Objectives

To test the interrater reliability of a standardized method to analyze knee bone mineral density (BMD) using dual-energy x-ray absorptiometry (DXA); to compare spine, hip, and knee BMD of people with spinal cord injury (SCI) with able-bodied controls; and to determine the relation between hip BMD and knee BMD in SCI and able-bodied subjects.

Design

Criterion standard and masked comparison.

Setting

Primary care university hospital.

Participants

A convenience sample of 11 subjects with complete SCI was age and sex matched with 11 able-bodied control subjects.

Interventions

Not applicable.

Main Outcome Measures

Four raters analyzed regions of interest according to operational definitions recently developed to standardize the analysis of BMD of the knee. Subjects with chronic SCI and matched controls underwent conventional DXA scans of the spine and hips and “less conventional” scans of the distal femurs and proximal tibias. The relation between hip and knee BMD was analyzed.

Results

The knee measurements were highly reliable (femur intraclass correlation coefficient model 2,1 [ICC2,1]=.98; tibia ICC2,1=.89). Subjects with SCI had lower BMD values than controls at all hip and knee sites (P<.05). Lumbar spine BMD did not differ between groups. Hip BMD was moderately predictive of distal femur BMD (R2=.67), but less correlated with the proximal tibia (R2=.38).

Conclusions

Knee BMD can be reliably analyzed using DXA with this protocol. Subjects with SCI have diminished knee and hip BMD. Low hip BMD is associated with low distal femur BMD.

Objective

The aim of the present study was to investigate the effect of risperidone-induced hyperprolactinemia on trabecular bone mineral density (BMD) in children and adolescents.

Methods

Medically healthy 7–17yo males chronically treated, in a naturalistic setting, with risperidone were recruited through child psychiatry outpatient clinics between November 2005 and June 2007. Anthropometric measurements and laboratory testing were conducted. Developmental and treatment history was obtained from the medical record. Volumetric BMD of the ultra-distal radius was measured using peripheral quantitative computerized tomography and areal BMD of the lumbar spine was estimated using dual energy X-ray absorptiometry.

Results

Hyperprolactinemia was present in 49% of 83 boys (n=41) treated with risperidone for an average of 2.9 years. Serum testosterone concentration increased with pubertal status but was not affected by hyperprolactinemia. As expected, bone mineral content and BMD increased with sexual maturity. After adjusting for the stage of sexual development, height and BMI Z-scores, serum prolactin was negatively associated with trabecular volumetric BMD at the ultra-distal radius (p<0.03). Controlling for relevant covariates, we also found treatment with selective serotonin reuptake inhibitors (SSRIs) to be associated with lower trabecular BMD at the radius (p=0.03) and BMD Z-score at the lumbar spine (p<0.05). These findings became more marked when the analysis was restricted to non-Hispanic Caucasians. Of 13 documented fractures, only two occurred after risperidone and SSRIs were started and none in patients with hyperprolactinemia.

Conclusions

This is the first study to link risperidone-induced hyperprolactinemia and SSRI treatment to lower BMD in children and adolescents. Future research should evaluate the longitudinal course of this adverse event to determine its temporal stability and whether a higher fracture rate ensues.

Objective

As the use of atypical antipsychotics in children and adolescents has increased, concerns have been raised about their long-term safety. We aimed to investigate the association between risperidone-induced weight gain, leptin concentration, and the leptin gene (LEP) -2548G/A variants in youths.

Methods

Medically healthy 7-17yo children and adolescents, in extended naturalistic treatment with risperidone, were recruited through pediatric psychiatry clinics. Anthropometric measures and laboratory testing were conducted. Growth and medication history was obtained from the medical record. The effect of the LEP genotypes on leptin concentration and on the slopes of the weight and body mass index (BMI) z score curves before and after the onset of risperidone treatment was investigated.

Results

In 74 subjects, chronically treated with risperidone, the A allele was associated with higher leptin concentration at low weight and BMI z scores. There was no effect of the LEP genotypes on weight or BMI z scores before risperidone was started. Afterwards, however, the A allele carriers showed a steeper rate of increase in weight and BMI z scores. As a result, the GG genotype carriers were 2.5 times less likely to be overweight/obese (i.e. having a BMI above the 85th percentile). This genetic effect on risperidone-associated weight gain did not extend to weight loss related to psychostimulants.

Conclusions

The LEP -2548G/A variants appear to moderate the weight-altering effect of risperidone but not psychostimulants. This may be related to genetic differences in tissue sensitivity to leptin, resulting in differential body composition.

Objective

To investigate the association between hyperprolactinemia and variants of the dopamine D2 receptor (DRD2) gene in children and adolescents in long-term treatment with risperidone.

