Bone Mineral Content and Bone Metabolism in Adolescents on Antipsychotic Therapy
Condition: Adolescent Depression
MeSH terms: Depression
Study type: Observational

Summary: 
      We hypothesize that antipsychotic induced hyperprolactinemia can decrease bone mineral
      accrual and decrease bone mineral content (BMC) in adolescents on antipsychotic therapy.

      Specifics Aims

        1. To determine if antipsychotic therapy leads to decreased bone mineral accrual and
           decreased bone mineral content in a group of adolescents on antipsychotic therapy by
           comparing them to an ethnicity, gender and pubertal stage matched control group.

        2. To determine the relationship between serum concentrations of prolactin, sex steroids
           and bone turnover markers in adolescents on antipsychotic therapy and an ethnicity,
           gender and pubertal stage matched control group.
    

Detailed description: 
      Recent studies have shown an increase in antipsychotic prescriptions among children and
      adolescents. Virtually all pediatric use of antipsychotics is "off-label," meaning without a
      Food and Drug Administration indication. To make matters worse, pediatric antipsychotic usage
      can lead to serious side effects like movement disorders and metabolic disturbances. Hence,
      it is concerning that despite the virtual absence of long term efficacy and safety data, the
      widespread use of antipsychotics in children and adolescents continues. One important adverse
      effects of antipsychotic therapy is hyperprolactinemia. Prolactin is a hormone secreted by
      the central nervous system. The main action of prolactin in females is the induction and
      maintenance of lactation. The main action of prolactin in females is the induction and
      maintenance of lactation. Antipsychotic therapy has shown to raise prolactin levels both, in
      the adult and pediatric population. Sustained hyperprolactinemia can cause a number of
      endocrinological abnormalities leading to a hypogonadal state and eventually bone
      demineralization and osteoporosis. There is evidence linking pediatric prolactinomas to
      decreased bone density. Also, adult studies suggest that the high rates of osteoporosis in
      schizophrenia may result from hypogonadism secondary to antipsychotic induced
      hyperprolactinemia. Our concern is that the sequela of antipsychotic induced
      hyperprolactinemia in children and adolescents, has received little attention, despite the
      important implications for bone health. This topic is especially important because peak bone
      mass is achieved during adolescence and is a key determinant of the lifetime risk of
      osteoporosis.

      We hypothesize that antipsychotic induced hyperprolactinemia can interrupt bone mineral
      accrual and reduce bone mineral content in adolescents on antipsychotic therapy. We plan to
      measure bone mineral content and peripheral markers of bone metabolism in adolescents on
      antipsychotic therapy and compare them with ethnicity, gender and pubertal stage matched
      controls. We also plan to measure serum levels of prolactin and other hormonal measures such
      as: estradiol, progesterone, testosterone, follicle stimulating hormone, luteinizing hormone
      and thyroid function tests in both the groups. Statistical analysis will be performed to
      compare bone mineral content between the study and control groups. Additionally, the
      association between the hormonal measures and bone mineral content will be determined.

      Osteoporosis is a major public health problem. In the United States today, 10 million
      individuals already have osteoporosis, and 18 million more have low bone mass, placing them
      at an increased risk for this disorder. Optimization of bone health is a process that must
      occur throughout the lifespan and factors that influence bone health at all ages are
      essential to prevent osteoporosis and its devastating consequences. To date, there are no
      published studies, examining the association between antipsychotic induced hyperprolactinemia
      and bone mineral content (BMC) and/or risk of osteoporosis in children or adolescents.
      Although there have been reports of antipsychotic induced hyperprolactinemia in both
      prepubertal and postpubertal children, it has been suggested that post pubertal children may
      be at a higher risk of decreased BMC. Thus, we plan to initially study the effects on
      adolescents. Potential implications of our research findings include: providing
      recommendations for preventing, diagnosing and monitoring bone mineral content/density during
      pediatric antipsychotic therapy. Since this is an unexplored area, yet very crucial field,
      findings from our study can be expected to have ramifications for clinical practice within
      one to two years of project completion.
    

Intervention name(s): Bone Density Test
Intervention type(s): Radiation
Intervention description(s): Evaluating bone mineral content and bone metabolism in adolescents on antipsychotic therapy compared to healthy adolescents
Observational model: Case-Control
Time perspective: Retrospective
Sampling method: Non-Probability Sample
Study population: 
        Subjects will be recruited from within the clinic as well as community psychiatrists
      
Keywords: bone mineral; antipsychotic therapy; bone mineral accrual; bone mineral content