Wednesday June 27, 2007
What is the right time to treat osteoporosis with alendronate?
What is the right time to treat osteoporosis with alendronate?
Urdinola Jaime MD
CS AK 9 116-20 326 - Medical Association of the Andes - Bogotá DC Colombia
Phone: 571 / 215 23 00 - Phone: 57 / 315 236 August 28
e-mail:
jaimeurdinolamd@gmail.com blogger:
http://www.urdinola.blogspot.com
http://www.urdinolamenopausia.blogspot.com
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Symposium / Lunch on Menopause - Wednesday, June 27, 2007
Board Room - First Floor, Medical Association
Andes Bogotá DC Colombia
not yet know the optimal duration of treatment of women with osteoporosis, which in many cases can continue indefinitely.
Few studies have examined the effects of the use of bisphosphonates beyond 5 years or suspend the effects of after this time.
So far, a small number of participants in phase 3 study on alendronate were followed for 10 years of continuous treatment 1. Among women who continued alendronate, bone mineral density (BMD) at vertebral level increased throughout the entire treatment period, keeping the increases in BMD of the hip. Women who discontinued alendronate experienced small decreases in BMD of the hip, but maintained the BMD of the vertebrae.
In turn, few data on fracture risk are available on long-term treatment with bisphosphonates, although this study supports the long-term safety of alendronate, showing that the risk of fracture is not increased for 10 years.
pharmacokinetics studies have shown that bisphosphonates remain in bone matrix for many years and incorporated the bisphosphonate remains inactive until it is released gradually as the bone that contains it is reabsorbed. The terminal half-life of alendronate is similar to bone mineral, approximately 10.5 years. For this reason is that the skeletal effects of alendronate and other bisphosphonates may last up to several years after treatment has been suspended. These findings suggest that stopping treatment after 4 to 5 years can result in residual clinical efficacy, but the magnitude and duration of this effect is not yet known with certainty.
FIT study (The Fracture Intervention Trial = Intervention Study on Fracture), randomized, masked, placebo controlled trial, examined the effect of alendronate on BMD and fracture risk in postmenopausal women with low BMD. Had an average follow-up for 3.8 years, continuing in the form of open treatment after the completion of the designated term.
discussed here are data on long-term extension (Long-term Extension = FLEX), which was designed to assess the effects on BMD below 5 or 10 mg / day of alendronate for 10 years or discontinuation after approximately 5 years in 10 clinical centers in the U.S. 1 099 postmenopausal women participated randomized to receive alendronate in the FIT study, treatment with an average of 5 years prior therapy with alendronate, 5 mg / day n = 329, 10 mg / day and placebo n = 333 n = 437 2.
analysis The primary outcome was BMD at the hip. Secondary measures were BMD at other sites and markers of bone remodeling. An exploratory outcome was the incidence of fractures.
The results showed that compared with continuing alendronate, switching to placebo for 5 years resulted in a decrease in total hip BMD (-2.4% confidence interval = 95% CI -2.9% to -1.8%, P < .001 ) y en vértebras ( -3.7 %; IC 95 % -4.5 % a -3.7 %; P<.001). Pero los niveles se mantuvieron cerca de ó por encima de los niveles pretratamiento encontrados 10 años antes. Después de 5 años, el riesgo acumulativo de fracturas no vertebrales ( RR, 1.00; IC 95 % 0.76 – 1.32 ) no fué significativamente diferente entre aquellas que continuaron (19%)
and those discontinued (18.9%) alendronate. Among those who continued, there was a significantly lower risk of clinically recognized vertebral fractures (5.3% for placebo and 2.4% for alendronate; RR, 0.45, CI 0.24 to 0.85) but no significant reduction in morphometric vertebral fractures (11.3% for placebo and 9.8% for alendronate; RR, 0.86, 95% CI 0.60-1.22). A small sample of bone biopsies showed no abnormality transiliac qualitative.
can conclude with the data from this study that women who discontinued alendronate after 5 years showed a moderate decline in BMD, but no increased risk of fractures, with the exception of vertebral fractures. The results indicate that for most women, discontinuation of alendronate after 5 years does not appear to significantly increase the risk of fracture.
should be noted however, that women who are at high risk for clinical vertebral fractures, those who have had vertebral fractures or very low BMD, may benefit from continued treatment beyond 5 years. These results also confirm once again the safety of long-term use of alendronate for up to 10 years.
This study has several limitations, since the effect of alendronate on risk of fracture was exploratory purpose and the trial had limited power to detect modest differences in fracture rates, reflected this in the wide CIs for the outcome of fractures. The FIT participants received 5 mg / day of alendronate for the first 2 years so the results with 10 mg / day for 10 years may have differed. Furthermore, the average baseline age of participants was 73 years, so that the results may not be applicable young women, men or the very old. But this is a common problem in osteoporosis studies on young women, who despite being able to present osteoporosis, its prevalence is not very large, making them ideal candidates for this purpose does not study.
