Ayurvedic Treatment of Osteoporosis, Low Bone Density

The Truth About Osteoporosis

Discover Easy Strategies To Maintain Optimal Bone Health And Reverse Osteoporosis. Here is a quick preview of the valuable information youll have at your fingertips: Statistics can lead to false conclusions. Bone Quality or Quantity? Density or Strength? Find what matters! What happens to unabsorbed calcium? How do prescribed medications fit in the equation? What is the 4-R Program and can it help reverse osteoporosis? What part does protein play in bone health? What contribution does lifestyle make? Am I unknowingly my own worst enemy? What about inflammation and stress? How do they impact my bones?Does an acidic system affect the progress of osteoporosis? Who would suspect this sneaky culprit (in your tap water) as contributing to loss of bone health? Discover 4 easy steps for relieving stress. What part do hormones play in osteoporosis? How to encourage new bone growth. Find 7 steps to a workable exercise program. Look at the whole body. 12 steps to changing habits effortlessly.

The Truth About Osteoporosis Summary


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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). 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 and laboratory blood...

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...

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...

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.


In the Nurses Health Study, investigators followed 61,200 initially healthy postmenopausal women (aged 40-77 years) and found that walking for at least 4 h per week was associated with a 41 lower risk of hip fracture (RR, 0.59 95 CI, 0.37-0.94) compared with walking less than 1 h per week (Feskanich et al, 2002). The reduced risk of hip fractures has also been observed in a prospective cohort study of men, such that men who engaged in vigorous physical activity (e.g., at least running or jogging) had a significantly lower risk of hip fracture (hazard ratio, 0.38 95 CI, 0.16-0.91) relative to men who did not (Kujala et al, 2000). In addition, exercise may be an effective adjunctive treatment for individuals with osteoporosis, as it has been shown to relieve symptoms, improve quality of life, and maintain physical mobility (Sharkey et al, 2000).

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...

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...

Differing types of claim nutritional and health claims

Claims that suggest that foods or food components have an impact on health - in improving good health or a condition related to a disease - have been called health claims.5,10 An important subgroup of claims are disease-risk reduction claims. They state that a food or its component may help to reduce the risk of a disease. Examples of such claims include 'Adequate intake of calcium may help to reduce the risk of osteoporosis', 'Adequate intake of folate by women may reduce the risk of having children with neural tube defect', 'Food low in fat and cholesterol can help to reduce the risk of coronary heart disease'.

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.

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

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...

Project Title Cvd Risk Health In Postmenopausal Phytoestrogen Users

Summary (Adapted from Investigator's Abstract) In the United States, heart disease is the leading cause of death in postmenopausal women. Estrogen replacement therapy is beneficial for heart disease risk factors as well as for bone density. However, a large proportion of postmenopausal women are not compliant with therapeutic regimens. Phytoestrogens are naturally occurring compounds found in plants and soy products that have estrogenic effects, and may represent an alternative treatment for the prevention of heart disease and osteoporosis in postmenopausal women. However, few intervention trials have examined the extent to which it is possible to improve heart disease risk factors, bone density, and quality of life in postmenopausal women through use of a dietary supplement of Phytoestrogen. The proposed randomized, double-blind, placebo controlled study is designed to determine the acceptability and benefits of use of a dietary supplement of Phytoestrogen (genistein) versus placebo...

Oral diseases and cariogenicity

Oral refers to the mouth, and includes the teeth and gums (gingival) and their supporting tissues, the hard and soft palate, the mucosal lining of the mouth and throat, the lips, salivary glands, chewing muscles, and upper and lower jaw bones. Digestion begins in the oral cavity, and there are numerous supporting structures for the mouth including the nervous, vascular, and immune systems. Humans contract oral diseases for a number of reasons including genetics, poor hygiene, poor nutrition, alcohol and tobacco use, drug abuse (Shaner et al., 2006), and complications from other diseases such as diabetes (Sandberg et al., 2000, Twetman et al., 2002), cancer (Woo et al., 1993), obesity (Ritchie and Kinane, 2003), and osteoporosis (Norlen et al., 1993). Oral infections themselves may play a role in progressing pathogenesis of many systemic diseases in healthy individuals, ill patients, and those immunocompromised (Ridker et al., 1998). The theory is that oral infections, specifically...

