Advances in osteoporosis therapy
A GP quizzes an expert to take a medical issue beyond the textbook
GP Dr Stefan Cembrowicz in conversation
with consultant geriatrician
Dr Theresa Allain
Practical points l
PTH could be a very effective treatment
Bisphosphonates only work if patient is calcium and vitamin D replete
Beware of fracture risk in patients with prostate problems
Hip protectors can be very effective
Vitamin D supplements will also help prevent falls in the elderly
Bone health is on the agenda as we have an ageing population, and their fractures lead to much morbidity, mortality (and health costs). What are the latest developments in tackling osteoporosis?
What's about to get the most publicity is the launch of parathyroid hormone. PTH actually works as an anabolic agent, it increases bone formation; most other treatments are anti-resorbtive and inhibit bone breakdown. The only currently available anabolic agent is fluoride which is confined to use in specialist centres and has an ambiguous affect on bone.
PTH is very effective at reducing fractures, but the limiting factor is going to be cost and the fact it has to be given subcutaneously by daily injection.
We are waiting for NICE guidance as to who will be eligible for PTH treatment. I suspect it's going to be women with extensive vertebral disease who are continuing to fracture or lose bone and are already taking a bisphosphonate.
What is the place for added calcium?
What often gets forgotten is that in the original studies showing bisphosphonates reduce fractures, all subjects received concomitant calcium and were known to be vitamin D replete or on supplements. Many patients who are probably short of calcium and vitamin D are being given bisphosphonates without co-supplementation of calcium and vitamin D.
Another new drug is a soluble calcium and vitamin D supplement called Calfovit D3. This contains the same constituents as the evidence-based drugs such as Calcichew D3, Adcal D3 and Calcios but it is easier to get down, it can be put down nasogastric tubes and PEG tubes. It is also cheaper.
Bisphosphonates don't work effectively unless the patient is calcium and vitamin D replete. This may mean co-prescribing supplements.
With etidronate there is actually a risk that you can precipitate osteomalacia if your patient isn't vitamin D replete. Incidentally, etidronate is not as potent as alendronate and risedronate. Most patients on it should be changed over to newer, more potent bisphosphonates.
Using DEXA scanning effectively
What part does a DEXA scan play in assessing a patient's risk and what other factors need considering?
First, who should we be DEXA scanning in the first place? Population screening by DEXA scan for osteoporosis is not appropriate. Current guidelines say DEXAs should be used in targeted patients who are at risk of osteoporosis. Most practices have computer databases so it is quite easy to identify your at-risk populations and single them out for scanning. For example, good groups to look at would be:
· Patients who have taken long-term steroids (more than 1,350mg lifelong in total)
· People who've had a previous fragility fracture (but if they've had a vertebral fracture there is no need to get a DEXA scan, they should be treated straightaway with bisphosphonates)
· Women with other risk factors such as inflammatory bowel disease, coeliac disease, rheumatoid arthritis, early menopause under the age of 45, or significant amenorrhoea in younger life lasting for longer than six months and not related to pregnancy
· Combinations of softer risk factors such as being very underweight, being immobile, a heavy smoker and maybe a history of thyroid disease or a positive family history.
How do you interpret DEXA results?
The WHO definition of osteoporosis is a DEXA
T-score of less than -2.5. That group are advised to take a specific bone-strengthening agent. Patients with a DEXA T-score between -1 and -2.5 have osteopenia and should be advised about lifestyle measures to preserve bone health, ideally with a repeat scan in five years time. Patients who have a very high risk factor such as steroid exposure or a previous fracture and a T-score of less than -1.5 should also be given specific therapy such as bisphosphonates and don't forget the calcium and vitamin D!
But that means some relatively young people (early post-menopause or fit and active but who happen to have low bone density) may end up taking drugs that won't improve fracture risk for years.
Doctors who decide on a strategy for osteoporosis are looking at ways of calculating a 10-year fracture risk. This would be analogous to the Sheffield Tables used for deciding when to treat cholesterol in the primary prevention of heart disease. It would be very convenient if we could plug risk factors and bone density measurement into a table to tell whether people need bone-strengthening drugs.
What other risk groups should we be aware of?
Another group is men on treatment for prostate disease, either zoladex and other GnRH agonists, for the treatment of prostate cancer or occasionally finasteride and other anti-androgens for the treatment of benign prostatic hypertrophy. Because these treatments are so effective at treating the cancer these men survive, but are severely hypogonadal for many years. On one recent orthopaedic ward round three of the elderly men on the ward with fractured necks of femur were on zoladex. None had bony metastases, all the fractures related to reduced bone density probably because of hypogonadism.
