The skeletal subsystem as an integrative physiology paradigm

Aaron J. Weiss, Jameel Iqbal, Neeha Zaidi, Jeffrey I. Mechanick

Research output: Contribution to journalReview articlepeer-review

11 Scopus citations


Homeostatic bone remodeling depends on precise regulation of osteoblast-osteoclast coupling through intricate endocrine, immune, neuronal, and mechanical factors. The osteoblast-osteoclast model of bone physiology with layers of regulatory complexity can be investigated as a component of a local skeletal subsystem or as a part of a complete whole-body system. In this review, we flip the traditional investigative paradigm of scientific experimentation ("bottom-top research") to a "top-bottom" approach using systems biology. We first establish the intricacies of the two-cell model at the molecular signaling level. We then provide, on a systems level, an integrative physiologic approach involving many recognized organ-level subsystems having direct and/or indirect effects on bone remodeling. Lastly, a hypothetical model of bone remodeling based on frequency and amplitude regulatory mechanisms is presented. It is hoped that by providing a thorough model of skeletal homeostasis, future progress can be made in researching and treating skeletal morbidities.

Original languageEnglish
Pages (from-to)168-177
Number of pages10
JournalCurrent Osteoporosis Reports
Issue number4
StatePublished - Dec 2010


  • Bone remodeling
  • Immune system
  • Integrative physiology
  • Osteoblast
  • Osteoclast
  • Osteocyte
  • Systems biology
  • Vitamin D


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