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...

Monogenic genes as genetic risk factors in common disease

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...

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.

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...

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...

Consumption of soybean and reduced incidence of disease

Soybean isoflavonoids may also have potential in natural chemoprevention therapies against long term health problems associated with menopause, particularly for osteoporosis (44-47). After menopause, the ovaries stop producing estrogen. Because estrogen positively affects the metabolism of calcium, lack of sufficient estrogen can lead to bone loss and osteoporosis (48). Hormone replacement therapy (HRT) can reduce bone loss and the risk of osteoporosis in postmenopausal women, but unfortunately appears to also increase the risk for certain estrogen linked cancers (49-51). Current osteoporosis prevention research is focused on the development of estrogenlike compounds (selective estrogen receptor modulators, or SERMs) that can selectively act against bone loss without causing negative estrogenic action against the uterus (52). The soybean isoflavonoid genistein has shown SERM activity in ovariectomized mice (53). When provided at optimal dosages, soybean isoflavonoids (especially...

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...

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...

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

Range of biomarkers used to investigate health benefits

Some promising or developing targets include bone and cardiovascular health and mental state performance. Thus, numerous biomarkers related mostly to disease have been exhaustively listed in previous publications (Crews et al., 2001 Saris et al., 2002). The reader is particularly referred to two recent supplements of the European Journal of Nutrition (Asp et al., 2003, 2004). In these supplements, biomarkers presently available for assessing the effects of food components on cardiovascular disease bone health and osteoporosis physical performance and fitness body weight regulation, insulin sensitivity and diabetes risk diet-related cancers mental state and performance gut health and immunity are thoroughly described and discussed.

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.

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....

Estrogen Deprivation Increases Risk for Depression and Medical Illness

Not only is estrogen withdrawal associated with increased risk for depression and cardiovascular disease, but it is also associated with other negative health effects, the most notable of which may be osteoporosis. Osteoporosis is a disease characterized by the loss of bone mass and strength that leads to fragility fractures. That estrogen deficiency is critical to the pathogenesis of osteoporosis came initially from the evidence that postmenopausal women are at highest risk for the disease (see Raisz, 2005 for review). Bone remodeling is a dynamic process in which old bone is removed from the skeleton and new bone is added. It consists of two phases - resorption and formation - that involve activity of cells called osteoclasts and osteoblasts. Usually the removal and formation of bone are in balance and maintain skeletal strength and integrity. In postmenopausal women there is both an increase in bone resorption and a diminishment of the Osteoporosis is particularly common in white...

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.

Defects in Genome Maintenance Observations for Aging and Cancer

Both models display early osteoporosis and kyphosis, major forms of aging-related pathology in both mice and humans. The p44 mice show early fertility loss, to some extent caused by a breakdown of the reproductive axis (H. Scrable, personal communication). This loss of the hypothalamic pituitary gonadal axis is very similar to the situation in natural human and mouse aging (Wise et al., 1997). This loss of fertility is not observed in the M mutant, but again, the symptoms in that model are generally much less severe. Both mouse models suffer from a typical aging-related redistribution of fat resulting in loss of subcutaneous fat. Other typical aging-related phenotypes in these mice are skin problems and various forms of atrophy. Of note, increased rates of apoptosis (programmed cell death) in these two mutant mouse models have not been observed (H. Scrable and L. Donehower, personal communication). Indeed, the hyperactive p53 protein most likely causes its effects through increased...

The Importance Of Dna Doublestrand Break Repair

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

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)

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.

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.

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 ta-moxifen 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...

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...

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.

Vitamins and minerals

The role of microelements zinc and chromium in glycaemic control is also difficult to determine, as they are present in minute amounts and their deficiency is not easily assessed. The ADA dietary guidelines recommend the intake of 1.000 1.500 mg day of calcium to older people to reduce the risk of osteoporosis.

