Instant Treatments for Osteoporosis

The Osteoporosis Reversing Breakthrough

eres just a few things youll learn about how to get back into health. and conquer Osteoporosis. Those not-so innocent yet everyday substances that are currently attacking your body, perpetuating and aggravating your Osteoporosis. What to do and what Not to do to overcome your Osteoporosis effectively and permanently. How to create the energy you need to be able to work full time and feel confident you will be able to take care of your loved ones. How the pharmaceutical and food industry are conspiring to poison you and make you sick (Hint: American medical system is now the leading cause of death in the US). Which food industries use advertising to encourage doctors to tell you that their food is good for you just like those cigarette ads in the 1950s! The single most effective fruits and vegetables in cleaning up excess acidic waste and how to cleanse your inner terrain completely from systemic acidosis. Why, what your Doctor has told you is wrong, and why many medications actually increase the side effects and complications of Osteoporosis (primarily by depleting vital vitamins, minerals and nutrients from your body). Which supplements every patient must take to stop the symptoms and boost your body's ability to reverse Osteoporosis. How to naturally reduce your cravings for toxic foods. Lifestyle and food choices to reverse your Osteoporosis fast, naturally, and for good. Why treating the symptoms of disease is like using an umbrella inside your house instead of fixing the roof. The most powerful creator of health (Hint: its not a food or vitamin!) The best way to simplify the task of making a health-conscious lifestyle adjustment. A miraculous scientific discovery that jump-starts your body to do its natural work, which is to heal itself and restore your Health. More here...

The Osteoporosis Reversing Breakthrough Overview

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Osteopenia Osteoporosis

HIV-infected individuals have a lower bone density than uninfected individuals (Loiseau-Peres 2002). Bone density is determined by the measurement of X-ray absorption (e.g. DEXA scan) or ultrasound waves. Results are given as the number of standard deviations (the T-score) from the mean value in young, healthy individuals. Values between -1 and -2.5 standard deviations (SD) are referred to as osteopenia, values above -2.5 SD as osteoporosis. In addition to HIV infection, other factors such as malnutrition, diminished fat tissues, steroid treatment, hypogonadism, immobilization and treatment with PIs and NRTIs, seem to play a role in the pathogenesis of this disorder. Osteopenia and osteoporosis are often asymptomatic. Osteoporosis occurs mainly in the vertebrae, lower arms and hips. The following tests should be performed on all patients with AIDS a lumbar spine X-ray in the standard anteroposterior and lateral views, bone density measurement (DEXA scan) of the lumbar spine and hip...

Ghd And Osteoporosis Childhood Onset GHD and Osteoporosis

Studies of adult patients with a history of childhood-onset GHD also demonstrate relative osteopenia compared to age-matched controls. Degerblad et al. (18) studied six young adults who had previously received GH replacement for GHD. Bone density of the proximal and distal forearm, primarily reflecting cortical and trabecular bone, respectively, was markedly diminished compared with healthy controls. A larger study of 30 GH-deficient men, 18-46 yr, reached a similar conclusion. Despite a history of GH replacement, bone density in the proximal forearm, distal forearm, and lumbar spine of these patients was significantly lower than normal (19). To determine whether pituitary deficiencies other than GH were responsible for the lower bone density seen in the patients, the eight patients with isolated GH deficiency were analyzed separately. In this subgroup, bone density at all sites remained below that of the normal controls, although because of the small sample size, this difference...

Adult Onset GHD and Osteoporosis

One study of 95 adults, ranging in age from 21-74 yr and identified as GH deficient on the basis of provocative tests, showed low bone density of the lumbar spine compared to normal controls. This significant deficit in bone density persisted when patients with untreated hypogonadism were excluded (20). Two smaller studies showed reduced bone density of the total body (21), femoral neck, Ward's triangle, and greater trochanter (22) in patients with adult-onset GHD compared to normals. In both of these studies, a significant correlation was found between bone density and serum levels of IGF-1, an integrated marker of GH secretion. Because patients with adult-onset GH deficiency were by definition endocrinologically intact through adolescence, they presumably had normal skeletal development and reached a normal peak bone mass. Therefore, osteopenia in such patients, can only be explained on the basis of accelerated loss of bone during adulthood. Adult-onset GHD is often associated with...

Osteoporosis Prevention

Pharmaceutical HRT is sometimes used for preventing loss of bone following menopause however, a growing number of users are concerned about the increased risk of breast cancer associated with long-term HRT. As such, phyto-oestrogens have been used as an alternative to prevent osteoporosis. Most research has focused on soy isoflavones, although there is some evidence that red clover-derived isoflavones may also be of benefit. In a recent trial by Atkinson et al, loss of lumbar spine bone mineral content and bone mineral density was significantly reduced in women taking red clover-derived isoflavones (43.5 mg day) compared to placebo in a double-blind, placebo-controlled, randomised trial in 205 women over 12 months (Atkinson et al 2004c). Bone formation markers were also significantly increased however, no improvement in hipbone mineral content or bone mineral density was noted. A double-blind study of 46 postmenopausal women investigated the effects of a red clover isoflavone...

GH Administration for Age Related Osteoporosis

Only a small number of studies have evaluated the effects of GH administration on bone density in women with postmenopausal osteoporosis and elderly men. The sample sizes of these studies have typically been small and overall fail to demonstrate a positive effect of GH on bone density. Aloia et al. (49) performed a series of three studies evaluating the effectiveness of GH in the treatment of post-menopausal osteoporosis. The first of these included eight patients who received pituitary-derived human GH for up to 12 mo (49). Bone resorption increased as measured by urine hydroxyproline, and bone density of the radius decreased. A subsequent study compared 24 mo of combination treatment with GH and calcitonin to calcitonin alone in 25 post-menopausal women, and showed a deleterious effect of the addition of GH on radial bone density (50). The third study compared a regimen of alternating GH and calcitonin to calcitonin alone in 14 women over 24 mo, and showed no significant difference...

Osteoporosis and Cardiovascular Disease in the Elderly

Osteoporosis and cardiovascular disease are common disorders that increase with aging. Accumulating evidence indicates that both disorders may share common pathophysiologic mechanisms as well as risk factors. Besides age and sedentary lifestyle, diabetes, hypertension, dyslipidemia, estrogen deficiency, and hyperhomo-cysteinemia are common risk factors for both disorders. Furthermore, therapeutic agents for osteoporosis have antiatherosclerotic properties and agents such as statins that are atheroprotective, and appear to increase bone mass and perhaps protect against fractures. In this chapter, we discuss the basis for a common hypothesis for both osteoporosis and atherosclerosis, highlighting pathophysiologic mechanisms and risk factors common to both disorders, and we discuss therapeutic agents that could potentially be beneficial in the treatment of both disorders.

Association of Osteoporosis and CVD

The association between low bone mineral density (LBMD) and atherosclerosis has been demonstrated in several studies. In the Rotterdam study, a population-based cohort study of 7,983 men and women over the age of 55 years, designed to assess risk factors for progression of atherosclerosis measured at multiple sites (van der Meer et al., 2003), and a cross-sectional analysis examining the association between BMD and peripheral arterial disease (PAD) was performed (van der Klift et al., 2002). Data on BMD and PAD for 5,268 individuals (3,053 women and 2,215 men) were available, and the association between PAD and low BMD at the femoral neck was demonstrated in women, but not in men, suggesting estrogen deficiency as a common denominator between osteoporosis and PAD. LBMD is also associated with early stages of atherosclerosis as measured by pulse wave velocity (PWV) (Hirose et al., 2003). In a study involving 7,865 Japanese individuals age 50 years or older, PWV, which reflects early...

Common Underlying Mechanisms for Atherosclerosis and Osteoporosis

Several proteins are involved in both osteoporosis and atherosclerosis, such as osteocalcin (OC), matrix Gla protein (MGP), bone sialoprotein (BSP), bone morpho-genetic protein-2 and -4 (BMP -2, BMP -4), osteonectin (ON), osteopontin (OPN), osteoprotegerin (OPG), and receptor-activated nuclear Factor-Kappa B ligand (RANKL) (Dhore et al., 2001). Involvement of these Figure 58.1 Common cellular mechanisms underlying both vascular disease and osteoporosis. NO Nitric oxide eNOS Endothelial nitric oxide synthase INOS Inducible nitric oxide synthase Est Estrogen ox-LDL Oxidized-low-density lipoprotein HDL High-density lipoprotein OPG osteoprotegerin RANKL receptor-activated nuclearfactor-kappa B ligand RANK Receptor-activated nuclearfactor-kappa B BMP Bone morphogenetic protein MGP Matrix Gla protein OC Osteocalcin IL-6 Interleukin-6 M-CSF Macrophage-colonystimulating factor IL-1 Interleukin-1 TNF Tumor necrosis factor PGE2 Prostaglandin E2 TGFj Transforming growth factor-beta OPN...

