2007

Tuesday, November 27, 2007

Difference Between Lglutathione Or Glutathione

Drospirenone, a plus in hormone therapy

November 28, 2007
Drospirenone, a plus in hormone therapy
Drospirenone, a plus in hormone therapy

Jaime MD Urdinola
Medical Association
Andes Bogotá DC Colombia Telephone 571/215 23 00
e-mail: jaimeurdinolamd@gmail.com
jurdinol@uniandes.edu.co
blogger: www.urdinola.blogspot.com

www.urdinolamenopausia.blogspot.com www.urdinolamenopausia2.blogspot.com
Colloquium / Luncheon on Women's Health and Menopause Medical Association
Andes - Boardroom
Wednesday November 28, 2007

Drospirenone 1 derived from spironolactone, is a novel synthetic progestin has antimineralocorticoid activity and androgen. This activity can be seen from the clinical point of view in its effects on physiological parameters, body weight, general welfare and related symptoms retnción or liquids.

These characteristics of drospirenone, which allow to describe its role in menopausal hormone therapy (1 mg 17β-estradiol + 2 mg drospirenone = Angeliq ®, Bayer Schering Pharma) as a plus as see below. This continuous combined preparation for administration, prevent salt retention obtained by estrogens, thus preventing increased blood pressure. Los estrógenos estimulan la producción de angiotensina, la que a su vez eleva los niveles de aldosterona y de sodio, aumentando la retención hídrica 2 .

Ya se cuenta con estudios clínicos que han sido diseñados específicamente para evaluar los efectos del tratamiento sobre el peso corporal y la función cardiovascular, ya que ambos pueden verse influenciados por el antagonismo sobre el receptor de aldosterona 3 .

Se ha aducido que la ganancia de peso durante el tratamiento con la terapia hormonal tradicional es una de las razones principales para pobre cumplimiento con la terapia y su discontinuación. Las Women who received Angeliq ®, did not provide weight gain or have experienced slightly decreased, while those who received only estradiol tend to gain weight. The average body weight after 1 year of treatment with 1 mg 17β-estradiol + 2 mg drospirenone decreased 1.2 kg (p ˂ 0001) 4 . Studies have been conducted using different doses of drospirenone combined with estradiol, indicating that the effect on body weight is dependent on the dose of drospirenone, which is directly due to the activity of drospirenone antimineralocorticoid.

A variety of physical and emotional changes have been associated with hormonal fluctuations during the menstrual cycle. These symptoms related to fluid retention as mastalgia, "swelling" feeling of abdominal swelling and skin changes can affect the sense of well being and quality of life. Psychological symptoms such as fatigue and depressed mood have been studied too, appreciate a significant improvement with therapy with drospirenone, with average rates in the Health Survey for Women (Women's Health Questionnaire 4-5) higher that estradiol treatment alone. The improvement was observed mainly in symptoms somatic anxiety / fear and the difficulties of cognition., between 7 and 13 cycles of treatment.

potential benefits offered by the drospirenone as the progestogen component of combined hormone therapy with estradiol result in positive effects on blood pressure, 4 documented in recent publications. The research covers

analysis of two randomized double-blind parallel group for 24 hours in 24 postmenopausal women nonsmokers, compared with the inhibitor of the angiotensinogen-converting enzyme (ACE) inhibitor, enalapril. The results of this study suggest an additive effect on blood pressure, allowing reduce cardiovascular risk in postmenopausal women and the complications of target organs such as kidneys 6.

Another multicenter randomized study was conducted in 230 postmenopausal women from 44 to 70 years with diabetes mellitus type 2 (n = 82) or without this condition (n = 148) treated with an ACE inhibitor or a receptor angiotensin II for 28 days compared with drospirenone / estradiol. The treatment was not associated with higher incidence of hyperkalemia in either group. To avoid masking the hyperkalemia, the nondiabetic group was given ibuprofen for 5 days. It was found also that therapy with drospirenone had antihypertensive effect in this high risk population 7.

In a large-scale research, randomized and controlled for a year at 1 142 hypertensive patients evaluated in comparison with estradiol only, we obtained a decrease of 9 mm Hg from baseline (p ˂ 0.05) by 3.7 mm Hg versus drospirenone in the estradiol group, regardless of concomitant use of ACE inhibitors or angiotensin II receptor. This confirms the positive effect due to lowering properties antialdosterone 4 .

Publication latest year of 2007, is held in a single center, double-masked, randomized, placebo-controlled, 2 treatments as crusaders for a period of 4 weeks each, making the comparison with hydrochlorothiazide. Participants were monitored with blood pressure control for 24 hours a day. It was also found once again the additive hypotensive effect on systolic and diastolic pressure, combined with hydrochlorothiazide. In turn, Drospirenone also produces a potassium-sparing effect, which counteracts the potassium-losing effect induced by hydrochlorothiazide 8.

Points ●
important Drospirenone is a novel progestogen with positive beneficial properties
on weight and blood pressure
● These two, among its many features as gestagen make it very attractive
for the management of patients with cardiovascular risk factors
as hypertension without inducing weight gain. figures U.S. indicate that 80% of ˃ 60 years women have hypertension. figures are not known Colombian 9
● Has an additive hypotensive effect in conjunction with ACE inhibitors or
of angiotensin II receptor and with hydrochlorothiazide
● Because of its similarity with spironolactone, it has also saving
potassium
● These reasons positioning it as the oral combined hormone therapy use
in postmenopausal women preferred

Referencias
1- Sitruk-Ware R. Progestogens in hormonal replacement therapy: new molecules, risks, and
benefits. Menopause. 2002; 9: 6-15.
2- Oelkers WK. Effects of estrogens and progestogens on the rennin-aldosterone system and
blood pressure. Steroids. 1996; 61: 166-71.
3- Foidart JM. Added benefits of drosperinone for compliance. Climacteric. 2005; 8 Suppl: 28-
34.
4- Archer DF, Thorneycroft IH, Foegh M, Hanes V, Glant MD, Bitterman P, Kempson RL. Long-
term safety of drospirenone-estradiol for hormone therapy: a randomized, double-blind,
multicenter trial. Menopause. 2005; 12: 716-727.
5- Hunter MS. The Women's Health Questionnaire (WHQ):frequently asked questions.(FAQ).
Health Qual Life Outcomes. 2003; 1:41.
6- Preston RA, Alonso A, Panzitta D, Zhang P, Karara AH. Additive effect of drospirenone/17-β-
estradiol in hypertensive postmenopausal women receiving enalapril. Am J Hypertens.
2002; 15: 816-822.
7- Preston RA, White WB, Pitt B, Bakris G, Norris PM, Hanes V. Effects of drosperinone/17- β
estradiol on blood pressure and potassium balance in hypertensive postmenopausal women.
Am J Hypertens.2005; 18: 797-804.
8- Preston RA, Norris PM, Alonso AA, Pingping N, Hanes V, Karara AH. Randomized, placebo-controlled trial
of the effects of drospirenone-estradiol on blood pressure and potassium balance in hypertensive postmenopausal
Women receiving hydrochlorothiazide. Menopause.
2007, 14: 408 - 414.
9 - Collins P, Rosano G, Casey C, Daly C, Gambacciani M, Hadji P, Kaaj R, Mikkola T, Palacios S, Preston
R, Simon T, Stevenson J, Stramba-Badiale M. Management of Cardiovascular Risk in the peri-menopausal
woman: a consensus statement of European Cardiologists
and Gynaecologists. Eur Heart J. 2007, 28: 2028-40.

