Psychiatry Investig.  2011 Sep;8(3):256-261.

Effects of Long-Term Combination Treatment with Valproate and Atypical Antipsychotics on Bone Mineral Density and Bone Metabolism in Premenopausal Patients with Bipolar Disorder: A Preliminary Study

• Yang J
• Joe SH
• Lee MS
• Ko YH
• Jung IK
• Kim SH

Abstract

OBJECTIVE
We investigated bone mineral density (BMD) and bone metabolism in female bipolar patients who were undergoing long-term treatment with valproate combined with a low-dose atypical antipsychotic.
METHODS
Nineteen premenopausal women with bipolar disorder who were treated with valproate combined with atypical antipsycho-tics for at least 2 years were evaluated. The BMD was measured at lumbar spine and femur sites using dual-energy X-ray absorptiometry (DE-XA). The biochemical markers of bone turnover and circulating levels of gonadal hormones were assessed. Subjects with abnormal DEXA scans were compared to those with normal scans.
RESULTS
Nine (47%) of nineteen subjects showed osteopenia or osteoporosis. The T-score for subjects with abnormal DEXA scans was -1.988. Decreased BMD was more prominent in the proximal femur than in the lumbar spine. Subjects with abnormal DEXA scans had high phosphorus and low testosterone levels relative to subjects with normal scans (p=0.008 and p=0.028, respectively). There was a significant negative correlation between phosphorus, osteocalcin, and femur neck BMD (p<0.05). However, multivariate analysis did not show a significant association between femur and lumbar BMD and biochemical markers of bone turnover.
CONCLUSION
Long-term treatment with valproate combined with low-dose atypical antipsychotics may adversely affect BMD in premenopausal women with bipolar disorder. A prospective, controlled-study with a larger population is warranted, and assessment of BMD and bone metabolism should be taken into consideration in long-term therapy with valproate and atypical antipsychotics.

Keyword

Bipolar disorder; Bone density; Bone metabolism; Females; Valproate

MeSH Terms

Absorptiometry, Photon
Antipsychotic Agents
Biomarkers
Bipolar Disorder
Bone Density
Bone Diseases, Metabolic
Female
Femur
Femur Neck
Gonadal Hormones
Humans
Multivariate Analysis
Osteocalcin
Osteoporosis
Phosphorus
Spine
Testosterone
Valproic Acid
Antipsychotic Agents
Gonadal Hormones
Osteocalcin
Phosphorus
Testosterone
Valproic Acid