Osteoporosispseudoglioma syndrome

Osteoporosis-pseudoglioma syndrome (OPPG) is a rare autosomal recessive condition characterized by juvenile-onset osteoporosis with increased fracture risk and skeletal deformities. Children with OPPG are frequently blind at birth due to vitreous opacities. Inactivating mutations in LRP5 have recently been shown to cause this disorder in homozygous individuals (Gong et al., 2001), while heterozygous carriers exhibit intermediate reductions in bone mass and have an increased fracture risk (Gong et al., 1996). More recently compound heterozygosity for two novel mutations was found in two family members with OPPG (Cheung et al., 2006). LRP5 is a coreceptor for Wnt (Figure 27.1) and it plays an essential role in osteoblast proliferation and differentiation (Kato et al., 2002). Inactivation of LRP5 can severely limit osteoblast production and lead to osteo-porotic phenotypes. Activating mutations associated with high bone mass will be further discussed below.

Growth Hormone and Age Related Osteoporosis

Because both GHD and normal aging are associated with decreases in bone density, it has been hypothesized that reduced GH secretion may account in part for age-related loss of bone mass (24). However, a causal relationship between GHD and osteoporosis has not been established. Nocturnal serum GH peaks average 20 ng mL in 30-yr-old men, but this value declines steadily to 3 ng mL by age 80 (24). These values are reflected in the fall of IGF-1 levels, which also occurs with aging (24). Because aging is associated with numerous physiological and hormonal changes, it has been difficult to determine definitively the degree to which the age-related decline in GH levels is responsible for bone loss. Bone density peaks at age 30, then declines progressively. In men, 25 of trabecular bone is lost by age 75 (25). One study of women with osteoporosis and vertebral compression fractures showed no difference in the GH response to insulin-induced hypoglycemia in these patients compared to...

Osteoporosis

The loss of minerals in the bones that accompanies aging reduces bone mass and increases the porosity and brittleness of bones. The result may be chronic pain in the joints of the lower spine and hips, a height reduction of several inches, other skeletal deformities (eg, dowager's hump), and an increased danger of fractures to the vertebrae, hips, ribs, and wrists. These are the symptoms of osteoporosis, a disorder that is four times more common among postmenopausal women than men in the same age range (45-50 years). Osteoporosis affects almost half of all women over 50, and as many as 90 of women over 70. It is more common among whites and Asians than among blacks and is also associated with chronic hyperthyroidism, long-term steroid therapy, and heredity. Foods rich in calcium and vitamin D, or daily supplements of these and other substances (e.g., estrogens, fluoride, vitamin K, magnesium, growth hormones) are prescribed treatments for osteoporosis. Preventive treatments include...

What Is Osteoporosis

Osteoporosis is a disease characterized by low bone bone mass, microarchitectural deterioration of bone tissue, and a consequent increase in fracture risk Copenhagen Consensus Conference (1990). Osteoporosis is a bone density 2.5 standard deviations below the mean for young white adult women at lumbar spine, femoral neck or forearm The World Health Organization (1994). Osteoporosis is . a systemic skeletal disease characterized by low bone mass and microarchitectural deterioriation of bone tissue with a consequent increase in bone fragility and susceptibility of fractures The Hong Kong and Amsterdam Consensus Conferences (1996). Osteoporosis is .characterized by a failure to maintain bone architecture sufficiently robust to withstand the loading ofeveryday life without substantial risk offracture Ehrlich and Lanyon (2002). Osteoporosis is a skeletal disorder characterized by compromised bone strength predisposing to an increased risk offracture National Institutes of Health (cited by...

Supportive Therapeutics

The exact dose of steroids necessary for each patient will vary depending on the histology (i.e., benign or malignant), size and location of the tumor, and amount of peritumoral edema. In general, most patients with malignant tumors will require between 8 and 16 mg of dexamethasone per day to remain clinically stable. The lowest dose of steroid that can control the patient's pressure-related symptoms should be used 1,21 . This approach will minimize some of the toxicity and complications that can arise from long-term corticosteroid usage, which includes hyperglycemia, peripheral edema, proximal myopa-thy, gastritis, infection, osteopenia, weight gain, bowel perforation, and psychiatric or behavioral changes (e.g., euphoria, hypomania, depression, psychosis, and sleep disturbance) 1,27-31 . Patients with dexa-methasone-induced proximal myopathy will often improve when the dosage is reduced 30,31 . In addition, the proximal leg muscles can usually be strengthened if the patient is...

Reaching beyond Researchers

A number of Web sites aim to inform the general public, but prove useful for researchers. They can help with teaching or setting scientific work in a broader context. The American Federation for Aging Research's Info-Aging, for example, offers explanations of a number of topics under several headings. Topics in the ''Biology of Aging'' section include oxidative damage, telomeres, stem cells, and biomarkers of aging. Each one summarizes crucial issues, addresses basic questions, provides links to related research, and points readers toward other resources in addition, they are reviewed by experts in each field. The ''Disease Center'' similarly contains key information and questions on some age-related illnesses, such as Alzheimer's disease, macular degeneration, and osteoporosis, and the ''Healthy Aging Center'' discusses issues such as nutrition, stress, hearing, and immunization. Other resources explain particular age-related diseases. The Centers for Disease Control Cardiovascular...

Organizations And Ethics

Much of the research on human subjects is sponsored by public and private organizations or foundations. For example, public support for research and training programs that benefit older Americans comes from federal agencies such as the Administration on Aging, the Office of Nursing Home Affairs, the National Institute on Aging, and the Department of Education. The National Institute on Aging (NIA), in particular, sponsors biological research on Alzheimer's disease, osteoporosis, drug reactions in older people, and prosthetic devices. In its research support functions, the NIA tries to strike a balance between medicine, biology, psychology, and other sciences concerned with aging. Basic research on aging conducted by specialists in geriatrics, gerontology, and other professions is also sponsored by the British Council on Aging and similar organizations in other countries.

Complications And Prognosis

Glucocorticosteroid treatment-related adverse events occur commonly among these elderly patients, and at least 65 of patients may have at least one adverse event (3). Patients are at a risk for diabetes mellitus and osteoporosis with osteoporotic fractures, which occur in this patient group at a rate two to five times higher than in age-matched controls. Complications are more frequent in patients over the age of 75 and patients receiving higher doses of steroids (3). All patients should receive calcium and vitamin D supplementation and appropriate treatment for osteoporosis including bisphosphonates.

Treatment of acute DVT

UFH was the standard treatment for DVT in pregnant women prior to the introduction of LMWHs. Warfarin is generally avoided because of the risk of warfarin embryopathy and other potential teratogenic effects. UFH has a number of limitations, including heparin-induced osteoporosis, the need for twice-daily subcutaneous injections, and the necessity for aPTT monitoring. These disadvantages are virtually eliminated with LMWH. Although there have been no randomised controlled trials comparing UFH with LMWH in pregnancy, there is no reason to expect that the advantages of LMWH in the non-pregnant population would not apply to pregnant women.166 In addition to the convenience of once-daily injection without the need for frequent laboratory monitoring, like UFH, LMWH does not cross the placenta. Therefore, it is not teratogenic and is not excreted into breast milk. Pregnant women are treated throughout their pregnancy with LMWH and arrange for a planned induction of labour

Musculoskeletal System

Aging is also associated with greater sponginess and fragility of the dense part of the bones, a significant increase in stiffness and pain in the joints of the lower spine, hips, and knees, and fractures of the vertebrae, ribs, and hips. Decreased density and greater porosity of bones, and a consequent tendency to fracture more easily are associated with osteoporosis. In this disorder, which is more common during later life and particularly in older women, there is a gradual long-term loss of bone mass.

Bone Density Protection

It has been suggested that modulation of Insulin by chromium may have positive effects on bone density, reducing bone resorption and promoting collagen production by osteoblasts (McCarty 1995). One placebo-controlled study using chromium picolinate (equivalent to 200 fjg chromium day for 60 days) has shown a 47 reduction in the urinary hydroxyproline creatinine ratio, indicating a decrease in calcium excretion and a potential role in the prevention of osteoporosis (Evans et al 1995).

Estrogen Progesterone and Androgen Receptors

Reproductive and homeostatic systems, respectively. The sex steroid receptors ER, PR, and AR direct transcription of genes involved in sexual development, differentiation, and specification (Tables 3.4, 3.5). As a result of their growth-promoting activities in these processes, these receptors are pharmacologically targeted in a number of neoplastic reproductive tissues. Receptors ERa and ERjS are predominantly expressed in reproductive tissues, as well as in vasculature, cardiac muscle, and bone. Their activity is subject to estradiol availability, which is regulated by hormonal cascades generated from the ovary and other steroidogenic tissues. Confirmation of the role of ERs in the regulation of the reproductive tract was achieved by targeted deletion of ERa and ERjS alleles in transgenic mice, which develop normally but are infertile or suffer ovarian dysfunction, respectively.296,297 In addition to reproductive maintenance, specialized roles for ERs include regulation of bone...