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Tuesday, October 30, 2007

Suffering From Sudden Motion Sickness

Beautiful Agony Pepper

What the study tells us about endometrial Thebes?

October 31, 2007

the study tell us about endometrial Thebes?

Urdinola Jaime MD

Medical Association Andes Bogotá DC Colombia

Phone 571/215 23 00

e-mail: jaimeurdinolamd@gmail.com jurdinol@uniandes.edu.co

blogger: www.urdinola.blogspot.com

www.urdinolamenopausia.blogspot.com

www.urdinolamenopausia2.blogspot.com

Symposium / Luncheon on Women's Health

Andes Medical Association - Board Room Wednesday October

31, 2007

THEBES study 1 means an abbreviation for the Study of Endometrial Histology Tibolone on Breast and end point.
This is a multicenter (73 centers in the U.S., 69 in Europe and 4 in Chile), randomized, double-masked, which was designed to address and respond objectively to the conflicting reports have appeared in scientific literature Endometrial safety with tibolone (either with 1.25 or 2.5 mg / day). Tibolone therefore treatment was compared with continuous combined conjugated equine estrogen (CEE) and acetate medroxyprogesterone (MPA) (0.625 mg + 2.5 mg / day).

Participants in the study, average age 54.4 + 4.4 years, were randomized into 3 groups in the following ratio 1:1:2 with tibolone 1.25 mg / day, 2.5 mg / day and CEE / MPA, respectively. The confidence interval 95% (95%) were evaluated for the incidence of abnormal endometrial histology (hyperplasia or carcinoma) and hyperplasia and carcinoma separately for each treatment group and combined treatment group, after 1 and 2 years of treatment with tibolone.

were randomized to a total of 3 240 women. Of these 3 224 received at least one dose of study medication. The incidence and 95% of abnormal endometrium (hyperplasia or carcinoma) and hyperplasia and carcinoma separately, were calculated at the end points 1 and 2 years after treatment, the incidence being 0.0 (0.5), 0.0 (0.4 ) and 0.2 (0.5) respectively in the proportion that was recorded earlier. The presence of amenorrhea was reported more frequently with tibolone, throughout the study, 1.25 mg = 78.7% and 2.5 mg = 71.4%, with EEC / MPA = 44.9%.

The research team concludes that the results confirm previous findings:
- that tibolone does not induce endometrial hyperplasia or carcinoma in postmenopausal women
- that is associated with better vaginal bleeding profile than CEE / MPA

Tibolone has been used for the management of menopausal symptoms in postmenopausal women, with positive effects on mood, sexual wellness, vaginal atrophy, urogenital symptoms and bone loss, low incidence of vaginal bleeding and mastalgia. The standard dosage has been so far of 2.5 mg / day. Estrogenic effects in a tissue selective act on brain, vagina and bone but not on the breast or endometrium.

turn, tibolone on the endometrium becomes irreversibly to Δ-4 isomer that binds to receptors progesterone and androgen 2. Furthermore, tibolone and Δ-4 isomer induce enzymes that inactivate estrogens such as 17-β hydroxysteroid dehydrogenase and sulfotransferase. Sulfatase also inhibit and enhance local deactivation of active estrogen metabolites. Other studies have shown that the metabolites 3-α and 3-β hidroxitibolona progestins act as cultured human endometrial cells, probably due to intracellular conversion of these metabolites to tibolone and to the Δ-4 isomer. For this reason it is required to add a progestogen to the treatment with tibolone.

Security endometrial cancer with tibolone had been demonstrated in many previous clinical studies, which showed a high incidence of atrophic endometrium without hyperplasia and no increase in endometrial thickness compared with the administration of combined hormone therapy (estrogen + progesterone).
This was questioned following the publication of the million women study 3, although the validity of the methodology of this publication has been questioned by many publications and tibolone was prescribed more frequently and more selectively , women at increased risk for endometrial or breast cancer. No cases

carcinoma or endometrial hyperplasia in women treated with tibolone, as main finding of this study.
2 cases of endometrial hyperplasia occurred in the CEE + MPA group: one case of atypical hyperplasia 1 year, confirmed by curettage and hysteroscopy. The other case was complex hyperplasia year 2, when the participant had completed the study period. A subsequent biopsy of this last 3 months showed only atrophic endometrium.
Although no cases of endometrial carcinoma, it was a case of endometrial stromal sarcoma of low grade, in the CEE + MPA group with 1 year of treatment.

The number of polyps Endometrial was similar in the 3 groups, 33 subjects (2.6%) in the 2 groups with tibolone and 40 cases (3.10%%) in the CEE + MPA group during the first year of treatment. 24 cases (2.5%) and 25 cases (2.5%) per year 2. No cases of carcinomatous polyps, although there were hyperplastic polyps, 8 in the tibolone group and 1 in the CEE + MPA group as one of the pathologists, and only a hyperplastic polyp in the tibolone groups according to the second pathologist.

groups in any of the endometrial thickness exceeded 4 mm.

18 cases were confirmed breast cancer, 10 in the 2 groups with tibolone and 8 in the CEE + MPA group. 3 Where tibolone groups were not confirmed by the independent Adjudication Committee Breast and Gynecological Cancer. One was a ductal carcinoma in-situ and in the other 2 cases were considered inadequate cytology or pathology reports to make a definitive diagnosis.

also were confirmed 3 cases of ovarian cancer, 2 in the tibolone group and one in the other group.

A case of cervical carcinoma was confirmed in the CEE + MPA group.

In conclusion, the study THEBES faith a relatively large study, with duration of 2 years and comparative. The incidence of atrophic / inactive at the end of the study was higher in groups with tibolone than with CEE + MPA, 87.8% vs. 79.8%. Proliferative endometrium, secretory and menstrual was more frequent in the CEE + MPA group.
There were no cases of venous thromboembolism in any of the 3 groups, although it should be noted that previous use of sex steroids as contraceptive or hormone therapy was on average across groups of 67.7%.

