The investigators conducted the population-based, international, prospective, multicenter, observational MrOS study to explore the potential association of serotonin levels with fracture risk and falls among elderly men, taking into account the established association of serotonin with bone mineral density (BMD) and muscle strength. A total of 950 men aged 69 to 81 years were enrolled in the MrOS Gothenburg cohort.
Of the 950 participants, 3% (n=33) were taking selective serotonin reuptake inhibitors (SSRIs) and had a significantly lower mean serotonin value compared with non-SSRI users (31.2 μg/L vs 159.4 μg/L; P <.00001). Current smokers (72 of 950) had significantly higher mean serotonin levels compared with nonsmokers (182.1 μg/L±78.3 μg/L vs 156.8 μg/L±70.5 μg/L; P =.01).
During a 10-year follow-up, 224 men experienced fractures, which included 97 nonvertebral osteoporotic fractures (57 hip fractures) and 86 vertebral fractures. Serotonin was linked to hip fracture in linear analysis (hazard ratio [HR], 1.27; 95% CI, 1.03-1.58).
When quintiles of serotonin were included as a quadratic term, a statistically significant nonlinear relationship was reported between serotonin levels and incident fractures (HR, 1.12; 95% CI, 1.04-1.21; P =.004), hip fracture (HR, 1.24; 95% CI, 1.05-1.45; P =.009), and nonvertebral osteoporotic fractures (HR, 1.21; 95% CI, 1.08-1.37; P =.002), but not with vertebral fractures (HR, 1.07; 95% CI, 0.94-1.21; P =.29). Furthermore, serotonin concentrations were positively associated with hand-grip strength (r=0.08; P =.02) and inversely associated with hip BMD (r=-−0.10; P =.003).
To examine the association between SSRIs and falls and fractures, investigators examined the total MrOS Sweden cohort of 3014 men. Among the 90 SSRI users in the total cohort, SSRI users had a significantly increased prevalence of falls compared with non-SSRI users (33% vs 16%, respectively; P =.0001). Moreover, SSRI users vs nonusers experienced a significantly increased rate of incident fractures (44.7 vs 28.0 per 1000 person-years; P =.018).
The investigators concluded that the novel data presented in this study demonstrate that high levels of serum serotonin can predict increased risk for hip fractures, incident fractures, and nonvertebral osteoporotic fractures among elderly men. The authors note that the almost 3-fold increased risk for hip fractures reported among those with high serotonin levels is particularly striking, as well as that the risk is independent of BMD hip and muscle strength.
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