Management of hypothalamic dysfunction

Hypoestrogenic women are at risk for osteoporosis and cardiovascular disease. Oral contraceptives are appropriate in young women. Women not desiring contraception should take estrogen, 0.625 mg, with medroxyprogesterone (Provera) 2.5 mg, every day of the month. Calcium and vitamin D supplementation are also recommended.

Pharmacologic therapy for symptoms of menopause

More than 250,000 hip fractures occur annually. Estrogen deficiency is the primary cause of osteoporosis, although many other secondary causes for osteoporosis exist (eg, poor diet, glucocorticoid excess). Thus, women at risk for osteoporosis should be considered candidates for HRT. Minimum Effective Dosages of Estrogens for Prevention of Osteoporosis

Hormone replacement therapy administration and regimens

HRT should not be a universal recommendation. The benefits and risks associated with HRT must be weighed on an individual basis. A woman with significant risk factors for osteoporosis or CHD may benefit from long-term HRT. A woman with a personal or strong family history of breast cancer may not benefit from long-term HRT. C. Effective doses of estrogen for the prevention of osteoporosis are 0.625 mg of conjugated estrogen, 0.5 mg of micronized estradiol, and 0.3 mg of esterified estrogen. G. Bisphosphonates inhibit osteoclast activity. Alendronate (Fosamax) is effective in increasing BMD and reducing fractures by 40 percent. Alendronate should be taken in an upright position with a full glass of water 30 minutes before eating to prevent esophagitis. Alendronate is indicated for osteoporosis in women who have a contraindication to estrogen. modulator, FDA-labeled for prophylactic treatment of osteoporosis. This agent offers an alternative to traditional HRT. The modulator increases...

What is Your Diagnosis

Osteoporosis If the normal continuous formation and breakdown of the bone derails in such a fashion that the cancellous bone loses its density and stability to a greater degree than normal for that age, fractures may occur spontaneously or after minor trauma. Such a degree of demoralization of bone is termed osteoporosis. Bone density is the highest around 35 years of age. After that it declines steadily estrogen-depleted postmenopausal women are at a greater risk than men. The consequences of osteoporosis pathological fractures and vertebral height loss due to progressive collapse lead to the typical loss of body height and stature (the famous infamous little old lady). Another major complication is, of course, the femoral neck fracture. Standard radiographs of the thoracic and lumbar spine show the osteoporosis best. The density of the vertebral bodies is decreased the vertebral end plates therefore appear enhanced. If the vertebral end plates fracture, the typical fish vertebra...

Clinical manifestation

Lipodystrophy was originally described as a condition characterized by regional or generalized loss of subcutaneous fat. The non-HIV-associated forms, such as congenital or familial partial lipodystrophy, have a very low prevalence. Generally, these forms are associated with complex metabolic abnormalities and are difficult to treat. The term lipodystrophy syndrome in association with HIV, was introduced to describe a complex medical condition including the apparent abnormal fat redistribution and metabolic disturbances seen in HIV-patients receiving protease inhibitor therapy (Carr 1998). Since then, other conditions, such as osteopenia and hyperlactemia, have been summarized under the diagnosis of the lipodystrophy syndrome. But, even years after its first description, there is still no consensus on a case definition for lipodystrophy syndrome in HIV patients. Thus, the diagnosis of lipodystrophy in clinical practice often relies on a more individual interpretation than on an...

Is achieving extreme old age worthwhile the centenarian phenotype

Independently functioning at age 92 (Hitt et al., 1999). Most subjects experienced a decline in their cognitive function only in the last three to five years of their lives (Perls, 1997 Silver et al., 1998). Upon further examination of the ages of onset for ten common age-associated diseases (hypertension, heart disease, diabetes, stroke, non-skin cancer, skin cancer, osteoporosis, thyroid condition, Parkinson's disease, chronic obstructive pulmonary disease and cataracts) among 424 centenarians (323 males and 101 females), the subjects were noted to fit into three morbidity profiles ''survivors,'' ''delayers'' and ''escapers'' (Evert et al., 2003). Survivors, individuals who were diagnosed with age-related illness prior to age 80, accounted for 24 of the male and 43 of the female centenarians (p 0.0009). Delayers, individuals who delayed the onset of age-related diseases until at least age 80, accounted for 44 of the male and 42 of female centenarians. Escapers, individuals who...

Prediction of Material Properties of Trabecular Bone Based on Image Data

Quantification of the material properties of bone, such as strength and elastic modulus, using noninvasively measured parameters is important to predict fracture risk and evaluate effects of treatment for osteoporotic patients. Osteoporotic change is initiated from trabecular bone within both ends of long bones, vertebral bodies of the spine, flat bones such as the pelvis, and carpal and tarsal bones. Therefore, fractures related to osteoporosis occur in the trabecular-bone-rich regions. The vertebral body, distal radius (wrist joint), and proximal femur (hip joint) are the most common sites for fractures associated with the osteoporosis. There are three major approaches (assumptions) to predicting material properties (Fig. 10).

Heterogeneous and Anisotropic Model

Because of ease of measurement, the bone density measurement has been widely used to predict material properties of the bone. Strong correlation between the material properties and bone density has been reported. However, the relationship between the bone density and the material properties has been reported to be nonlinear 6 . Clinical investigations show the limitation of the density measurement in predicting fracture risk. Changes in the trabecular orientation in osteoporotic patients is widely recognized by the clinician and sometimes evaluated in the grading system of osteoporosis in vertebral bodies and the proximal femur. Material properties measured by compressive tests and ultrasound velocity (USV) showed high correlation with bone mineral density (BMD) measured from a soft X-ray of the test specimen. If the parameter of the trabecular orientation is incorporated, however, a higher correlation is obtained. The correlations between the compressive stiffness or USV and the BMD...

Terminology and Definitions

The term andropause indicates a particular type of hypogonadism that is related to aging in men and is said to consist of the following diminished sexual desire and erectile function, decrease in intellectual activity, fatigue, depression, decrease in lean body mass, skin alterations, decrease in body hair, decrease in bone mineral density resulting in osteoporosis, and increase in visceral fat and obesity (24). The word andropause is an attempt to draw a parallel in men to

Prevention and treatment strategies

Are not willing or incapable of receiving estrogen therapy and have osteopenic bone densities may consider alendronate and raloxifene. After the age of 65, a bone density test should be performed to decide if pharmacologic therapy should be considered to prevent or treat osteoporosis. Drugs for Osteoporosis Calcium alone may not prevent osteoporosis

Antiretroviral agents in pregnancy

So far, severe mitochondriopathies have been observed at least twice in pregnant women taking a combination therapy of the nucleoside analogues d4T+ddI plus nelfinavir or nevirapine (Sarner 2002). For this reason, the combination d4T+ddI is advised against in pregnancy (Bristol-Myers 2001). Hepatic toxicity with hyperbilirubinemia was described under AZT+3TC+efavirenz therapy. Following the administration of AZT+3TC+nelfinavir, one pregnant woman died of sudden acute liver failure (Hill 2001). Tenofovir did not show any maternal toxicity in animal experiments, but did cause a fetal growth retardation of 13 as well as a slight decrease in the bone mineral density (Tarantal 2002).

Protease inhibitors PIs

All protease inhibitors can be used in combination with 2 NRTIs. PIs differ from each other in respect to their tolerability and side effects. As with adults, dyslipide-mia is associated with the use of protease inhibitors (Lainka 2002). It includes elevated total cholesterol, triglycerides (TG), and low density lipoprotein cholesterol (LDL-c) and decreases in high density lipoprotein cholesterol (HDL-c) In lipodys-trophy, there is a loss of subcutaneous fat (lipoatrophy) and or a deposition of fat tissue subcutaneously or in visceral stores (lipohypertrophy) including the presence of dorsocervical fat accumulation (buffalo hump) and increased waist-to-hip ratio. Lipoatrophy is marked by thinning of subcutaneous fat in the face, buttocks, and extremities associated with a prominent appearance of peripheral veins. The body habitus changes usually occur gradually over months to years. The exact prevalence of lipodystrophy in children is unknown and there are no clear diagnostic...

Dexamethasone Decadron

Adverse effects delayed wound healing, seizures, osteoporosis, hyperglycemia, diarrhea, nausea, GI bleeding, cushingoid effects. Comments use with caution in patients with hypothyroidism, cirrhosis, hypertension, CHF, ulcerative colitis, thromboembolic disorders may cause adrenocortical insufficiency (Addison's crisis) with abrupt withdrawal.

The Extremities and Bone

For example, painful sacral fractures are a late effect of pelvic radiation that can be concerning for local recurrence or osseous spread of a malignancy like rectal cancer. A history of radiation is associated with increased risk of spinal compression fractures within the field. Recently an increased risk of hip fracture has also been recognized following pelvic radiation.44 Providers must recognize that in these patients osteopenia and osteoporosis may be focal, and if present, consider interventions such as bisphosphonates and recommendations for weight-bearing and muscle-strengthening exercise.

