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

CS

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.

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
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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