According to these data and in conclusion, the safety profile of tibolone is acceptable, no evidence of endometrial hyperplasia or carcinoma in this study with 2 years.

Highlights
● Study Study THEBES or tibolone Endometrial Histology of Breast and as an endpoint, was a multicenter investigation in the form in 2 continents. Randomized, double-masked comparison between 2 doses of tibolone (1.25 and 2.5 mg / day) and the combination of CEE + MPA (0.625 mg + 2.5 mg / day), with randomization of 3 240 women and a proportional distribution, respectively, 1:1:2
● According to the results, tibolone does not induce endometrial hyperplasia or endometrial cancer or
● It has a better vaginal bleeding profile and a higher proportion of women in amenorrhea with treatment, the combination of CEE + MPA
● No need to add a progestogen to tibolone, as the endometrium becomes isomer Δ-4 or induce enzymes that inactivate estrogens at this level between the various mechanisms that have been reported about its effect on the endometrium
● unfavorable findings million women study on endometrium (study very much in doubt because of methodological limitations) appear to be undermined by THEBES study, relatively large study lasting 2 years
● In this study the safety profile of tibolone is acceptable, no evidence of endometrial hyperplasia or carcinoma

References 1 - Archer DF, Hendrix S, Gallagher JC, Rymer J, Skouby S, Ferenczy A, den Hollander W, Stathopoulos V and Helmond FA, for the Tibolone Histology of the Endometrium and Breast Endpoints ( THEBES ) Study Group. Endometrial Effects of Tibolone. J Clin Endocrinol Metab 2007; 92: 911-918.
2- L. J. Blok, P. E. De Ruiter, E. C. M. Kühne, E. E. Hanekamp, J. A. Grootegoed, E. Smid-Koopman, S. C. J. P. Gielen, M. E. De Gooyer, H. J. Kloosterboer and C. W. Burger. Progestagenic Effects of Tibolone on Human Endometrial Cancer Cells. J Clin Endocrinol Metab 2003; 88: 2327-2334.
3- Beral, V, BullD, Reeves G for the Million Women Study Collaborators. Endometrial cancer and hormone-replacement therapy in the Million Women Study. Lancet 2005, 365:1543-1551.

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Spielautomaten

Tuesday, August 28, 2007

Will Mild To Moderate Cervical Stenosis Get Worse

Phytosterols in Hypercholesterolemia

Agosto 29, 2007

Qué hacen los Fitosteroles ( Fitolip ®) en la Hipercolesterolemia ?

Qué hacen los Fitosteroles ( Fitolip ®) en la Hipercolesterolemia ?

Jaime Urdinola M.D.
Asociación Médica de los AndesBogotá D.C. Colombia
Teléfono 571 / 215 23 00
e-mail: jaimeurdinolamd@gmail.com
jurdinol@uniandes.edu.co
blogger: www.urdinola.blogspot.com
www.urdinolamenopausia.blogspot. com
www.urdinolamenopausia2.blogspot.com
Symposium / Luncheon on Women's Health Medical Association
Andes - Boardroom
Wednesday August 29, 2007

Cardiovascular disease (CVD) is the most prevalent serious diseases facing Colombian women in the early years of the century XXI. Affects mortality at 50.7 per 1 000 women with cerebrovascular disease and 67.1 per 1 000 women with ischemic heart disease 1.

interventions related to prevention of these problems are needed, such as measures to control dyslipidemia, whether pharmacological or not.

What are Phytosterols?

also called plant sterols, are steroid molecules that are abundant in the seeds of legumes and inhibit the absorption of cholesterol. Its cholesterol-lowering effect has been known since 1950.
The best known is the β-sitosterol, belonging to the group the 4-desmethylsterols, so do not have a methyl group at carbon 4, with campesterol and stigmasterol.

Cholesterol also is a sterol, but present only in animals and humans.

In its free form, phytosterols are insoluble in water and slightly soluble in fats. Are esterified to make them soluble, which also possess greater power Lovastatin. Precisely for esterification of vegetable oils is needed seed and soybean, sunflower, corn, canola, olive, etc..

Vegetarians consume in their diet about 500 mg daily, while the usual Western diet provides 150-350 mg of phytosterols, or is an amount almost equal to the intake of cholesterol. But these amounts do not produce significant reductions in cholesterol levels, since they require at least 1 g / day and ideally from 1.5 to 3 g / day to achieve 11-14% lower LDL cholesterol 2.

diet in preventing cardiovascular problems is essential, according to epidemiological studies and investigations of dietary intervention. If people consume plenty of carbohydrates and fats, cardiovascular mortality is lower than in the population who eat plenty of animal fats and cholesterol.

Moreover, the phytosterols alone or in foods enriched with them, could be considered as functional food, since they have proved scientifically, which are midway between food and medicines, nutraceuticals also consequently classified.

Phytosterols have been modified over time to make them more efficient. Initially administered in free form and in high doses. In a second stage is still administered in free form but at lower doses. Currently the administration is in esterified form and in small doses, and can be mixed with margarine or other fat products. Currently there is also the pharmaceutical.

Mechanism of action

Phytosterols and cholesterol are structurally similar, just different sterol ring the presence of a methyl group in the campesterol, sitosterol or ethyl, in the 24 carbon chain. Stigmasterol to sitosterol is similar, but with one more double bond in the carbon 22.

sterols are absorbed less cholesterol, depending on the length of the string. Campesterol is absorbed than sitosterol. This is the most abundant in nature and absorbs only a proportion of 5%. Stanols, sterols, saturated or is no double bond in the sterol ring and produced by hydrogenation of sterols, are absorbed below 1%.

Western diet contains phytosterols in quantities similar to cholesterol, but minimal absorption cause their blood levels are much lower than those of cholesterol. Phytosterols as cholesterol, are metabolized in the large intestine by bacteria to form coprostanol and coprostanonas.

But unlike cholesterol, phytosterols are not converted into bile acids. The molecular similarity of human and plant sterols is the reason why, when ingested in sufficient amounts, between 1.5 and 3 g daily, they compete with cholesterol for solubilization into micelles, which are compounds responsible for the intestinal transport polymolecular lipid insoluble, having greater affinity for these than the human cholesterol, which inhibit its absorption.

Remember that 30% of cholesterol comes from dietary intake, mainly from egg yolk, liver of mammals and crustaceans and 70% by training in liver and biliary excretion. Thus, cholesterol absorption in the intestine is reduced by about 50%, affecting the cholesterol from the diet and the bile enterohepatic circulation.

