Análisis de La Posición Europea: Guías europeas para el diagnóstico y manejo de la osteoporosis en la mujer postmenopáusica
Thursday September 18, 2008
European Position Analysis: European guidelines for diagnosis and management of osteoporosis in postmenopausal women
Urdinola Jaime MD
Medical Association Andes CS AK 9116 20 326 Bogotá DC Colombia
Phone 571/215 23 00
e-mail: jaimeurdinolamd@gmail.com - blogger: http://www.urdinola.blogspot.com / www.urdinolamenopausia2.blogspot.com
Symposium / Luncheon on Women's Health and Menopause
Andes Medical Association Board Room - Thursday, September 18, 2008
Background The European Foundation for Osteoporosis and Bone Disease (later established as the International Osteoporosis Foundation) published in 1997 the first Guidelines for the diagnosis and management of osteoporosis. Those discussed here are the most recent, published in electronic form in February 2008 1.
For reasons of space and time, emphasis will be summarized in aspects such as bone mineral density, the concept of osteopenia, general management measures, major pharmacological interventions available type and use the web through the instrument developed by WHO to calculate for the next 10 years, the probability of hip fracture or major osteoporotic fracture.
is suggested that other interesting subjects that can be found in the publication referred to, as the quantification of the burden of osteoporosis and the calculation of disability and lost life years (DALYs called in English) expansion of information on techniques for measuring bone mineral, the possibility of using combined and sequential treatments, adherence to treatment and the control thereof, other ways of assessing fracture risk, the investigation of patients with osteoporosis and health economics related to osteoporosis, will be consulted directly on it.
The most common sites for osteoporotic fractures are vertebral column, hip, distal forearm and proximal humerus. The remaining probability over the life of a menopausal woman to suffer fractures in any of these sites is approx. 40%, compared with 12% for breast cancer. Fractures in addition to being a major cause of morbidity, also can cause pain, loss of function, need for hospitalization and slow recovery and rehabilitation often incomplete. They can also be asymptomatic and recurrent as in the case of vertebral fractures and their social and personal costs are high. Also concerned that most / osteoporosis patients remain untreated.
measures bone mineral density (BMD) In \u200b\u200baddition to providing a diagnostic criterion, BMD measurements should indicate the prognosis of the likelihood of future fractures and a baseline that allows monitoring the natural history of the condition treated or not.
The currently used technique is DXA (dual energy absorptiometry of X-rays), which is very sensitive to tissue calcium content, which bone is the most important. Other techniques include quantitative ultrasound (QUS), quantitative computed tomography (QCT) applied to the appendicular skeleton and spine, peripheral DXA, the digital radiogrametría X-ray, X-ray absorptiometry. X-ray technology can also determine bone strength of cortical bone and trabecular bone, including macro and micro.
Prevalence of osteoporosis
Using the criteria of the World Health Organization (WHO) the prevalence of osteoporosis in Sweden is approx. 6% in men and 21% in women 50 to 84 years age. In other words, men over 50 years is 3 times less frequent than in women, which is comparable to the difference in the risk for osteoporotic fractures among men and women. Although the International Society for Clinical Densitometry recommends that BMD is determined both lumbar spine and hip, does not improve the prediction using multiple sites to determine BMD. Osteopenia
should not be considered osteopenia as a disease category. It is useful to the description of osteopenia for purposes of the epidemiology of osteoporosis and to identify patients who will develop osteoporosis Over the next 10 years.
Limitations of the application of DXA The presence of osteomalacia as a complication of malnutrition in elderly patients with decreased BMD due to decreased bone mineralization. The osteartrosis and osteoarthritis of the spine and hip are common in the elderly, increasing BMD, but not its strength. Osteoarthritis, a previous fracture or scoliosis produce heterogeneity of BMD and should be excluded from the analysis. As BMD is two dimensional and measure the area and no bone volume, the volume of bone density is increased. This error will be beneficial to the extent that large bones have more strength.
Limitations of the application of DXA The presence of osteomalacia as a complication of malnutrition in elderly patients with decreased BMD due to decreased bone mineralization. The osteartrosis and osteoarthritis of the spine and hip are common in the elderly, increasing BMD, but not its strength. Osteoarthritis, a previous fracture or scoliosis produce heterogeneity of BMD and should be excluded from the analysis. As BMD is two dimensional and measure the area and no bone volume, the volume of bone density is increased. This error will be beneficial to the extent that large bones have more strength.
