energy balance. The rat model of exercise has been used extensively to study the physiological effects of physical activity using such exercise modalities as swimming (24, 32), running (20,29,41,49,52), jumping (57), tower climbing (43), rising to an erect bipedal stance (11, 64), and weight lifting (62). The effects of exercise on bone have been widely characterized in the rat. Ovariectomized rats undergo changes in bone structure that are nearly identical to those seen in human osteoporosis (28,42), and these animals have proven useful for the study of exercise interventions in osteoporosis treatment (36).In examini...

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“…Also consistent with this hypothesis, many studies have found associations of depression with high bone turnover [58–60]. Individuals with major depression have increased levels of proinflammatory cytokines [61–63] and circulating cortisol [64–66], as do socially disadvantaged individuals [67–75].…”

Section: Discussionmentioning

confidence: 80%

Socioeconomic status, race, and bone turnover in the Midlife in the US Study

et al. 2011

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Purpose To determine socioeconomic status (SES) and race differences in levels of bone turnover. Methods Using data from the Biomarker Substudy of the Midlife in the U.S. (MIDUS) study (491 men, 449 women), we examined cross-sectional associations of SES and race with serum levels of bone turnover markers (bone-specific alkaline phosphatase [BSAP], procollagen type I N-terminal propeptide [PINP], and N-telopeptide [Ntx]) separately in men and women. Linear multivariable regression was used to control for body weight, menopausal transition stage, and age. Results Among men, low family poverty-to-income ratio (FPIR) was associated with higher turnover, but neither education nor race was associated with turnover. Men with FPIR <3 had 1.808 nM BCE higher Ntx (P = 0.05), 3.366 U/L higher BSAP (P = 0.02), and 7.066 higher PINP (P = 0.02). Among women, neither education nor FPIR was associated with bone turnover, but Black women had 3.688 nM BCE higher Ntx (P = 0.001), 5.267 U/L higher BSAP (P=0.005), and 11.906 μg/L higher PINP (P=0.008) compared to non-Black women. Conclusions Economic adversity was associated with higher bone turnover in men, and minority race status was associated with higher bone turnover in women, consistent with the hypothesis that higher levels of social stresses cause increased bone turnover. The magnitude of these associations was comparable to the effects of some osteoporosis medications on levels of turnover.

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Depression and Bone Metabolism

Cited by 53 publications

References 297 publications

Serotonin–Norepinephrine Reuptake Inhibitor and Selective Serotonin Reuptake Inhibitor Use and Risk of Fractures: A New-User Cohort Study Among US Adults Aged 50 Years and Older

Serotonin–Norepinephrine Reuptake Inhibitor and Selective Serotonin Reuptake Inhibitor Use and Risk of Fractures: A New-User Cohort Study Among US Adults Aged 50 Years and Older

Short-term voluntary exercise in the rat causes bone modeling without initiating a physiological stress response

Socioeconomic status, race, and bone turnover in the Midlife in the US Study

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