Avian Models For Reproductive And Neuroendocrine Aging

The bones of female birds generally serve as a repository for calcium and other minerals needed for egg production. Female quail develop increasingly fragile bones as they age these birds are a well-characterized model for the effects of hormones, vitamins and other factors on osteoporosis (see, for example, Keatzel and Soares, 1985).

Cardiovascular Complications

Bone Health Bone health can be impaired in many ways. Premature menopause induced in women by any of the mechanisms related to surgery, radiation, or systemic therapy predisposes to osteopenia and osteoporosis. Steroids, whether given as part of primary treatment or as adjunctive therapy with analgesics or antinauseants also weaken bone. They are also associated with avascular necrosis. Lastly, hormonal treatments for breast and prostate cancer accelerate bone loss, osteoporosis, and fractures.62 The endocrinology is complex, however. Tamoxifen can preserve bone mineral density in post-menopausal women but is associated with bone loss in younger women.63 Aromatase inhibitors adversely affect bone density in all ages.64 Consequently, ASCO recommends regular monitoring of bone mineral density with dual energy x-ray absorptiometry, dietary intake of calcium and vitamin D, weight-bearing exercise, and smoking cessation.65 Bisphosphonates can be useful for the treatment of...

Future Lines of Research

Future research using the bat as a model for the study of aging may reveal mechanisms that confer resistance to expected senescent processes observed in other long-lived mammals. Elucidation of the physiological mechanisms that give rise to the exceptional longevity observed in bats may provide insight into the development of novel treatments and therapies of degenerative diseases associated with senescence in humans. Chien and Karsenty (2005) describe the typical manifestation of the aging phenotype in long-lived mammals as development of osteoporosis, reduction in body weight, lean-reduced fat tissue, loss of hair or alopecia, cardiomyopathy, early loss of fertility in females, anemia with extramedullary hematopoiesis, reduction in physical activity, and lack of obvious cause of death. Following is a brief review of potentially heuristic lines of research using the bat as a model for the study of aging.

Treatment Of Venous Thromboembolism Vte In Neurosurgical Patients

Concern about the risk of bleeding then intravenous UFH maybe used in the first instance, aiming for an APTT ratio at the lower limit of the therapeutic range. The advantage of this approach includes the short half-life of the heparin together with the availability of an antidote in protamine. An alternative approach is the initial use of split doses of LMWH ensuring smoother anticoagulation control, with lesser peaks and higher troughs. If monitoring is required, due to concerns about bleeding risk, anti-factor Xa levels may be measured. LMWH is as efficacious as UFH in the treatment of DVT and submassive PE and is more convenient, with the use of once or twice daily subcutaneous injections without routine monitoring. Adverse effects such as hep-arin induced thrombocytopenia and osteoporosis are reduced. In the bleeding patient, however, it must be remembered that LMWH's anticoagulant effect lasts 18 to 24 hours and protamine will reverse only a fraction of this.

Aging General Characteristics

Aging in the rhesus monkey has many similarities to human aging. The incidence of cancer, type 2 diabetes, and other diseases increase in the rhesus monkey similar to humans. In addition, diseases and clinical conditions, such as osteoporosis, that occur in aging women also occur in the rhesus female. Changes that occur during aging fall into two categories those associated with declining physiological function and those contributing to a disease state (Hadley et al., 2005). Obvious signs of aging in nonhuman primates and humans include loss of posture due to muscle loss (sarcopenia). Recent evidence has directed new attention to the important role of immune system function as a central element in a possible range of health-related issues and disease states that emerge as the individual ages (Nikolich-Zugish and Messaoudi, 2005). In addition, visual and auditory systems undergo an age-related decline, similar to humans (Torre and Fowler, 2000 Roth et al., 2004). Similarly, there is...

Inhibition Of Aromatase

Inhibition of estrogen action is generally the first-line adjuvant therapy for patients with metastatic estrogen receptor (ER)-positive breast cancers. Recent trials have demonstrated superiority of aromatase inhibitors such as anas-trozole over traditional estrogen receptor antagonists in this setting,66 and there is therefore much interest in the development of more effective aromatase inhibitors, both as treatment and as preventive agents.67 Estrogen receptor antagonists and aromatase enzyme inhibitors inhibit estrogen action in a global fashion, particularly in bone tissue and this inhibition may cause osteoporosis.68 Although this might be of less consequence in advanced postmenopausal breast cancer, the effects of estrogen deprivation in bone of young postmenopausal women could be significant. In addition, other sequelae of estrogen deprivation with anti-estrogen therapy for breast cancer such as hepatic steato-sis69-71 and cognitive impairment,72,73 have been described. For...

Bisphosphonates alendronate Fosamax

Alendronate is an oral bisphosphonate approved for the treatment and prevention of osteoporosis. Alendronate exerts its effect on bone by inhibiting osteoclasts. 2. The dose for prevention of osteoporosis is 5 mg per day. This dose results in significant increases in densities of 2-3.5 , similar to those observed in ERT. The dose for treatment of osteoporosis is 10 mg per day. Alendronate provides a 50 reduction in fracture risk.

Acute Lymphoblastic Leukemia

Clinical presentation is variable symptoms may be subtle and develop over months or they may be acute and quite severe. The presenting symptoms are directly related to the degree of bone marrow failure or extramedullary involvement (see Table 11.3). Symptoms that are seen in about half of the patients include fever that stems from the leukemic process itself (tumor burden) and from the neutropenia and pallor and fatigue that are caused by the anemia. Bleeding, purpura, and bone and joint pain are other common presenting complaints. Children often present with a limp or the inability to walk due to the pain caused by the leukemic infiltration of the periosteum (bone covering) or due to the actual bone itself causing osteoporosis or bone ero-

Hormonereplacement Therapy

Years) hormone-replacement therapy (HRT). Beral et al.57 found an excess incidence of six breast cancers in 1000 women who had used HRT for more than 10 years. In addition, the risks were greater when a combined estrogen and progesterone preparation was used compared with estrogen alone.58,59 For the majority of women, the benefits in terms of protection against osteoporosis outweigh the breast cancer risk. However, one model has shown that, for women who have a > 30 lifetime breast cancer risk and an average risk of cardiac events, life expectancy is no longer increased. In this group, HRT should be used with caution or for short

Agerelated Changes in Hormones and Their Receptors in Animal Models of Female Reproductive Senescence

Traditionally, the onset and progression of menopause in humans has been attributed to ovarian follicular decline. Because the follicles are the primary source of circulating estrogens, these age-related changes lead to a number of symptoms such as hot flashes, mood swings, irritability, and depression, as well as increased risk of osteoporosis, cardiovascular disease, and age-associated diseases. Recent research indicates that along with the ovarian changes at menopause, the hypothalamic and pituitary levels of the reproductive axis also undergo significant changes during reproductive aging. Indeed, current research suggests a neural, as well as hormonal, mechanism involved in the menopausal process. A number of animal models are available to study these processes, most commonly the nonhuman primates and rodents, and to a lesser extent, avian systems. Here, we will discuss Old and New World monkey models, rats, mice (wild type, transgenic, and genetically modified), and birds as...

Levodopa And Homocysteine

The relation between disease progression and HC level also warrants further study. Whether PD patients treated with levodopa require supplementation with vitamins B6, B12, and folate or with COMT inhibitors to prevent elevation of HC levels still needs to be studied. Three small trials with the COMT inhibitor entacapone have demonstrated that its use prevents the elevation of HC to some extent (141-143). The impact of this effect on the health of PD patients will require the completion of a long-term prospective trial. A final finding is that elevated HC levels may be associated with the development of osteoporosis and secondary fractures. One study examined 199 women with PD and found that patients with the highest quartile level of HC were at greater risk for hip fractures (144). These results warrant further examination.

The Prader Willi Syndrome

The minor diagnostic criteria include poor fetal movements, infantile lethargy, weak cry, and compulsive behavior with tantrums and outbursts. Also of note are sleep disturbances or apnea, short stature, hypopigmentation, small or narrow hands and feet, ocular anomalies, thick but scant saliva, speech articulation defects, and a tendency to skin ''picking.'' Other findings that often support the diagnosis include a high pain threshold, decreased vomiting, body temperature instability, kypho-scoliosis, osteoporosis, early adrenarche, unusual visual-spatial skills as seen from the ability to complete jigsaw puzzles, and normal neuromuscular abilities.

Effects of GH Replacement on BMD and Bone Metabolism in GHDeficiency

In summary, adult GH-deficiency is associated with reduced bone mass as assessed by bone mineral density measurements. The available data provide evidence that GH is an osteo-anabolic hormone when given to GH-deficient adults. The findings in most of the trials suggest that GH has a biphasic effect following an initial predominance of bone resorption, stimulation of bone formation leads to a net gain in bone mass after 12-24 mo of treatment.

