[Frontiers in Bioscience S2, 468-482, January 1, 2010]

Bone remodeling, humoral networks and smart biomaterial technology for osteoporosis

Milena Fini1,2, Angelo Carpi3 , Veronica Borsari1, Matilde Tschon1, Andrea Nicolini4, Maria Sartori1, Jeffrey Mechanick5, Roberto Giardino1,6

1Laboratory of Surgical and Preclinical Studies , Rizzoli Orthopaedic Institute, Bologna Italy,2Specialized Centre "Preclinical Studies on Innovative Technological and Therapeutical Strategies", Rizzoli Orthopaedic Institute, Bologna Italy, 3Department of Reproduction and Ageing, University of Pisa, Italy, 4 Department of Internal Medicine, University of Pisa, Italy, 5 Division of Endocrinology, Diabetes and Bone Disease, Mount Sinai School of Medicine, New York, Usa,6 Chair of Surgical Pathophysiology, University of Bologna Italy

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Physiologic bone remodeling
3.1. General aspects
3.2. Systemic regulation: the role of hormones
3.3. Local regulation: the role of cytokines
3.4. Integration of systemic and local factors with whole body function: a systems approach
4. Bone remodeling and osteoporosis
4.1. General considerations
4.2. Local dysregulation: the role of cytokines
5. Therapeutic considerations: biological therapies and biomaterials
5.1. Current chemotherapeutics
5.2. Biological therapies
5.3. Biomaterials
6. Conclusions
7. Acknowledgements
8. References

1. ABSTRACT

One of the unfortunate sequelae of increased life expectancy is a growing number of age-related degenerative diseases, a prime example being osteoporosis. This form of metabolic bone disease and related co-morbidities consume tremendous resources and costs from a nation's health care system. Osteoporosis results from genetic, age-related, and hormone-dependent causes as well as a compendium of secondary pathophysiological states. The presence of osteoporosis as a comorbidity confers a significant negative prognostic element following orthopedic procedures. In vitro and in vivo studies of osteoporotic bone implicate microarchitectural bone rarefaction, microenvironmental and functional disturbance of osteoblast-osteoclast coupling, and abnormal tissue and signalling molecule repertoires, each having detrimental effects on the regenerative and osteointegration processes. This review explores the pathophysiology of bone remodeling from a macro- and micro- systems biology standpoint with a focus on cytokine interactions. Furthermore, therapeutic interventions exploiting vulnerable nodes in these physiological networks will be posited. One exciting development in this area is the use of novel biomaterials.