General management
Mobility and falls
Immobilization is a major cause of bone loss. The loss for one week of immobilization in bed can be equivalent to the annual loss. The exercise is therefore integral to the management and rehabilitation after a fracture. It should also pay special attention to preventing falls, especially in patients at risk, corrected visual acuity decreased, reducing the consumption of drugs that alter alertness and balance and improve the conditions of the home. Nutrition
The elderly high prevalence failure of calcium, protein and vitamin D. Adequate amount of protein intake is necessary to maintain the integrity and function of organs such as skeletal muscles and bones. Calcium supplements for at least 1 000 mg / day and vitamin D at doses of 800 IU per day reduced the risk of secondary hyperparathyroidism and the risk of proximal femoral fracture, and 1 g / kg of body weight per day of protein for management of patients with osteoporosis. Main
The elderly high prevalence failure of calcium, protein and vitamin D. Adequate amount of protein intake is necessary to maintain the integrity and function of organs such as skeletal muscles and bones. Calcium supplements for at least 1 000 mg / day and vitamin D at doses of 800 IU per day reduced the risk of secondary hyperparathyroidism and the risk of proximal femoral fracture, and 1 g / kg of body weight per day of protein for management of patients with osteoporosis. Main
pharmacological interventions
● SERMS (selective estrogen receptor modulators)
SERMs are agents related nonsteroidal estrogen receptor, acting as agonists or antagonists of estrogen, depending on the tissue where the action is exercised. The concept started to observe the action of tamoxifen, an antagonist in breast tissue but a partial agonist on the bone, reduce bone loss in postmenopausal women. At present, raloxifene is the only SERM approved available for prevention and treatment of osteoporosis, reducing 30-50% the risk of vertebral fracture in postmenopausal women with decreased BMD or osteoporosis with or without previous vertebral fracture. Has not shown significant reduction in nonvertebral fractures. In the MORE trial and in placebo-controlled follow-up for 4 years, CORE study, the rare but serious adverse event was increased deep venous thromboembolism. The significant and sustained decrease in risk for invasive breast cancer was nearly 60% in high-risk population. The RUTH trial in postmenopausal women at high risk for cardiovascular disease showed no effects on cardiovascular death or the incidence of coronary heart disease or stroke. ●
Bisphosphonates are stable analogues of pyrophosphate. The power of those who have been synthesized depends on the chain length and structure side. They have a great affinity for the apatite, both in vitro and in vivo, which is the basis for clinical use. Are potent inhibitors of bone resorption, exerting their effect by reducing the recruitment and activity of osteoclasts and increasing apoptosis. Its potency to inhibit bone resorption varies greatly, and its range extends to 10 000 times in vitro. This allows us to understand why vary the doses used clinically.
anti-fracture efficacy of the treatments most frequently used in postmenopausal osteoporosis when given with calcium and vitamin D, randomized and placebo-controlled
Effect on risk Effect on vertebral fracture vertebral fracture risk
establecidaa Agent osteoporosis osteoporosis osteoporosis osteoporosis establecidaa
Alendronate + + ND + including hip
Risedronate + + ND + including hip
Ibandronate ND ND + + b
zoledronate + + ND ND + c
TH + + + + + +
Raloxifene Teriparatide
ND ND ND + ND +
ranelate + + + + includes hip hip includes
Strontium Osteoporosis osteoporosis = - + = effective medication - ND = no available evidence - a = woman previous vertebral fracture
- b = only in subgroups of patients (post-study analysis) - c = JWG patients / without prevalent vertebral fractures - Updated as 2-3 in 1
The oral availability is low, between 1 to 3% of the dose taken and interfered with by food, calcium, iron, coffee, tea and orange juice. Are purged rapidly from plasma, 50% deposited in bone and the remainder excreted in the urine. Its half-life is prolonged.
Risedronate 35 mg weekly and alendronate 70 mg weekly are most commonly used bisphosphonates in the world.
In the FIT study, alendronate shown to reduce the incidence of vertebral, wrist and hip in approximately half of the cases, women with prevalent vertebral fractures. In women without prevalent vertebral fractures, there was no significant reduction in clinical fractures in the total population, although the reduction was significant in 1 / 3 of patients had a T value of baseline in hip BMD ˂ -2.5 standard deviations. Risedronate
shown to reduce the incidence of vertebral and non vertebral fractures by 40 to 50% and 30 to 36%, respectively. In a large population of elderly women Risedronate significantly reduced the risk of hip fracture by 30% and the effect was greater among women aged 70 to 79 years old with osteoporosis, 40%.
dose ibandronate 2.5 mg daily reduces the risk of vertebral fractures by 50 - 60%, while the effect on nonvertebral fractures has only been demonstrated so far in postestudio analysis of women with a baseline value of T in BMD ˂ - 3 standard deviations. A noninferiority trial has shown the equivalence of the oral dose of 150 mg monthly, allowing approval for the treatment of postmenopausal osteoporosis. Similarly, comparative studies between oral and IV doses led to the adoption of the IV dose of 3 mg.