Methods

Medically healthy 7–17-year-old patients chronically treated with risperidone but receiving no other antipsychotics were selected for a cross-sectional evaluation. Four DRD2 variants were genotyped and prolactin concentration was measured. Medication history was obtained from the medical record. The effect of the TaqIA variants of the DRD2 on the risk of risperidone-induced hyperprolactinemia was the primary outcome measure.

Results

Hyperprolactinemia was present in 50% of 107 patients (87% males) treated with risperidone for an average of 2.9 years. Age, stage of sexual development, and the dose of risperidone independently predicted a higher prolactin concentration, whereas the dose of psychostimulants was negatively correlated with it. However, these four predictors became nonsignificant when risperidone serum concentration was entered into the model. Adverse events potentially related to hyperprolactinemia were more common in participants with elevated prolactin concentration in girls (45%) compared with boys (10%). After controlling for risperidone concentration and the dose of psychostimulants, the TaqIA A1 and the A-241G alleles were associated with higher prolactin concentration, whereas the -141C Ins/Del AQ1and C957T variants had no significant effect. In addition, adverse events potentially related to hyperprolactinemia were four times more common in TaqIA A1 allele carriers.

Conclusion

Prolactin concentration is closely related to central DRD2 blockade, as reflected by risperidone serum concentration. Furthermore, the TaqIA and A-241G variants of the DRD2 gene could be useful in predicting the emergence of hyperprolactinemia and its potential adverse events.

Objective

The aim of this study was to investigate the prevalence of clinical and laboratory metabolic abnormalities during long-term risperidone treatment in children and adolescents.

Methods

Medically healthy 7- to 17-year-old children chronically treated, in a naturalistic setting, with risperidone were recruited through child psychiatry clinics. Anthropometric measurements and laboratory testing were conducted. Developmental and medication histories were obtained from medical records.

Results

In 99 patients treated with risperidone for an average of 2.9 years, a significant increase in age- and gender-adjusted weight and body mass index (BMI) (i.e., z-scores) was observed. Concomitant treatment with psychostimulants did not attenuate this weight gain. Risperidone-associated weight gain was negatively correlated with the BMI z-score obtained at the onset of risperidone treatment. Compared to lean children, overweight and obese children had higher odds of metabolic abnormalities, including increased waist circumference, hypertriglyceridemia, and low high-density lipoprotein cholesterol (HDL-C). They also tended to have a higher insulin level and homeostasis model assessment insulin resistance (HOMA-IR) index. As a result, upon recruitment in the study, children with excessive weight were 12 times more likely to have at least one laboratory metabolic abnormality and seven times more likely to have at least one criterion of the metabolic syndrome compared to lean subjects. In contrast to excessive weight status, gaining ≥0.5 BMI z-score point during risperidone treatment was not associated with a significantly higher occurrence of metabolic disturbances.

Conclusions

The long-term use of risperidone, especially when weight is above normal, is associated with a number of metabolic abnormalities but a low prevalence of the metabolic syndrome phenotype. Future studies should evaluate the stability of these abnormalities over time.

Abstract

Objective

The aim of this study was to investigate the prevalence of clinical and laboratory metabolic abnormalities during long-term risperidone treatment in children and adolescents.

Methods

Medically healthy 7- to 17-year-old children chronically treated, in a naturalistic setting, with risperidone were recruited through child psychiatry clinics. Anthropometric measurements and laboratory testing were conducted. Developmental and medication histories were obtained from medical records.

Results

In 99 patients treated with risperidone for an average of 2.9 years, a significant increase in age- and gender-adjusted weight and body mass index (BMI) (i.e., z-scores) was observed. Concomitant treatment with psychostimulants did not attenuate this weight gain. Risperidone-associated weight gain was negatively correlated with the BMI z-score obtained at the onset of risperidone treatment. Compared to lean children, overweight and obese children had higher odds of metabolic abnormalities, including increased waist circumference, hypertriglyceridemia, and low high-density lipoprotein cholesterol (HDL-C). They also tended to have a higher insulin level and homeostasis model assessment insulin resistance (HOMA-IR) index. As a result, upon recruitment in the study, children with excessive weight were 12 times more likely to have at least one laboratory metabolic abnormality and seven times more likely to have at least one criterion of the metabolic syndrome compared to lean subjects. In contrast to excessive weight status, gaining ≥0.5 BMI z-score point during risperidone treatment was not associated with a significantly higher occurrence of metabolic disturbances.

Conclusions

The long-term use of risperidone, especially when weight is above normal, is associated with a number of metabolic abnormalities but a low prevalence of the metabolic syndrome phenotype. Future studies should evaluate the stability of these abnormalities over time.