Children Of Centenarians

Health histories of a nationwide sample of centenarian offspring (n 176) and controls (n 166). The controls consisted of offspring whose parents were born in the same years as the centenarians but at least one of whom died at age 73, the average life expectancy for that birth cohort. The average age at death of the other parent was 77 years, the same as the spouses of the centenarians. Centenarian offspring were found to have a 56 reduced relative prevalence of heart disease, a 66 reduced relative prevalence of hypertension, and a 59 reduced relative prevalence of diabetes in multi-variate analyses that controlled for age, gender, years of education, annual income, IADL score, ethnicity, marital status, exercise, smoking, and alcohol use. There were no significant differences in the prevalence of a number of other age-related diseases including cancer, stroke, dementia, osteoporosis, cataracts, glaucoma, macular degeneration, depression, Parkinson's disease, thyroid disease, and COPD....

Identification of Candidates for Chemoprevention

Come from studies of white women thus, little is known about the impact of ethnic diversity. Finally, with the exception of women with predisposing genetic mutations, the majority of women with risk factors will not develop breast carcinoma. A recent study of the fraction of breast cancer cases in the United States attributable to risk factors152 found that fewer than 50 of women who develop the disease have any identifiable risk factors. Family history of breast cancer accounted for only 9 of cases, while relatively minor risk factors, such as later age at first birth and nulliparity, were seen in 29 of cases. In a similar study, Seidman et al.153 noted that only 21 of breast cancer cases in women aged 30-54 and 29 of cases in women aged 55-84 occurred in women with at least one of 10 common breast cancer risk factors. The majority of women had minor risk factors, which increase the RR of breast cancer only twofold, and most had only a single risk factor. This level of increased risk...

Royal Marsden Pilot Study

In contrast, tamoxifen exerted antiestrogenic or estrogenic effects on bone density, depending on menopausal status. In premenopausal women, early findings demonstrated a small but significant (p < 0.05) loss of bone in both the lumbar spine and hip at 3 years. In contrast, postmenopausal women had increased bone mineral density in the spine (p < 0.005)

Allergic rhinosinusitis

A more effective approach to nasal congestion and inflammation is the use of a topical nasal corticosteroid spray. This class of agent is the most potent and effective modality for the treatment of allergic rhinitis and is effective against all of the manifestations of this disorder (8). Common side effects include local nasal irritation and occasional thrush. Less common, but possibly important in the case of long-term use, are an increase in incidence of glaucoma, cataracts, and osteoporosis. These drugs diminish the inflammatory influx of cells into the nasal mucosa and diminish the strength of the local allergic response.

Molecular Cellular And Histologic Effects Of Gh

Extensive experimental evidence in vitro and in vivo therefore indicates that GH plays an important role in maintenance of the skeleton. These data have also provided a rationale to explore the possible therapeutic benefit of GH on bone density in states of GH deficiency and osteoporosis. In humans, however, these issues are complex, because GH deficiency (GHD) may vary in timing, etiology, and severity. Because GH is administered as an injection, whereas endogenous GH secretion occurs in pulses, physiologic administration of GH may be difficult, and symptoms and signs of GH excess may result from GH administration, even with the most careful dosing schedules. Furthermore, GH has diverse metabolic actions apart from its effects on bone, which may limit its clinical utility, especially for therapy of osteoporosis in the GH sufficient patient.

Study Of Tamoxifen And Raloxifene

The results of the STAR trial are expected by 2006. Clearly, it will be invaluable to establish the overall benefits of the drugs with regard to breast cancer incidence, coronary heart disease, and osteoporosis. Comparisons of endometrial cancer will be especially interesting because the standard of care, i.e., self-reporting, will be employed in the STAR trial rather than routine screening with annual biopsies.

Agerelated Changes in Respiratory Mechanics

Decreased compliance of the chest wall (i.e., stiffening of the chest wall) is explained to some extent by calcifications and other structural changes within the rib cage and its articulations. Changes in the shape of the thorax as a result of osteoporosis and vertebral fractures, resulting in dorsal kyphosis and increased antero-posterior (AP) diameter (barrel chest), also affect chest wall compliance. Indeed, prevalence of vertebral fractures in the aged is high and increases with age in Europe, for female subjects aged over 60, the prevalence of vertebral fractures is 17 in the 60 to 64 age group, increasing to 35 in the 75 to 79 age group (Cummings et al., 2002). Males also have an increase in vertebral fractures with age, but rates are approximately half those of the female population. The increase in AP diameter of the chest decreases the curvature of the diaphragm and has a negative effect on its force-generating capabilities. Respiratory muscle performance in older subjects is...

The Rhesus Macaque as a Model of Human Aging and Age Related Disease

The rhesus monkey (Macaca mulatta) offers an advantageous model for biomedical research because of the close relatedness of this species to humans. As in humans, the rhesus monkey experiences deteriorating function of multiple physiological systems during aging, as well as an increasing incidence of pathologies and other health issues. These health issues are generally considered part of normal aging. However, there are health problems that arise, which contribute to disease states that become more prevalent in aging populations, such as osteoporosis and metabolic disorders, including diabetes. In addition, the rhesus female provides a valuable experimental model for understanding the biological changes that accompany the process of ovarian aging and the perimenopausal transition, which is an area of high visibility and intense research at this time. Rhesus males also experience age-related increases in health issues despite the fact that they do not have the precipitous hormonal...

The Future Of Prevention

The major clinical question for the current application of tamoxifen as a chemopreventive is when the 5-year course should be taken and how long the effects will protect a woman at elevated risk for breast cancer. The simple answer to the first part of the question is that a woman who fits the elevated risk criteria for breast cancer will receive benefit through a 55 risk reduction whenever she takes tamoxifen. However, since there are no rules that define when a woman will develop breast cancer, earlier rather than later would be an appropriate strategy. In regard to the duration of therapy, the answer is less clear but there are clues that 5 years of tamoxifen therapy results in protection for at least 5 years after the drug is stopped, based on contralateral breast cancer data from the overview analysis.47 At this time, further follow-up is not available. It will be important to discover the mechanism for the long-term beneficial effects of tamoxifen as a chemopreventive as this...

Osteoporotic Change in Trabecular Pattern of the Vertebral Body

Osteoporosis is characterized not only by a reduction in bone mass but also by alteration in the architecture of trabecular bone. Changes in BMD have long been considered the most important factor in the diagnosis of osteoporosis and in predicting the risk of fractures caused by osteoporosis. However, recent studies have demonstrated that similar BMD values have been associated with different osteoporosis-induced fracture outcomes. Changes in the trabecular architecture of the osteoporotic vertebral body are well known, An increasing number of studies indicate that, in addition to BMD, trabecular microstructure is an important factor in the assessment of osteoporosis. The prediction of fracture risk in osteoporotic bone based on BMD measurement alone has been reported to be insufficient. The prediction of fracture risk using BMD measurement could be improved by incorporating the changes in trabecular orientation of vertebral body.

GH Administration in Adult Onset GHD

Studies of GH administration in patients with adult-onset GHD have shown results consistent with those in childhood-onset patients. Initial short-term studies have shown GH-induced increases in bone turnover, while subsequent longer-term, often noncontrolled studies have demonstrated improvements in bone density. Bengtsson and coworkers have published three studies of GH administration in patients with adult-onset GHD that have included evaluations of bone turnover markers and bone density. The first of these involved 10 patients and demonstrated GH-induced increases in osteocalcin and the aminoterminal propeptide of type 3 procollagen within 6 wk with further increases noted at 6 mo (42). A subsequent study by this group involved 25 patients who participated in a 6 mo, placebo-controlled trial of GH administration, followed by an open-label trial for a total of 12 mo of GH treatment in 12 of the patients (43). At 6 mo, significant increases in bone formation markers were seen,...

Gonadotropinhormonereleasing Hormone Analogues In Combination

Estrogenic symptoms, including hot flushes, vaginal dryness, and sleep disturbances. In the majority of studies with protracted GnRH analogue treatment, loss of bone mineral density (BMD) has been evident. As oophorectomy at a young age is associated with an increased risk of cardiovascular disease, long-term use of GnRH analogues is of concern. While the side effects and risks associated with hypoestrogenemia are acceptable in the setting of metastatic breast cancer and in the adjuvant treatment of early breast cancer, such effects may not be acceptable to women only at risk for the development of the disease. While a GnRH analogue should achieve major reduction in a woman's lifetime breast cancer risk, the benefit will occur only if the agent were to be continued for prolonged periods of time. To permit such protracted use, methods for reducing the side effects and morbidity must be considered. The effect of protracted GnRH analogue treatment on BMD has prompted consideration of...

Directions For Future Research

Interventions for site-specific behavioral changes As we learn more about the late effects of cancer treatment, interventions are needed to reduce these late effects. For example, research has indicated the multiple benefits of exercise on cancer survivors to improve mood, increase flexibility, maintain weight and bone mineral density. Our literature review did not find many intervention studies, let alone one's whose purpose was to improve the QOL of cancer survivors.