One study some years ago showed most bone loss in these men occurs in the first six months and if they're given a bisphosphonate then, they preserved bone density.
That requires urologists to be more aware of this problem and unfortunately it doesn't seem to happen. In primary care my advice would be to review these men to see if they have any concomitant risk factors and make sure they have adequate calcium and vitamin D. You wouldn't start a bisphosphonate without a DEXA scan.
Why diet is key
As we look at preventing osteoporosis in the whole population, what issues should we be thinking about in children and adolescents?
Once bones have become osteoporotic it is difficult to prevent fractures. Much more attention has to be directed towards prevention. Peak bone mass is an important determinant of your later fracture risk.
About 80 per cent of the peak bone mass we achieve around about the age of 35 is genetic but 20 per cent is down to environmental factors, particularly exercise and nutrition when we're younger. It has been estimated that if the peak bone mass of the nation as a whole could be increased by 10 per cent then the rate of hip fractures in our older population could be reduced by as much as 50 per cent.
This is a very desirable effect to achieve. Children who have calcium supplements have denser bones. This is a good argument for school milk and a healthy balanced diet. Quite a lot of studies comparing couch potato children with their more active peers show children who are more active have healthier bones. These observations need to be incorporated into national policy but until then all of us health professionals and parents should be mindful of this and try to promote bone health in our young patients and relatives.
It sounds as if we should be using many more vitamin D supplements in the at-risk groups. What is the best
The grade A evidence is still for oral combined calcium and vitamin D with 1.2g of calcium a day and 800 units of vitamin D. Unfortunately that isn't always practical. There is continuing debate about whether added calcium or just vitamin D alone is needed.
Vitamin D injection 300,000 units intramuscularly once a year has grade B evidence to support its use. We are still waiting for ongoing research to be published on the vitamin D injection.
An interesting study from Cambridge showed an intermittent high dose of oral vitamin D can prevent fractures. Patients who took 10,000 units orally of vitamin D every four months showed a significant reduction in fractures over two years.
For patients who don't wish to take oral medication,
what foods give you this amount of vitamin D?
The recommended daily allowance (RDA) is 200iu for young adults, 400iu for ages 50-69 or 600iu for the over-70s. Four ounces of salmon or mackerel provides 400iu and a tablespoonful of cod liver oil provides 1,360iu. An egg provides 25iu and 4oz of beef liver about 35iu. The RDAs are probably inadequate, and many older people are at risk of calcium deficiency.
Falls prevention and hip protectors
Bone health is one factor relating to fracture
how should falls prevention be addressed?
The importance of preventing falls is becoming increasingly recognised. The National Osteoporosis Society has now embraced falls prevention as one of its agendas and is working jointly with the British Geriatric Society to develop a strategy and is funding research in nursing homes.
Vitamin D supplements in the elderly not only improve bone health but can improve balance and reduce falls. This is even in relatively fit older adults who do not have any overt muscular problems or signs of osteomalacia; presumably the benefit of vitamin D is because it is correcting sub-clinical myopathy in those patients.
This is an additional argument for making sure all our old folk with falls and fractures, and those at risk of falls and fractures, get on to vitamin D supplements.
Hip protectors are now available what is the place for their use and who will most benefit from them?
Further studies done in nursing homes continue to show good benefit from using hip protectors with up to 50 per cent fracture reduction.
There is enough evidence that we should be using them widely in the nursing home and residential care setting.
In the community though, studies fairly consistently show negative results for the use of hip protectors.
These are looking at end points such as fractures. At the moment there is no good evidence that we should be using hip protectors widely in community-living older adults.
Having said that, in my clinic I have a number of elderly frail who fall frequently or have already broken bones who use hip protectors at home very effectively. They find it really boosts their confidence and they wouldn't go out without them. So although I can't advocate widespread use in the community there are a few who gain a lot of benefit.
Unfortunately, they are not prescribable and I would recommend only using the brands mentioned in the big studies as they are known to work.
Calcium content of foods (per 100g)
Whole milk 115mg
Semi-skimmed milk 120mg
Cheddar cheese 720mg
Fruit yoghurt 160mg
White bread 110mg
Brown bread 100mg
Wholemeal bread 54mg
Boiled spinach 160mg
Boiled cabbage 38mg
Boiled carrots 37mg
Baked beans 47mg
RCP osteoporosis guidelines
National Osteoporosis Society