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Advanced Drug Delivery Reviews 58 (2006) 123 – 124


Drug delivery in degenerative joint disease B

Osteoarthritis is by far the most common disorder of the skeletal system affecting more than 50% of the elderly population in a clinically relevant fashion. This disease mostly affects the larger weight-bearing joints leading to pain and severe disablement of the affected patients. Osteoarthritis is a multifactorial complex disease for which the relevant genetic alterations are only in part identified, yet. The high prevalence makes degenerative joint disease to one of the urgent challenges, both to the quality of life of the individual as well as the health care budget. So far, the treatment of osteoarthritis is largely restricted to symptomatic approaches as pointed out in many contributions in this issue of Advanced Drug Delivery Reviews: this includes mostly personal exercise and physical therapy, but also drugbased treatment for pain and inflammation. Finally, however, after years of disablement, the joints very often need to get replaced by endoprothetic surgery. Thus, there is a high need for drug development for degenerative joint disease. Despite the enormous size of the potential market with estimated worldwide costs of billions of dollars only for treatment, there are no (potent) drugs for osteoarthritis available yet (at least which are disease-modifying). In this issue of Advanced Drug Delivery Reviews, the basic clinical starting point and basics of the pathology and pathobiology of the disease are identified as well as major targets of therapeutic intervention. B

This preface is part of the Advanced Drug Delivery Reviews theme issue on bDrug Delivery in Degenerative Joint DiseaseQ, Vol. 58/2,2006. 0169-409X/$ - see front matter D 2006 Elsevier B.V. All rights reserved. doi:10.1016/j.addr.2006.01.004

The most important aspect addressed in this issue of Advanced Drug Delivery Reviews is the question how treatment (drugs, genes, etc.) can be delivered efficiently to the different structural compartments of the joint (i.e. articular cartilage, synovial membrane and bone): thus, whereas the bone and the synovial membrane are well accessible by systemic treatment, articular cartilage is located in a very remote place in the body: the joint. Cartilage itself has no blood supply and therefore delivery of potential drugs does not work directly as in other organs. On the other hand, a largely closed system like the joint space offers the opportunity to achieve appropriate local concentrations of a given drug with low systemic exposure, thereby reducing site effects in other organ systems. This renders the articular cartilage a highly interesting tissue for drug delivery. Clearly, this is true for direct intraarticular drug application as pointed out in the contribution by Gerwin et al., but also opens up the opportunity of localized gene therapy described in its various potential facettes in the contributions of Evans et al., Gelse and Schneider, and Gay and colleagues. All these approaches use the very special localization of articular cartilage. A special approach in this sense is also represented by all sorts of tissue engineering approaches described by Mainil-Varlet and colleagues. Obviously, another major route to target involved tissues is addressed by the treatment of pain, which involves peripheral nerves as well as the central nervous system (Schaible and colleagues). Clearly, osteoarthritis therapy has a great potential in terms of market perspectives as well as benefit for



the individuals; however, it represents also a very challenging field for effective intervention. The theme editors wish to express their thanks to the authors for their excellent contributions. Thomas Aigner (Theme editor) Institute of Pathology, University of Leipzig Liebigstrabe 26, 04103 Leipzig, Germany E-mail:

Nicole Gerwin (Theme editor) Bone & Cartilage Program Novartis Institutes for BioMedical Research Novartis Pharma AG, CH-4002 Basel, Switzerland E-mail:


Preface B This preface is part of the Advanced Drug Delivery Reviews theme issue on bDrug Delivery in Degenerative Joint DiseaseQ, Vol. 58/2...