Pharmacological Research 58 (2008) 1–7
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Pharmacological Research
journal homepage: www.elsevier.com/locate/yphrs
Perspective
The disease modifying osteoarthritis drug (DMOAD): Is it in the horizon?
Per Qvist
a,*
, Anne-Christine Bay-Jensen
a
, Claus Christiansen
a
, Erik B. Dam
a
,
Philippe Pastoureau
b
, Morten A. Karsdal
a
a
Nordic Bioscience A/S, Herlev Hovedgade 207, DK-2730 Herlev, Denmark
b
Institut de Recherches Servier, 11 rue des Moulineaux, 92150 Suresnes, France
article info
Article history:
Accepted 3 June 2008
Keywords:
DMOAD
Osteoarthritis
Treatment
abstract
Till date, the pharmaceutical industry has failed to bring effective and safe disease modifying osteoarthritic
drugs (DMOADs) to the millions of patients suffering from this serious and deliberating disease. We
provide a review of recent data reported on the investigation of DMOADs in clinical trials, including com-
pounds inhibiting matrix-metalloproteinases (MMPs), bisphosphonates, cytokine blockers, calcitonin,
inhibitors of inducible nitric oxide synthase (iNOS), doxycycline, glucosamine, and diacereine.
We discuss the challenges associated with the drug development process in general and with DMOADs in
particular, and we advance the need for a new development paradigm for DMOADs. Two central elements
in this paradigm are a stronger focus on the biology of the joint and the application of new and more
sensitive biomarkers allowing redesign of clinical trials in osteoarthritis.
© 2008 Elsevier Ltd. All rights reserved.
Contents
1. Introduction ............................................................................................................................................ 1
2. Drug development in OA: do we need a new development paradigm? .............................................................................. 2
2.1. A new development paradigm in OA ........................................................................................................... 2
2.2. Challenges in clinical study design ............................................................................................................ 2
2.3. An OA model encompassing early structural changes ......................................................................................... 3
3. DMOADs in development .............................................................................................................................. 4
3.1. MMP inhibitors ................................................................................................................................. 4
3.2. Bisphosphonates ............................................................................................................................... 4
3.3. Cytokine inhibitors ............................................................................................................................. 5
3.4. Calcitonin ....................................................................................................................................... 5
3.5. Other DMOADs ................................................................................................................................. 5
4. Concluding remarks ................................................................................................................................... 5
References ............................................................................................................................................. 6
1. Introduction
Osteoarthritis (OA) is one of the leading causes of disability in the
world, with more than 10% of the elderly population having symp-
tomatic disease [1]. The incidence increases with age, and by age 65
approximately 80% has radiographic evidence of OA [2]. Therefore,
osteoarthritis is a serious burden both to the patient and the society.
Perspective articles contain the personal views of the authors who, as experts,
reflect on the direction of future research in their field.
*
Corresponding author.
E-mail address: pq@nordicbioscience.com (P. Qvist).
However, at present there is little to offer the affected individuals
for prevention of the disease or treatment in the early stages [3]. For
many patients, joint replacement is eventually the only treatment
option.
Although the pathogenesis of osteoarthritis is not fully under-
stood at present, it is evident that a central hallmark in this slow,
chronic disease is progressive destruction of the articular joints,
which consists of bone, cartilage and the synovium. In particu-
lar, the cartilage has attracted much attention, and the different
grades and stages of OA cartilage histopathology have recently been
described in detail by a working group under OARSI [4]. This system
encompasses seven grades (or severity levels) with involvement of
the deeper cartilage layers in more advanced OA disease, and when
1043-6618/$ – see front matter © 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.phrs.2008.06.001