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High Serum Serotonin Predicts Increased Risk for Hip Fracture and Nonvertebral Osteoporotic Fractures : The MrOS Sweden Study

Kristjansdottir, Hallgerdur Lind; Lewerin, Catharina; Lerner, Ulf H.; Waern, Ewa; Johansson, Helena; Sundh, Daniel; Karlsson, Magnus LU ; Cummings, Steve R.; Zetterberg, Henrik LU and Lorentzon, Mattias, et al. (2018) In Journal of Bone and Mineral Research 33(9). p.1560-1567
Abstract

Because several studies have implicated serotonin as a regulator of bone mass, we here explore its potential association on fracture risk and falls, as on bone mineral density (BMD) and muscle strength, in humans. Serum levels of serotonin were analyzed in 950 men (aged 69 to 81 years), participating in the Gothenburg part of the population-based study MrOS Sweden. Men taking selective serotonin reuptake inhibitors (SSRIs) had a mean value of 31.2 μg/L compared with 159.4 μg/L in those not taking SSRIs. SSRI users were excluded from further analysis. During 10-year follow-up, 224 men exhibited fractures, including 97 nonvertebral osteoporotic fractures (57 hip fractures), and 86 vertebral fractures. Serotonin was associated with hip... (More)

Because several studies have implicated serotonin as a regulator of bone mass, we here explore its potential association on fracture risk and falls, as on bone mineral density (BMD) and muscle strength, in humans. Serum levels of serotonin were analyzed in 950 men (aged 69 to 81 years), participating in the Gothenburg part of the population-based study MrOS Sweden. Men taking selective serotonin reuptake inhibitors (SSRIs) had a mean value of 31.2 μg/L compared with 159.4 μg/L in those not taking SSRIs. SSRI users were excluded from further analysis. During 10-year follow-up, 224 men exhibited fractures, including 97 nonvertebral osteoporotic fractures (57 hip fractures), and 86 vertebral fractures. Serotonin was associated with hip fracture in linear analysis (hazard ratio [HR] = 1.27, 95% confidence interval [CI] 1.03–1.58) and to all fractures in a nonlinear manner, when quintiles of serotonin was included in quadratic terms (HR = 1.12, 95% CI 1.04–1.21). Men in serotonin quintile 5 had, in multivariable analysis, a HR of 2.30 (95% CI 1.31–4.02) for hip fracture and 1.82 (95% CI 1.17–2.85) for nonvertebral fractures compared with men in quintiles 1 to 4. Men in quintile 1 had, in multivariable analysis, a HR of 1.76 (95% CI 1.03–2.99) for nonvertebral fractures compared with men in quintiles 2 to 4. No association was found with vertebral fractures. Individuals in serotonin quintile 1 had higher prevalence of falls compared with quintiles 2 to 5 (odds ratio = 1.90, 95% CI 1.26–2.87). Serotonin was positively associated with hand-grip strength (r = 0.08, p = 0.02) and inversely with hip BMD (r = −0.10, p = 0.003). To assess the association between SSRIs and falls and fractures, the total MrOS Sweden cohort was examined (n = 3014). SSRI users (n = 90) had increased prevalence of falls (16% versus 33%, p = 0.0001) and increased rate of incident fractures (28.0 versus 44.7 per 1000 person-years, p = 0.018). We present novel data showing that high levels of serotonin predict an increased risk for hip fracture and nonvertebral osteoporotic fractures.

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published
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keywords
BMD, FALLS, FRACTURES, SERUM SEROTONIN, SSRI
in
Journal of Bone and Mineral Research
volume
33
issue
9
pages
8 pages
publisher
AMBMR
external identifiers
  • scopus:85052505765
ISSN
0884-0431
DOI
10.1002/jbmr.3443
language
English
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yes
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a70d08ca-51a1-4e9c-8df1-e603004fe267
date added to LUP
2018-09-25 13:02:21
date last changed
2019-07-16 03:56:15
@article{a70d08ca-51a1-4e9c-8df1-e603004fe267,
  abstract     = {<p>Because several studies have implicated serotonin as a regulator of bone mass, we here explore its potential association on fracture risk and falls, as on bone mineral density (BMD) and muscle strength, in humans. Serum levels of serotonin were analyzed in 950 men (aged 69 to 81 years), participating in the Gothenburg part of the population-based study MrOS Sweden. Men taking selective serotonin reuptake inhibitors (SSRIs) had a mean value of 31.2 μg/L compared with 159.4 μg/L in those not taking SSRIs. SSRI users were excluded from further analysis. During 10-year follow-up, 224 men exhibited fractures, including 97 nonvertebral osteoporotic fractures (57 hip fractures), and 86 vertebral fractures. Serotonin was associated with hip fracture in linear analysis (hazard ratio [HR] = 1.27, 95% confidence interval [CI] 1.03–1.58) and to all fractures in a nonlinear manner, when quintiles of serotonin was included in quadratic terms (HR = 1.12, 95% CI 1.04–1.21). Men in serotonin quintile 5 had, in multivariable analysis, a HR of 2.30 (95% CI 1.31–4.02) for hip fracture and 1.82 (95% CI 1.17–2.85) for nonvertebral fractures compared with men in quintiles 1 to 4. Men in quintile 1 had, in multivariable analysis, a HR of 1.76 (95% CI 1.03–2.99) for nonvertebral fractures compared with men in quintiles 2 to 4. No association was found with vertebral fractures. Individuals in serotonin quintile 1 had higher prevalence of falls compared with quintiles 2 to 5 (odds ratio = 1.90, 95% CI 1.26–2.87). Serotonin was positively associated with hand-grip strength (r = 0.08, p = 0.02) and inversely with hip BMD (r = −0.10, p = 0.003). To assess the association between SSRIs and falls and fractures, the total MrOS Sweden cohort was examined (n = 3014). SSRI users (n = 90) had increased prevalence of falls (16% versus 33%, p = 0.0001) and increased rate of incident fractures (28.0 versus 44.7 per 1000 person-years, p = 0.018). We present novel data showing that high levels of serotonin predict an increased risk for hip fracture and nonvertebral osteoporotic fractures.</p>},
  author       = {Kristjansdottir, Hallgerdur Lind and Lewerin, Catharina and Lerner, Ulf H. and Waern, Ewa and Johansson, Helena and Sundh, Daniel and Karlsson, Magnus and Cummings, Steve R. and Zetterberg, Henrik and Lorentzon, Mattias and Ohlsson, Claes and Mellström, Dan},
  issn         = {0884-0431},
  keyword      = {BMD,FALLS,FRACTURES,SERUM SEROTONIN,SSRI},
  language     = {eng},
  month        = {05},
  number       = {9},
  pages        = {1560--1567},
  publisher    = {AMBMR},
  series       = {Journal of Bone and Mineral Research},
  title        = {High Serum Serotonin Predicts Increased Risk for Hip Fracture and Nonvertebral Osteoporotic Fractures : The MrOS Sweden Study},
  url          = {http://dx.doi.org/10.1002/jbmr.3443},
  volume       = {33},
  year         = {2018},
}