Do Serotonin Reuptake Inhibitors (SSRIs) Affect Bone Mass in Adolescents (SSRI_BMD)
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|ClinicalTrials.gov Identifier: NCT02147184|
Recruitment Status : Completed
First Posted : May 26, 2014
Results First Posted : October 24, 2017
Last Update Posted : October 24, 2017
|Condition or disease|
|The Skeletal Effects of SSRIs|
Bone mass achieved by early adulthood is a major determinant of lifetime risk for osteoporosis. Therefore, optimizing peak bone mass is crucial to avoiding bone fracture with its associated morbidity and mortality.
Emerging evidence suggests that serotonin plays a central role in bone metabolism. For example, preclinical experiments have shown that bone cells express the serotonin transporter and a variety of functional serotonin receptors whose activity modulates bone turnover. Epidemiologic studies have linked SSRIs to reduced bone mineral density and increased fracture risk in the elderly. SSRIs are widely used in youths to treat a number of psychiatric disorders. However, while their short-term efficacy and safety have been established, their long-term safety remains little investigated.
The investigators aim to recruit, in a 2-year prospective observational study, 15 to 20 year-old participants upon the initiation of SSRI treatment. During the study period, bone mineral density of the lumbar spine and whole body will be measured using dual-energy x-ray absorptiometry (DXA) and of the radius using peripheral quantitative computed tomography (pQCT). A detailed psychiatric assessment will be conducted to control for psychopathology, as a potential confounding factor affecting bone mineralization. Changes in psychiatric treatment during the follow up period will also be documented and accounted for. By using a group of controls, of comparable age and sex distribution, the investigators aim to evaluate 1) whether psychopathology, at baseline, is associated with low bone mass, 2) if treatment with SSRIs suppresses bone mineralization, and 3) if the discontinuation of the SSRI is followed by a restoration of bone mineral accrual. 4) Furthermore, genetic testing will investigate whether variants of the serotonin system genes moderate the effect of SSRI treatment on bone mineral density.
In sum, this work aims to improve the long-term safety of psychiatric treatments in order to optimize functioning and the quality of life of those who suffer from psychiatric disorders.
|Study Type :||Observational|
|Actual Enrollment :||287 participants|
|Official Title:||Serotonin Reuptake Inhibitors and Bone Mineralization in Adolescents|
|Actual Study Start Date :||September 2010|
|Actual Primary Completion Date :||April 2016|
|Actual Study Completion Date :||April 2016|
Participants within one month of starting an SSRI
No treatment with SSRIs
- Total Body Less Head Bone Mineral Content (TBLH BMC) Z-score (Adjusted for Age-sex-height-race) [ Time Frame: At baseline and every 8 months up to 2 years. ]Whole-body dual energy x-ray absorptiometry (DXA) scan was obtained using a Hologic QDR DELPHI-4500A unit or a Hologic Discovery A unit (Hologic, Inc, Bedford, MA). The two DXA units were cross-calibrated.
- Trabecular Volumetric Bone Mineral Density at the Ultradistal Radius [ Time Frame: At baseline and every 4 months up to 2 years. ]Volumetric bone mineral density (vBMD) at the nondominant radius (4% and 20% sites) was measured, at study entry and every four months, with peripheral quantitative computed tomography (pQCT), using a Stratec XCT-2000 scanner (Stratec, Inc., Pforzheim, Germany). Image analysis was performed using the manufacturer's software package, version 6.0. pQCT scans compromised by movement were rejected. Quality control and calibration of the equipment were performed daily.
- Osteocalcin to C-terminal Telopeptide Ratio [ Time Frame: At baseline and every 4 months up to 2 years. ]Osteocalcin (ng/mL) is a bone formation marker and C-terminal telopeptide (ng/mL) a marker of bone resorption.
- Bone-specific Alkaline Phosphatase to C-terminal Telopeptide Ratio [ Time Frame: At baseline and every 4 months up to 2 years. ]Bone-specific alkaline phosphatase (ng/mL) is a marker of bone formation while C-terminal telopeptide (ng/mL) is a marker of bone resorption.
- Lumbar Spine Bone Mineral Density (BMD) Z-score [ Time Frame: At baseline and every 8 months up to 2 years. ]This is a Z-score adjusted for sex, age, race, and height.
- Cortical Volumetric BMD at 20% Radius [ Time Frame: At baseline and every 4 months up to 2 years. ]
- Cortical Thickness at 20% Radius [ Time Frame: At baseline and every 4 months up to 2 years. ]This is cortical thickness as measured by pQCT.
- The Moderating Effect of the Short Allele of the Serotonin Transporter-Linked Polymorphic Region (5HTTLPR) Gene on the Association Between SSRI Use and the Primary Outcomes [ Time Frame: 2 years ]
Biospecimen Retention: Samples With DNA
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02147184
|United States, Iowa|
|University of Iowa Hospitals and Clinics|
|Iowa City, Iowa, United States, 52242|
|Principal Investigator:||Chadi Calarge, MD||University of Iowa|