4.3 Drug treatment for osteoporosis: bisphosphonates

Bisphosphonates are the most common drugs that are used to treat osteoporosis and reduce fracture risk. They are anti-resorptives, which work by preventing the action of osteoclasts (as discussed in section 2) and so reduce bone re-modelling, with a shift towards bone formation and increased BMD. They reduce fracture risk substantially, almost halving risk over 3 years.

Bisphosphonates can be administered orally on a weekly basis. The most potent is alendronate, which is licensed for post-menopausal women, men with osteoporosis, and to prevent glucocorticoid (steroid) induced osteoporosis. It has been shown to reduce fractures to the hip, spine and wrist. Risedronate has the same licence and pattern of efficacy though is slightly less potent. There is also a monthly preparation (ibandronate) but there is less evidence in its favour and it is only licensed in women to prevent vertebral fractures.

Bisphosphonates are poorly absorbed, especially if taken with any food. They can also irritate the oesophagus. To avoid these problems patients must be told how to take the drug effectively:

  • first thing in the morning, an hour before breakfast or before any other food, drink or tablets
  • washed down with a whole glass of water (not orange juice or any other drinks), to ensure the tablet passes through the oesophagus and into the stomach
  • remaining upright (sitting or standing is fine, but not bending over or lying down) for 30-60 minutes to avoid the drug refluxing into the oesophagus.

The dosage instructions for oral bisphosphonates can be challenging, especially in Parkinson’s where people may already have swallowing problems or cognitive difficulties. The most common side effect is gastrointestinal upset, especially dyspepsia. If patients get significant symptoms, they should suspend treatment and consult their GP. However, most people tolerate these medicines without side effects, and if they understand the need for such treatment then adherence can be good.

More information is available from the Royal Osteoporosis Society in their patient fact sheet, Alendronate [Tip: hold Ctrl and click a link to open it in a new tab. (Hide tip)] (alendronic acid or Fosamax)

The main contraindications to bisphosphonates are renal disease (avoid if eGFR NOGG full guideline.

Where the oral bisphosphonates are not tolerated (most commonly for swallowing, oesophageal or compliance issues), an intravenous preparation of bisphosphonate (zoledronate) can be used instead. This is now low cost, and even more potent at reducing fracture risk. However, in most areas its administration requires referral, usually to rheumatology services, though it is likely to become more widely available. The dose is repeated once yearly for 3 years. It cannot be used where the eGFR is below 35 ml/min. It is essential that vitamin D deficiency is corrected before administration, to avoid hypocalcaemia. The main side effect of intravenous bisphosphonates, affecting up to 40% of patients, is flu-like symptoms that can last 1-3 days, but which can be managed with simple analgesia such as paracetamol and good hydration.

4.3.1 Rare but serious side effects of bisphosphonates