Medicine is needed to prevent fractures in patients who have already had a fracture or have a bone density measurement that shows osteoporosis. Many of these medications are pills given daily or weekly or every month. These include medications such as raloxifene (Evista), alendronate (Fosamax), residronate (Actonel), ibandronate (Bonviva). Strontium ranelate (Protos) is given daily as a satchet which is made into a drink.

Recently the USA FDA has approved IV zoledronate (Aclasta) 5 mg every year for the treatment of osteoporosis. The studies show that it prevents spine and hip fractures in those with osteoporosis based on BMD and also in those who already had fractures. This is the only drug so far where even patients with hip fractures are studied. In such patients, further fractures are prevented and the chance of dying is reduced.

Currently the availability of anti-TNF blockers such as Remicade (infliximab), Enbrel (etanercept) and Humira (adalimumab) have revolutionized the treatment of rheumatoid arthritis, ankylosing spondylitis, juvenile idiopathic arthritis and psoariasis.

For patients with rheumatoid arthritis who fail treatment with anti-TNF blockers, they can use rituximab (Mabthera) or abatacept (Orencia), both of which are approved by several health authorities for this purpose. Both of these drugs are also being studied for the treatment of lupus.

Studies are also going on with drugs targeting new sites such as tocilizumab (Actemra) which block IL6. Newer versions of anti-TNF such as golimumab and anti-CD 20 such as ocrelizumab are being developed.

Twenty years ago there were not too many medications which treat osteoporosis and prevent fractures from happening. There was only hormone replacement therapy (HRT) and calcitonin both of which are now out of favour. HRT is associated with a risk of developing breast cancer after prolonged use of more than about 5 years. Calcitonin is relatively expensive and the research that shows whether or not it can prevent fractures is weak.

In the present day, the most commonly used drugs are alendronate (Fosamax), risedronate (Actonel) and raloxifene (Evista). There are recent reports of a rare complication with Fosamax and Actonel called osteonecrosis of the jaw (ONJ). These are very rare and do not occur in the majority of patients. There are 2 sets of reports where some patients who are on Fosamax experience unusual fractures. However a causal link is not established and some of these patients with unusual fractures were not on Fosamax. Some of those on Fosamax did not have osteoporosis. Therefore it is not a good idea to start a drug too early in patients who do not have osteoporosis yet. On the other hand both Fosamax and Actonel are extremely effective in preventing hip fractures in those above the age of 70. So they should be used when it is appropriate to use them. Using them up to five years is safe, from 5 to 10 years it is grey but probably safe. After ten years we do not know if anything adverse will happen, probably not but we do not know.

Evista recently had some research done to show if it helps prevent heart attacks. A large study called RUTH clearly shows that it has neutral effects, that is, it does not increase or decrease heart attacks. However in this group of patients at high risk of heart attacks, it was shown that there was a slight increase in fatal strokes. So the drug should not be used in those with existing stroke or in those at risk for stroke. Evista is known also to increase blood clots in the venous system. However it prevents spine fractures from happening to patients who have osteoporosis. Several large studies show that it can reduce the risk of breast cancer.

Newer drugs just approved for osteoporosis are teriparetide (Forteo) and strontium ranelate (Protos). Forteo is a bone forming agent but its use is restricted to 24 months as in animal studies bone cancers occurred. This is very unlikely to happen in humans as they will need to be exposed to the drug for their whole life. Protos is a useful addition but it can cause diarrhoea in some patients. Oral ibandronate (Bonviva) is given once a month but it has been shown only to reduce spine fractures.

Therefore there is no perfect drug. This is true for high blood pressure, diabetes and also for osteoporosis. Each patient is unique and the best drug for that person will depend on many factors. To choose a drug, the doctor will weigh the pros and cons and in consultation with the patient, a drug will be chosen where the benefits far outweigh the risks.

Recently there has been much news about coxibs, a group of  anti-inflammatory pain killers which was found to be associated with increased heart attacks if used for too long. Vioxx or rofecoxib and Bextra or valdecoxib were withdrawn on this basis. Bextra in addition had problems with a severe drug reaction called Steven Johnson Syndrome.

There are still two coxibs left on the market, namely Celebrex or celecoxib and Arcoxia or etoricoxib. Then there are still the traditional NSAID’s (non-steroidal anti-inflammatory drugs) such as Voltaren (diclofenac), Synflex (naproxen), Mobic (meloxicam), Brufen or Neurofen (ibuprofen).

There has been some research now suggesting that even  these traditional NSAID’s have some risk for heart attacks although the type of study showing this is not as ideal as the trials done for Vioxx.

