Selective Serotonin Reuptake Inhibitors (SSRIs) and Markers of Bone Turnover in Men

Abstract

Selective serotonin reuptake inhibitors (SSRIs) have been shown to have a clinically significant impact on bone metabolism. To explore this further, we aimed to determine whether these agents are associated with serum markers of bone turnover utilising a population-based sample of men (n = 1138; 20-96 year) participating in the Geelong Osteoporosis Study. Blood samples were obtained and the bone resorption marker, C-telopeptide (CTx) and formation marker, type 1 procollagen amino-terminal-propeptide (PINP) were measured. Anthropometry and socio-economic status (SES) were determined and information on medication use and lifestyle was obtained via questionnaire. Lifetime mood disorders were assessed using semi-structured clinical interviews. Thirty-seven (3.3%) men reported using SSRIs. Age was an effect modifier in the association between SSRIs and markers of bone turnover. Among younger men (20-60 year; n = 557), adjusted mean CTx and PINP values were 12.4% [16.7 (95% CI 14.6-18.8) vs 19.1 (95% CI 18.7-19.4) pg/ml, p = 0.03] and 13.6% [5.6 (95% CI 4.9-6.3) vs 6.4 (95% CI 6.3-6.6) pg/ml, p = 0.02] lower among SSRI users compared to non-users, respectively. No differences in SSRI use and markers of bone turnover were detected among older men (61-94 year; all p > 0.05). These patterns persisted after further adjustment for activity, alcohol, smoking, SES, depression, bone active medications and other antidepressants. Our data suggest that SSRI use is associated with alterations in bone turnover markers among younger men. The observed decreases in both CTx and PINP are likely to contribute to a low bone turnover state and increased skeletal fragility with this potential imbalance between formation and resorption resulting in subsequent bone loss.

Biochemistry of Drugs Action and their Resistance Mechanism: A Brief Discussion

“…MAOIs remained the principal types of drugs responsible to treat depression. They are convincing, but they have generally been replaced by antidepressants which are safer and cause fewer reactions (Williams et al, 2018). In specific cases, they ease stress when different medicines have fizzled.…”

Bone Metabolism in Patients Treated for Depression

“…Identification of risk factors is important for early diagnosis and treatment, resulting in a significant public health benefit [ 7 ]. Recently, depression and its treatment were suspected as risk factors for osteoporosis development [ 8 , 9 , 10 ]. The problem is a significant public health issue since depression affects 98.7 million people globally, being a major cause of disability worldwide [ 11 ].…”

“…Moreover, the increased risk of fracture in patients with depression was demonstrated; 26% when the hazard risk was assessed ( n = 309,862) and 39% when the risk ratio was determined ( n = 64,975) [ 9 ]. Data on the influence of depression therapy on bone metabolism, especially with SSRIs (selective serotonin reuptake inhibitors), are conflicting [ 10 , 12 ]. There are many hypotheses associating depression with osteoporosis [ 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 ].…”

“…The second mechanism is related to overproduction of inflammatory cytokines, such as interleukins IL-1β, IL-2, IL-6, and tumor necrosis factor-alpha, in patients with depression [ 16 ]. Other, probably coexisting factors to consider are the propensity to fall [ 17 ], low mobility [ 18 ], adoption of poor health behaviors (e.g., smoking and physical inactivity), and drugs, especially SSRIs [ 10 , 12 , 18 ]. Vitamin D deficiency seems to be an important factor, connecting osteoporosis with depression [ 8 , 9 , 10 ].…”

“…Other, probably coexisting factors to consider are the propensity to fall [ 17 ], low mobility [ 18 ], adoption of poor health behaviors (e.g., smoking and physical inactivity), and drugs, especially SSRIs [ 10 , 12 , 18 ]. Vitamin D deficiency seems to be an important factor, connecting osteoporosis with depression [ 8 , 9 , 10 ]. Vitamin D has a dual role in the human body, acting as a hormone and fat-soluble vitamin, regulating the expression of over 900 genes by binding to the vitamin D receptor (VDR) [ 19 ].…”