Men's Osteoporosis Support GroupLong term bisphosphonate therapy J Clin Endocrinol Metab. 2010 Feb 19. [Epub ahead of print].Long-Term Use of Bisphosphosphonates in Osteoporosis. Watts NB, Diab DL. PMID: 20173017. This article is a review of the literature regarding tthe pharmacology and mechanism of action of bisphosphonates and the clinical studies that support their efficacy. As well, it reviews the literature for longer-term studies and reports of possible side effects that were not seen in clinical trials. The authors point out that the bisphosphonates have been shown to be effective in decreasing fractures in multiple controlled clinical trials. There are studies showing 10-year effectiveness for alendronate (Fosamax) and 7-year effectiveness for risedronate (Actonel). But there have been some rare, but severe side effects noted, particularly osteonecrosis of the jaw, musculoskeletal complaints, and atypical fractures. Because of the long half-life of these medications, people appear to retain the anti-fracture reduction if they have been on long-term therapy, even after the drugs are stopped for a few years. The authors suggest those on long-term bisphosphonate therapy consider a drug holiday. Specifically they recommend, "Patients at mild risk might stop treatment after 5 yr and remain off as long as bone mineral density is stable and no fractures occur. Higher risk patients should be treated for 10 yr, have a holiday of no more than a year or two, and perhaps be on a nonbisphosphonate treatment during that time." Editor's comments. These recommendations agree with a previous study reported in a 2006 Update. This was by Black DM and others who concluded: “Women who discontinued alendronate after 5 years showed a moderate decline in BMD and a gradual rise in biochemical markers but no higher fracture risk other than for clinical vertebral fractures compared with those who continued alendronate. These results suggest that for many women, discontinuation of alendronate for up to 5 years does not appear to significantly increase fracture risk. However, women at very high risk of clinical vertebral fractures may benefit by continuing beyond 5 years.” (Note this study involved only women, as many osteoporosis studies do. However, there is no reason to expect the results wouldn't equally apply to men.) It appears that some of the more serious side effects, such as osteonecrosis of the jaws and atypical fractures, may be caused by over suppression of bone turnover by the bisphosphonates. Taking a drug holiday should resolve that problem and concomitantly decrease the risk of these serious side effects. Since it appears that stopping the bisphosphonates for as much as five years doesn't increase fracture risk, the drug holiday appears to be a safe procedure with potential benefits and minimal risks. Talk to your physician about this drug holiday if you have been on long-term therapy for osteoporosis with one of the bisphosphonates. I would recommend you ask to have your biochemical markers of bone turnover, such as urine or serum CTX, followed on at least a yearly basis. If there should be a big increase in these it would indicate you might not want to prolong the drug holiday and that you should have a dual-energy X-ray absorptiometry done if in doubt.
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