The Opgranklrank System

OPG binds to RANKL leading to inhibition of the osteoclastic activation (see Figure 58.1) (Khosla et al., 2001). OPG Knock-out mice develop arterial wall calcification as well as osteoporosis (Min et al., 2000). Reversal of these abnormalities is observed in OPG transgenic restoration (Min et al., 2002). Furthermore, intravenous injection of recombinant OPG protein reverses the osteoporotic phenotype observed in OPG-deficient mice (Min et al., 2000). Also, in a randomized, double-blinded, placebo-controlled study, a single subcutaneous injection of OPG was found to be effective in reducing bone turnover in postmenopausal women, highlighting its potential as a therapeutic agent for osteoporosis (Bekker et al., 2001). In a prospective study involving 490 white women aged 65 years or more, OPG was associated with diabetes and with cardiovascular mortality, raising the possibility that OPG might be a cause marker for vascular calcification (Browner et al., 2001). These findings highlight...

Gammacarboxyglutamic Acid Gla Proteins

Gla proteins, including matrix Gla protein (MGP) and osteocalcin (OC), are vitamin K-dependent bone proteins that play a key role as mediators and inhibitors of osteoid formation (Price et al., 1982 Pauli et al., 1987). MGP is a secretory protein that is widely expressed in tissues including bone and vasculature (Price et al., 1982). Chronic Warfarin therapy leads to depletion of these vitamin K-dependent Gla proteins, resulting in an excessive mineralization disorder and closure of the growth plate with cessation of longitudinal growth (Price et al., 1982). These features are similar to those observed in the warfarin embryopathy due to exposure of the human fetus to warfarin anticoagulation in early pregnancy (Pauli et al., 1987). Knockout mice lacking MGP develop to term but die within two months due to arterial calcification and blood-vessel rupture (Luo et al., 1997). Additionally, these MGP-deficient mice exhibit inappropriate calcification of the growth plate leading to short...

Osteopontin OPN and Bone Morphogenetic Proteins BMP

OPN is essential in the development of postmenopau-sal osteoporosis. OPN knockout mice are resistant to ovariectomy-induced bone resorption, compared to wildtype mice (Yoshitake et al., 1999). Furthermore, in the absence of OPN, PTH-induced increase in bone resorption is suppressed, via osteoclastic inhibition (Ihara et al., 2001). In calcified atheromatous tissues, OPN is upregu-lated (Dhore et al., 2001), probably as a compensatory response to the decrease in the mineralization process. OPN is also likely to play an important role in atherosclerosis (Isoda et al., 2002). Transgenic mice over-expressing the OPN gene develop both medial thickening without injury and vascular remodeling, and restenosis after angioplasty (Isoda et al., 2002).

Bone Density Assessment

It is important to evaluate and compare bone mineral densities in various aging mouse cohorts and for any study that attempts to show the effect of any type of treatment on bone. Trabecular bone density can be measured by three established methods. These three methods include trabecular bone volume by histomorphometry (BV TV ), trabecular bone density by peripheral quantitative computerized tomography (pQCT), and areal bone density of trabecular bone by duel-energy x-ray absorptiometry (DEXA). DEXA can be used to measure bone mineral content (BMC) and areal bone mineral density (BMD) (BMC cm2).37 Osteoporosis is a common bony disease of aging women. This disease process involves loss of bone mass with subsequent skeletal fragility. A mouse model has been developed and specific phenotyping techniques can be employed to study this model. Conventional radiography as well as microradiography can be performed to evaluate bone density. Biomechanical studies such as whole-bone three- or...

Organ Systems Affected By Low T Levels

Men undergo a gradual loss in bone mass beginning in their 30s. It is estimated that two million men in the United States have osteoporosis and that one in eight men over age 50 will have an osteoporosis-related fracture (NIAMS, 2003). Risk factors for osteoporosis include family history of osteoporosis, smoking, excessive alcohol intake, physical inactivity, poor nutrition, vitamin D deficiency, Osteopenia and osteoporosis are common in males with congenital causes of hypogonadism, and severe T deficiency occurring later in life also results in bone loss. For example, androgen deprivation therapy for prostate cancer has been shown to result in rapid bone loss, osteopenia, and osteoporosis (Smith, 2003). Although less severe T deficiency in aging men appears to increase osteopenia and osteoporosis, population-based studies suggest that estrogen levels are better correlated with loss of BMD in men (Greendale et al., 1997 van den Beld et al., 2000)....

Clinical Presentation

The symptoms of bone disease are few and rather non-specific. The most common symptom is pain, which may be of variable intensity. Severe unremitting pain continuing at night in bed is insidious and suspicious of malignancy. Pain relieved by non-steroidal inflammatory agents is suggestive of a benign osteoid osteoma. Remember that sometimes pain felt in one bone may be referred pain that is, disease originating elsewhere. A swelling is indicative of a primary bone tumour. Pathological fracture - a fracture occurring due to low-impact trauma - is indicative of a diseased bone and suggests osteoporosis, multiple myeloma or metastatic disease.

Background And Relevant Pharmacokinetics

Vitamin D (as D3) is also produced in the body as a result of the conversion of a cholesterol-based precursor, 7-dehydrocholesterol, which is produced in the sebaceous glands of the skin. Exposure to sunlight (UVB) converts this precursor into cholecalciferol over a 2-3 day period. Prolonged exposure to UVB can inactivate some of the newly-formed vitamin D and its precursors so that eventually a state of equilibrium is reached between vitamin D synthesis and catabolism. Therefore, short periods of sun exposure are considered more efficacious than long periods (Working Group of the Australian and New Zealand Bone and Mineral Society, Endocrine Society of Australia and Osteoporosis Australia 2005). Some vitamin D is stored in adipose tissue and can be mobilised during periods when exposure to sunlight is reduced or shortages develop (Nowson & Margerison 2002). Vitamin D and its metabolites are primarily excreted through bile and the degraded active form is removed via the kidney....

Deficiency Signs And Symptoms

Unlike many other vitamins, vitamin D is not only ingested through the diet but is also produced and stored in the body. As such, endogenous production, which is reliant on adequate exposure to sunlight, will greatly influence whether deficiency states develop. It has been estimated that exposing the skin to UVB radiation produces approximately 90 of the vitamin D3 (cholecalciferol) that is bioavailable in the body. Currently, the NHMRC reports that it is almost impossible to get sufficient vitamin D from dietary sources alone, stressing the importance of UVB exposure. Deficiency more prevalent than once thought Inadequate vitamin D is becoming recognised as a real concern, according to the 2005 position statement released by the Working Group of the Australian and New Zealand Bone and Mineral Society, Endocrine Society of Australia and Osteoporosis Australia. It states that there are a significant number of Australians who demonstrate a combination of poor dietary intake and...

Vasomotor Symptoms

Menopause hormone therapy (MHT), however, is very effective for treatment of hot flashes and night sweats and by secondary gain can be useful for treating sleep disturbances that result from waking related to hot flashes. Prior to 2002 when the Women's Health Initiative (WHI) was halted because of increased risk for women taking estrogen and progestin therapy for breast cancer (anticipated) and for increased risk for heart disease, stroke, and other thromboembolic events (unanticipated), MHT was recommended for all postmenopausal women to protect against osteoporosis and heart disease as well as for treatment of symptoms including hot flashes, vaginal dryness, mood changes, sleep disturbances, and sexual dysfunction. Subsequently, the estrogen-only arm of the WHI was discontinued as well, because of the increased risk of stroke (RR 1.4 for women on estrogen alone). In addition, data from the WHI demonstrated increased risk of dementia and urinary incontinence with use of MHT (Hendrix...

Gross Description

Other significant autopsy findings included bilateral adrenal gland atrophy (combined weight 3 g, normal 8 g), small female genital organs, excessive epidural lipomatosis and severe osteopenia of the spine with multiple compression fractures in the thoracic and upper lumbar regions.

Side Effects Of Hormonal Therapy Similarities And Differences

Hormonal therapy for prostate cancer eventually produces decreases in libido and potency in virtually all patients regardless of the modality used.34,124 Additional side effects include lethargy, depression, anorexia, breast swelling with or without tenderness, hot flashes, anemia, and osteoporosis with potential for pathological fracture.14,125-130 Most side effects, including impotence and infertility, are slowly reversible with cessation of therapy. However, reduced bone mineral density often does not reverse after prolonged hormonal suppression. There is a consensus that irreversible changes occur more often after suppression of longer than 18-24 months.

