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  1. Article ; Online: Update in serotonin and bone.

    Bliziotes, Michael

    The Journal of clinical endocrinology and metabolism

    2010  Volume 95, Issue 9, Page(s) 4124–4132

    Abstract: Context: Serotonin (5-HT) may be an important regulatory agent in bone, and agents that modify 5-HT signaling, such as selective serotonin reuptake inhibitors (SSRIs), are in widespread clinical use.: Evidence acquisition: Evidence was obtained by ... ...

    Abstract Context: Serotonin (5-HT) may be an important regulatory agent in bone, and agents that modify 5-HT signaling, such as selective serotonin reuptake inhibitors (SSRIs), are in widespread clinical use.
    Evidence acquisition: Evidence was obtained by PubMed search and the author's knowledge of the field.
    Evidence synthesis: Recent data suggest that gut-derived 5-HT may mediate the skeletal effects of LDL receptor-related protein 5, stimulating intense interest in a novel mechanism for regulating bone mass. However, the specific biochemical nature of serotonergic pathways influencing bone and their direct and/or indirect effects on bone metabolism are still unclear. The weight of epidemiological evidence suggests that SSRIs are associated with reduced bone mass, increased bone loss, and increased risk of fractures. Interpretation of these studies is complicated by the confounding effects of depression, the usual indication for treatment with SSRIs. The mechanisms for putative SSRI-induced deleterious effects on the skeleton are unknown, and are likely multifactorial.
    Conclusions: 5-HT may have regulatory effects on bone. Initial preclinical data suggest that its effects may be deleterious and may be regulated by low-density lipoprotein receptor-related protein 5. These studies need confirmation, as well as elucidation, of the biochemical pathways utilized and the feedback loops involved among bone, gut, and perhaps brain. Paradoxically, targeting of 5-HT synthesis and/or signaling in selective tissues may hold promise as an anabolic intervention for bone. Epidemiological data suggest that clinicians should be vigilant about detection of bone disease in patients who are using SSRIs.
    MeSH term(s) Animals ; Bone and Bones/drug effects ; Bone and Bones/metabolism ; Bone and Bones/physiology ; Central Nervous System/drug effects ; Humans ; Intestinal Mucosa/metabolism ; Intestines/physiology ; LDL-Receptor Related Proteins/physiology ; Low Density Lipoprotein Receptor-Related Protein-5 ; Models, Biological ; Serotonin/metabolism ; Serotonin/pharmacology ; Serotonin/physiology ; Serotonin Uptake Inhibitors/pharmacology ; Signal Transduction/drug effects
    Chemical Substances LDL-Receptor Related Proteins ; LRP5 protein, human ; Low Density Lipoprotein Receptor-Related Protein-5 ; Serotonin Uptake Inhibitors ; Serotonin (333DO1RDJY)
    Language English
    Publishing date 2010-09-07
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Review
    ZDB-ID 3029-6
    ISSN 1945-7197 ; 0021-972X
    ISSN (online) 1945-7197
    ISSN 0021-972X
    DOI 10.1210/jc.2010-0861
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Male osteoporosis: new insights in an understudied disease.

    Haney, Elizabeth M / Bliziotes, M Michael

    Current opinion in rheumatology

    2008  Volume 20, Issue 4, Page(s) 423–428

    Abstract: Purpose of review: Osteoporosis in men is increasingly recognized as an important health problem. New research contributes to our knowledge of gender differences in osteoporosis risk, diagnosis and management. We undertook this review to summarize ... ...