The decrease in intestinal cholesterol absorption induced by phytosterols liver promotes two regulatory effects. The first is the increase in endogenous synthesis cholesterol. The second is to stimulate the expression of LDL receptors, thereby increasing the uptake of circulating LDL. This is why the end result is a decrease from 10 to 15% of plasma LDL.

Recent studies suggest that cholesterol uptake by the micelles within the intestinal mucosa is mediated by Niemann Pick C1 Like Protein, a specific carrier that can be inhibited by ezetimibe 3.

should also be noted that cholesterol absorption is controlled not only by its input, or the inward flow (influx), but also for its output or flow out (efflux). This could explain why under normal circumstances, the efficiency of cholesterol absorption decreases as the amount ingested increases. For this reason might be the hyperresponders to absorb more dietary cholesterol than unresponsiveness 4 . Other findings indicate that phytosterols also influence cellular cholesterol metabolism within intestinal enterocytes 5 .

Interest in the effects of stanols in the diet to reduce cholesterol levels, motivated and in 2001 met in Stresa, Italy 32 experts in lipid nutrition and diseases heart 6, under the auspices of the Italian Foundation for Nutrition, to discuss the efficacy, safety and future of research into stanols. A meta-analysis of 42 clinical trials 7 showed that the intake of 2 g / day of stanols or sterols decreased low density lipoprotein (LDL) by 10%. Larger quantities added little to the effect obtained with the doses noted.

The effects can be additional to the diet or drug interventions. If you eat food low in saturated fat and cholesterol and high in stanols, LDL can be reduced further, even 20%.

If added sterols or stanols to statin therapy, it is more effective than doubling the dose of statins 8.9.

In patients with diabetes mellitus, 3 g / day of phytosterols reduced LDL additional 6% when combined with pravastatin.

In patients with coronary disease and familial hypercholesterolaemia receiving simvastatin, the same dose of 3 g / day of phytosterols reduced LDL 16 to 20% compared with simvastatin alone 10 .

Of importance to the management of patients in middle age or old age, a meta-analysis 11 showed that plasma levels of vitamins A and D are not affected by the action of the sterols or stanols. Alpha carotene, lycopene and vitamin E levels remained stable in relation to its carrier molecule, LDL. The levels of β ̶ carotene decreased, but do not expect adverse health outcomes for this reason;, likewise, this could be corrected by adding additional fruits and vegetables to the diet.

Another of the concerns are fitosterolemia patients with homozygous, due to a marked increase in atherosclerosis in these patients, but it is considered that the risk is hypothetical, and that any increase due to the small increase in plasma plant sterols can be virtually ruled out by the decrease in plasma LDL.

are insufficient data to suggest that the sterols or stanols can prevent or promote colon cancer. This phenomenon is tracked, but the power of studies to capture the unusual increase of common diseases, is limited. A clinical study to analyze outcomes such as thickening of the intima media layer of the vessel might corroborate the expected efficacy in reducing the phenomenon of atherosclerosis.

But with the available data we may assume that the evidence is sufficient to promote the use of sterols and stanols in people with an increased risk for coronary heart disease. -

Long-term efficacy of phytosterols

Published studies suggest that the effect of cholesterol reduction by phytosterols is less marked in long-term studies compared with studies short term. There is a slight decrease in serum antioxidant soluble in lipids. Furthermore, phytosterols down regulate bile acid synthesis to 21%, which in turn attenuates the efficacy in reducing cholesterol, but further study is needed to confirm this effect and allow quantify the effects in time 12.

Highlights

● Cardiovascular Disease now kills thousands of women in Colombia

● hypercholesterolemia can intervene medically,
contributing to the prevention of this disease

● Phytosterols are plant sterols similar to cholesterol.
compete with this in their absorption in the intestine

● The administration of 1.5 to 3 g / day of phytosterols reduced by at least 10 to 14
% LDL cholesterol

● It is effective and safe for the patient, add phytosterols to
treatment with statins, doubling the dose of the latter

References 1 - Gender, Health and Development in the Americas - Basic Indicators 2005. Pan American Health Organization. Regional Office of World Health Organization.
2 - Plaza I. Phytosterols, cholesterol and cardiovascular disease prevention. Clin Invest Arteriosclerosis. 2001, 15:209 - 218.
3 - Altmann SW, Davis Hr Jr, Zhu LJ, Yao X, Hoos LM, Tetzloff G, Iyer SP, Maguire M, Golovko A, Zeng M, et al. Niemann ̶ Pick C1 Like protein is critical for intestinal colesterol absorption. Science. 2004; 303: 1201 ̵ 1204.
4- Thompson GR, Grundy SM. History and development of plant sterol and stanol esters for cholesterol-̵ lowering purposes. Am J Cardiol. 2005; 96 ( suppl ) : 3D ̶ 9D.
5- Plat J, Mensink RP. Plant stanol and sterol esters in the control of blood cholesterol levels: mechanism and safety aspects. Am J Cardiol. 2005; 96 ( suppl ) : 15D ̶̶ 22 D.
6- Katan MB, Grundy SM, Jones P, Law M, Miettinen T, Paoletti R, for the Stresa Workshop Participants. Efficacy and safety of plant stanols and sterols in the management of blood cholesterol levels. Mayo Clin Proc. 2003; 78: 965 ̶ 978.
7- Law M. Plant sterol and stanol margarines and health. BMJ. 2000; 320 : 861 ̶ 864.
8- Blair SN, Capuzzi DM, Gottlieb SO, Nguyen T, Morgan JM, Cater NB. Incremental reduction of serum total cholesterol and low ̶ density lipoprotein cholesterol with the addition of plant stanol ester ̶ containing spread to statin therapy. Am J Cardiol. 2000 ; 86: 46 ̶ 52.
9- Vuorio AF, Gylling H, Turtola H, Kontula K, Ketonen P, Miettinen TA. Stanol ester margarine alone and with simvastatin lowers serum cholesterol in families with familial hypercholesterolemia caused by the FH ̶ North Karelia mutation. Arterioescler Thromb Vasc Biol. 2000 ; 20 : 500 ̶ 506.
10- Thompson GR. Additive effects of plant sterol and stanol esters to statin therapy. Am J Cardiol. 2005; 96 ( suppl ) : 37D ̶̶ 39 D.
11- Raeini ̶ Sarjaz M, Ntanios FY, Vanstone CA, Jones PJ. No changes in serum fat ̶ soluble vitamin and carotenoid concentrations with the intake of plant sterol ⁄ stanols esters in the context of a controlled diet. Metabolism. 2002; 1 : 652 ̶ 656.
12- O'´Neill FH, Sanders AB, Thompson GR. Comparison of efficacy of plant stanol ester and sterol ester: short ̵ ̵ term and Long term studies. Am J Cardiol. 2005, 96 (suppl): 29D, 36D ̵.