Plant phenolics in human health and as antioxidants

It is evident that plant phenolic compounds constitute one of the most numerous and widely distributed groups of substances with more than 8000 phenolic structures currently known (28). In addition to stress linked phenolics coming only from the shikimate and phenylpropanoid pathways, a number of the phenolic compounds are found in plants, including the flavonoids that contribute to the characteristic flavor and fragrance of vegetables, fruits, tea, and wine. These compounds, which come from phenylpropanoid and polyketide (acetate-malonate) pathways, also have biological properties that are beneficial to human health. Flavonoids such as quercetin and catechin and isoflavonoids, genistein for example, are being investigated for properties which may reduce the incidence of cancer (22,23). Flavonoids and isoflavonoids are a class of phenolic compounds that have appeared sequentially during plant evolution and are simple aromatic compounds generated from both the phenypropanoid and...

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).

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.

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)....

Spinal cord compression

Primary neoplasms occur in the spine and are similar to those occurring in bones elsewhere in the body such as osteogenic sarcoma, osteoclastoma, chondroma and chron-drosarcoma. In children, Ewing's sarcoma may occur in the vertebrae and neuroblastoma within the extradural space. In patients with osteoporosis, particularly in post-menopausal women, collapse fractures can occur spontaneously or with minimal trauma (pathological fractures). Such fractures may be single or multiple. Osteomalacia can also lead to pathological fractures (see Chapter 20).

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...

The Cysteine Sulfhydryl Proteases

The best-studied typical cysteine protease is papain, which will be discussed here because of its major uses in the food industry for chill proofing of beer and meat tenderization, as well as synthesis of peptides and other organic compounds. The lysosomal cathepsins are important because of their physiological roles in turnover of proteins in the body and their possible role in diseases, such as muscular dystrophy, osteoporosis, inflammatory heart diseases, and tumor invasion (19).

Regulation of Calcium and Phosphate Balance

The protein component of the bone matrix is digested by enzymes, primarily one called cathepsin K, released by the os-teoclasts. The osteoclast can then move to another site and begin the resorption process again, or be eliminated. Interestingly, there is evidence that estrogen, often given to treat osteoporosis in postmenopausal women, works in part by stimulating the apoptosis (cell suicide) of osteoclasts. resorption in healthy people on earth. In the micro-II gravity (essentially, weightlessness) of space, however, astronauts have suffered from a slow, progressive loss of calcium from the weight-bearing bones of the legs and spine. For reasons that are not presently understood, about 100 mg of calcium are lost per day, which has reduced bone mineral density up to 20 in some astronauts who have been in space for several months. This loss cannot be countered simply by giving astronauts calcium, since hypercalcemia may cause kidney stones and other problems. The exercise machines...

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.

Werner Syndrome as a Model of Human Aging

This chapter reviews clinical and basic science aspects of Werner syndrome (WS), a heritable human disease that displays features suggestive of premature aging. The resemblance of changes in WS to those observed in normal aging has long suggested WS may be a useful model in which to study the biology of aging and to identify mechanistic pathways responsible for age-associated diseases that are prevalent in WS patients and in normal aging such as atherosclerosis, neoplasia, diabetes mellitus, and osteoporosis. This chapter summarizes our understanding of the WS clinical phenotype. Current understanding of in vivo functions of the Werner syndrome protein is summarized, together with a discussion of how the loss of WRN function may promote disease pathogenesis in WS patients and in normal individuals. Subsections provide an historical overview of WS and WS research a description of WS as a clinical disease entity, together with diagnostic criteria for WS a discussion of the relationship...

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.

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...

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.

Acute Lymphoblastic Leukemia

Macrophage Peritoneal Fluid

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-

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.

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.

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.

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...

Related titles

Dairy products constitute one of the most important types of functional food. Edited by two of the leading authorities in this area, this major collection reviews how functional dairy products help to prevent such chronic diseases as cancer, osteoporosis and cardiovascular disease. Part II considers product development and such issues as clinical trials and safety evaluation. Part III examines particular types of product from oligosaccharides to lactic acid bacteria.