    Abstract Purpose of review: Osteoporosis in men is increasingly recognized as an important health problem. New research contributes to our knowledge of gender differences in osteoporosis risk, diagnosis and management. We undertook this review to summarize recent developments in the field of male osteoporosis.
    Recent findings: The paper reviews recently published studies that reveal new insights into male osteoporosis. It addresses epidemiology, risk factors, use of clinical risk assessment tools, diagnosis and treatment. New data continue to suggest that men have higher mortality rates than women after hip fracture, and that men may experience fractures at higher bone mineral density values than women. Treatments for osteoporosis have been studied mostly in women, but trials including both men and women are now being conducted. Likewise, there are several newer cohorts with bone and fracture outcomes that include men and women. The Osteoporotic Fractures in Men (MrOS) study is the first United States-based cohort to include only men; this study is contributing importantly to our understanding of epidemiology and risk factors for osteoporosis in men.
    Summary: Men and their physicians should be aware of the risk for osteoporosis and the gender differences that exist within this disease. Further research is needed to continue to understand differences in pathophysiology, epidemiology and risk factors, and to promote appropriate therapies among men.
    MeSH term(s) Adult ; Aged ; Humans ; Male ; Middle Aged ; Osteoporosis/diagnosis ; Osteoporosis/epidemiology ; Osteoporosis/therapy ; Risk Assessment ; Risk Factors ; Sex Factors
    Language English
    Publishing date 2008-06-04
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Review
    ZDB-ID 1045317-9
    ISSN 1531-6963 ; 1040-8711
    ISSN (online) 1531-6963
    ISSN 1040-8711
    DOI 10.1097/BOR.0b013e3283025eb0
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Effects of selective serotonin reuptake inhibitors on bone health in adults: time for recommendations about screening, prevention and management?

    Haney, Elizabeth M / Warden, Stuart J / Bliziotes, M Michael

    Bone

    2009  Volume 46, Issue 1, Page(s) 13–17

    Abstract: Evidence regarding a functional serotonin (5-hydroxytryptamine) signaling system in bone has generated considerable recent interest. The specific biochemical nature of serotoninergic pathways and their direct and/or indirect effects on bone metabolism ... ...

    Abstract Evidence regarding a functional serotonin (5-hydroxytryptamine) signaling system in bone has generated considerable recent interest. The specific biochemical nature of serotoninergic pathways and their direct and/or indirect effects on bone metabolism are still unclear. Clinical evidence supports an effect of serotonin and altered serotonin signaling on bone metabolism. Serotonin is involved in the pathophysiology of depression, and therefore studies of depression and antidepressant treatments (as modulators of the serotonin system) are relevant with regard to bone outcomes. Studies on the effect of depression on bone mineral density (BMD) and fractures have been mixed. Studies on the associations between antidepressant use and BMD and/or fractures are more consistent. SSRIs have been associated with lower BMD and increased rates of bone loss, as well as increased rates of fracture after accounting for falls. These studies are limited by confounding because depression is potentially associated with both the outcome of interest (BMD and fracture) and the exposure (SSRIs). With mounting evidence for an effect on bone, this review considers the question of causality and whether selective serotonin reuptake inhibitors should be considered among those medications that contribute to bone loss, and therefore prompt clinicians to evaluate BMD proactively. Future research will be required to confirm the serotoninergic effects on bone and the biochemical pathways involved, and to identify clinical implications for treatment based on this novel pathway.
    MeSH term(s) Adult ; Antidepressive Agents/adverse effects ; Antidepressive Agents/pharmacology ; Antidepressive Agents/therapeutic use ; Bone Density/drug effects ; Bone and Bones/drug effects ; Depression/drug therapy ; Humans ; Serotonin Uptake Inhibitors/adverse effects ; Serotonin Uptake Inhibitors/pharmacology ; Serotonin Uptake Inhibitors/therapeutic use
    Chemical Substances Antidepressive Agents ; Serotonin Uptake Inhibitors
    Language English
    Publishing date 2009-08-05
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Review
    ZDB-ID 632515-4
    ISSN 1873-2763 ; 8756-3282
    ISSN (online) 1873-2763
    ISSN 8756-3282
    DOI 10.1016/j.bone.2009.07.083
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Variants of the serotonin transporter gene, selective serotonin reuptake inhibitors, and bone mineral density in risperidone-treated boys: a reanalysis of data from a cross-sectional study with emphasis on pharmacogenetics.