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Monday, July 23, 2007

Make Noise Makers For Cheer Competition

Wednesday July 25, 2007

Ibandronate IV: Step forward in the treatment of osteoporosis

Jaime

Urdinola MD

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

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Symposium / Luncheon on Women's Health - Wednesday, July 27, 2007

Boardroom - First Floor, Medical Association of the Andes - Bogotá DC Colombia

no doubt about the overall effectiveness of bisphosphonates for the treatment of postmenopausal osteoporosis. These drugs have been constituted today, the mainstay of treatment for postmenopausal osteoporosis 1-2.

This year 2007 was marked by the appearance of intravenous bisphosphonate therapy, which means a step forward in the treatment of osteoporosis. It is assumed that parenteral treatment can be an advantage for women who have problems of intolerance to these drugs when given orally. But given the simplicity and safety with the use of ibandronate may be considered that this could be the paradigm, a nitrogenous bisphosphonate powerful and easy to administer an IV.

The excellent tolerance to be shown by mouth and features that allow its connection to the bone, allowed ibandronate can be administered not only orally but also via the extended intervals in dose.

Pierre Delmas et al 3 performed a randomized study (DIVA called by its acronym), double-blind, double dummy "(roughly translated as double placebo), of inferiority, comparing 2 regimens intermittent IV injections of ibandronate (2 mg c / 2 months and 3 mg every 3 months) with a regimen of 2.5 mg daily oral ibandronate. The latter has already proven anti-fracture efficacy.
This clinical trial includes 1 395 women aged 55 to 80 years, and who were at least 5 years postmenopause stage. We require all of them had osteoporosis (lumbar T Index in bone mineral density (BMD) L2-L4 < 2.5 ). A todas las participantes se les administró diariamente calcio ( 500 mg ) y vitamina D ( 400 UI ). El desenlace primario que se analizó al año, fue el cambio de la DMO desde la línea basal en relación a la columna vertebral. Se midieron también la DMO de la cadera así como el telopéptido C del colágeno tipo I ( CTX ) y la seguridad y la tolerabilidad de los tratamientos.

was not accepted for women who had received prior IV bisphosphonate therapy at any time.
Or to those who have received during the 6 months preceding oral bisphosphonates or any type of medication affect bone metabolism, or had renal impairment or a history of upper gastrointestinal disease or allergy to bisphosphonates, because they were excluded. The study was conducted in 58 centers in the U.S., Canada, Mexico, Europe, Australia and South Africa.

A year after the treatment performed, BMD increased 5.1% in 353 patients who received 2 mg IV ibandronate c / 2 months, 4.8% among 365 patients treated w / 3 months with 3 mg IV ibandronate and 3.8% between 377 patients who received 2.5 mg oral ibandronate day.
Both IV regimens were not not only not less, but the analysis showed their superiority (P < 0.001 ).
BMD rose hip which was higher in the groups receiving IV medication in the group who took orally. CTX
strong decreases were observed in all study groups.
Both IV regimens were well tolerated and did not compromise renal function.

The authors conclude that, taking into account the assessed BMD, IV injections of ibandronate (2 mg c / 2 months or 3 mg every 3 months) are as effective as the regimen of 2.5 mg / day orally, which has previously demonstrated anti-fracture efficacy (52% at 3 years with the daily dose and 50% with intermittent doses in relation to vertebral fractures). With the application

IV have raised concerns about the presentation of "influenza-like illness."
This may also occur with oral bisphosphonates. In the study, the incidence was higher in the groups that received IV than in the mouth, 5.1% and 4.9% in group IV c / 2 c / 3 months, respectively, vs. 1.1% in the oral group.
Considering the typical onset of this condition, which occurs within 3 days of dosing and lasts < 7 días, la incidencia respectiva en los 3 grupos de tratamiento fue 3.8 %, 3.6 % y 0.6 % respectivamente.
= or 80% of affected patients reported no symptoms recur.

Having the availability of IV therapy, the concern arises only if those patients with problems for the administration of the preparation by mouth would be the candidates for IV therapy, such as those with gastrointestinal intolerance to the drug, patients with cognitive problems (dementia, etc..), those receiving multiple medications by mouth those with abnormalities of the esophagus that delay emptying them, or will prevail in the future comfort of the IV w / 3 months, on the other reasons?
IV injection to be administered in the office, in 15 to 30 seconds, an advantage over the other annual presentation that requires an infusion in a hospital or temporary placement.

Highlights
● Bisphosphonates are currently the mainstay in the treatment of osteoporosis in postmenopausal women, for their proven
● bisphosphonate ibandronate is a potent nitrogen, which has proven anti-fracture efficacy and good tolerance, research on oral treatment
● The DIVA study, which considered two regimes IV, shows superiority over oral regimen
● The "influenza-like illness" can occur with IV or oral administration of bisphosphonates , but more often with IV therapy. No repeats in most cases with subsequent doses and does not seem important factor in discontinuation of therapy
● Finally, the IV treatment for its simplicity and convenience, you can replace in many cases the oral, not only in cases of digestive intolerance or difficulties in administration, signifying a step forward in the treatment of osteoporosis

References 1 - Chesnut CH III, Skag A, Christiansen C, Recker R, Stakkestad JA, Hoiseth A, Felsenberg D, Huss H, Gilbride J, Schimmer RC, Delmas PD, Oral Ibandronate Osteoporosis Vertebral Fracture Trial in North America and Europe (BONE). J Bone Miner Res 2004, 19: 1241-9.
2 - Baussan F, Russel RG. Ibandronate in osteoporosis: preclinical data and rationale for intermittent dosing. Osteoporosis Int 2004, 15: 423-33.
3 - Delmas PD, Adami S, Strugala C, Stakkestad JA, Reginster JY, Felsenberg D, Christiansen C, Civitelli R, Drezner MK, Recker RR, Bolognese M, Hughes C, Masanauskaite D, Ward P, Sambrook P, Reid DM. Injections Intravenous ibandronate in postmenopausal Women with osteoporosis: one-year results from the dosing Intravenous administration study. Arthritis Rheum 2006, 54: 1838-1846.

If you have any comments, questions or concerns, you can "click" on comments and sending your message. Or if you prefer, can send comments, questions or concerns e-mail: jaimeurdinolamd@gmail.com

Monday, June 25, 2007

How To Make A Cheap Podium

A Sample Paper Of Moh Exam For Dentist

What is the Right Time to Treat osteoporosis with alendronate? Aspirin and Mortality

Wednesday June 27, 2007

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
http://www.urdinolamenopausia2.blogspot.com
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

● 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:

● - 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?

