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

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 antipsychotics for at least 2 years were evaluated. The BMD was measured at lumbar spine and femur sites using dual-energy X-ray absorptiometry (DEXA). 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.