The dental implications of bisphosphonates and bone disease

The document attached has been archived with permission from the Australian Dental Association. An external link to the publisher’s copy is included.In 2002/2003 a number of patients presented to the South Australian Oral and Maxillofacial Surgery Unit with unusual non-healing extraction wounds of the jaws. All were middle-aged to elderly, medically compromised and on bisphosphonates for bone pathology. Review of the literature showed similar cases being reported in the North American oral and maxillofacial surgery literature. This paper reviews the role of bisphosphonates in the management of bone disease. There were 2.3 million prescriptions for bisphosphonates in Australia in 2003. This group of drugs is very useful in controlling bone pain and preventing pathologic fractures. However, in a small number of patients on bisphosphonates, intractable, painful, non-healing exposed bone occurs following dental extractions or denture irritation. Affected patients are usually, but not always, over 55 years, medically compromised and on the potent nitrogen containing bisphosphonates, pamidronate (Aredia/Pamisol), alendronate (Fosamax) and zolendronate (Zometa) for nonosteoporotic bone disease. Currently, there is no simple, effective treatment and the painful exposed bone may persist for years. The main complications are marked weight loss from difficulty in eating and severe jaw and neck infections. Possible preventive and therapeutic strategies are presented although at this time there is no evidence of their effectiveness. Dentists must ask about bisphosphonate usage for bone disease when recording medical histories and take appropriate actions to avoid the development of this debilitating condition in their patients

Complex I-Associated Hydrogen Peroxide Production Is Decreased and Electron Transport Chain Enzyme Activities Are Altered in n-3 Enriched fat-1 Mice

The polyunsaturated nature of n-3 fatty acids makes them prone to oxidative damage. However, it is not clear if n-3 fatty acids are simply a passive site for oxidative attack or if they also modulate mitochondrial reactive oxygen species (ROS) production. The present study used fat-1 transgenic mice, that are capable of synthesizing n-3 fatty acids, to investigate the influence of increases in n-3 fatty acids and resultant decreases in the n-6∶n-3 ratio on liver mitochondrial H2O2 production and electron transport chain (ETC) activity. There was an increase in n-3 fatty acids and a decrease in the n-6∶n-3 ratio in liver mitochondria from the fat-1 compared to control mice. This change was largely due to alterations in the fatty acid composition of phosphatidylcholine and phosphatidylethanolamine, with only a small percentage of fatty acids in cardiolipin being altered in the fat-1 animals. The lipid changes in the fat-1 mice were associated with a decrease (p<0.05) in the activity of ETC complex I and increases (p<0.05) in the activities of complexes III and IV. Mitochondrial H2O2 production with either succinate or succinate/glutamate/malate substrates was also decreased (p<0.05) in the fat-1 mice. This change in H2O2 production was due to a decrease in ROS production from ETC complex I in the fat-1 animals. These results indicate that the fatty acid changes in fat-1 liver mitochondria may at least partially oppose oxidative stress by limiting ROS production from ETC complex I

Effects of capsaicin, bradykinin and prostaglandin E2 in the human skin

The actions and interactions of putative mediators of inflammation, such as substance P (SP), histamine, bradykinin and prostaglandins (PGE2) were studied in human skin. In addition, the effects of capsaicin were examined as it is known to release (and to deplete) SP and calcitonin gene-related peptide from C-fibres. The flare evoked by bradykinin was abolished by pretreatment with lignocaine (local anesthetic), compound 48/80 (mast-cell histamine liberator), mepyramine (H1-receptor antagonist) and indomethacin (cyclo-oxygenase inhibitor) but was unaffected by atropine and ketanserin (serotonin antagonist). The weal response was not reduced by any of the drugs. The flare evoked by capsaicin was abolished by lignocaine and indomethacin but was unaffected by compound 48/80, mepyramine, atropine and ketanserin. The weal response was reduced by indomethacin. The flare response to bradykinin seems to reflect the activation of C-fibres and associated mast cells, while the flare response to capsaicin seems to reflect the activation of C-fibres only. Repeated injections of capsaicin and bradykinin produced tachyphylaxis (and cross-tachyphylaxis) and greatly reduced the SP-evoked flare. Capsaicin produced tachyphylaxis also after treatment of the skin with a local anaesthetic, suggesting that it develops independently of C-fibre impulse flow. The tachyphylaxis produced by bradykinin and capsaicin seems to reflect the depletion of messenger peptides from the C-fibres. The flare response to SP following capsaicin- or bradykinin-induced desensitization gradually returned to normal after 5-8 weeks. The erythema evoked by PGE2 was reduced by 30% following pretreatment with lignocaine, mepyramine or compound 48/80