Fluoxetine treatment increases trabecular bone formation in mice

Department of Cytokine Biology, Forsyth Institute, Boston, Massachusetts 02115, USA.
Journal of Cellular Biochemistry (Impact Factor: 3.37). 04/2007; 100(6):1387-94. DOI: 10.1002/jcb.21131
Source: PubMed

ABSTRACT Mounting evidence exists for the operation of a functional serotonin (5-HT) system in osteoclasts and osteoblasts, which involves both receptor activation and 5-HT reuptake. In previous work we showed that the serotonin transporter (5-HTT) is expressed in osteoclasts and that its activity is required by for osteoclast differentiation in vitro. The purpose of the current study was to determine the effect of treatment with fluoxetine, a specific serotonin reuptake inhibitor, on bone metabolism in vivo. Systemic administration of fluoxetine to Swiss-Webster mice for 6 weeks resulted in increased trabecular BV and BV/TV in femurs and vertebrae as determined by micro-computed tomography (microCT). This correlated with an increase in trabecular number, connectivity, and decreased trabecular spacing. Fluoxetine treatment also resulted in increased volume in vertebral trabecular bone. However, fluoxetine-treated mice were not protected against bone loss after ovariectomy, suggesting that its anabolic effect requires the presence of estrogen. The effect of blocking the 5-HTT on bone loss following an LPS-mediated inflammatory challenge was also investigated. Subcutaneous injections of LPS over the calvariae of Swiss-Webster mice for 5 days resulted in increased numbers of osteoclasts and net bone loss, whereas new bone formation and a net gain in bone mass was seen when LPS was given together with fluoxetine. We conclude that fluoxetine treatment in vivo leads to increased bone mass under normal physiologic or inflammatory conditions, but does not prevent bone loss associated with estrogen deficiency. These data suggest that commonly used anti-depressive agents may affect bone mass.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Psychotropic drugs are a crucial element of treatment for psychiatric disorders; however there is an established association between many classes of psychotropic medications and fracture risk among older adults, and growing evidence that some classes of medications may also impact bone mineral density (BMD). In this paper we review recent epidemiologic research on the association between psychotropic medications and osteoporosis, and discuss current controversies and unresolved issues surrounding this relationship. Key areas in need of focused inquiry include resolving whether the apparent association between psychotropic medications and BMD is due to confounding by indication, whether this relationship differs for men and women, and whether the implications of these medications for bone health vary over the life course. Clinical research to delineate the risk/benefit ratio of psychotropic medications for older adults, particularly those who are at high risk for fracture, is also needed to facilitate prescribing decisions between patients and physicians.
    Current Osteoporosis Reports 09/2012; 10(4). DOI:10.1007/s11914-012-0121-4
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: AIM: To evaluate the morphological aspects of coronal dentinogenesis in the first molars of 1- and 5-day-old rats whose mothers were treated with fluoxetine hydrochloride during pregnancy.METHODS: Twelve pregnant Wistar rats were divided randomly into three groups: group C (control), group FL (fluoxetine administered at 10 mg/kg bodyweight), and group FX (fluoxetine administered at 20 mg/kg bodyweight). Saline (0.9%) solution or fluoxetine hydrochloride was administered subcutaneously for the first 21 days of pregnancy. Subsequently, the offspring of these animals was subdivided into subgroups according to age of tooth germ development to be studied: 1 and 5 days of life. C1 and C5 (control group 1 and 5 days of age); FL1 and FL5 (groups treated with 10 mg/kg fluoxetine at 1 and 5 days of age); FX5 and FX1 (groups treated with 20 mg/ kg fluoxetine at 1 and 5 days of age).RESULTS: No structural changes in the dentin-pulp complex of rats whose mothers were treated with fluoxetine hydrochloride were observed at either dose.CONCLUSIONS: Fluoxetine, at the doses administered during pregnancy in this study, did not alter the morphological development of the coronal dentin-pulp complex in their offspring.
    Brazilian Journal of Oral Sciences 03/2013; 12(1):30-36. DOI:10.1590/S1677-32252013000100007
  • [Show abstract] [Hide abstract]
    ABSTRACT: Objectives. Studies have reported an association between serotonin reuptake inhibitors (SRIs) and accelerated bone loss. Genetic variation in the serotonin system might modulate bone metabolism changes during SRI treatment. In a clinical trial we examined functional genetic polymorphisms of serotonin transporter and receptors involved in bone metabolism to determine whether they predict changes in bone metabolism during SRI treatment. Methods. In 69 adults (age ≥ 60) participating in a 12-week, open-label trial of the SRI venlafaxine for major depression, serum markers of bone formation (P1NP) and resorption (β-CTX) were assayed before and after treatment. Participants were genotyped for putative high- versus low-expressing polymorphisms in the serotonin transporter (5HTTLPR) and 1B receptor (HTR1B) genes. Results. Bone formation was significantly reduced with administration of venlafaxine in participants with the high-expressing 5HTTLPR genotype and those with the low-expressing HTR1B genotype. This primarily occurred in individuals with the combination of the high-expressing 5HTTLPR genotype and the low-expressing HTR1B genotype. Conclusions. These preliminary findings indicate that genetic variation in the serotonin receptors predicts changes in bone metabolism during SRI use. If these results are replicated and clinically confirmed, we will have identified a genetic subgroup at high risk for deleterious bone outcomes with the use of SRIs.
    The World Journal of Biological Psychiatry 09/2013; DOI:10.3109/15622975.2013.832380 · 3.57 Impact Factor