Osteoporosis International

, Volume 27, Issue 10, pp 3091–3101 | Cite as

Room temperature housing results in premature cancellous bone loss in growing female mice: implications for the mouse as a preclinical model for age-related bone loss

  • U. T. Iwaniec
  • K. A. Philbrick
  • C. P. Wong
  • J. L. Gordon
  • A. M. Kahler-Quesada
  • D. A. Olson
  • A. J. Branscum
  • J. L. Sargent
  • V. E. DeMambro
  • C. J. Rosen
  • R. T. Turner
Original Article



Room temperature housing (22 °C) results in premature cancellous bone loss in female mice. The bone loss was prevented by housing mice at thermoneutral temperature (32 °C). Thermogenesis differs markedly between mice and humans and mild cold stress induced by standard room temperature housing may introduce an unrecognized confounding variable into preclinical studies.


Female mice are often used as preclinical models for osteoporosis but, in contrast to humans, mice exhibit cancellous bone loss during growth. Mice are routinely housed at room temperature (18–23 °C), a strategy that exaggerates physiological differences in thermoregulation between mice (obligatory daily heterotherms) and humans (homeotherms). The purpose of this investigation was to assess whether housing female mice at thermoneutral (temperature range where the basal rate of energy production is at equilibrium with heat loss) alters bone growth, turnover and microarchitecture.


Growing (4-week-old) female C57BL/6J and C3H/HeJ mice were housed at either 22 or 32 °C for up to 18 weeks.


C57BL/6J mice housed at 22 °C experienced a 62 % cancellous bone loss from the distal femur metaphysis during the interval from 8 to 18 weeks of age and lesser bone loss from the distal femur epiphysis, whereas cancellous and cortical bone mass in 32 °C-housed mice were unchanged or increased. The impact of thermoneutral housing on cancellous bone was not limited to C57BL/6J mice as C3H/HeJ mice exhibited a similar skeletal response. The beneficial effects of thermoneutral housing on cancellous bone were associated with decreased Ucp1 gene expression in brown adipose tissue, increased bone marrow adiposity, higher rates of bone formation, higher expression levels of osteogenic genes and locally decreased bone resorption.


Housing female mice at 22 °C resulted in premature cancellous bone loss. Failure to account for species differences in thermoregulation may seriously confound interpretation of studies utilizing mice as preclinical models for osteoporosis.


Animal models Osteoporosis Sympathetic signaling Thermogenesis 


Compliance with ethical standards

The experimental protocols were approved by the Institutional Animal Care and Use Committee, and the mice were maintained in accordance with the NIH Guide for the Care and the Use of Laboratory Animals.


This study received financial support from NIH AR060913, NASA NNX12AL24, and USDA 38420–17804.

Conflicts of interest


Supplementary material

198_2016_3634_MOESM1_ESM.xlsx (14 kb)
ESM 1 (XLSX 13 kb)


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Copyright information

© International Osteoporosis Foundation and National Osteoporosis Foundation 2016

Authors and Affiliations

  • U. T. Iwaniec
    • 1
    • 2
  • K. A. Philbrick
    • 1
  • C. P. Wong
    • 1
  • J. L. Gordon
    • 1
  • A. M. Kahler-Quesada
    • 1
  • D. A. Olson
    • 1
  • A. J. Branscum
    • 3
  • J. L. Sargent
    • 4
  • V. E. DeMambro
    • 5
  • C. J. Rosen
    • 5
  • R. T. Turner
    • 1
    • 2
  1. 1.Skeletal Biology Laboratory, School of Biological and Population Health SciencesOregon State UniversityCorvallisUSA
  2. 2.Center for Healthy Aging ResearchOregon State UniversityCorvallisUSA
  3. 3.Biostatistics Program, School of Biological and Population Health SciencesOregon State UniversityCorvallisUSA
  4. 4.College of Veterinary MedicineOregon State UniversityCorvallisUSA
  5. 5.Maine Medical Center Research InstituteScarboroughUSA

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