Effect of selective serotonin reuptake inhibitors on bone mineral density: a systematic review and meta-analysis
Abstract
Our work is the first systematic meta-analysis to investigate the effect of selective serotonin reuptake inhibitor (SSRI) medication on bone mineral density. Through meta-analyzed 11 studies, our findings suggested that compared with nonusers, use of SSRIs was significantly associated with lumbar spine BMD reduction, particularly for old people. The use of selective serotonin reuptake inhibitors (SSRIs) has already been associated with bone mass loss. Their effects on bone mineral density (BMD) for the different bone sections have, however, thus been inconsistent. Here, we aim to assess the effects of SSRIs on BMD using a meta-analysis. We searched PubMed, Scopus, ISI Web of Knowledge, the Cochrane Library, and PsycINFO for all English-written studies investigating the effects of SSRIs on BMD and published before November 2017. BMD was compared between non-SSRI users and SSRI users using a random-effect model with standardized mean differences (SMD) and 95% confidence intervals (CIs). Furthermore, subgroup analyses were performed based on study design, age, and sex in order to find the origins of high heterogeneity. Eleven studies met the inclusion criteria and were used for the meta-analysis. Our study demonstrated that the use of SSRIs was significantly associated with lower BMD values (SMD - 0.40; 95% CI - 0.79 to 0.00; p = 0.05) and BMD Z-scores (SMD - 0.28; 95% CI - 0.50 to - 0.05; p = 0.02) of the lumbar spine, but not of the total hip and femoral neck. In addition, SSRI use was associated with a greater bone loss in older people. SSRI use is a risk factor of lower BMD of the lumbar spine, especially for older people. Future studies into the relationship between SSRI use and bone metabolism and bone mass need to be conducted with larger sample sizes for both men and women at different bone sites.
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MDD is associated with poor bone health.
“A growing body of evidence shows that MDD is associated with poor bone health106-109.”
From Comorbidity between major depressive disorder and physical diseases: a comprehensive review of epidemiology, mechanisms and management (2023) · cites this paper as [107]
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“Following long-term use, SSRIs have been associated with several side effects, including reduced bone mineralization (Ak et al., 2015; Feuer et al., 2015; Moura et al., 2014; Seifert and Wiltrout, 2013; Stutzman, 2021; Tsapakis et al., 2012; Zhou et al., 2018).”
InfluentialManagement of Routine Lithium Related Adverse Effects
Meyer, J. M., & Stahl, S. M. (2023) · Cambridge University Press eBooks · doi:10.1017/9781009225069.008
Feng, Q., Song, X., Liu, L., Zhou, X., & Chen, Z. (2024) · Journal of orthopaedic surgery · doi:10.1177/10225536231187181
Psychiatry in the General Hospital
Ramanuj, P., & Ashby, A. (2024) · Cambridge University Press eBooks · doi:10.1017/9781911623861.034
Medications for Mental Health Disorders and Impact on Bone
Leslie-Allen, N. L., Bolton, J. M., & Leslie, W. D. (2025) · Springer eBooks · doi:10.1007/978-3-031-73363-5_126
Lethbridge, L. N., Nagle, M., Johnson, E., Richardson, C., & Dunbar, M. (2025) · Hip International · doi:10.1177/11207000251374546
Kurbanov, F., Dussik, C. M., Phan, A. T., Rouege, Z., Wilbur, D. M., & Ketonis, C. (2026) · Journal of Hand Surgery Global Online · doi:10.1016/j.jhsg.2025.100930
“6,7 Evidence on fracture healing after upper-extremity ORIF in the setting of SSRI exposure remains sparse.”
Serotonergic antidepressant use as a risk factor for nonunion after closed long bone fractures
Mahatme, R. J., Moore, S. A., Woolnough, T., Gangavaram, A., Moon, E., Reddy, E., & Beltran, M. J. (2026) · Injury · doi:10.1016/j.injury.2026.113127
He, S., Yan, Y., Zhou, S., Hong, Z., Huang, S., Liu, Y., Tang, E., Xi, Y., Chen, Y., & Zhang, Z. (2026) · American Journal of Clinical Nutrition · doi:10.1016/j.ajcnut.2026.101466
Self-citationPonna, A. K., Soma, S., Demetriou, Z. J., Giakas, A. M., & Ilyas, A. M. (2026) · Cureus · doi:10.7759/cureus.114976
“Together, these mechanisms yield a well-characterized pattern of skeletal decline in SSRI-exposed patients, including reduced bone mineral density, cortical bone deterioration, elevated fracture risk, and higher rates of osteoporosis [9-13].”
Alfonsi, S. P., Zickler, C. L., Yadav, A. S., Ahmad, F., Terhune, E. B., & Burnett, R. A. (2026) · The Journal of Arthroplasty · doi:10.1016/j.arth.2026.10.008
- Authors
- Zhou, C., Fang, L., Chen, Y., Zhong, J., Wang, H., & Xie, P.
- Affiliations
- The Affiliated Yongchuan Hospital of Chongqing Medical University (CN)
- Chongqing Medical University (CN)
- Corresponding author
- Xie, P.
- Venue
- Osteoporosis International
- Published
- 2018-02-12
- Volume
- 29
- Issue
- 6
- Pages
- 1243-1251
- ISSN
- 0937-941X (ISSN-L)
- 1433-2965
- OpenAlex
- W2787234719
- Cited by
- 59
- References
- 42
- Citations by year
- 2026: 9 · 2025: 6 · 2024: 4 · 2023: 9 · 2022: 4 · 2021: 6 · 2020: 5 · 2019: 9 · 2018: 7
- FWCI
- 1.38
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Osteoporosis International (publishedVersion)
- PubMed (publishedVersion)
- Funders
- The National Key Research and Development Program of China (No.2017YFA0505700)
- National Natural Science Foundation of China (No. 81701361)
- China Postdoctoral Science Foundation funded project (Project No. 2017M612924)
- Topics
- Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
- Health Sciences › Medicine › Oncology › Bone health and treatments
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Pharmacological Effects and Toxicity Studies
- Keywords
- selective serotonin reuptake inhibitors, bone mineral density, lumbar spine, bone loss, older adults, antidepressant side effects, sex differences
- MeSH terms
- Age Factors, Femur Neck, Hip Joint, Humans, Lumbar Vertebrae, Osteoporosis, Bone Density, Selective Serotonin Reuptake Inhibitors, Antidepressive Agents, Second-Generation
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