Full Length ArticleEffects of antidepressants on postmenopausal bone loss — A 5-year longitudinal study from the OSTPRE cohort
Introduction
Major depression, regardless of age, is one of the leading causes of disease burden worldwide [1]. It is also twice as common in women compared to men and its incidence has been shown to increase following menopause [2]. The use of antidepressants has doubled in the last decade [3], with 8% of Europeans using them in 2010 [4]. The side effects of antidepressants, e.g., anticholinergic effects, are common and more recently have also been noted the negative effects on bone [5].
Antidepressants target monoamines, particularly serotonin (5-hydroxytryptamine, 5-HT) and noradrenalin (NA) in synapses by blocking their transporters [6], [7]. Interestingly, bone cells (osteoblasts, osteoclasts and osteocytes) have been shown to contain both 5-HT transporters (5-HTT) and 5-HT receptors [8], [9]. Osteoblasts, responsible for bone formation, have also been studied to express the NA transporter (NET), with NA increasing both bone formation and resorption [10], [11]. Recently, selective serotonin reuptake inhibitors (SSRIs), the most widely prescribed antidepressant [12], have been shown to inhibit human osteoblast and osteoclast formation and function [13].
The association between antidepressant use and bone has been investigated in an increasing number of epidemiological studies, mainly been cross-sectional and focused on SSRIs. Among postmenopausal women, use of SSRIs has been shown to be associated with lower bone mineral density (BMD) [14], [15], [16] and accelerated bone loss over time [14], although some have shown no association [17], [18]. In regards to tricyclic antidepressants (TCA), there has generally been null findings across varying populations of women [14], [18], [19], with one study finding the agents to actually be associated with increases in BMD [15].
Thus, we aimed to investigate the association between different types of antidepressants and BMD change over time in a large group of postmenopausal women. To our knowledge this is the first large longitudinal and population-based study that examines quantitatively not only SSRIs or TCAs, but also other antidepressants and poly use. As postmenopausal women are at high risk of bone loss [20], this population group was selected to form the study sample.
Section snippets
Study design and subjects
The initial postal enquiry of the Kuopio Osteoporosis Risk Factor and Prevention Study (OSTPRE) was sent in 1989 to all women born between 1932 and 41 and residing in Kuopio Province, Finland (n = 14.220). Of the 13,100 respondents, 3222 were participating to bone densitometry with Dual X-ray Absorptiometry (DXA). This densitometry group included 2025 randomly selected women and all the 1197 women, who had either menopause within 2 years, at least three health behavior risk factors or disease or
Study population characteristics
According to the prescription register, 319 of the 1988 participants (16.0%) had purchased antidepressants during the 5-year follow-up. Of all the participants, 92 (4.6%) had used only TCAs, 118 (5.9%) only SSRIs and 56 (2.8%) only other antidepressants, while 52 (2.6%) women were poly users (Table 1). Moreover, one woman had used MAO inhibitors. The group of other antidepressants included users of mirtazapine (n = 40), mianserin (n = 7), venlafaxine (n = 5) and trazodone (n = 4).
Mean baseline femoral
Discussion
This longitudinal study investigated the associations between antidepressant use and postmenopausal femoral neck BMD change over a 5-year period. Accelerated bone loss was associated with the use of TCAs and SSRIs. In addition, use of other antidepressants (mainly mirtazapine) was associated with accelerated bone loss, however only in low-weight women.
Previously, Diem et al. [14] reported a 0.82% annual mean total hip bone loss in postmenopausal SSRI users compared with a 0.47% loss in
Conclusions
In conclusion, the use of SSRIs seems to accelerate postmenopausal bone loss in a dose-response manner. A relationship between TCA and other antidepressant use with bone loss may also exist. Thus, the risk of osteoporosis should be considered when antidepressants are prescribed for postmenopausal women.
Conflict of interest
All authors state that they have no conflicts of interest.
Source of funding
Research has been supported by the strategics of the University of Eastern Finland, by the Academy of Finland (grants 115969 and 250707), Ministry of Education and Culture and Kuopio University Hospital Funding (VTR). PR received research support from Finnish Concordia Fund, National Doctoral Programme of Musculoskeletal Disorders and Biomaterials, North Savo Regional Fund of Finnish Cultural Foundation (GNT 65142185) and Saastamoinen Foundation, and an EVO grant from Lapland Hospital District.
Acknowledgements
PR, HK-H and RH designed the study. PR conducted data analysis, data interpretation, and the writing of the manuscript. HK-H and RH were responsible for the data and contributed to data interpretation and writing of the manuscript. LW contributed to data interpretation and writing of the manuscript. RH, MT and HK were responsible for the original OSTPRE study design. All the authors contributed to the revision of the manuscript and approved the final version.
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