Osteoporosis is one of those disorders which some think is simply an invention of the pharmaceutical industry. Try telling the 65-year-old woman with height loss and a bent back (kyphosis – Fig 1) that it is a problem dreamed up in the Board Rooms of our major drug companies!
Osteoporosis is not a manufactured disorder but simply the definition of the problem is based on bone density measurements. Bone density measurements are simply a risk factor for excess fracture risk just as high blood pressure is a risk factor for future stroke and high cholesterol is a risk for future heart attacks.
How common are fractures?
One in 2 women and 1 in 5 men over the age of 50 will sustain a fracture that could be related to osteoporosis . The commonest sites are the wrist (Colles fracture), the shoulder, the vertebra (back bone) and the hip but really almost any bone fracture can be related to osteoporosis perhaps with the exception of the skull, fingers and toes.
How can risk of fractures be assessed?
Unfortunately there are two different online clinical risk factor calculators which work out an individual’s 10-year risk of major osteoporotic fracture and hip fracture alone and both have been “approved” in NICE Clinical Guidance 146 .
Q Fracture has the advantage of including many clinical risk factors but the disadvantage of not linking to arguably the strongest risk factor, bone mineral density (BMD).
The FRAX tool has far fewer risk factors but crucially includes BMD of the hip when available. It also has the arguable advantage of linking directly to the National Osteoporosis Guideline Group recommendations of thresholds for BMD measurement and treatment.
Assessment of BMD (Bone Mineral Density)
This is ideally undertaken by a Dual Energy X-ray Assessment (DEXA) (Fig 2).
Generally BMD at two sites (usually lumbar spine and total hip) are measured with minimal radiation exposure. Increasingly a 3rd site is measured with a view of the spine taken from the side (lateral scan – Fig 3) which has the advantage that for a minor increase in radiation exposure and 5-minutes added to the 15-20 minute scan session, fractures in the spine bones (vertebrae) can be identified. As these can occur without significant injury or even pain, it is very valuable to know if they exist as they significantly predict future fractures at the spine and other bone sites.
Who should be assessed for Osteoporosis and Fracture risk?
Individuals who are at particular risk and will benefit from a full risk assessment include those with:
- A Family History of osteoporosis or fractures
- Women with an early menopause
- Men and women with a previous fracture
- Those a Heavy Alcohol Intake (more than 2 units per day in women and 3 in men)
- Chronic steroid (glucocorticoid) users (>7.5 mg prednisolone per day or equivalent)
- Chronic liver or kidney disease
- Patients receiving drugs for breast or prostate cancer
- Eating Disorders especially anorexia nervosa
- Coeliac Disease or other cause of Food malabsorption
- Overactive Thyroid or Parathyroid glands
- Frequent fallers
- Limited mobility due to neurological disease
- Rheumatoid arthritis, ankylosing spondylitis
The presence of many of these risk factors will allow a DEXA scan to be undertaken at NHS clinics and sites but anyone over the age of 40 who has anxiety about osteoporosis can have a DEXA measurement in the private sector.
How can fracture risk be reduced?
The role of active weight bearing exercise, good nutrition and access to adequate reserves of vitamin D derived from sunlight, the diet or supplement is very important for maintaining good bone health. The role of sunlight exposure in the latter is problematic and recent advice has been published by NICE.
It would be ideal if improving lifestyle factors alone could reduce risk but in those with increased significant risk of fracture or diagnosed with osteoporosis drug therapy is almost certainly required. The subject for advised intervention thresholds using risk factor calculators and/or DEXA scan results is still controversial with NOGG favouring a straightforward algorithm approach based on the FRAX analysis , while new guidelines from the Scottish Integrated Guideline Network suggest treating most patients over the age of 50 assuming their 10-year fracture risk is 10% or more and their DEXA scan at spine or hip ≤ -2.5. Rather confusing for both health professionals and patients!
Which drugs reduce fracture risk?
For more than two decades we have known that drugs which reduce the rate of bone breakdown (bone resorption) significantly reduce fracture risk at the spine, hip and limbs but generally only in those with osteoporosis as defined by bone density measurements.