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.


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


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 ).

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).

Menkes Disease

Lysyl oxidase (LOX) is a secreted enzyme that catalyzes crosslinking of elastin and collagen, and it is found extracellularly attached to its substrates. A deficiency of LOX will virtually affect all organs containing connective tissue. In Menkes disease, skin, bones, and blood vessels are profoundly affected, leading to symptoms like loose skin and joints, osteoporosis, abnormal facies, hernias, bladder diverticula, arterial aneurysms, petechial hemorrhage. Apart from its role in the connective tissue disturbance, LOX deficiency also has an indirect contribution to the CNS degeneration through arterial changes (2). Decreased LOX activity has been demonstrated in cultured skin fibroblasts of MD patients by several researchers (34-41).

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...

Antitumor Actions

Raloxifene inhibits the growth of DMBA-induced rat mammary carcinoma180 and, more importantly for the proposed evaluation as a preventive, reduces the incidence of N-nitrosomethylurea-induced tumors if given after the carcinogen but before the appearance of palpable tumors17,181 (Fig. 12.10). As would be anticipated with a drug that has a short biological half-life, raloxifene is not superior to tamoxifen at equivalent doses. There is no doubt that ralox-ifene and its analogues are effective and potent inhibitors of the growth of breast cancer cells in culture,182,183 but the complication of firstpass metabolism in vivo reduces potency. For this reason, doses above 60 milligrams daily have been tested in clinical trials to prevent osteoporosis. Figure 12.10 Comparison of the effects of raloxifene on femur ash density in ovariec-tomized (OVEX) rats and incidence of rat mammary tumors after administration of V-nitrosomethylurea. Data illustrate the target site specificity of a drug...

New Agents

Newer SERMs with slight modifications of chemical structure are being studied with the goal of increasing the spectrum of antitumor activity and reducing toxicity (Fig. 12.11). The ongoing investigation of several molecules may demonstrate applications as breast cancer and or osteoporosis treatments. Most importantly, the drugs may be multifunctional medicines useful for the prevention of osteoporosis, coronary heart disease, and breast cancer. The ideal agent would (1) not produce premature drug resist


The research group at Wyeth-Ayerst has developed two new SERMs, ERA-923 and TSE-424 which are highly selective with non-estrogenic profiles on rat uterine tissue.223 These drugs showed no uterine stimulation when dosed alone and were able to completely block the effect of estrogen. TSE-424 prevented bone loss and reduced total cholesterol in animal models. ERA-923 is in phase II clinical trials for the treatment of hormone-dependent metastatic breast cancer, and TSE-424 has completed phase II clinical trials for the treatment of post-menopausal osteoporosis.

Sex Steroids

In contrast to estrogen, well-designed and adequately powered interventional trials examining the effects of testosterone replacement on bone metabolism in elderly men are lacking. Therefore, the effects of androgen supplementation on BMD are largely unknown. Testosterone has been shown to retard atherosclerosis in rodent models however, prospective or cross-sectional studies have failed to reveal any consistent association of testosterone levels and coronary artery disease (Alexandersen et al., 1999). Similarly, there is no convincing evidence supporting an association of DHEA(S) with atherosclerosis. These studies suggest that estrogen, but not testosterone or DHEA(S), plays a key role in osteoporosis and atherosclerosis.


Inflammation is an important underlying mechanism in both atherosclerosis and osteoporosis. In atherosclerosis, inflammation correlates with the severity of the disease (Libby, 2002). Inflammatory markers such as C-reactive protein (CRP), TNF-X, IL-6, and MCP-1 have been suggested as nontraditional cardiovascular risk factors (McFarlane et al., 2001). Recent clinical trials indicate that CRP is a stronger predictor for cardiovascular disease events than LDL-cholesterol (Ridker et al., 2002). Inflammatory cytokines are intricately involved in the various processes that culminate in atherosclerosis such as angiogenesis and neointimal thickening (McFarlane et al., 2002). These cytokines are produced by Osteogenic differentiation of CVC is stimulated by monocytes and macrophages through the production of inflammatory cytokines such as TNF-alpha (Shioi et al., 2002). These cytokines are also potent stimulators of 1,25 dihydroxy vitamin D in macrophages. Finally, the causal relationship of...