Clinical Progression Of Ws

The progression of clinical changes in WS can usefully be thought of as having three distinct phases. The first of these comprises the absence of an adolescent growth spurt followed over the subsequent decade by the appearance of graying and loss of hair, the development of skin changes, and of cataracts. A second wave of changes, often first seen late in the third or in the fourth decades of life, include skin ulceration, hypogonadism, and reproductive failure, together with a progressive worsening of the primary changes. A third phase may follow with the development of clinically important disease processes such as atherosclerosis, osteoporosis, diabetes mellitus, and cancer. These diseases occur proportionately earlier in WS patients than in otherwise normal individuals of comparable age, and are an important cause of premature morbidity and mortality. The three leading causes of death in WS patients are atherosclerotic cardiovascular disease, neoplasia, and, in a minority of...

Additional Work Needed To Better Characterize Ws

Quantitative differences between WS and normal aging include the greater extent or severity of the loss of hair or hair color of the extent of calcification of heart valve leaflets of atherosclerosis and of osteoporosis and of the loss of reproductive function. Qualitative differences between WS and normal aging include the unusual type of cataract observed in WS patients as opposed to normal aged individuals the unusual changes observed in skin and subcutaneous connective tissue of the face and extremities, together with nontrophic ulceration the unusual spectrum of neoplasms the location and extent of soft tissue calcification and the autosomal recessive nature of WS (Epstein et al., 1966).

Biological Functions of Shps

Accumulations of alveolar macrophages and neutrophils. The macrophage population in me mice is expanded and exhibits abnormal differentiation, with a dramatic increase in CD5+ monocytoid cells and a decrease in cells expressing tissue marginal zone macrophage markers 99,100 . Some dendritic cell populations are increased, whereas others are diminished 100 osteoclast numbers and function are enhanced, leading to osteopenia in me mice 101 . Shp1-deficient mice on either a nude or rag knockout background still develop inflammatory disease 102 , and the disease can be reproduced by transplantation of bone marrow cells and prevented by treatment with Mac-1 antibodies 103 . Thus, lymphoid cells are dispensable, and defects in the myeloid lineage are critical, if not sufficient, for development of the me inflammatory syndrome.

The Importance Of Dna Doublestrand Break Repair

Importance Span Control

One of the most prominent aging-related phenotypes occurring early in the mutants is lordokyphosis, the lateral curvature of the spine that is also present in the p53 mutants (see Figure 49.2). Lordokyphosis in these mice is likely due to osteoporosis because histology showed the older Ku80-mutant and control bones to exhibit osteopenia (thinning of the bone and reduced trabeculae). Figure 49.3 shows growth plate closure, a well-known age-related phenotype that is a part of maturation, not senescence, in humans. Mice are different

Monogenic genes as genetic risk factors in common disease

Mobogenic Sexy Video

Several such examples come from studies on the genetic basis of osteoporosis. Osteoporosis is a complex disease characterized by reduced bone mass (see Chapter 27), deterioration of the skeleton and increased risk of fracture. The most important clinical predictor of fracture risk is bone mineral density (BMD). Twin and family studies have shown that genetic factors account for 50-85 of the variation in BMD. One of the most convincing genetic risk factors for BMD is the type I collagen gene. Type I collagen is the most abundant protein in bone and is a heterotrimer made up of two collagen type I al protein chains (encoded by the COL1A1 gene) and one collagen type 1 a2 chain (encoded by the COL1A2 gene). Mutations in the coding region of COL1A1 are found in 90 of cases of osteogenesis imperfecta, a rare condition associated with reduced BMD and multiple fractures. A polymorphism in the first intron of the COL1A1 gene was found to be associated with BMD and restriction analysis has...

Nonhuman Primate Models Old World Monkeys

Researchers can use this model to look toward modifications in brain structures as well as ovarian hormones when considering reproductive aging. Thus, differences in neuronal morphology, neuronal populations, and receptor density in the aging brain can be observed. Additionally, studies examining age-associated genetic alterations and relations to neural changes, and age-associated diseases, such as osteoporosis, cardiovascular diseases, and vasomotor symptoms (e.g., hot flash) can be undertaken in this model. These factors make the aged OWM a favored model for studies of reproductive senescence. reported that administration of estrogen followed by progesterone in OVX macaque monkeys decreases ERa mRNA and protein expression in the ventromedial hypothalamus, an area associated with sexual behavior, but has minimal effects on ER . Age-associated decreases in ER populations in various nuclei of the hypothalamus very likely contribute to declines in sexual...

Ocular Use Of Steroids

Glucocorticoids have catabolic and antianabolic effects in lymphoid and connective tissue, muscle, fat, and skin. Supraphysiologic amounts of glucocorticoids lead to decreased muscle mass and weakness, thinning of the skin, osteoporosis, and reduce growth in children. They appear to antagonize the effect of vitamin D on calcium absorption.

Somatosensory Symptoms

Osteoporosis is another concern for patients with MS and another source of pain. Cosman et al. (52) reported a history of fractures in the absence of major trauma in 22 of MS patients compared with only 2 of controls (P < 0.002). Determining bone mass by dual X-ray absortiometry, the authors observed that over two years of prospective follow-up both women and men with MS lost substantially more bones than controls. There was a trend, which did not reach statistical significance, for diminished ambulatory status and long duration of steroid therapy to predict higher bone loss. In another study, however, this group noted that after controlling for age, cumulative steroid use was not a determinant of bone mineral density,''(53) a finding of Schwid et al. (54). However, low vitamin D intake and diminished exposure to sunlight appear to be major contributors to the problem.

Nonneoplastic Conditions

Metabolic bone disease osteoporosis is very effectively diagnosed using DEXA (dual energy X-ray absorptiometry) and is almost never routinely biopsied. Osteomalacia is most uncommon in the UK but may rarely be seen in renal failure or in patients taking long-term phenytoin therapy. Paget's disease is easily diagnosed using plain X-ray, serum alkaline phosphatase and urinary hydroxyproline so it is almost never biopsied.

Severe Chronic Neutropenia Patients

The initial observation of bone pain and pathologic fractures in a number of our patients led us to investigate bone mineral density in a cohort of 30 patients (36) 15 30 patients (50 ) showed evidence of osteopenia osteoporosis, and in 5 of these 15 patients osteoporosis became a clinical problem with either pathologic fractures or moderate back pain. Within the SCNIR, bone density measurements have been reported for 121 patients with congenital neutropenia measured by different techniques including quantitative computer tomography, dual-energy X-ray absorptiometry, single-photon absorptiometry, and lumbar X-ray. Sixty-six of the 121 patients (54.4 ) had varying degrees of abnormal results however, these results were not quantified. Most patients did not show clinical symptoms of osteopenia osteoporosis, such as bone pain or fractures, explaining why diagnostic procedures for bone density evaluation were not reported in > 70 of SCNIR patients. The real...

Many Metabolic Genetic Disorders Involve Bone

Osteoporosis is a generalized progressive reduction in bone tissue mass per unit volume causing skeletal weakness. The ratio of mineral to organic elements is unchanged in the remaining normal bone. Fractures of various bones, such as the head of the femur, occur very easily and represent a huge burden to both the affected patients and to the health care budget of society. Among other factors, estrogens and interleukins-1 and -6 appear to be intimately involved in the causation of osteoporosis.

Cytoplasmic Receptors

Cytoplasmic receptors are ligand binding transcription factors. All except the aryl-hydrocarbon receptor (AhR, a basic helix-loop-helix-PAS bHLH-PAS family member) are members of the classical steroid family, which is now part of the nuclear receptor (NR) superfamily (for recent reviews see Refs. 26-29). Because AhR was originally characterized in biochemical studies as a steroid receptor, other putative steroid receptors may actually be bHLH-PAS structural family members. The biochemical features of cytoplasmic receptor ligands are tailor made for drug discovery efforts they are small lipophilic compounds that average 350 daltons, show exquisite specificity and efficacy, and mediate physiological processes that are vital in arthropods and vertebrates. Steroids and synthetic mimics have medical utility for many conditions including osteoporosis, cancer, and a variety of inflammatory disorders, as well as agricultural utility to enhance production in livestock. The majority of these...

David J Bentrem V Craig Jordan

Gen was true for both tamoxifen and ralox-ifene.16,17 Lacassagne's7 goal of developing an antagonist to estrogen action to prevent breast cancer in healthy women would not have been met if the available drugs increased the risk of osteoporosis and coronary heart disease.

Interactions Between Cadmium and Other Metals

There are indications that contributing factors for Itai-Itai disease were low intakes of calcium and other minerals, vitamin D, and protein. The poor nutritional conditions in many areas of Japan during World War II were discussed and a comparison between diets in the endemic region of Itai- , Toyama prefecture, Japan as a whole and Sweden was presented by Kjellstrom in 1986. Lower dietary intakes calcium and of fat-soluble vitamins compared with Sweden and the practice by women in the endemic area of wearing clothes covering their whole body, including hands and face, may have provided only marginally adequate calcium intake and marginal or less than marginal vitamin D activity. Such conditions most probably made this population more sensitive to the development of bone effects of Cd than populations in other countries (Kjellstrom, 1986 Nordberg, 1974). Although it is clear that the high cadmium intake in the endemic area was the main causal factor for development of the disease (cf...