    Calarge, Chadi A / Ellingrod, Vicki L / Zimmerman, Bridget / Bliziotes, Michael M / Schlechte, Janet A

    The Journal of clinical psychiatry

    2012  Volume 72, Issue 12, Page(s) 1685–1690

    Abstract: Objective: Selective serotonin reuptake inhibitors (SSRIs) may reduce bone mineral density (BMD). Here, we investigate whether variants of the serotonin transporter-linked polymorphic region (5-HTTLPR) of the serotonin transporter gene moderate this ... ...

    Abstract Objective: Selective serotonin reuptake inhibitors (SSRIs) may reduce bone mineral density (BMD). Here, we investigate whether variants of the serotonin transporter-linked polymorphic region (5-HTTLPR) of the serotonin transporter gene moderate this association in boys.
    Method: Between November 2005 and August 2009, medically healthy boys, aged 7 to 17 years, were enrolled in a cross-sectional study exploring the effect of risperidone-induced hyperprolactinemia on BMD. Volumetric BMD of the ultradistal radius was measured using peripheral quantitative computed tomography, and areal BMD of the lumbar spine was estimated using dual energy x-ray absorptiometry. Multiple linear regression analysis tested whether the 5-HTTLPR genotypes interacted with SSRI treatment status to affect BMD, adjusting for relevant confounders. Participant enrollment was conducted at the University of Iowa, Iowa City.
    Results: Of 108 boys (mean ± SD age = 11.7 ± 2.8 years), with DSM-IV clinical diagnoses based on chart review, 52% (n = 56) had been taking an SSRI for a median duration of 2.8 years. After adjusting for pubertal development, anthropometric measures, physical activity, calcium intake, and prolactin concentration, there was a significant 5-HTTLPR genotype × SSRI treatment interaction effect on total lumbar spine BMD z score (P < .05) in non-Hispanic whites. The interaction effect on BMD at the ultradistal radius failed to reach statistical significance. Among LS genotype carriers, those treated with SSRIs had lower lumbar BMD z score and trabecular BMD at the radius compared to those not treated (P < .02 and P < .008, respectively).
    Conclusions: These findings add to the growing evidence implicating the serotonin system in bone metabolism. They suggest the potential use of 5-HTTLPR genotypes to guide the safer long-term prescribing of SSRIs in youths. However, prospective confirmation in a controlled matched population is warranted.
    MeSH term(s) Adolescent ; Alleles ; Antipsychotic Agents/therapeutic use ; Bone Density/drug effects ; Child ; Cross-Sectional Studies ; Genetic Variation/drug effects ; Genetic Variation/physiology ; Genotype ; Humans ; Male ; Pharmacogenetics/methods ; Polymorphism, Genetic/drug effects ; Risperidone/therapeutic use ; Serotonin Plasma Membrane Transport Proteins/genetics ; Serotonin Uptake Inhibitors/adverse effects
    Chemical Substances Antipsychotic Agents ; SLC6A4 protein, human ; Serotonin Plasma Membrane Transport Proteins ; Serotonin Uptake Inhibitors ; Risperidone (L6UH7ZF8HC)
    Language English
    Publishing date 2012-01-13
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 716287-x
    ISSN 1555-2101 ; 0160-6689
    ISSN (online) 1555-2101
    ISSN 0160-6689
    DOI 10.4088/JCP.10m06198
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Book: Osteoporosis

    Orwoll, Eric S / Bliziotes, Michael

    pathophysiology and clinical management

    (Contemporary endocrinology)

    2003  

    Author's details edited by Eric S. Orwoll and Michael Bliziotes
    Series title Contemporary endocrinology
    MeSH term(s) Osteoporosis/physiopathology ; Osteoporosis/therapy
    Language English
    Size xi, 614 p. : ill., ports.
    Publisher Humana Press
    Publishing place Totowa, N.J
    Document type Book
    ISBN 9780896039339 ; 0896039331
    Database Catalogue of the US National Library of Medicine (NLM)

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  6. Article: Possible mechanisms for the skeletal effects of antipsychotics in children and adolescents.

