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Propranolol Reverses Impaired Fracture Healing Response Observed With Selective Serotonin Reuptake Inhibitor Treatment
Author(s) -
Lee Sooyeon,
Remark Lindsey H,
Buchalter Daniel B,
Josephson Anne M,
Wong Madeleine Z,
Litwa Hannah P,
Ihejirika Rivka,
Leclerc Kevin,
Markus Danielle,
Yim Nury L,
Tejwani Ruchi,
BradaschiaCorrea Vivian,
Leucht Philipp
Publication year - 2020
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1002/jbmr.3950
Subject(s) - propranolol , fluoxetine , medicine , endochondral ossification , bone healing , reuptake inhibitor , pharmacology , paroxetine , serotonin , serotonin reuptake inhibitor , endocrinology , anesthesia , surgery , receptor , anatomy , cartilage
ABSTRACT Selective serotonin reuptake inhibitors (SSRIs) are one of the most commonly prescribed antidepressants worldwide and recent data show significant impairment of fracture healing after treatment with the SSRI fluoxetine in mice. Here, we provide evidence that the negative effects of SSRIs can be overcome by administration of the beta‐blocker propranolol at the time of fracture. First, in vitro experiments established that propranolol does not affect osteogenic differentiation. We then used a murine model of intramembranous ossification to study the potential rescue effect of propranolol on SSRI‐induced impaired fracture healing. Micro‐CT analysis revealed that fluoxetine treatment resulted in a smaller bony regenerate and that this decrease in bone formation can be overcome by co‐treatment with propranolol. We then tested this in a clinically relevant model of endochondral ossification. Fluoxetine‐treated mice with a femur fracture were treated with propranolol initiated at the time of fracture, and a battery of analyses demonstrated a reversal of the detrimental effect of fluoxetine on fracture healing in response to propranolol treatment. These experiments show for the first time to our knowledge that the negative effects of SSRIs on fracture healing can be overcome by co‐treatment with a beta‐blocker. © 2019 American Society for Bone and Mineral Research.