Medications to Treat or Prevent Osteoporosis

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In addition to the use of non-pharmacological therapies, calcium, and vitamin D, there are an increasing number of medications that strengthen bone and reduce the chance of fracture.

One of the first of these used, in women, was hormone replacement therapy (HRT).  The sex hormones, particularly oestrogen, are an important factor in bone biology.  Consequently, when females pass through the menopause and levels of these hormones fall, the rate of bone loss accelerates.  This explains why osteoporosis is more common in females.  Therefore, it followed that replacing these hormones would be an effective therapy for osteoporosis.  This was subsequently proven in large clinical studies that showed the rate of spinal and non-spinal fractures significantly reduced.  However, these same studies found a few concerning aspects, which included an increase in the risk of breast cancer as well as a higher risk of cardiovascular disease in those over 70 years of age.  It should be noted though, that the risk for a number of other cancers in fact reduced.  As a result of these overall findings, the use of these medications has reduced.  Nevertheless it remains an option in certain patients.

The problems with HRT led onto the development of a non-hormonal therapy that is able to stimulate certain oestrogen receptors whilst not affecting others, called Selective oEstrogen Receptor Modulators (SERMs).  The most commonly used medication of this class is called Evista (Raloxifene).  A study by the acronym MORE showed that the risk of spinal (vertebral) fractures was reduced by up to 50% and favourably the risk of breast cancer was not increased but instead decreased by about 35%!  However, the SERMs were similar to HRT in respect to an increased risk of blood clots within veins (called venous thrombosis).  Consequently, these medications should be avoided in those at risk of thrombosis.

Probably the greatest impact on the treatment of osteoporosis has been achieved with the development of the group of medications called bisphosphonates.

These are given the descriptive term of being anti-resorptive since they target the cells termed Osteoclasts, which are responsible for removing bone.  There are a number of these medications now on the market, with Actonel (Risedronate) and Fosamax (Aledronate) being the most popular oral agents.  Initially these were taken daily but recently formulations allow them to be used weekly and even monthly (with Actonel).

Aclasta (Zolendronate) is given intravenously on a yearly basis.  This class of medication has been shown to be very effective in reducing the risk of both vertebral and non-vertebral fractures by about 50%.

A current debate about the use of bisphosphonates revolves around how long patients should receive this therapy.  That is, should patients use these medications lifelong or can they be stopped after a certain number of years.

The bisphosphonates have attracted attention from the media (read blog post on this) in relation to their potential side effects, especially regarding osteonecrosis of the jaw (ONJ).  Unfortunately, as is common in the media, the risk has been grossly overexaggerated.  The group who have had the highest risk are those who receive the medication for the treatment of elevated calcium or bone pain due to cancer.  In this group, the intravenous form of the medication is given very much more frequently than is usual for osteoporosis treatment and at higher doses.  However, the risk of ONJ in the treatment of osteoporosis (which involves much smaller doses) is actually rare.  Nevertheless, the current recommendation is that patients see their dentist and have any major dental work performed prior to commencing treatment and attention be paid to dental hygiene in those already using the medication.

The more common side effects include oesophagitis, which is inflammation of the gullet.  This may manifest with indigestion or an increase in reflux symptoms.  This is experienced only in those taking the oral medications (being Actonel and Fosamax) and as a result the advice is that the patient take the medication on an empty stomach 30 minutes prior to eating and to remain upright during that time.  Actonel now comes in an enteric coated form (EC), which is thought to address this problem, as is the case with the intravenous Aclasta.  Some patients experience bone pain and flu-like symptoms. The use of Paracetamol can help this.  These medications are avoided in those with moderate to severe impairment of renal function.

There are some treatments used that actually build bone such as recombinant PTH (Forteo) and Strontium Ranelate (Protos).  Forteo is given as a daily subcutaneous injection, which is often not popular with most patients.  Nevertheless, it is very effective in reducing the risk of fracture by as much as almost 70%!  Unfortunately the medication is prohibitively expensive, receiving no government subsidy in Australia as an initial treatment, such that very few patients are able to afford it.  Subsidy has recently been given for those who continue to sustain fractures whilst taking the other osteoporotic therapies.  Protos comes in a powder form that is mixed with water prior to being taken on a daily basis.

The most recent addition to the armamentarium is a medication called Denosumab (Prolia).  This is a biological therapy, which means it is an engineered antibody, which specifically targets the messenger that stimulates the osteoclasts to resorb bone.  This messenger is given the acronym RANKL.  A number of studies have now shown that this treatment is similar in efficacy as the bisphosphonates in reducing the risk of both vertebral and non-vertebral fractures.  An advantage is that the medication is given as a sub-cutaneous injection once every 6 months and can be given in those with moderate renal (kidney) impairment.  The potential complications are otherwise relatively similar in terms of the risk of flu-like symptoms and bone pain.  This seems more common in those who are vitamin D deficient and so clinicians should usually replace this vitamin prior to the commencement of Prolia (and in all the other anti-osteoporosis medications).  Rarely the blood level of calcium can fall and inflammation of the Pancreas (pancreatitis) can occur.  To lessen the chance of the former patients are recommended to take supplemental calcium (which is commonly used anyway as part of their treatment).

In conclusion, the future promises the addition of other therapies, particularly those that target the bone forming cells. We are already in a very fortunate position with the number of effective therapeutic options that we have at our disposal to reduce the risk of fracture.

It is for this reason that the neglect in identifying and treating this most serious of diseases is so tragic.