    Calarge, Chadi A / Ivins, Stephanie D / Motyl, Katherine J / Shibli-Rahhal, Amal A / Bliziotes, Michael M / Schlechte, Janet A

    Therapeutic advances in psychopharmacology

    2013  Volume 3, Issue 5, Page(s) 278–293

    Abstract: The increasing use of antipsychotics (APs) to treat pediatric psychiatric conditions has led to concerns over the long-term tolerability of these drugs. While the risk of cardiometabolic abnormalities has received most of the attention, preclinical and ... ...

    Abstract The increasing use of antipsychotics (APs) to treat pediatric psychiatric conditions has led to concerns over the long-term tolerability of these drugs. While the risk of cardiometabolic abnormalities has received most of the attention, preclinical and clinical studies provide preliminary evidence that APs can adversely impact bone metabolism. This would be most concerning in children and adolescents as suboptimal bone accrual during development may lead to increased fracture risk later in life. However, the potential mechanisms of action through which APs may impact bone turnover and, consequently, bone mineral content are not clear. Emerging data suggest that the skeletal effects of APs are complex, with APs directly and indirectly impacting bone cells through modulation of multiple signaling pathways, including those involving dopamine D2, serotonin, adrenergic, and prolactin receptors, as well as by affecting gonadotropins. Determining the action of APs on skeletal development is further complicated by polypharmacy. In children and adolescents, APs are frequently coprescribed with psychostimulants and selective serotonin reuptake inhibitors, which have also been linked to changes in bone metabolism. This review discusses the mechanisms by which APs may influence bone metabolism. Also covered are preclinical and pediatric findings concerning the impact of APs on bone turnover. However, the dearth of clinical information despite the potential public health significance of this issue underscores the need for further studies. The review ends with a call for clinicians to be vigilant about promoting optimal overall health in chronically ill youth with psychopathology, particularly when pharmacotherapy is unavoidable.
    Language English
    Publishing date 2013-10-29
    Publishing country England
    Document type Journal Article
    ZDB-ID 2646542-5
    ISSN 2045-1261 ; 2045-1253
    ISSN (online) 2045-1261
    ISSN 2045-1253
    DOI 10.1177/2045125313487548
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article: Periosteal remodeling at the femoral neck in nonhuman primates.

    Bliziotes, Michael / Sibonga, Jean D / Turner, Russell T / Orwoll, Eric

    Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research

    2006  Volume 21, Issue 7, Page(s) 1060–1067

    Abstract: Unlabelled: Periosteal bone turnover is poorly understood. We documented intramembranous periosteal bone turnover in the femoral neck in intact nonhuman primates and an increase in osteoclast numbers at the periosteal surface in sex steroid-deficient ... ...

    Abstract Unlabelled: Periosteal bone turnover is poorly understood. We documented intramembranous periosteal bone turnover in the femoral neck in intact nonhuman primates and an increase in osteoclast numbers at the periosteal surface in sex steroid-deficient animals. Our studies are the first to systematically document periosteal turnover at the femoral neck.
    Introduction: Bone size is an important determinant of bone strength, and cellular events at the periosteal surface could alter bone dimensions. We characterized periosteal cellular activity with dynamic histomorphometric studies of nonhuman primate femoral neck and shaft.
    Materials and methods: Femur specimens from 16 intact adult male and female nonhuman primates (Rhesus [Macaca mulatta, n = 9] and Japanese Macaque [Macaca fuscata, n = 7]) were analyzed. Animals were double-labeled with tetracycline, and necropsy was performed 2-7 days after the last dose. We characterized periosteal resorptive activity in an additional group of five intact and four castrate female animals. Multiple group comparisons in intact animals were performed by one-way ANOVA followed by a Fisher PLSD posthoc test. In gonadectomized animals, Fisher's exact test was used for dichotomous and Mann-Whitney U-test for continuous variables.
    Results: Bone turnover in the periosteum of the femoral neck in intact animals was more rapid than at the femoral shaft but slower than in femoral neck cancellous bone. Similarly, in these intact animals, the eroded surface of cortical bone at the femoral neck periosteal surface was significantly greater than in the cancellous bone compartment (p < 0.0001) or on the femoral shaft (p < 0.0001). Gonadectomized female animals showed an increase in osteoclast number on the periosteal surface compared with intact controls (p < 0.01).
    Conclusions: We documented intramembranous periosteal bone turnover in the femoral neck by histomorphometric analyses. The tissue level bone formation rate was sufficient to add substantively to femoral neck size over time. Periosteal osteoclastic activity was not the result of the emergence of intracortical tunneling at the bone surface. Sex steroid deficiency produced an increase in osteoclast numbers at the periosteal surface. This is the first systematic documentation of periosteal turnover at the femoral neck.
    MeSH term(s) Animals ; Bone Resorption/metabolism ; Female ; Femur Neck/cytology ; Femur Neck/physiology ; Macaca mulatta ; Male ; Orchiectomy ; Osteoclasts/cytology ; Osteoclasts/physiology ; Ovariectomy ; Periosteum/cytology ; Periosteum/physiology
    Language English
    Publishing date 2006-07
    Publishing country United States
    Document type Comparative Study ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 632783-7
    ISSN 1523-4681 ; 0884-0431
    ISSN (online) 1523-4681
    ISSN 0884-0431
    DOI 10.1359/jbmr.060414
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: The emerging role of serotonin (5-hydroxytryptamine) in the skeleton and its mediation of the skeletal effects of low-density lipoprotein receptor-related protein 5 (LRP5).