A Phase III study of postmenopausal women with 7 500 osteoporosis to determine the effectiveness of the annual infusion of 5 mg zoledronate for 3 years found that the incidence of vertebral fractures was reduced by 70% and 40% hip.
Etidronate is a weak bisphosphonate proven to reduce vertebral fractures after 2 years of use but not thereafter, without significant effect on nonvertebral fractures. For this reason it is not recommended as first-line treatment for osteoporosis
should be emphasized that the safety profile of bisphosphonates is generally favorable. Oral bisphosphonates are associated with mild gastrointestinal disorders and some of them, alendronate and pamidronate, may rarely cause esophagitis. Aminobisphosphonates IV can induce a transient acute reaction with fever and muscle and bone pain, which usually disappears or decreases in the course of the following applications. Osteonecrosis of the jaw has been described in cancer patients receiving large doses of pamidronate or zoledronate. The incidence in osteoporotic patients treated with oral and IV bisphosphonates appear to be extremely low, about 1 in 100 000 cases and so far the causal relationship to bisphosphonate therapy has not been established. ●
Peptides and family of parathyroid hormone (PTH)
continuous endogenous production of PTH, assessed in the primary or secondary hyperparathyroidism, or exogenous administration can lead to deleterious consequences for the skeleton, particularly on cortical huesio. But intermittent administration, such as daily SC injections may increase the number and activity of osteoblasts, increasing bone mass and improving bone architecture at sites of cancellous and cortical bone. The intact molecule has amino acids 1 to 84 and teriparatide N-terminal fragments 1 to 34, the latter being equivalent in their respective molecular weight to 40% of the PTH. These 2 agents have been shown to significantly reduce the risk vertebral fractures and teriparatide has also shown an effect on nonvertebral fractures during studies of 18 to 24 months, with beneficial effects of teriparatide on nonvertebral fractures that persist 30 months after its suspension. The most common side effects are nausea, pain in limbs, headaches and dizziness. The transient elevation of calcium in normocalcemic patients peaks between 4 and 6 h, returning to baseline 16 to 24 h after each dose. This change is small and does not require calcium values \u200b\u200bmonitored during treatment. The incidence of hypercalciuria is no different from what occurs in patients treated with placebo. However, these agents should be used with caution in patients with active or recent urolithiasis. Have reported transient episodes of hypotension, which spend a few hours later and do not prohibit continued treatment. Peptides are contraindicated in conditions teriparatide increased bone turnover, as in the case of hypercalcaemia, metabolic bone diseases such as primary osteoporosis, including hyperparathyroidism, Paget's disease of bone, unexplained elevation of alkaline phosphatase, or external radiation through the implantation of the skeleton in patients with skeletal malignancies or bone metastases. Kidney failure is another contraindication. Although teriparatide studies in rats administered high doses and for prolonged time have shown increased incidence of osteosarcoma, this does not seem to be relevant in humans treated with much lower doses. ●
strontium ranelate
is an agent recently approved for the treatment of postmenopausal osteoporosis to reduce the risk of vertebral and hip fractures. The evidence indicates that inhibits bone resorption and stimulates bone formation. Studies conducted over 5 years have proven effective in a wide range of patients, both those with osteopenia to women 80 years with osteoporosis, with or without previous vertebral fracture. The decrease risk is similar to that observed with oral bisphosphonates. The recommended daily dose is one sachet daily oral 2 g, whose absorption is reduced by food, milk or milk, ideally administered at bedtime and 2 hours after eating. Not recommended for use in patients with renal failure. The most common side effects are nausea and diarrhea, generally mild and transient, reported at the beginning of treatment and usually disappear after the third month of treatment. Has reported an increased incidence of venous thromboembolism, when analyzed together all Phase III studies, but has not established a causal link with medicine. Regulatory authorities, therefore, not considered contraindicated in patients with a history of thromboembolism but should be used cautiously in these patients.
● Calcitonin
As endogenous polypeptide hormone inhibits osteoclastic resorption. The salmon is 40 - 50 times more potent than human, the most used clinically. It can be used in injectable form or nasal. The latter provides a biological activity of 25 to 50% of the injected form. Calcitonin modestly increases lumbar spine BMD and forearm, reducing the risk of vertebral fracture, but the magnitude of impact on these fractures is questionable and its effect on nonvertebral fractures still equivocal. You can have an analgesic effect in women with acute vertebral fracture, which appears to be an independent effect of its effects on bone resorption of osteoclasts. Repeated injections or the high cost of the nasal formulation prevents its use as first-line treatment for osteoporosis. ●
hormonal therapy (HT) in menopausal sex steroids
Estrogens reduce the accelerated bone turnover induced menopause and prevent bone loss at all skeletal sites, regardless of age and duration treatment.
