Osteoporosis – new drugs are making a difference
Reproduced from Issue 133 of Arthritis Today
Stuart Ralston and Phillip Riches look at the current drugs that are transforming the treatment of brittle bone disease.
Professor Stuart Ralston
Huge advances have been made in developing new treatments for osteoporosis over the past 25 years and clinicians now have at their disposal a wide range of drug treatments for this condition. Most of the currently available treatments for osteoporosis work by preventing bone loss but some treatments are available which promote formation of new bone. The aim of treatment is to reduce the risk of bone fractures occurring, and the best treatments prevent fractures in about 40 per cent of cases. Although none of the treatments currently available can completely prevent fractures it is likely that this will improve as new drugs are developed and clinicians learn to use existing drugs more effectively.
What is osteoporosis?
Osteoporosis is a common disease which is caused by reduced bone mineral density (BMD). This reduction in BMD causes the bones to become fragile and break easily. The diagnosis of osteoporosis is made by BMD scanning usually using a technique called DEXA. Most doctors like to obtain a DEXA scan to make sure their patients have osteoporosis before starting treatment.
What causes osteoporosis?
Osteoporosis is unusual in young people but gets progressively more common with increasing age because bone density falls with age. Osteoporosis is more common in women because rates of bone loss increase after the menopause (change of life), but men can also be affected by the disease.
Treatments for osteoporosis
The drugs that are currently available work by preventing the breakdown of bone or by promoting the formation of new bone. Some treatments prevent all types of fracture and these are the ones that are used as “first line” treatments whereas others only prevent spine fractures and these are used as “second line” treatments (Table 1).
Calcium and Vitamin D
Calcium and vitamin D supplements can slow the rate of bone loss but on their own are not enough to prevent fractures occurring in people with osteoporosis. Calcium and vitamin D treatment can be useful, however in people who have a poor diet or those that are at risk of vitamin D deficiency for other reasons. They are also usually prescribed along with other treatments for osteoporosis to make sure that they work properly.
Bisphosphonates
Bisphosphonates are effective treatments for osteoporosis and are the most widely prescribed drugs for the condition. They work mainly by preventing bone loss but also increase BMD to an extent. Bisphosphonates are poorly absorbed from the gut and need to be taken on an empty stomach with plain water.
Etidronate (Didronel® PMO) is given for two weeks, followed by 13 weeks of calcium tablets. Etidronate is also effective for the treatment of osteoporosis in men and osteoporosis in people who are receiving corticosteroids. Etidronate reduces the risk of spine fractures, but doesn't appear to be effective at reducing fractures of other bones such as hip fractures. In view of this, its use has diminished over recent years as more powerful bisphosphonates have been developed.
Alendronate (Fosamax®) is the most widely prescribed bisphosphonate. It reduces the risk of all fractures by about 40 per cent and also works in men and people on corticosteroids. The most common side effect is stomach upset.
Risedronate (Actonel®) works in a similar way to alendronate and is also taken once a week. Like alendronate it reduces the risk of all fractures by about 40 per cent and also works in patients with osteoporosis secondary to corticosteroids treatment.
Ibandronate (Bonviva®) is a once-monthly oral treatment for osteoporosis and is also available as a three-monthly injection. The once-monthly treatment is convenient for patients, but only seems to prevent spine fractures. In view of this, ibandronate is not a suitable treatment for most patients with osteoporosis. The ibandronate injection is given every 3 months and is likely to be a useful treatment option for patients who have problems with stomach upset with other osteoporosis treatments. A common side effect with the injection is a flu-like illness which occurs in about 25 per cent of people. This reaction only lasts for 1-2 days and does not tend to recur after further injections.
Pamidronate (Aredia®) is used for the treatment of osteoporosis in patients who cannot take treatments by mouth. It is usually given by an infusion over 2 hours and can also cause a flu-like illness as described for ibandronate.
Strontium ranelate Strontium ranelate (Protelos®) reduces the risk of vertebral and non-vertebral fractures in women with osteoporosis. The preventative effect on spine fracture is similar to bisphosphonates but for non-spine fracture, the effects of strontium do not seem to be quite as good. Also, the onset of action for strontium seems to be a bit slower than bisphosphonates. Strontium is a liquid which is taken on an empty stomach usually at night. the most common side effect is diarrhoea.
Hormone replacement therapy (HRT)
Stuart Ralston is arc Professor of Rheumatology and Dr Phillip Riches is lecturer
in rheumatology at the Rheumatic Diseases Unit in the Western
General Hospital in Edinburgh. Hormone replacement therapy is known to prevent all types of fracture, but HRT is used much less often now, because long term treatment significantly increases the risk of breast cancer, heart disease and strokes. Oestrogen–only HRT in women who have had a hysterectomy seems to be safer, but even with this there is a slight increase in the risk of stroke. In view of this, HRT is now mainly used for preventing osteoporosis in patients with an early menopause where it is safe and effective. Tibolone Livial®) is a special type of HRT that is used in the prevention of osteoporosis. It is currently unclear whether tibolone carries the same risk of heart disease and breast cancer as other forms of HRT, but research is underway at present to evaluate this.
Calcitonin
Calcitonin prevents bone loss and reduces the risk of spine fracture. Calcitonin can be given by an injection, but more usually it is given by a nasal spray. One benefit of calcitonin over other osteoporosis drugs is that it can sometimes help back pain. However the downside of calcitonin is hat it does not appear to prevent non-spine fractures.
Raloxifene
Raloxifene (Evista®) reduces the risk of spine fractures but is not effective at reducing the risk of other fractures. Although raloxifene works in a way that is similar to HRT, it actually reduces the risk of breast cancer and does not increase the risk of heart disease or stroke. Side effects are not generally a problem but those that can occur include muscle cramps, hot flushes and an increased risk of blood clots.
Parathyroid hormone
Parathyroid hormone (Forteo®) is an effective treatment for osteoporosis which works by promoting formation of new bone. Parathyroid hormone treatment reduces the risk of both spine and non-spine fractures. It is given as a daily injection using a “pen” device for up to 18 months and after this patients are usually switched onto another treatment to prevent bone loss such as a bisphosphonate. Although parathyroid hormone is effective, it is about ten times more expensive than other treatments and because of this it is generally reserved for patients with severe osteoporosis or those that have not responded well to other treatments.
New and emerging treatments
Several new treatments are being developed for osteoporosis. These include zoledronic acid, a bisphosphonate which has a very long duration of action and which appears to be effective when given as a once-yearly injection. Large scale trials are in progress to evaluate the effects of this agent on fractures. Another formulation of parathyroid hormone is also being developed (the 1-84 fragment of PTH; Preos®) and is likely to be available for routine clinical use in the next few months. Clinical studies with 1-84 PTH indicate that it reduces the risk of vertebral fracture, but it has not been shown to reduce the risk of non-vertebral fractures. Several pharmaceutical companies are developing inhibitors of the enzyme Cathepsin K as treatments for osteoporosis. These drugs are antiresorptive agents and are currently in clinical trials for osteoporosis. Another inhibitor of bone resorption which is under development is Denosumab® which is effective at preventing bone loss for periods of up to six months when given by a single injection. Further research to investigate the effects of this agent on fractures is in progress.