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Tuesday, May 29, 2007

Aubrey Miles Prosti Watch Online

Wednesday May 30, 2007

Long-Term Mortality in Women taking aspirin - Results Observational Study of Nurses Harvard University

Urdinola Jaime MD

AK 9 116-20 326 - Medical Association of the Andes - Bogotá DC Colombia
Phone: 571 / 215 23 00 - Phone: 57 / 315 236 28 August
e-mail: jaimeurdinolamd@gmail.com
blogger:
http://www.urdinola.blogspot.com
http://www.urdinolamenopausia.blogspot.com

http://www.urdinolamenopausia2.blogspot.com Symposium / Luncheon on Menopause - Wednesday, May 30, 2007 Board Room - First Floor, Medical Association
Andes Bogotá DC Colombia

In the medical journal Archives of Internal Medicine March 26, 2007, researchers at Harvard University reported on a strong association between aspirin use and reduction in cardiovascular mortality in middle-aged women and elderly a . This analysis of nearly 80 000 women stems from the findings of the study called the Nurses, a research effort led well known and already has nearly 30 years of experience.

For this purpose, we should also remember the Symposium last Wednesday November 29 2006 on Women Preventive aspirin? , Which is in www.urdinolamenopausia.blogspot.com on the Study of Women's Health (WHS = Women's Health Study) 2-3. This report carried out for 11 years in almost 40 000 women postulated that aspirin therapy had no effect on cardiovascular mortality or other, only about stroke.
The question is which of these 2 mega is correct? Somehow both or neither?

Table 1. Characteristics of Cohort Studies of Health of Nurses (NHS) 1 and the Health of Women (WHS) 2-3
WHS NHS
Features - Length of follow (Years) 24 (1980 - 2004) - 10 (1993 - 2004)
- Aspirin Dose 1 to> 14 tablets per week - 100 mg every second day
- No. of participants 79 439 - 39 876
- No. Cardiovascular disease deaths
1 991-246
Cancer 4 469 to 583
-
risk characteristics Average age in years 58 to 55
% Hypertension 33 - Diabetes mellitus
% 26 5 to 3 Hypercholesterolemia
% from 43 to 30
% Current smokers 16 to 13 Postmenopausal
% from 83 to 54
% Current users of hormone from 39 to 55
-% cardiac risk factors (in addition to the above includes index body mass> 30)
0 33 to 42
1 from 1937 to 1934
February 22 to 18
> March 8 to 6

in Colombia and the U.S., the 2 leading causes of death are, first of Cardiovascular Disease (CVD) and second term cancer. The study discussed today is interesting because it is still unclear whether treatment with aspirin may influence significantly the risk of death, especially in women.

Researchers prospectively examined the influence of long-term treatment with aspirin on the risk of death from all causes, as well as those arising in CVD or in cancer, then monitored for 24 years, including 9 477 deaths . The women who participated in this study provided information about drug use, on a biennial basis since 1980, which allowed assessment of the relative risk (RR) of death according to the use of aspirin before the incidental diagnosis of CVD or cancer and during the corresponding period for each control subject. The

Multivariate RR for women who reported current use of aspirin for all causes was 0.75 (confidence interval = 95% CI, 0.71 -0.81) compared with women who never used aspirin regularly.
The reduction in risk was more apparent for death from CVD (RR, 0.62, 95% CI, 0.55 to 0.71) that because of cancer (RR, 0.88, 95% CI, 0.81 to 0.96).

The use of aspirin for 1 to 5 years was associated with a significant reduction in cardiovascular mortality (RR, 0.75;) 95% CI, 0.61 to 0.92). In contrast, the reduction in cancer death only came to see after 10 years of treatment with aspirin (Linear trend P = 0,005).

The other data that may lend itself to controversy, although the survey data support the low dose WHS is that benefit of aspirin use was confined to low and moderate doses and was significantly greater in elderly patients ( P for interaction < n =" 0.02">

identified only 41 cases of death associated primarily with gastrointestinal bleeding and can not be reliably estimate the effect of aspirin use on the final outcome. But the fact is interesting in itself.

But
the findings of this and other studies support the need for continuing research into the use of aspirin in preventing de las enfermedades crónicas.

Referencias
1- Chan AT, Manson JE, Feskanich D, Stampfer MJ, Colditz GA, Fuchs CS . Long-term Aspirin Use and Mortality in Women. Arch Intern Med 2007; 167: 562-572.
2- Ridker PM, Cook NR, I-Min L, Gordon D, Gaziano JM, Manson JE, Hennekens CH, Buring JE. A Randomized Trial of Low-Dose Aspirin in the Primary Prevention of Cardiovascular Disease in Women. N Engl J Med 2005; 352: 1293 – 1304.
3- Cook NR, Lee IM, Gaziano JM, Gordon D, Ridker PM, Manson JE, Hennekens CH, Buring JE. Low-dose aspirin in the primary prevention of cancer: the Women’s Health Stduy: a randomized controlled trial. JAMA 2005, 294: 47-55.

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Or if you prefer, you can send your comments, questions or concerns e-mail
jaimeurdinolamd@gmail.com

Tuesday, May 15, 2007

Kithcen For Rent Ohio

Strontium ranelate - The New in the Treatment of Osteoporosis

Wednesday May 16, 2007

strontium ranelate = PROTOS ®
's New in the Treatment of Osteoporosis

Urdinola Jaime MD

CS AK 9 116-20 326 - Medical Association de los Andes - Bogotá DC Colombia
Phone: 571 / 215 23 00 - Phone: 57 / 315 236 28 August
e-mail: jaimeurdinolamd@gmail.com
blogger:
http://www.
urdinola.blogspot.com http://www.urdinolamenopausia.blogspot.com
http://www.urdinolamenopausia2.blogspot.com
Symposium / Luncheon on Menopause - Wednesday, May 16, 2007 - Restaurant Olio-3rd. Piso - Calle 110 No 9 B 04 - Centro Comercial Santa Ana Bogotá DC Colombia

osteoporotic drugs

is known that osteoporosis is characterized by reduced bone mass and deterioration of bone microarchitecture, which results in an increase in bone fragility and increased susceptibility to fractures.

The most common cause of osteoporosis in women is declining estrogen levels that occurs after menopause. Estrogen deficiency increases bone remodeling, ie, greater bone resorption than formation, resulting in a negative bone balance at the tissue level, deterioration of bone architecture and decreased bone mass.

