COBRE Projects -3 2017-10-26T13:14:17+00:00

COBRE in Mesenchymal and Neural Regulation of Metabolic Networks

COBRE PROJECTS

Project 3:  Beta blockers and their impact on fracture risk in nursing home residents taking atypical antipsychotics. —  Dr. Christine Duarte

Motivation

  • Atypical Antipsychotic (AA) drug use in elderly adults is associated with an up to twofold increased risk of fractures1-3
  • Reasons for AA-related fracture risk are unknown
    • May involve the sympathetic nervous system (SNS)
    • SNS can cause bone loss through beta adrenergic signaling in bone cells
  • Animal models show AA-induced bone loss can be reduced with co-therapy with BBs 4

 Hypothesis

  • Concurrent BB use in incident AA users will result in reduction in fracture risk

 Proposed Study

  • Large observational study to measure concurrent BB effect on fracture risk in elderly nursing home residents initiating AAs
  • Large national database of linked clinical data (Minimum Data Set or MDS) and diagnosis/drug data from Medicare Parts A and D for the majority of U.S. long-stay residents in the years 2007-2013

 Anticipated Results

  • Evidence on whether BB exposure mitigates fracture risk from AA treatment, and how that effect varies by BB drug
  • Insight into the mechanisms underlying fracture risk due to use of AAs, BBs that can inform animal model research
  • Preliminary data to support BB-based mechanisms to treat AA-induced fracture risk

 References

  1. Fraser LA, Liu K, Naylor KL, Hwang YJ, Dixon SN, Shariff SZ, Garg AX. Falls and fractures with atypical antipsychotic medication use: A population-based cohort study. JAMA Intern Med. 2015;175:450-452
  2. Rigler SK, Shireman TI, Cook-Wiens GJ, Ellerbeck EF, Whittle JC, Mehr DR, Mahnken JD. Fracture risk in nursing home residents initiating antipsychotic medications. J Am Geriatr Soc. 2013;61:715-722
  3. Bakken MS, Schjott J, Engeland A, Engesaeter LB, Ruths S. Antipsychotic drugs and risk of hip fracture in people aged 60 and older in norway. J Am Geriatr Soc. 2016;64:1203-1209
  4. Motyl KJ, DeMambro VE, Barlow D, Olshan D, Nagano K, Baron R, Rosen CJ, Houseknecht KL. Propranolol attenuates risperidone-induced trabecular bone loss in female mice. Endocrinology. 2015;156:2374-2383

Overview of Experimental of Study Design


This project is a translational study addressing the combination of AA and BB use in the nursing home, which will be supported by concomitant studies (Project 4) addressing bone physiology in a mouse model. The figure shows the project overview (left) and relation to mouse studies in collaborating project (Motyl, right).