The lessons to draw are:

1. NSAID’s and coxibs may cause heart attacks if used for more than 18 months. They should be avoided in patients who have risk factors for heart attacks such as high blood pressure and diabetes.
   
   
2. Traditional NSAID’s can cause stomach ulcers which can become serious. In patients who previously had stomach or duodenal ulcers, NSAID’s need to be partnered with gastric protecting drugs such as Losec or Nexium. A coxib may also be helpful as the risk for ulcers is less, provided the patient does not have a risk for heart attacks.

The most important lesson is that NSAID’s and coxibs are merely pain killers. The rheumatologist will make an accurate diagnosis of the underlying illness causing the pain and use treatment that treats the underlying disease and not just the symptoms.

LUPUS AND LIPIDS

SLE used to be very serious and in the 1960’s half of the patients perished within 5 years. Nowadays the prognosis is much better. The chances of living for 10 years is 90%. Many patients can have normal life span. Because of this new problems have arisen.

A study in Singapore by Leong et al showed that in a group of SLE patients with average age of 32, 35% of them had blood cholesterol levels that are very abnormal. The bad cholesterol is more than 200 mg/dl. This is alarming as other studies around the world also showed that SLE patients have a chance of getting strokes and heart attacks earlier than the normal population.

Further research showed that the cholesterol problems are linked to the presence of kidney disease in lupus, the overall severity of lupus and the use of steroids in the treatment of lupus. Therefore good control of lupus activity is important and using as low a dose of steroid as possible is important. This may mean adding a second drug such as Cellcept or azathioprine or Plaquenil depending on the condition of the patient. The patient must not adjust the medication herself as the lupus must not be allowed to flare.

Lupus specialists need to be aware that blood cholesterol levels need to be checked regularly in lupus patients. If the patients have abnomal lipid levels treatment must be started to lower the levels so that the risk of strokes and high attacks is lessened.

Many types of arthritis are caused by the immune system becoming overactive. The immune system normally fights off germs and protects the body but in autoimmune disease there is a failure to recognize self from non-self. The body’s own tissues eg joints, kidney, blood cells are attacked as though they are foreign substances. Examples of autoimmune disease which cause arthritis are rheumatoid arthritis, ankylosing spondylitis and psoriatic arthritis.

When this immune system attacks the joints, they become swollen, red, warm and painful. There is also stiffness first thing in the morning which lasts more than an hour. Usually by the afternoon it subsides. If left untreated the joints become damaged, deformed and useless.

Treatment involves treating the symptoms but the underlying problem must also be treated to prevent relapses and joint damage.

To treat symptoms painkillers of different sorts can be used. They include simple painkillers like paracetamol (eg Panadol, Tylenol); paracetamol mixed with muscle relaxants (eg, Norgesic, Anarex); tramadol, NSAID’s (non-steroidal anti-inflammatory drugs). NSAID’s reduce not only pain but also inflammation and are useful in the short term. They however do not treat the underlying problem and can have side effects if used for too long. Common side effects are stomach and duodenal ulcers, water retention, worsening of blood pressure and in the elderly, the kidney function may be affected. Corticosteroids ( eg, prednisolone, methylprednisolone or Medrol, dexamethasone) are effective and powerful medicines which rapidly reduce pain and inflammation. They should be used sparingly or not at all unless prescribed by an experienced doctor. Many side effects can occur if used in too high doses for too long. These include infection, high blood pressure, osteoporosis, cataracts, weight gain, high blood cholesterol and diabetes.

Therefore it is more important to treat the underlying problem with medications called DMARD’s (Disease Modifying Anti-Rheumatic Drugs). They calm the immune system down so that it will stop attacking the joints and other tissues. Side effects can occur in about 1 out of 500 patients but the usage is safe when blood test monitoring is done every 1 to 3 months. Examples of DMARD’s are methotrexate (MTX), sulphasalazine (Salazopyrin), hydroxychloroquine (Plaquenil), lefluonamide (Arava) and the new medicines called Anti-TNF (Anti-Tumour Necrosis Factor).

Anti-TNF drugs are biological agents which target only one specific part of the immune system so that fewer side effects occur. Because of this magic bullet effect they are extremely effective and very safe. Studies show that in patients in whom existing treatments such as MTX fails, anti-TNF will work to control the disease. Examples are Remicade (infliximab), Enbrel (etanercept) and Humira (adalimumab). Remicade and Enbrel are approved for use by the FDA in USA and other health authorities for treatment of rheumatoid arthritis, ankylosing spondylitis, psoariatic arthritis and psoriasis skin disease. Remicade is also approved for Crohn’s disease and Enbrel for juvenile idiopathic arthritis in children. Humira is approved for adult rheumatoid arthritis and psoriatic arthritis only up to now but in future other conditions may be included when research is completed. Other biological agents are in the research phase such as tocilizumab which targets interleukin 6 and abatacept which is a co-stimulatory molecule.