Based on the observation that bone remodeling increases with age and during osteoporosis, osteoporotic drugs have been developed in accordance with its specific effect on bone turnover:

- currently available anti-catabolic drugs as estrogen, SERMs (selective estrogen receptor modulators = selective estrogen receptor modulators) and aminobisphosphonates, the which act by inhibiting bone turnover, reducing bone resorption and a secondary reduction in bone formation. This effect produces a positive balance in bone remodeling by increasing bone strength, thus observing a decrease in the incidence of fractures in postmenopausal women.

- A second class of drugs osteoporotic, bone anabolic called, can increase bone mass and strength by increasing bone remodeling. The first drug in this class is parathyroid hormone (PTH rh - peptide 1-34), which increases bone formation more than bone resorption, which results in increased bone mass and microarchitecture and leading to a marked reduction of fractures.

- The third concept is based on the possibility that another mode of action, simultaneously combining antiresorptive actions and forming bone, may have beneficial effects on bone mass and strength.

Strontium ranelate (SR) is the first drug that works with this combined effect on bone metabolism within the group of agents dual action on bone (in English, Dual Action Bone Agents = DABA) 1-2.
Therefore, the RE is now the novelty in the treatment of osteoporosis, which is explained later in a highly summarized.

analysis of iliac crest biopsies from postmenopausal osteoporotic patients histomorphometric way, have shown that women treated with RE increases the rate of mineralization and osteoblast surface and tends to decrease the surface of osteoclasts, compared with women who were given placebo.

addition, the analysis of 3-dimensional MicroTAC observed a higher number of trabeculae, decreased separation of the same, and increased cortical thickness. This has provided evidence for an improvement in the trabecular and cortical bone microarchitecture 3.

One advantage recently revealed by in vitro analysis demonstrates that strontium activates the calcium receptor called calcium-sensing receptor , roughly translated as calcium sensing receptor. It also activates the differentiation of stromal cells in the bone marrow, stimulating production of prostaglandin E-mediated activation of cyclooxygenase 2 (COX-2). Finely

on this topic, recent data indicate that RE can be adjusted upward osteoprotegerin (OPG), a cytokine that prevents the conversion of macrophages to osteoclasts, and decrease the expression of the ligand nuclear factor kappa B (RANK = receptor activator of nuclear factor kappa B activating osteoclasts) in human osteoblastic cells, suggesting that RE can reduce bone resorption to modulate the RANK / RANK Ligand / OPG, which is essential for osteoclastogenesis.

Pharmacokinetics

RE bioavailability is obtained by linking or attaching an organic molecule ranelic acid, two atoms of stable strontium. Strontium is absorbed onto the glass surface of bone calcium and only 10 is replaced in peak form in the apatite crystal in-vivo, indicating that strontium replaces calcium in minimally treated bone 4 .

This indicates the safety of the RE and the results confirm that therapeutic doses of IR does not alter the deposition of bone mineral in the studied species, including humans.

IR absorption is low and appears to be saturable as the dose increases (6-26%) with no observable metabolites, with a short half-life ~ 1 h after administration of

2 000 mg, trade.

The dose should be administered at bedtime, since if done simultaneously with calcium or food, this markedly reduced the bioavailability of RE. Absolute bioavailability is 2.5% after a dose of 2 g of ER, due to its low lipophilicity and low solubility.

No gender differences were observed in the absorption 5 .

excretion is almost complete, 93 to 99%, 7 days after administration of radiolabeled compound sharply. Excretion is rapid and occurs mainly via the urine after IV administration (83 - 92%) or through the gut after oral administration (83 - 92%). This confirms the absence or very low secretion gastrointestinal / biliary ranelic acid and confirms its low absorption and rapid elimination properties of the molecule.

RE Clinical efficacy of osteoporosis

have been published several clinical studies so far. ●

who discussed below was one of the first, in order to deal preventively bone loss after menopause 6. Itself was not directed to the treatment of osteoporosis.
A 160 postmenopausal women were given prospective, randomized RE for 24 months in a double-masked, placebo-controlled trial. The doses used were 125, 500 and 1 000 mg / day. All of them received 500 mg / day of elemental calcium. Average age 54 years, duration of menopause 3 years who had a T = -1.4 + 1.4.
the end of the study, bone mineral density (BMD) in spine increased progressively without an observed plateau effect. The percentage difference between SR and placebo was +5.53 vs. -0.75%, Respectively (confidence interval 95% CI = 3.90 vs. 8.67, respectively, p < 0.001.
In total hip and femoral neck, the average percentage increase was 3.2 and 2.5% respectively. The percentage of variation in the group received 1 000 mg of ER compared with placebo was significantly different vs +3.21. -0.88%, 95% CI 1.86 and 6.31, respectively, +2.46 vs. -0.87 95% CI 0.69 and 5.96, respectively, p <>

The dose of 1 000 mg orally induced no significant adverse reaction compared with placebo. Based on these results, we have taken the daily dose of 1 000 mg of RE as a possible preventive treatment of bone loss after menopause. According to these findings, although there is now a very big debate on the issue and no final consensus available, could be managed with this dose osteopenia?

● In postmenopausal women with osteoporotic vertebral fractures assessed the effects of RE for a double-masked, placebo-controlled 7.

RE was administered in doses of 500, 1 000 and 2 000 mg or placebo, to 353 Caucasian women, average age 66 years with index of -3.9 + 1.0 T, with an average of vertebral fractures per patient was 2.7 + 2.5, mean duration of menopause of 18 + / - 8 years, body mass index (BMI) of 25 + / - 3 kg / m2. All women were given a supplement of 500 mg / day of calcium and 800 international units (IU) of vitamin D3.

The annual increase in BMD in the group that received 2 000 mg of RE was of + 7.3% (p <>

addition, the dose of 2 000 mg of RE associated with a 44% reduction in the number of patients experiencing a new vertebral deformity. Histomorphometry showed no mineralization defects.

10% of patients in both groups withdrew due to adverse effects.

The RE was placed in the new bone in a dose-dependent manner, with a significantly higher content in the cancellous bone and compact form according to the quantitative microradiographs.

● A large Phase III program began in 1996, which includes two large clinical trials for the treatment of established osteoporosis.

- Therapeutic Intervention Osteoporosis Vertebral Column (Spinal Osteoporosis Therapeutic SOTI = Intervention) with the aim to assess the effects of SR on vertebral fracture risk.

- The Treatment of Peripheral Osteoporosis (TROPOS = Treatment of Peripheral Osteoporosis ) whose main purpose was to evaluate the effects of RE on the peripheral fractures or nonvertebral.

All patients included in these two studies had previously participated in the study FIRST = Fracture International Run-in Strontium ranelate Trials.