    Warden, Stuart J / Robling, Alexander G / Haney, Elizabeth M / Turner, Charles H / Bliziotes, Michael M

    Bone

    2009  Volume 46, Issue 1, Page(s) 4–12

    Abstract: Novel molecular pathways obligatory for bone health are being rapidly identified. One pathway recently revealed involves gut-derived 5-hydroxytryptamine (5-HT) mediation of the complete skeletal effects of low-density lipoprotein receptor-related protein ...

    Abstract Novel molecular pathways obligatory for bone health are being rapidly identified. One pathway recently revealed involves gut-derived 5-hydroxytryptamine (5-HT) mediation of the complete skeletal effects of low-density lipoprotein receptor-related protein 5 (LRP5). Mounting evidence supports 5-HT as an important regulatory compound in bone with previous evidence demonstrating that bone cells possess functional pathways for responding to 5-HT. In addition, there is growing evidence that potentiation of 5-HT signaling via inhibition of the 5-HT transporter (5-HTT) has significant skeletal effects. The later is clinically significant as the 5-HTT is a popular target of pharmaceutical agents, such as selective serotonin reuptake inhibitors (SSRIs), used for the management of major depressive disorder and other affective conditions. The observation that 5-HT mediates the complete skeletal effects of LRP5 represents a significant paradigm shift from the traditional view that LRP5 located on the cell surface membrane of osteoblasts exerts direct skeletal effects via Wnt/beta-catenin signaling. This paper discusses the mounting evidence for skeletal effects of 5-HT and the ability of gut-derived 5-HT to satisfactorily explain the skeletal effects of LRP5.
    MeSH term(s) Animals ; Bone and Bones/metabolism ; Humans ; LDL-Receptor Related Proteins/metabolism ; Low Density Lipoprotein Receptor-Related Protein-5 ; Osteoporosis/metabolism ; Osteoporosis/physiopathology ; Serotonin/metabolism
    Chemical Substances LDL-Receptor Related Proteins ; LRP5 protein, human ; Low Density Lipoprotein Receptor-Related Protein-5 ; Serotonin (333DO1RDJY)
    Language English
    Publishing date 2009-07-08
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Review
    ZDB-ID 632515-4
    ISSN 1873-2763 ; 8756-3282
    ISSN (online) 1873-2763
    ISSN 8756-3282
    DOI 10.1016/j.bone.2009.06.029
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article: Acute estramustine-induced hypocalcemia unmasking severe vitamin D deficiency.

