Running an Unnecessary Risk of Fracture

Summarized by Robert W. Griffith, MD
February 5, 2007

Summary

People with osteoporosis are poor compliers in taking their prescribed medication, and even those that start off correctly often drop out later (poor persistence). Failure to take medication leads to continued loss of bone mineral density and a greatly heightened risk of fractures.

Introduction

Osteoporosis affects up to 45 million US citizens; 10 million have actual osteoporosis, while 35 million have a lessened bone mineral density (BMD), which is a forerunner to osteoporosis. The big problem with osteoporosis, of course, is the greatly increased likelihood of sustaining fractures after trivial injury, or even spontaneously. Several effective oral treatments can halt the loss of bone mass, and can even increase BMD. But it seems probable that many of the millions of people 'at risk' just don't take their prescribed medications.

A report on compliance with osteoporosis medications has been posted on Medscape, a web site for health professionals. We summarize the main points here, in the hope that readers will come to recognize the necessity of taking preventive medication.

Adherence to osteoporosis medication

Adherence to a medication regimen is defined as the extent to which patients take their medications as prescribed by their physician. In other words, how closely they follow a prescribed treatment regimen. It's usually reported as the percentage of the prescribed doses of a medication actually taken over a given period.

The term persistence is used to describe continuous therapy on the same drug over a long period. For instance, it might be measured as the percentage of patients who continue to take osteoporosis therapy each month for a 3-year period.

A recent study of over 10,000 women taking medication to maintain their BMD was reported at a conference in Rome in 2005.¹ The bisphosphonate drugs alendronate (Fosamax^®) and risedronate (Actonel^®) had adherence values of 61% and 58%, respectively; raloxifene (Evista^®), which acts in a similar way to estrogen, had a 54% adherence value. The authors call this "poor, at best". Persistence at 12 months, however, was much worse: 23%, 19%, and 16% for these 3 drugs, respectively.

Another study reported at the same meeting² gave only slightly better results for persistence. The investigators were comparing daily with once-weekly medications in over 2,500 women. Persistence was 32% at one year for daily medication, vs. 44% for weekly bisphosphonates. Expressed another way, the average times to discontinuation were 139 days for daily and 269 days for weekly medication.

It's clear that both adherence and persistence with osteoporosis medication is poor. Reducing the frequency of administration from daily to weekly improves persistence, but the end results are still unsatisfactory. Compliance is measured In clinical trials of efficacy and safety, and it has to be good for the results of the study to be used as acceptable evidence. Obviously, if compliance in a real-life situation is poor, the effectiveness will also be poor, or non-existent.

Are these problems confined to osteoporosis medication?

Osteoporosis has an important feature in common with several cardiovascular conditions - especially high blood pressure: both are symptomless, until a serious event occurs (e.g. a fracture or a stroke). The motivation to take medication regularly is small, while the temptation to drop the treatment is considerable, especially if there are side effects, or the drug is expensive. All disorders that don't produce obvious symptoms face the same problem of poor compliance (adherence and persistence) with treatment.

What are the special compliance problems with osteoporosis?

Unlike high blood pressure (and several other symptomless conditions), the effect of not taking prescribed medication will not show up within a short period. Although even short-term medication can reduce fracture risk in actual practice, there is no measurable effect on the usual measure of BMD within the first 18-24 months of treatment with bisphosphonates. It's discouraging for the patient, and more difficult for the physician, if the patient cannot be shown objective test numbers that indicate the medication is doing what it should.

A further problem for people prescribed bisphosphonates is the remotely possible risk of esophageal irritation or even erosion. For this reason, such patients are required to take their medication 30-60 minute before breakfast with a full glass of water, and to remain upright for at least 30 minutes. Following these instructions is an inconvenience, whereas failure to follow them runs the risk of an unknown but possibly serious side effect. Small wonder that some patients feel they would rather avoid the problem, especially when they feel perfectly well. Of course, a less-frequent dosing regimen (e.g. once a week or once a month) reduces the inconvenience considerably, and is associated with increased compliance, as we have seen above.

What healthcare professionals must do

Every osteoporosis patient is potentially a poor complier. For the reasons outlined above, they are quite likely to discontinue their medications, even after a long period of regular compliance. So what should the health professional do to address this problem?

1. The patient should be encouraged to continue adequate calcium and vitamin D supplements
2. Physical activity, including daily weight-bearing, strength, and balance exercises, are important. Apart from stabilizing bone mineral density, they may help prevent falls and fractures by strengthening muscles and improving balance.
3. Try to find out what may be hindering the patient from taking their meds - cost, side effects, inconvenience, lack of information about fracture risk, and so on. Then try to help the patient overcome their particular problem, or problems.
4. Make sure the patient is fully aware of the increased likelihood of a disabling fracture if they ignore all therapy proposals. If it seems helpful, explain in simple language the underlying disease process, and show relevant X-rays.
5. Arrange to see the patient at regular intervals to check that they remain compliant.

Source

Compliance with osteoporosis medications: challenges for healthcare providers. DT. Gold , SL. Silverman, Medscape Ob/Gyn & Women's Health., 2005, vol. 10(1)

Footnotes
1. Boccuzzi SJ, Foltz SH, Omar MA, et al. Adherence and persistence associated with the phamacologic treatment of osteoporosis. Osteoporos Int. 2005;16(suppl 3):S24.
2. Cramer JA, Amonkar MM, Hebborn A, et al. Biphosphonate dosing influences treatment adherhence in postmenopausal women. Osdteoporos Int. 2005;16(suppl 3):S3.