Observational studies and randomized controlled trials with placebo have shown that estrogen reduces the risk of vertebral and nonvertebral, including hip, about 30% regardless of baseline BMD.
But when HT is discontinued, bone loss is restarted at the same rate that occurs after menopause, although the fracture protection may persist for several years.
The findings of the WHI study (Study of the Health Initiative of Women) suggests however, that the long-term risks outweigh the benefits, 30% increase in risk for coronary heart disease and breast cancer, as well as 40 % de aumento en el riesgo para accidente cerebrovascular.
Mujeres histerectomizadas que recibieron sólo estrógenos conjugados presentaron aumento significativo para accidente cerebrovascular, pero no en enfermedad cardíaca coronaria ni en cáncer de seno, sugiriendo un efecto deletéreo del acetato de medroxiprogesterona. Aún se debate exdtensamente si los beneficios de la TH con otro tipo de gestágeno y en mujeres postmenopáusicas jóvenes podrían exceder los riesgos, pero no hay disponible un estudio aleatorizado y controlado con placebo que demuestre la seguridad a largo plazo de esta alternativa.
Finalmente, se debe recordar que en la mayoría de países del mundo, el uso de la TH sólo está approved for the management of menopausal symptoms in the lowest dose possible and for a limited period of time.
So today is not recommended as first line therapy treatment for the prevention and treatment of osteoporosis. ●
Observational studies and randomized controlled trials with placebo have shown that estrogen reduces the risk of vertebral and nonvertebral, including hip, about 30% regardless of baseline BMD.
But when HT is discontinued, bone loss is restarted at the same rate that occurs after menopause, although the fracture protection may persist for several years.
The findings of the WHI study (Study of the Health Initiative of Women) suggests however, that the long-term risks outweigh the benefits, 30% increase in risk for coronary heart disease and breast cancer, as well as 40 % de aumento en el riesgo para accidente cerebrovascular.
Mujeres histerectomizadas que recibieron sólo estrógenos conjugados presentaron aumento significativo para accidente cerebrovascular, pero no en enfermedad cardíaca coronaria ni en cáncer de seno, sugiriendo un efecto deletéreo del acetato de medroxiprogesterona. Aún se debate exdtensamente si los beneficios de la TH con otro tipo de gestágeno y en mujeres postmenopáusicas jóvenes podrían exceder los riesgos, pero no hay disponible un estudio aleatorizado y controlado con placebo que demuestre la seguridad a largo plazo de esta alternativa.
Finalmente, se debe recordar que en la mayoría de países del mundo, el uso de la TH sólo está approved for the management of menopausal symptoms in the lowest dose possible and for a limited period of time.
So today is not recommended as first line therapy treatment for the prevention and treatment of osteoporosis. ●
vitamin D derivatives
Alfacalcidol is a synthetic analogue of calcitriol metabolite (1,25-dihydroxyvitamin D) and is metabolized to calcitriol in the liver, although less potent than the latter. Several studies of both agents showed a decrease in vertebral fracture risk, but their effects on BMD have been less studied. Some reports speak of their direct positive effect on muscle strength, decreasing the likelihood of falls, especially in the elderly. But the biggest problem with the use of derivatives of vitamin Des risk of hypercalcemia and hypercalciuria, which in prolonged can lead to renal failure and nephrocalcinosis. The narrow therapeutic window requires frequent monitoring of serum and urinary calcium in these patients. Therefore, calcium supplementation should be avoided or used with great care. ●
algorithm developed by WHO
That integrates clinical risk factors for fracture with fracture risk developed with or without information on BMD, developed by the Collaborating Centre for Metabolic Diseases WHO in Sheffield, UK. Called FRAX and calculates the probability at 10 years of hip fracture or major osteoporotic fracture.
http://shef.ac.uk/FRAX
Summary of Important
http://shef.ac.uk/FRAX
Summary of Important
● The International Osteoporosis Foundation provides some updated guidelines for diagnosis and management of osteoporosis, reviewing the role of determining bone mineral density for the diagnosis, assessment of fracture risk general management and drug therapy, treatment control, how to do research for patients and economic analysis of treatment
References
1 - Kanis JA, Burlet N, Cooper C , Delmas PD, Reginster JY, Borgstrom F, Rizzoli R, European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCE). European guidance for the diagnosis and management of osteoporosis in postmenopausal Women. Osteoporosis Int 2008, 19: 399-428.
2 - Delmas PD. Treatment of postmenopausal osteoporosis . Lancet 2002, 359: 2018-2026.
3 - Boonen S, Body JJ Boutsen Y, Devogelaer JP, Goemaere S, Kaufman JM, et al. Evidence-based guidelines for the Treatment of postmenopausal osteoporosis: a consensus document of the Belgian Bone Club. Osteoporosis Int 2005, 16: 239-254.
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