Fosamax Medication - how long

How will I to be taking Fosamax medication? This is one of the most frequent questions raised by those taking this drug for Osteoporosis.

Is one year long enough? What about 2 or 3 years?

A woman who has been taking this medication for over 4 years began to wonder if she would ever stop taking Fosamx medication.

Well, the medical community has been asking this same question. There are studies showing good results of increased bone density with this drug. But some question whether over the long term if increases in bone density are enough - that since the increase is due to a decrease in the activity of Osteoclasts, the cells that remove old bone, maybe the increased bone density it of 'compromised bone'.

There have been calls for long term trials or studies of Fosamx medication. And one was published in December 2006.

Journal of American Medical Association article.

Here is the abstract for that article about Fosamax medication.

The introductory paragraph gives the background for this study of Fosamax medication.

In the 10 years since the first results from the Fracture Intervention Trial (FIT) were published, it has been relatively straightforward to know when to start bisphosphonate therapy for women with postmenopausal osteoporosis1, 2. The trick has been knowing when to stop. Clinical Practice Guidelines have been almost completely mute on the subject3. Pharmacokinetic studies in both humans and animals demonstrated that bisphosphonates bind tightly to hydroxyapatite and are retained for prolonged periods in bone where they become locally active again when that bone packet is resorbed.4 This property raised the possibility of both prolonged clinical effectiveness and prolonged risk of harm. Previous clinical studies showed that up to 10 years of alendronate was associated with sustained gains in bone mineral density (BMD) and did not appear to be harmful,5 somewhat diminishing the concern that long-term suppression of bone turnover could lead to an accumulation of micro-fractures and diminished bone strength6. However, these long-term data included fractures only as a safety endpoint. The best we could advise women tired of their complicated bisphosphonate regimen or concerned about the highly-publicized risk of osteonecrosis of the jaw was that the risks of continued treatment were small. The study by Black and colleagues in this week’s Journal allows us to better discuss the benefit side of the equation as well.

It then continues with the Fosamax medication FLEX trial information

That study provides the results of the Fracture Intervention Trial Long-term Extension (FLEX) trial, in which 1099 of the original FIT participants who had received alendronate for roughly 5 years were randomized a second time to receive an additional 5 years of alendronate or placebo. FIT participants were excluded from continuing into FLEX if they had extremely low T scores (<-3.5) or BMD lower than their FIT baseline. investigators showed that women who switched to placebo after 5 years of alendronate lost a statistically significant, but clinically small 2–3% more bone density than those who continued alendronate for a full 10 years. Both groups remained well above their FIT baseline femoral neck, trochanter, and lumbar spine BMD. Similar to previous long-term bisphosphonate trials, there was no excess of adverse events in the 10 year treatment group, and no cases of osteonecrosis of the jaw. A small number of histomorphometry specimens showed dual labeling in both groups, again providing reassurance that over-suppression of bone turnover was not seen during prolonged therapy with bisphosphonates.

The abstract then goes on to analyze the data related to their Fosamx medicatin study:

More clinically interesting were the “exploratory” fracture endpoints. Despite the small difference in BMD between the groups, there was no excess in all clinical fractures or morphometrically detected vertebral fractures in those women who stopped therapy after 5 years. There was a significant 2.9% absolute risk increase in clinically detected vertebral fractures in the placebo group, indicating that 34 women would need to be treated for an additional 5 years to prevent 1 clinically apparent vertebral fracture. The trial was powered to detect bone density changes rather than fractures, and the authors calculated post-hoc that they had 80% power to detect a relative risk reduction of 13.5 to 33%. Thus, a 6% absolute risk increase in all clinical fractures could have occurred without detection. However, the consistency of the relative hazard ratios around 1.0 for all types of non-vertebral fractures is reassuring that no “trend” toward decreased non-vertebral fracture in the 10-year treatment arm exists. It appears that for some women, 5 years of bisphosphonate therapy may be enough to reap the fracture reduction rewards.

But which women are they? It is important to recall that because the BMD threshold that defines osteoporosis was changed during the FIT trial, three important subgroups of women were enrolled: those with a baseline vertebral fracture, those with baseline osteoporosis (femoral neck T score ≤-2.5) but without a vertebral fracture, and those without osteoporosis. FIT showed clear fracture reduction benefits for the first 2, but not the latter group1, 2, 7. The FLEX authors found no significant group by treatment interaction for any of these subgroups, although the weakness of this statistical test limits the confidence that no important subgroup effects exist. When the risks of fracture in the various subgroups is examined, the greatest absolute reductions in clinical vertebral fractures (3.6–4%) occurred in those with T scores at the beginning of FLEX of ≤ -2.5 (RR 0.57, 95% confidence interval 0.23–1.4), and those with baseline vertebral fracture (RR 0.47, 0.19–1.1). The authors reasonably conclude that women who are at high risk for vertebral fracture because of previous vertebral fractures might be considered for continued therapy. Previous non-vertebral fracture, another major risk factor for additional clinical fractures, was a stratification variable in FLEX, but we are not provided with the fracture results for this important population. Although a long-term study powered on fractures rather than BMD would ideally provide the best information to guide treatment decisions among these subgroups, such a study would be extraordinarily expensive. The FLEX trial therefore provides the best data we are likely to have available on this question.

The next part of the abstract talks about practical consequences of this trial of long term Fosamax medication

This trial has several important clinical implications. First, women who have a good response to 5 years of bisphosphonate therapy (3–5% increase in hip BMD, 8–10% increase in spine BMD, T score >-3.5) and are not otherwise at increased risk for vertebral fracture can consider a “holiday” period of up to 5 years off therapy. This strategy would clearly improve the already attractive cost-effectiveness of bisphosphonates.8, 9 However, the importance of careful BMD monitoring will increase in such women; those rapidly losing BMD (in FLEX the thresholds were >8% in 1 year, >10% in 2 years, or >5% from baseline) will likely require resumption of bisphosphonate therapy or a switch to an alternative agent. Clinicians must bear in mind that substantial differences in absolute BMD and T scores are obtained when different brands of DEXA machines are used with the same patient, and that measurement error can be a significant problem in some test centers.10 Thus, it is important to use a reliable center and the same machine whenever possible. An alternative to frequent BMD measurement might be to follow serum markers of bone turnover. The increases in these markers in the treatment and control groups mirrored the changes in BMD in FLEX, and higher bone turnover marker levels have previously been associated with the a greater anti-fracture effect of bisphosphonates.11 This strategy would, however, require validation and establishment of decision cut-points before it could be clinically useful. It is unclear at this time whether resuming bisphosphonate therapy in women at the end of their “holiday”, or when their BMD has declined below a given threshold, will result in additional fracture reduction benefit. Decisions about additional treatment should consider the individual fall and fracture risk, response to previous therapies, and remaining life expectancy.

And their final remarks about this trial of Fosamx medication follow

We knew from FIT and similar trials that starting post-menopausal women with osteoporosis or a low trauma fracture on a bisphosphonate substantially reduces their risk of vertebral and non-vertebral fractures, pain, and disability.12 Armed with FLEX data, we now may be able to begin telling women when they have had enough of a good thing. So that should be good news for those taking Fosamax medication. You may not need Fosamx medication for the rest of your life! This trial indicates that there may be an 'end point' to treatment with Fosamx medication.

Of course you will want to consult your health care professional about any changes in your Fosamax medication regime. Do not just stop taking your Fosamax medication on your own. Talk with your doctor first!

If you want to read additional abstracts about Fosamax medication, go to PubMed and type Fosamax medication in the search box.