Antiarthritics can exacerbate other inflammatory diseases like periodontitis

Inflammatory diseases can occur simultaneously in distinct sites in the same patient, complicating treatment because a medication effective for one disorder may exacerbate the other. One such example is the anti-arthritic medication dexamethasone, which alleviates joint disease but can worsen periodontal bone disease. A study in the August issue of The American Journal of Pathology highlights the effects of a new class of anti-arthritic drugs, specifically DTrp8-ɣMSH (DTrp), that acts via the melanocortin (MC) system to reduce both arthritic joint inflammation and periodontitis.

“This research, a joint program with the Universidade Federal de Minas Gerais in Brazil, indicates that MC receptor agonists, possibly better if selective for MC3, represent a novel class of anti-arthritic therapeutics able to target joint disease without aggravating unwanted effects on distant organs and tissues,” says Mauro Perretti, PhD, of Queen Mary University of London, Barts, and The London School of Medicine and Dentistry (UK).

More than 60 years ago, adrenocorticotropic hormone (ACTH) was shown to be effective for treating rheumatoid and gouty arthritis, yet its current clinical use is very sporadic. It is now appreciated that some of the anti-inflammatory actions of ACTH are mediated via the peripheral MC system on MC receptors expressed in bone cells, fibroblasts, and immune cells. Research has shown that activation of MC receptors by ACTH or other MC peptides can lead to a variety of protective actions against bone loss, including increased matrix deposition, reduced osteoclast activation, and enhanced proliferation of bone-forming cells.

In this study, researchers first determined whether mice that were induced with experimental arthritis also manifested bone loss in the alveolar (tooth socket) bone. They found that bone loss in the jaw correlated with the severity of localized inflammation in the joints of the mice.

They next compared the effects of a peptide that selectively activates MC3 receptors in mice on both arthritis and alveolar bone loss, and compared the effects to other known medications. The glucocorticoid dexamethasone exerted potent anti-arthritic effect, which were, however, inversely correlated with protection against bone loss. This was markedly distinct from the effect seen with DTrp, which showed a highly positive correlation between clinical score and bone loss (ie reduced bone loss associated with better anti-arthritic effect). Calcitonin had little effect on arthritis but did protect against alveolar bone loss. “This finding is of relevance as prolonged steroid therapy is associated with bone density loss, osteoporosis, and fractures; melanocortin-based therapeutics could spare these unwanted actions,” says Dr. Perretti.

“DTrp could be viewed as a starting point for a new class of bone-sparing anti-arthritic agents,” says John L. Wallace, PhD, MBA, of the Department of Physiology and Pharmacology, University of Calgary, Calgary, Alberta, Canada and University of Toronto, in a commentary on these findings. “This study highlights the continued value of simpler and cheaper (for both the maker and the end-user) approaches to drug development, harnessing the potential of endogenous anti-inflammatory mechanisms.”

According to Dr. Wallace, drugs that harness endogenous anti-inflammatory mechanisms like the MC system offer a number of advantages: they produce a wide range of anti-inflammatory effects, promote the healing of injured tissue, and are potentially associated with very few adverse effects. He comments that these medications “hold out significant promise for safely treating a wide range of inflammatory disorders including, like MC3 agonists, co-existing inflammatory diseases in the same patient.”

http://www.medicalnewstoday.com/releases/279477.php

 

 

Partial knee replacement safer than total knee replacement

Partial knee replacement surgery is safer than total knee replacement according to a new study published in The Lancet.

A team of researchers from the University of Oxford, funded by Arthritis Research UK and the Royal College of Surgeons, found that:

• Although the risk of life-threatening complications from knee replacement surgery is very small, people who undergo total knee replacement are four times more likely to die in the first month after surgery compared to those who have partial knee replacement and 15 per cent more likely to die in the first eight years.
• Patients undergoing total replacement are twice as likely to have a thrombosis, heart attack or deep infection, three times as likely to have a stroke and four times as likely to need blood transfusions, compared to those having partial replacement. In addition, after total knee replacement patients are in hospital longer and the chance of being readmitted or requiring a reoperation during the first year is higher.
• Patients who had a partial knee replacement are 40 per cent more likely to have a re-operation, known as revision surgery, during the first eight years after the replacement, than those that had a total knee replacement.

Up to half of knees that require replacement, usually because of severe osteoarthritis, can be treated with either partial or total replacements. With partial replacements, also known as unicompartmental replacements, only the damaged parts of the knee are replaced and the remaining surfaces and all the ligaments are preserved.

Because of the higher revision rate of partial knee replacement surgery, which is traditionally regarded as the most important factor to determine the choice of implant, its use in the treatment of end-stage osteoarthritis is controversial, with only about 7,000 being performed annually in the UK. Partial knee replacements are often offered to younger people who, because of their higher activity levels, have increased failure rates.

Total knee replacement is one of the commonest surgical procedures, with over 76,000 performed annually in the UK. Only five per cent of patients require revision surgery over a 10-year period.

Revision, re-operation and death were uncommon outcomes of either procedure, stressed the research team.

Professor David Murray, from the Nuffield Departmental of Orthopaedics, Rheumatology and Musculoskeletal Sciences at the University of Oxford, who led the research, said: “For an individual patient, the decision whether to have a partial or total is based on an assessment of the relative risks and benefits. The main benefit of the partial knee is that it provides better function.

“The risks have been assessed in this study, which found that partial knees have fewer complications and deaths; however they do lead to more re-operations. Patients will however be more concerned to avoid death and major complications, such as heart attack or stroke, than reoperations.

“To put the risks in perspective, if 100 patients had a partial knee rather than a total knee replacement there would be one fewer death and three more re-operations in the first four years after surgery.”

If the number of partial replacement were to increase from eight per to 20 per cent, the NHS could potentially prevent 170 deaths, at the cost of 400 additional revisions. If the number of partial replacements was increased, then surgeons would become more experienced with the procedure and as a result there would probably actually be fewer additional re-operations.

Professor Murray added: “Patients will be concerned about death following joint replacement. However patients who have severe arthritis are very immobile and therefor tend to be unfit. Joint replacement overall, by making patients more mobile and fit tends to save lives.”

His colleague Alex Liddle, an Arthritis Research UK clinical research fellow, who ran the study, added: “Partial and total knee replacements are both successful treatments and a large proportion of patients with end-stage knee osteoarthritis are suitable for either.

“Both have advantages and disadvantages, and the choice of which procedure to offer will depend on the requirements and expectations of individual patient.”

The team’s extensive study used data from the National Joint Registry for England and Wales on the adverse outcomes of more than 100, 000 matched patients who had undergone both types of knee surgery.

Medical director of Arthritis Research UK Professor Alan Silman said: “This is a comprehensive study that provides both patients and surgeons with valuable information about the risk and benefits of two effective types of knee replacement operations. This new knowledge will enable them to make an informed decision about which type of surgery is best for particular individuals.

“Even in the elderly, with other health problems, knee replacement is a very safe and effective procedure. These data remind us that there are still patients, who fortunately very rarely, can develop life threatening complications following surgery and we still need to find surgical approaches that takes away these risks whilst retaining a successful outcome for patients.”

http://www.medicalnewstoday.com/releases/279306.php