Musculoskeletal Disorders

Musculoskeletal disorders represent another group of diseases whose incidence steeply increases with age and which are rarely fatal by themselves, but which account for a major share of detriments in quality of life, disability and costs for medical and nursing care among older adults. Up to 10 of cases of severe disability are mainly caused by these disorders (Ramroth et al., 2005). The most important disabling musculoskeletal disorders include osteoporosis and osteoarthrits. The former is

Physiological Aging

Animal model are similar to those seen in people. Equally relevant are reproductive changes with age, which include testis and ovary changes as well as the onset of reproductive senescence such as age of menopause. Many age-related changes and pathologies can also be studied and compared to human aging. A few parameters of interest include, but are not limited to, fat deposits, hormonal levels such as those of growth hormone, insulin and insulin-like hormones, and dehydroepiandrosterone (DHEA), atherosclerotic lesions, osteoporosis, arthritic changes, changes in reaction times with age, changes in senses, and the presence of cerebrovascular -amyloid protein (Finch, 1990). There are also examples of comparative studies aimed at specific age-related pathologies, and readers should consult other chapters in this book.

Calcium Deficiency

BONE MINERAL DENSITY (BMD) AND OSTEOPOROSIS PROPHYLAXIS Children A 2006 Cochrane review of 19 trials including 2859 participants found there was no effect of calcium supplementation on femoral neck or lumbar spine BMD (Winzenberg et al 2006). There was a small effect on total body BMC and upper limb BMD however, only the effect in the upper limb persisted after supplementation ceased. The effect is approximately equivalent to a 1.7 greater increase in supplemented groups, which at best would reduce absolute fracture risk in children by 0.1-0.2 annually. Additionally, there was no evidence of effect modification by baseline calcium intake, sex, ethnicity, physical activity or pubertal stage. Adolescents Peak bone mass is one of the main determinants of osteoporotic fracture in humans and therefore there is significant research dedicated to determining the influence of calcium status on the 40-50 peak bone mass accretion that occurs during adolescence. Overall, studies in adolescent...

Medical treatment

These agents (eg, leuprolide Lupron , goserelin Zoladex ) inhibit the secretion of gonadotropin. GnRH agonists are contraindicated in pregnancy and have hypoestrogenic side effects. They produce a mild degree of bone loss. Because of concerns about osteopenia, add-back therapy with low-dose estrogen has been recommended. The dosage of leuprolide is a single monthly 3.75-mg depot injection given intramuscularly. Goserelin, in a dosage of 3.6 mg, is administered subcutaneously every 28 days. A nasal spray (nafarelin Synarel ) may be used twice daily. The response rate is similar to that with danazol about 90 percent of patients experience pain relief.

Figure 817

Although rickets and osteomalacia are no longer major problems where nutrition is adequate, another form of insufficient bone mineralization is regularly seen In the condition known as osteoporosis. In this condition, bone tissue (both mineral and matrix) is diminished, presumably because resorption by osteoclasts exceeds deposition by osteoblasts. Osteoporosis develops as a conse

Figure 819

Microradiographic examination of a ground section of bone reveals that younger Haversian systems are less completely mineralized than older systems (Fig. 8.19). They undergo a progressive secondary mineralization that continues (up to a point) even after the osteon has been fully formed. Figure 8.19 also illustrates the dynamic internal remodeling of compact bone. In the adult, deposition balances resorption. In the aged, resorption often exceeds deposition. If this imbalance becomes excessive, osteoporosis develops (see page 199).

Steroids

Steroid side effects have been well defined over time and usually worsen with higher dose and longer duration of use. Side effects include weight gain, electrolyte disturbances, hyperglycemia, gastrointestinal irritation, osteoporosis, opportunistic infections (primarily Can

Diagnosis

Risk factors for osteoporosis include female gender, increasing age, family history, Caucasian or Asian race, estrogen deficient state, nulliparity, sedentarism, low calcium intake, smoking, excessive alcohol or caffeine consumption, and use of glucocorticoid drugs. Patients who have already sustained a fracture have a markedly increased risk of sustaining further fractures. Estrogen-deficient women at clinical risk for osteoporosis Individuals with vertebral abnormalities Individuals being monitored to assess the response of an osteoporosis drug

Raloxifene Evista

Raloxifene is approved for the prevention of osteoporosis. When used at 60 mg per day, raloxifene demonstrates modest increases (1.5-2 in 24 months) in bone density. This increase in density is half of that seen in those patients receiving ERT. Raloxifene has a beneficial effect on the lipid profile similar to that seen with estrogen.

Menopause

And consequent changes in the structure and functioning of certain body tissues and organs. Among the structural changes are a decrease in the size of the cervix and uterus cells in the vaginal walls also atrophy, causing the walls to become thinner. The reduction in estrogen contributes to the difficulty of uptaking calcium to strengthen the bones and a consequent thinning of the bones ( osteoporosis ).

For 3 days Dose ped

Acute spinal cord injury 30 mg kg IV over 15 minutes, followed in 45 minutes by a continuous infusion of 5.4 mg kg hr for 23 hrs. Clearance hepatic metabolism renal elimination. Contraindications serious infections except septic shock or tuberculous meningitis. Adverse effects may cause hypertension, pseudotumor cerebri, acne, Cushing's syndrome, adrenal axis suppression, GI bleeding, hyperglycemia, and osteoporosis. Comments use caution in hyperthyroidism, cirrhosis, nonspecific ulcerative colitis, hypertension, osteoporosis, thromboembolic tendencies, CHF, convulsive disorders, myasthenia gravis, thrombophlebitis, peptic ulcer, diabetes.

Clinical Overview

Physical manifestations of WBS usually include involvement of the cardiovascular system, most often as a narrowing of the ascending aorta (SVAS) although a generalized arteriopathy can lead to vascular stenoses in other vessels, and hypertension is common in later life. Stellate irides, flat nasal bridge, short, up-turned nose with anteverted nostrils, long philtrum, full lips and lower cheeks, and a small chin are the recognizable facial features. Other symptoms include hernias, visual impairment, hypersensitivity to sound, chronic otitis media, malocclusion, small or missing teeth, renal anomalies, constipation, vomiting, growth deficiency, infantile hypercalcemia, musculoskeletal abnormalities, and a hoarse voice (11,12). As WBS individuals grow older they may also present with premature graying of the hair, diabetes and impaired glucose tolerance, decreased bone mineral density, sensorineural hearing loss, and a high frequency of psychiatric symptoms (13).

Back To Mitochondria

Another example of a mouse model with a defect in genome maintenance especially designed to test the hypothesis that genomic instability is involved in aging is the PolgA proofreading-deficient mouse model. PolgA, the catalytic core of the mitochondrial DNA polymerase gamma (Polg), is a mtDNA polymerase, encoded in the nuclear genome. Hence, proofreading defects in this gene would be expected to lead to increased mutations in the mitochondrial genome. Mutations in both nuclear and mitochondrial DNA have been demonstrated to accumulate with age in a tissue-specific pattern (Arnheim and Cortopassi, 1992 Vijg and Dolle, 2002). Hence, in the PolgA deficient mouse we would expect to see the premature appearance of aging-related phenotypes, which turned out to be correct. Apart from a three- to fivefold increase in mtDNA mutations in brain, heart, and liver, and respiratory chain dysfunction in the heart, a host of premature aging symptoms was observed in this mutant, including...

Anorexia Nervosa

Anorexia nervosa, with its resultant hypoestrogene-mic and hypercotisolemic state, predisposes patients to osteoporosis, which may be severe. The best predictors of bone loss are low body weight, early onset, and long duration of amenorrhea (77,78). The role of estrogen replacement in anorexia nervosa in order to prevent osteoporosis is controversial, with studies yielding mixed results (79,80). The role of bisphosphonates in treating the osteopenia of anorexia nervosa has not been established. Calcium and vitamin D supplementation are recommended (75). Bone density does improve with weight recovery and resumption of menses, although it usually remains significantly below control levels many years later (77,81). Periodic assessment of bone mineral density by dual-energy x-ray absorptiometry is can be helpful in following the patient's fracture risk (75).

Indications

With varying degrees of osteolysis and osteoporosis. Both of these factors may lead to secondary displacement, migration, or implant subsidence. Patients who have RA and who have soft medullary bone or thin cortical bone and significant destruction or imbalance of the soft tissues should be approached with caution. If there is severe deformity with greater than 80 s of an extension lag or more than 45 of ulnar deviation, the use of standard silicone implants may be necessary. In cases of complete MP joint dislocation with proximal migration of the proximal phalanx, a pyrolytic implant should not be used 14 . Patients who fail arthroplasty because of recurrent subluxation or migration may be salvaged by revising the joint with a constrained silicone implant. Wrist stability should also be achieved before MP joint replacement, particularly in RA patients who have significant intercarpal supination, radial deviation, and ulnar translocation of the wrist. Relative contraindications for...

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