The primary group of drugs used are the bisphosphonates (specifically alendronate and risedronate) which in tablet form given weekly are now generic making them as “cheap as chips” meaning that NICE will allow them to be prescribed for anyone with osteoporosis.
Indigestion or dyspepsia can occur with the oral bisphosphonates and in that case or in the case of those unable to comply with the rather complex administration instructions, injectable drugs are available either in the form of an intra-venous bisphosphonate, zoledronic acid, given once yearly or, in some NHS environments, a different type of anti-resorptive drug, denosumab, which is given by a sub-cutaneous injection just under the skin every 6 months.
Clearly in those with very severe osteoporosis the ideal would be, not to prevent bone breakdown, but to stimulate new bone formation so called anabolic drugs. At present only one such drug is readily available, teriparatide, which is given by sub-cutaneous injection daily for up to 2 years. Sadly this therapy is very expensive and its use is thus very limited by NICE guidance meaning that is only available to those who have failed treatment with the bisphosphonates and have to low bone density or who can self-pay.
A new bone anabolic agent, abaloparatide may become available later in 2016 and as teriparatide goes off patent in 2017, bone anabolic drugs might well become less expensive in the near future. More information on the drugs currently licensed and in use is available from the National Osteoporosis Society
Are Vitamin D and Calcium important?
Of recent times the value of a high calcium intake whether in the form of dietary consumption or supplement has been questioned. It is still considered that an overall intake of 700 grams per day, which can be achieved by a pint of milk daily (skimmed or semi-skimmed is just as good as whole fat milk) or other calcium containing foods is sufficient and in those circumstances no calcium supplements are required. This change in advice is because of some controversial data suggesting that excess calcium consumption can be related to an excess risk of heart attacks or strokes.
The evidence for the value of Vitamin D in recent years has, unlike calcium, increased. Adequate vitamin D levels from the diet or by sunlight exposure is hard to achieve especially in the winter months or in those who expose little skin to the sun. Accordingly vitamin D supplements are often advised as adjunctive therapy i.e. used alongside other drugs to treat the condition. Before injectable drugs are to be used vitamin D levels need to be restored to avoid symptomatic low calcium levels (hypocalcaemia).
How is treatment monitored?
It is of course impossible to monitor by simply counting fractures.
Although the most potent drugs reduce the risk of spine fractures by up to 80%, hip fractures by 40% and limb fractures by 25% it is impossible to know when a fracture would have occurred in a patient if treatment had not been introduced. Although some experts advise monitoring by simply asking the patient whether they are taking the drugs, there is increasing use of monitoring by measuring bone markers in blood or urine before treatment starts and after 3-6 months.
Monitoring can also be done by repeating a bone density measurement but in most circumstances not until 2- years after treatment commences.
Are their long-term side effects of treatment and how long should drug therapy be continued?
There are no drugs used in medicine which have no side effects but the osteoporosis drugs so far seem to be remarkably safe overall. As indicated above dyspepsia can occur with the oral bisphosphonates and, somewhat bizarrely a flu-like illness after the first dose of the intra-venous drug, zoledronic acid.
Much anxiety has been generated recently about rare side effects of the long-term use of the bisphosphonates. In particular a rare condition producing often deep and relatively painless but very slow to heal lesions in the mouth termed “osteonecrosis of the jaw (ONJ)” have been related to the use of bisphosphonates and indeed denosumab. ONJ is very rare indeed when the drugs are used in the low doses used to treat osteoporosis but much commoner when the drugs are used in high dose to treat bone cancer.
Another rare condition termed “atypical femoral fracture” which can occur in both legs at the same time often with pain several weeks or month before the fracture becomes obvious is probably more common in those who have used long-term bisphosphonates. For this reason many clinicians now advise using treatment for a maximum of 5 years before a “drug holiday” unless the risk of osteoporosis fracture remains very high.
Methods of Identification of risk of osteoporosis and fracture followed by treatment to support Health Ageing have improved dramatically over the last 30 years. There are still some controversies and subtleties however. The National Osteoporosis Society is an excellent source of evidence based and up to the minute further information.