Patients received supplemental calcium and vitamin D, which were individually tailored according to your needs, either 500 or 1 000 mg of calcium and 400 or 800 IU vitamin D3 8.
above
Both studies were multinational, randomized, double-masked, placebo-controlled, with two parallel groups of 2 000 mg / day vs. RE. placebo, involving 75 clinical centers in 12 countries in Europe and Australia. The duration of the studies was 5 years with a major statistical analysis plan after the first 3 years of follow-up and performed with so-called people tried to treat (Intention-to-treat = ITT). Of the more than of 9 000 osteoporotic postmenopausal women who took part in the FIRST study, 1 649 were included in the study SOTI 9 with an average age of 70, and 5 091 with an average age of 77 included in the study TROPOS 10.

- The primary analysis of the SOTI study evaluating the effect of 2 000 mg of SR on vertebral fracture rates, showed 41% reduction in relative risk (RR) of experiencing a new vertebral fracture (semiquantitative assessment) for ER the period of 3 years when compared with placebo.
139 patients with vertebral fracture vs. 222 (RR = 0.59, 95% CI 0.48 and 0.73, respectively, p < 0.01. El riesgo de experimentar una nueva fractura se redujo significativamente en el grupo con RE. La DMO se incrementó en el grupo tratado si se compara con placebo, + 14.4 vs. -1.3 %, respectivamente; p <>

These beneficial effects were evident early, from the first year of treatment. RE was well tolerated without any specific adverse event (diarrhea [6.1% vs. RE. 3.6% placebo, p = 0.02] which disappeared after the third month and mild gastritis [3.6% vs ER. 5.5% placebo, p = 0.07).

- In the study troops also conduct the primary analysis to the 3rd. year, evaluating the effects of administration of 2 000 mg / day of SR on non-vertebral fractures, showed a reduction of 16% of all non-vertebral fractures, 36% of hip fractures and 31% of nonvertebral fractures in women over 80 years. Similar to the SOTI study, confirming previous findings, there was a 39% reduction in vertebral fractures in this group.

- Further additional analysis of all clinical studies mentioned above, with the pooled data from SOTI and TROPOS studies 11-12, which show very interesting data.

For example, vertebral fractures occur independently of baseline risk factors for osteoporosis but the presence of a wide range of risks for them.

can reasonably be inferred based on these data, that the beneficial effect of RE do not vary by baseline BMD. Therefore, there was a significant anti-fracture effect of RE in a subgroup of 176 women with osteopenia, and the number of incidental vertebral fracture events was low in it.

decreased risk in this subgroup was 72% (RR 0.28, 95% CI 0.07-0.99, P = 0.045).

is known that although BMD is an important determinant of fracture risk, however presents a proportion of fractures in women with a higher rate of T - 2.5. In women> 65 years, the proportion of fractures attributable to osteoporosis only, as defined by BMD T < - 2.5, oscila entre 10 a 44 %.

index
As noted at the beginning of this summary, not all osteopenic women should be treated, but as methods risk identification be improved, identify those with osteopenia have a high probability to present fracture and in which preventive treatment is indicated.

Highlights

● The strontium ranelate is the first drug with combined effect on bone metabolism: antiresorptive and bone formation. That is why it is called dual-action agent on bone (Dual Action Bone Agent = DABA)

● beneficial effects on increasing bone mass and strength bought back have been demonstrated by different methods

● Do not alter bone mineralization

● The safety and tolerance are very good

● Presents comprehensive clinical efficacy, preventing fractures vertebral and nonvertebral

● The preventive effect of fracture in women with osteopenia is interesting

● Based on these data, the availability of strontium ranelate for the treatment of osteoporosis is really novedad actual

Referencias

1- Marie PJ . Strontium ranelate: a novel mode of action optimizing bone formation and resorption. Osteoporos Int 2005; 16: 7-10.
2- Marie PJ . Strontium ranealte: a dual mode of action rebalancing bone turnover in favour of bone formation. Curr Opin Rheumatol 2006; 18 ( suppl 1 ): S11-S15.
3 - Arlot ME, Burt-Pichat B, Roux JP, et al. The effects of strontium ranelate on bone remodeling and bone safety assessed by histomorphometry in patients with postmenopausal osteoporosis. J Bone Miner Res 2005; 20 (Suppl. 1) :1084.
4- Bovin G, Deloffre P, Perrat B, et al. Strontium distribution and interactions with bone mineral in monkey iliac after strontium salt ( S 12911 ) administration. J Bone Miner Res 1996; 11: 1302-1311.
5- Reginster JY, Lecart M-P, Deroisy R, Lousberg C. Strontium ranelate: a new paradigm in the treatment of osteoporosis. Expert Opin Investig Drugs 2004; 13: 857 – 864.
6- Reginster JY, Deroisy R, Dougados M, Jupsin J, Colette J, Roux C . Prevention of early postmenopausal bone loss by strontium ranelate: a randomized, two-year, double-blind, dose-ranging, placebo controlled trial. Osteoporos Int 2002; 13: 925-931.
7- Meunier PJ, Slosman D, Delmas P, et al. Strontium ranelate: dose-dependent effects in established postmenopausal vertebral osteoporosis: a 2-year randomized placebo controlled trial. J Clin Endocrinol Metabolism 2002; 87: 2060-2066.
8- Reginster JY, Diez-Perez A, Ortolani S, Pors-Nielsen S, Meunier PJ . Calcium-vitamin D supplementation in clinical trials of osteoporosis should be titrated on the basis of pre-study assessments. Osteoporos Int 2002; 13 (S1): S24.
9- Meunier PJ, Roux C, Seeman E, Ortolani S, Badurski JE, Spector TD, et al. The Effects of Strontium Ranelate on the Risk of Vertebral fracture in Women with Postmenopausal Osteoporosis. N Engl J Med 2004; 350: 459-68.
10 - Renginster JY, Seeman E, De Vernejoul MC, Adami S, Compston C, Phenekos C, et al. Strontium ranealte Reduces the Risk of Nonvertebral Fractures in Postmenopausal Women with Osteoporosis: Treatment of Peripheral Osteoporosis ( TROPOS ) Study. J Clin Endocrinol Metab 2005; 90: 2816-2822.
11- Seeman, E. Strotium ranelate: vertebral and non-vertebral fracture risk reduction. Curr Opin Theumatol 2006; 18 (Suppl 1): S17-S20.
12- Roux C, Reginster JY, Fechtenbaum J, Kohtla S, Sawicki A,Tulassay Z, et al . Vertebral Fracture Risk Reduction with Strontium Ranelate in Women with Postmenopausal Osteoporosis Is Independent of Baseline Risk Factors. J Bone Miner Res 2006, 21: 536-542.

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