    Madison, Dana L / Beer, Tomasz M / Bliziotes, Michael M

    The American journal of medicine

    2002  Volume 112, Issue 8, Page(s) 680–681

    MeSH term(s) Aged ; Aged, 80 and over ; Estramustine/adverse effects ; Humans ; Hypocalcemia/chemically induced ; Male ; Parathyroid Hormone/blood ; Prostatic Neoplasms/drug therapy ; Vitamin D/analogs & derivatives ; Vitamin D/blood ; Vitamin D/therapeutic use ; Vitamin D Deficiency/blood ; Vitamin D Deficiency/complications ; Vitamin D Deficiency/diagnosis
    Chemical Substances Parathyroid Hormone ; Vitamin D (1406-16-2) ; Estramustine (35LT29625A) ; 25-hydroxyvitamin D (A288AR3C9H)
    Language English
    Publishing date 2002-06-01
    Publishing country United States
    Document type Case Reports ; Letter
    ZDB-ID 80015-6
    ISSN 1555-7162 ; 1873-2178 ; 0002-9343 ; 1548-2766
    ISSN (online) 1555-7162 ; 1873-2178
    ISSN 0002-9343 ; 1548-2766
    DOI 10.1016/s0002-9343(02)01101-4
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Serotonin (5-hydroxytryptamine) transporter inhibition causes bone loss in adult mice independently of estrogen deficiency.

    Warden, Stuart J / Nelson, Ian R / Fuchs, Robyn K / Bliziotes, Michael M / Turner, Charles H

    Menopause (New York, N.Y.)

    2008  Volume 15, Issue 6, Page(s) 1176–1183

    Abstract: Objective: Selective serotonin reuptake inhibitors (SSRIs) treat depression by antagonizing the serotonin (5-hydroxytryptamine) transporter (5-HTT). These drugs may also have skeletal effects given the presence of functional serotonergic pathways in ... ...

    Abstract Objective: Selective serotonin reuptake inhibitors (SSRIs) treat depression by antagonizing the serotonin (5-hydroxytryptamine) transporter (5-HTT). These drugs may also have skeletal effects given the presence of functional serotonergic pathways in bone and evidence demonstrating detrimental effects of SSRIs on postmenopausal bone changes. This study aimed to explore the influence of an SSRI (fluoxetine hydrochloride) on the bone changes associated with estrogen deficiency in adult mice.
    Design: Adult, female, Swiss-Webster mice underwent ovariectomy (OVX) or sham OVX and were treated daily for 4 weeks with either fluoxetine hydrochloride (5 or 20 mg/kg) or a vehicle solution (control). In vivo assessments of hindlimb areal and tibial volumetric bone mineral density were performed at baseline and after 4 weeks of intervention. Femurs and lumbar vertebrae were subsequently removed and assessed ex vivo for bone mineral density and trabecular bone architecture and turnover.
    Results: In vivo and ex vivo skeletal measures found no interactions between OVX (estrogen deficiency) and 5-HTT inhibition, indicating that the skeletal effects of these interventions were independent. 5-HTT inhibition had detrimental skeletal effects, with the fluoxetine-treated groups having reduced bone mineral density and altered trabecular architecture. These changes resulted from both a decrease in bone formation and increase in bone resorption.
    Conclusions: These data indicate that a commonly prescribed SSRI has a negative influence on the adult skeleton, independent of estrogen deficiency. This finding supports clinical data demonstrating SSRI use to be associated with accelerated bone loss after menopause and highlights a need for further research into the skeletal effects of SSRIs.
    MeSH term(s) Animals ; Bone Density/drug effects ; Bone Diseases, Metabolic/etiology ; Bone Diseases, Metabolic/pathology ; Female ; Fluoxetine/adverse effects ; Mice ; Ovariectomy ; Serotonin Uptake Inhibitors/adverse effects
    Chemical Substances Serotonin Uptake Inhibitors ; Fluoxetine (01K63SUP8D)
    Language English
    Publishing date 2008-11
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 1205262-0
    ISSN 1530-0374 ; 1072-3714
    ISSN (online) 1530-0374
    ISSN 1072-3714
    DOI 10.1097/gme.0b013e318173566b
    Database MEDical Literature Analysis and Retrieval System OnLINE

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