The use of antidepressants is linked to bone loss: A systematic review and metanalysis

Abstract

Introduction Depression and antidepressants are among risk factors for osteoporosis. However, there are still inconsistencies in literature regarding bone consequences of antidepressant drugs and the role of age and the natural decline of bone health in patients with depression. Objective To investigate the relationship between antidepressant and bone mineral density (BMD). Methods We conducted a systematic review and metanalysis according to PRISMA guidelines searching on PubMed/Medline, Cochrane Database, and Scopus libraries and registered with PROSPERO (registration number CRD42021254006) using generic terms for antidepressants and BMD. Search was restricted to English language only and without time restriction from inception up to June 2021. Methodological quality was assessed with the Newcastle-Ottawa scale. Results Eighteen papers were included in the qualitative analysis and five in the quantitative analysis. A total of 42,656 participants affected by different subtypes of depression were identified. Among the included studies, 10 used serotonin reuptake inhibitors (SSRIs) only, 6 involved the use of SSRIs and tricyclic antidepressants, and 2 the combined use of more than two antidepressants. No significant studies meeting the inclusion criteria for other most recent categories of antidepressants, such as vortioxetine and esketamine. Overall, we observed a significant effect of SSRI on decrease of BMD with a mean effect of 0.28 (95% CI = 0.08, 0.39). Conclusion Our data suggest that SSRIs are associated with a decrease of BMD. We aim to raise clinicians’ awareness of the potential association between the use of antidepressants and bone fragility to increase monitoring of bone health.

Emerging factors affecting peri‐implant bone metabolism

“…324 A recent review and metanalysis observed a significant decrease in bone mineral density after using SSSRIs with a mean effect of 0.28 (95% CI = 0.08, 0.39). 313 A retrospective comparison did not show a significant difference in the time of bone fractures to union between patients with chronic SSRI use and patients who had not been on SSRIs (time to heal 6.1 vs. 6.0 months). 323 Daily use of SSRIs in adults over 50 years was associated with a twofold increased risk of clinical fragility fracture, lower bone mineral density at the hip, and a trend toward lower bone mineral density at the spine.…”

“…312 As osteoblasts and osteoclasts have receptors for serotonin and can be exposed to this substance by autocrine, paracrine, or endocrine pathways, the levels of serotonin can affect bone metabolism. [313][314][315] Most of the in vitro studies found serotonin to exert a positive effect on osteoblast proliferation, differentiation, and mineralization [316][317][318] while others reported inhibitory effects on osteoblastic cells. [319][320][321] In detail, a study in rats found that low levels of serotonin inhibited osteoblast proliferation, differentiation, and mineralization whereas this role was mitigated at high 5-HT concentrations.…”

“…These drugs tend to increase the levels of brain serotonin by preventing the reuptake of 5‐hydroxytryptamine (5‐HT) 312 . As osteoblasts and osteoclasts have receptors for serotonin and can be exposed to this substance by autocrine, paracrine, or endocrine pathways, the levels of serotonin can affect bone metabolism 313–315 . Most of the in vitro studies found serotonin to exert a positive effect on osteoblast proliferation, differentiation, and mineralization 316–318 while others reported inhibitory effects on osteoblastic cells 319–321 .…”

“…Indeed, the use of SSRIs has been related to a negative impact on bone health, and SSRIs have been associated with significantly higher rates of all‐cause revision (OR 1.24) or aseptic revision (OR 1.24) after total shoulder arthroplasty 324 . A recent review and metanalysis observed a significant decrease in bone mineral density after using SSSRIs with a mean effect of 0.28 (95% CI = 0.08, 0.39) 313 . A retrospective comparison did not show a significant difference in the time of bone fractures to union between patients with chronic SSRI use and patients who had not been on SSRIs (time to heal 6.1 vs. 6.0 months) 323 .…”

Integrated approach to reducing polypharmacy in older people: exploring the role of oxidative stress and antioxidant potential therapy

“…Among these, SSRIs are the most safe and commonly prescribed class of antidepressants, making them the first-line treatment for older patients due to their limited effects on autonomic system activity and a lower impact on blood pressure [ 285 ]. Nevertheless, SSRIs may be associated with falls and osteoporosis [ 286 ].…”