Comparing with other drugs that have proven effective in reducing fracture risk in postmenopausal women with osteoporosis, also the optimal duration of these drugs is to establish yet. The gain in BMD with risedronate has been set up for 7 years, but the proof of long-term protection against fractures has been obtained only short-term treatment, 5 years with risedronate. The effect seen with raloxifene on BMD persist up to 4 years after administration for 8 years. The decrease in fracture risk was similar after 4 years. The safety profile in this case was similar, with significant risk reduction for invasive breast cancer with estrogen receptor positive, but with a persistent increase in the risk for deep vein thrombosis. However, it should be noted that there is a sharp decline in BMD after discontinuation of treatment with raloxifene.
Finally, it is worth remembering that the duration Optimal treatment should be determined individually, based on the analysis of each case and according to the results of routine and regular assessments to the risk of fracture 3.
Highlights
This study has several limitations, since the effect of alendronate on risk of fracture was exploratory purpose and the trial had limited power to detect modest differences in fracture rates, reflected this in the wide CIs for the outcome of fractures. The FIT participants received 5 mg / day of alendronate for the first 2 years so the results with 10 mg / day for 10 years may have differed. Furthermore, the average baseline age of participants was 73 years, so that the results may not be applicable young women, men or the very old. But this is a common problem in osteoporosis studies on young women, who despite being able to present osteoporosis, its prevalence is not very large, making them ideal candidates for this purpose does not study.
Comparing with other drugs that have proven effective in reducing fracture risk in postmenopausal women with osteoporosis, also the optimal duration of these drugs is to establish yet. The gain in BMD with risedronate has been set up for 7 years, but the proof of long-term protection against fractures has been obtained only short-term treatment, 5 years with risedronate. The effect seen with raloxifene on BMD persist up to 4 years after administration for 8 years. The decrease in fracture risk was similar after 4 years. The safety profile in this case was similar, with significant risk reduction for invasive breast cancer with estrogen receptor positive, but with a persistent increase in the risk for deep vein thrombosis. However, it should be noted that there is a sharp decline in BMD after discontinuation of treatment with raloxifene.
Finally, it is worth remembering that the duration Optimal treatment should be determined individually, based on the analysis of each case and according to the results of routine and regular assessments to the risk of fracture 3.
Highlights
● Do not yet know the optimal duration of treatment for osteoporosis
● However, there is already encouraging data on safety and efficacy of treatment of osteoporosis ●
alendronate alendronate treatment has the highest documented follow-up time reported so far, during 10 years
● According to the available evidence, the minimum time of treatment for postmenopausal women with osteoporosis is 5 years
● Minimum 5 years of treatment showed that BMD decreased only slightly and turn the risk for fracture significantly increases
● One should not forget that each case must be examined individually according to their risk of fracture, which determine the duration of individual treatment
References
1 - Bone HG, Hosking D, Devogelaer JP, Tucci JR, Emkey RD, Tonino RP, Rodriguez-Portales JA, Downs RW, Gupta J, Santora AC, Liberman UA; Alendronate Phase III Osteoporosis Treatment Study Group. Ten years’ experience with alendronate for osteoporosis in postmenopausal women. N Engl J Med 2004; 350: 1189-1199.
2- Black DM, Schwartz AV, Ensrud KE, Cauley JA, Levis S, Quandt SA, Satterfield S, Wallace RB, Bauer DC, Palermo L, Wehren LE, Lombardi A, Santora AC, Cummings SR; FLEX Research Group. Effects of continuing or stopping alendronate after 5 years of treatment. The fracture intervention trial long-term extension (FLEX): a randomized trial. JAMA 2006; 2927-2938.
3- Briot K, Tremollieres F, Thomas T, Roux C; Comité scientifique du Grio. How long should Medications for Patients take menopausal osteoporosis? Joint Bone Spine 2007, 74: 24-31.
Case report
● Female 71 years
- Postmenopausal
entering old age - are not receiving hormone therapy but was present from 52 years to 60 years
old
- Treatment with alendronate from 63 years of age
- Take 1 g / day of calcium without vitamin D
- Current results of BMD by DEXA, Index of T:
- Treatment with alendronate from 63 years of age
- Take 1 g / day of calcium without vitamin D
- Current results of BMD by DEXA, Index of T:
● - 2.0 at the lumbar spine
● - 1.4 in hip
● Some questions to guide
discussion - do not have other risk factors described
- What would be the right treatment to follow, as well as Alendronate?
- should continue in treatment with alendronate? If so, for how long?
If you have any comments, questions or concerns, you can "click" on comments and sending your message. Or if you prefer, you can send your comments, questions or concerns e-mail: jaimeurdinolamd@gmail.com
● - 1.4 in hip
● Some questions to guide
discussion - do not have other risk factors described
- What would be the right treatment to follow, as well as Alendronate?
- should continue in treatment with alendronate? If so, for how long?
If you have any comments, questions or concerns, you can "click" on comments and sending your message. Or if you prefer, you can send your comments, questions or concerns e-mail: jaimeurdinolamd@gmail.com
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