NSAIDs can have adverse effects on bone healing
Introduction
At the beginning of this century the term ‘osteoimmunology’ was used for the first time to describe the complex communication between the immune system and the skeleton. This interdisciplinary scientific field has been studying for several years now the interactions of signalling molecules, transcription factors and receptors between the skeletal and the immune systems. It shows that there are clear relationships between the immune system, inflammatory diseases and bone density [1], [2]. Furthermore, it states that prostaglandins and inflammatory proteins have an important influence on the development and differentiation of bone formation, while inflammatory proteins can have an important effect on the development and differentiation of bone-forming osteoblasts and bone-resorbing osteoclasts. Anti-inflammatory prostaglandins and modulating inflammatory proteins are able to inhibit the formation of osteoclasts. Thus, the immune system might be the allostatic hinge on which the ‘swing’ of bone metabolism moves to and fro between bone formation and bone resorption [3], [4].
Current treatment of bone related diseases does often include the use of anti-inflammatory drugs (NSAIDs). NSAIDs can be applied as analgesics or anti-inflammatory agents in fracture healing and post-operative orthopaedic interventions. The (non-)selective NSAIDs influence prostaglandin metabolism by inhibition of the synthesis of COX 1 and/or 2. The possible consequences of their use for the gastrointestinal tract are well documented: NSAIDs can have an eroding effect on the mucosae of the stomach, duodenum, small intestine and colon. Long-term use may result in bleeding, inflammation and perforation [5].
Section snippets
Background
When pathological conditions such as bone fractures arise, hypoxia occurs locally in bone tissue and osteocytes. The impediment of vascular blood flow and interruption of oxygen supply through the bone canals may cause significant reduction of local oxygen concentrations in the wound regions. Clinical studies of bone cell cultures have led to the conclusion that hypoxia is directly responsible for the production of prostaglandin E2 (PGE2) by osteoblasts [6]. Directly and locally, Prostaglandins
The hypothesis
NSAIDs can negatively influence the healing of bone tissue by disturbing the allostatic mechanisms of the involved immune system. NSAIDs influence prostaglandin metabolism by boldly inhibiting the synthesis of COX-enzymes. Their specific action is ascribed to the inhibitory effect of COX-2, while non-selective inhibition of the modulating COX-1 can be seen as ‘collateral damage’. Because COX-1, like COX-2, also has a function in both the intestinal mucosae and bone metabolism, inhibition of
Conclusion and discussion
It has been shown that prostaglandins and inflammatory proteins are of major importance for the regulation of bone homeostasis. They are able to influence bone metabolism directly, as well as indirectly. Local hypoxia and other types of physiological stress in bone tissue direct the synthesis of prostaglandins in the direction of growth and formation of osteoblasts and osteoclasts. Therefore the presence of COX-2 in bone healing is a functional one. By inhibiting the production of PGE2 via COX,
Authors’ contributions
RW van Esch executed an analysis and review of the relationship between bone cell interaction, PGs and NAIDs. He also drafted the manuscript. MM Kool reviewed the role of cytokines and developed the illustrations. S van As had a functional role in structuring the article and also acted as reviewer. All authors have approved the final manuscript.
Authors’ information
All authors treat patients with chronic diseases in a private practice. RW van Esch and MM Kool work as psychoneuroimmunologist and they combine forces with physicians. S van As, MD and former physician, is also author of medical literature on intestinal pathology and a recognised authority on this matter in the Netherlands.
Conflict of interest statement
The authors declare that they have no competing interests.
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