• Metabolic Bone Disease Clinical Trials
• Metabolic Bone Disease
• Psychopharmacology

The use of certain psychotropic medications may be enhancing an already high underlying risk for osteoporosis, according to several studies that were presented at the American Psychiatric Association 2010 Annual Meeting.

Psychotropic agents have been linked to fractures, and antidepressants have been associated with low bone mineral density (BMD). The studies that were presented validate these earlier findings and suggest that many patients may already be at high risk for bone disease.

In a large study from Canada, osteoporosis was found to be associated with the use of selective serotonin reuptake inhibitors (SSRIs), mood stabilizers other than lithium, and benzodiazepines but that the use of tricyclic antidepressants was protective.

A 40% increased risk for low BMD with SSRIs and a 37% reduced risk with tricyclic antidepressants were reported by James Bolton, MD, University of Manitoba, Winnipeg, Canada.

Data were derived from Manitoba's health care database, which captures all physician contacts and diagnoses, all prescribed medications, all hospitalizations, and census data, which were then linked to data from the Manitoba Bone Density Program, a clinical database of information from dual-energy X-ray absorptiometry scans (DXA).

Investigators were able to identify 7994 osteoporosis cases from database records covering the period 2000 to 2007. Cases were defined as persons with a T-score of −2.5 or lower at one of four sites (trochanter, femoral neck, total hip, or lumbar spine). Controls were 23,928 subjects who were matched for gender, age, and ethnicity. Three controls were matched for each osteoporosis case.

Dr. Bolton and colleagues assessed all psychotropic medications that were prescribed, all mental disorders that were diagnosed, and nearly 20 confounders (eg, body mass index, medical comorbidity, estrogen use, and bisphosphonate use).

The adjusted odds ratio was 1.39 for SSRIs (95% CI, 1.21 to 1.59), 1.35 for nonlithium mood stabilizers (eg, anticonvulsants) (95% CI, 1.10 to 1.66), 1.10 for benzodiazepines (95% CI, 1.01 to 1.20), and 0.63 for tricyclic antidepressants (95% CI, 0.56 to 0.72). Dr. Bolton suggested that perhaps because sample sizes were smaller, the odds ratio for lithium was 0.57, but the confidence interval crossed 1.0 (95% CI, 0.29 to 1.12). The same was true for typical antipsychotics (OR, 1.20; 95% CI, 0.81 to 1.77) and for atypical antipsychotics (OR, 1.55; 95% CI, 0.87 to 1.97). Other antidepressants had an odds ratio of 1.08 (95% CI, 0.91to 1.27).

Mental disorders themselves also had statistically significant osteoporotic effects, including dementia (HR, 1.34; 95% CI, 1.04 to 1.72), schizophrenia (HR, 1.92; 95% CI, 1.11 to 3.33), and alcohol dependence (HR, 1.53; 95% CI, 1.01 to 2.32). Risk was reduced, interestingly, with depression, which carried an odds ratio of 0.85 (95% CI, 0.75 to 0.95). Bipolar disorder and drug abuse or dependence was not significantly associated with osteoporosis.

Dr. Bolton concluded, “SSRIs, anticonvulsant mood stabilizers, and benzodiazepines are associated with osteoporotic changes in bone, independent of the effects of mental disorders and other confounders, and tricyclic antidepressants appear to be protective.”

A study by Barbara Gracious, MD, University of Rochester Medical Center, Rochester, NY, suggested that women who are treated for depression—and presumably are receiving SSRIs—have an underlying risk for osteoporosis that may be neglected.

The majority of study subjects was disabled by depression and had been on maintenance therapy with SSRIs for many years. They also had exposure to prolactin-elevating antipsychotic medications (associated with reduced estrogen and testosterone). “We found the risk factor burden of these patients was huge,” said Barbara Gracious, MD.

This study systematically examined osteoporosis risk factors via personalized screening to determine if osteoporosis prevention is warranted in midlife mood-disordered patients. Nineteen patients, mean age 47 years and 94% female, were recruited from a university psychiatric partial hospitalization program and an urban university neighborhood family medical center. The Mini-International Neuropsychiatric Interview (MINI) confirmed the Primary Axis 1 diagnosis of major depression and captured comorbid mental disorders. Structured interviews provided demographics, history, lifestyle, and medication risk.

The average patient was found to have 19 risk factors for osteoporosis. The most prevalent iatrogenic risk factors were history of SSRI use (89%), history of major surgery (89%), and history of prolactin-elevating antipsychotic exposure (68%). Prevalent lifestyle factors were decreased weight-bearing exercise (76%), low vitamin D levels (64%), alcohol use (59%), cigarette smoking (53%), and excess salt intake (41%).

Many had a family history of fractures (53%) or osteoporosis (29%) and irregular menstruation cycles (35%). Only about 50% of subjects were postmenopausal.

Investigators concluded that midlife patients who are treated for major depression have many lifestyle, iatrogenic, and historical risk factors that raise the likelihood of poor bone quality and osteoporotic fractures at younger ages.

“We believe that lifestyle interventions are appropriate for this population, including calcium and vitamin D supplementation and enhanced weight-bearing physical activity. In addition, coordinated primary care follow-up should be a priority, and heavy smokers and alcohol abusers should receive substance abuse treatment,” concluded Dr. Gracious.

• © 2010 MD Conference Express