Therefore autoimmune disease attacking joints such as RA, AS and psoriasis can damage the joints if not treated properly. Patients tend to be young, between 20-50 and the impact on their lives can be very great. Fortunately now we have many good and proven medications which not only reduce the pain and symptoms but more importantly to treat the underlying illness so that the joints will not be damaged.

Osteoporosis is a condition where the bones become brittle and break even after little trauma such as falling down in the bathroom.

Besides taking enough calcium, vitamin D, having adequate weight bearing exercise and taking precautions to avoid falling, medication is needed for those at high risk for fractures. Such patients include those who have already had fractures and those with a low bone mineral density on testing.

In the past there are many medications which are proven to be useful for preventing fractures. The most proven are alendronate (Fosamax), risedronate (Actonel) and raloxifene (Evista). They work by reducing bone loss.

Now there are two new drugs approved for the treatment of osteoporosis. The first is teriparetide or Forteo. This is a bone forming agent, unlike existing drugs. However it should not be used more than 18 months and it is given as a daily injection.

The other drug is strontium ranelate (Protos). This is given as a satchet which is put in water and ingested. This drug has a dual mode of action. It increases bone formation and reduces bone loss. Most important of all it has also been shown to reduce the chance of getting a fracture.

The treatment of autoimmune disease has changed greatly in the last ten years. In the past patient with swollen joints from rheumatoid arthritis psoriatic arthritis or ankylsoing spondylitis just slowly wait for the joints to get damaged while having some pain relief from pain killers.

Now we have magic bullet therapy which shuts down important pathways in the immune system so that it will stop attacking the patient’s joints and organs.

Up to now there are three main anti-TNF agents namely infliximab (Remicade), etanercept (Enbrel) and adalimumab (Humira). They are all approved for rheumatoid arthritis psoriatic arthritis and ankylosing spondylitis.

Newer drugs approved for RA are rituximab (Mabthera) and abatacept (Orencia). These two drugs are interesting in that they work even after the anti-TNF agents have failed. Research is now in progress to see if these two new drugs also benefit lupus patients.

Vioxx (rofecoxib) was withdrawn due to the finding that compared to placebo, it had a higher risk of heart attacks. This led to a change in the way doctors prescribed painkillers and more of the traditional NSAID's (non steroidal anti-inflammatory drugs) were again prescribed. Vioxx is part of a group of drugs called coxibs which have the advantage of being safer on the stomach and cause less ulcers than traditional NSAID's.

After vioxx was withdrawn two other coxibs remained available, namely Celebrex (celecoxib) and Arcoxia (etoricoxib). There were also studies looking at traditional NSAID's which indicated that they too may have increased risk of heart attacks when compared to people who are not on these drugs. However these were not the “gold standard” type of trials as they are case-control studies.

Recently a head to head comparison study was done between Arcoxia and Voltaren (diclofenac), a traditional NSAID. This is the proper way to compare two drugs in a research study. The MEDAL trial and MEDAL program found that Arcoxia and Voltaren had similar heart attack rates. It also confirmed that Arcoxia is safer on the stomach than Voltaren. Arcoxia was found to worsen high blood pressure to a mild extent.

Now that the dust has settled so to speak concerning coxibs, another coxib called lumiracoxib will be launched in Singapore once the HAS has given its approval.

The role of coxibs is for those who are at risk for NSAID induced peptic ulcers. These are patients who are elderly, who are also on steroid medicines and who have had previous peptic ulcers. However if a patient has heart disease, kidney disease or hypertension then both coxibs and traditional NSAID's must be used with caution. The main aim of any treatment is to treat the underlying disease rather than treating only the symptoms.

"Magic bullet" treatments are now a reality for cancers and autoimmune diseases such as rheumatoid arthritis. These are medications which home in on a specific molecule that is causing the illness and stops it from affecting the patient.

Osteoporosis is a disease of the bones where bone is lost faster than it can be replaced leading to brittle bones and fractures. Current treatments either reduce bone loss or make new bone. It is now recognized that there are key molecules which control bone formation and bone resorption.

One of the key molecules in bone formation is osteoprotegrin and the key molecule in bone loss is the RANK-RANK ligand complex. Recent studies have used a drug called desonumab. This is an anti-RANKL antibody and in clinical trials it reduces bone loss and improves bone density. Trials are in progress to determine if fracture risk is reduced. It may also have a role in reducing bony erosions in rheumatoid arthritis.

Targetted therapies are usually more effective and have fewer side effects than medications that are less focused. For osteoporosis, this line of research promises better treatments in future for this common and serious illness.