09 Sep Long-Term Bone Loss Linked to Antidepressants May Be Ameliorated By Beta Blockers
MedicalResearch.com Interview with:
Patricia Ducy, PhD
Department of Pathology & Cell Biology
New York, NY 10032
MedicalResearch.com: What is the background for this study?
Response: In the past few years, several large clinical studies have reported an association between the use of selective serotonin reuptake inhibitors (SSRIs) and an increased risk of bone fractures. Yet, a few studies conducted on small cohorts using these drugs for a short time showed a decrease in bone resorption parameters and thus minor bone gain.
To understand this paradox and to define how the deleterious effect of SSRIs could be prevented we conducted a series of studies in mice treated with fluoxetine, the active molecule of the widely prescribed SSRI Prozac.
MedicalResearch.com: What are the main findings?
Response: Our findings are threefold:
- When used for a very short-term fluoxetine has a positive effect on bone because it directly inhibits the cells (osteoclasts) in charge of breaking it down (bone resorption). This observation is in agreement with the clinical studies reporting short-term effects of SSRIs on bone biomarkers.
- When the fluoxetine treatment is extended, however, this beneficial effect is overwhelmed by an action on brain serotonin signaling. Fluoxetine exerts its mood controlling action by enhancing serotonin availability. Unfortunately, this increase ends up neutralizing the serotonin receptor most specifically regulating bone biology. This translates into an increase in sympathetic tone, which in turn impairs bone formation and enhances bone resorption. The net result is bone loss, which is consistent with the increased number of fractures observed in the large clinical studies that analyzed long-term users of SSRIs.
- Blocking the negative effect of this increase in sympathetic tone on bone cells with a low dose of a commonly used beta-blocker (propranolol) can protect bone mass in mice after a long-term treatment with fluoxetine. This, however, does not appear to alter its effect on behavior.
MedicalResearch.com: What should readers take away from your report?
Response: Our study provides a proof-of-principle that the deleterious effect on bone caused by a long-term treatment with SSRIs can be prevented by a combination therapy with a beta-blocker.
MedicalResearch.com: What recommendations do you have for future research as a result of this study?
Response: The first, easiest, step is to conduct retrospective studies to test whether patients taking both SSRIs and beta-blockers have less bone fractures than patients taking only SSRIs on the long run.
A second step would be to perform prospective studies in which different class of SSRIs and beta-blocker as well as different doses of the latter would be tested.
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Serotonin-reuptake inhibitors act centrally to cause bone loss in mice by counteracting a local anti-resorptive effect
María José Ortuño, Samuel T Robinson, Prakash Subramanyam, Riccardo Paone, Yung-yu Huang, X Edward Guo, Henry M Colecraft, J John Mann & Patricia Ducy
Nature Medicine (2016) doi:10.1038/nm.4166
Published online 05 September 2016
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