Hypertension is a well-established risk factor for atherosclerosis. High blood pressure is also associated with abnormalities in calcium homeostasis leading to hyper-calciuria (Cappuccio et al., 1999). This negative calcium balance is associated with decreased bone mineral density. In a prospective study involving 3676 white women, after adjusting for age, body weight, smoking, and baseline bone mineral density, higher blood pressure in elderly women was associated with increased bone loss at the femoral neck. Therefore, hypertension appears to be a common denominator in both osteoporosis and atherosclerosis in the elderly.

Diabetes Mellitus

In patients with type 1 DM, mechanisms of increased bone loss are largely unknown. These patients also suffer from increased hip fracture at a younger age (Forsen et al., 1999). Poor metabolic control in adolescents with type 1 DM is associated with increased risk for osteoporosis in adult age (Valerio et al., 2002). Studies involving animal models of type 1 DM suggest that advanced glycation end products (AGEs) inhibit osteo-blastic function through their interaction with receptors for AGE (RAGE) (Santana et al., 2003). Interestingly, the interaction of AGE with RAGE has been implicated in the vascular complications of diabetes through altered cell signaling, gene expression, release of pro-inflammatory molecules, and free radicals (Ahmed et al., 2005). These findings of inhibition of osteoblastic function as well as altered cell signaling in vascular tissue suggest common pathophysiologic mechanisms of osteoporosis and CVD.

Pharmacologic Agents

Agents that commonly are used for prevention and treatment of osteoporosis and CVD such as bisphos-phonates and statins have beneficial effects on both the bone and the vascular wall. That is not surprising given the common pathway and site of actions for each of these agents (McFarlane et al., 2002). Statins (3-hydroxy-3-methylglutaryl coenzyme-A (HMG-CoA) reductase inhibitors) commonly are used for treatment of dyslipidemia. These agents lower cholesterol by production and enhance LDL clearance. In addition, statins also reduce cellular isoprenoid intermediates, leading to decreased isoprenyla-tion and decreased activity of small GTP binding proteins from the Ras Rho family (McFarlane et al., 2002). Accumulating evidence indicate that these two classes of medications, which affect the mevalonate pathway, may modulate both osteoporosis and atherosclerosis (McFarlane et al., 2002). In addition to their pleiotropic effects on the cardiovascular system, statins also stimulate bone...


Iceland's founder population provides advantages for researchers studying complex disorders such as many of the age-associated diseases. This has been repeatedly demonstrated in recent years with the discovery of genes and biomarkers associated with cardiovascular disease, central nervous system diseases, osteoporosis, obesity, and cancer (Jonsson et al., 2004).

Ongoing research

More recent research impressively underscores the positive effect of testosterone substitution in HIV-infected hypogonadotropic men (Rabkin 2000, Grinspoon 1998). Testosterone deficiency can cause weight loss, loss of muscle mass, osteopenia, and depression (Grinspoon 1996, Huang 2001).

High bone mass

LRP5 activity is controlled by an antagonist known as Dickkopf (Dkk) (Figure 27.1). Dkk-family gene products can bind with high affinity to LRPs and prevent Wnt signaling. The LRP5 mutation associated with high bone mass allows it to escape inhibition by Dkk, and overstimulate osteoblast proliferation and differentiation, thus accounting for the phenotype (Boyden etal., 2002). Osteoporosis pseudoglioma, which has a low bone mass phenotype, is due to inactivating mutations. LRP5 mutations are of considerable importance not only in terms of understanding the pathophys-iology of bone mass, but also since the activating

Endocrine Changes

Although men do not experience a dramatic decline in sex steroid levels in midlife akin to the female menopause, there is a steady decline with aging. Around a third of men aged 70 years and over has levels of testosterone in the range that would normally be regarded as hypogonadal. Levels of the major adrenal androgen dehydroepiandrosterone also decline steadily with age. This decrease in androgen status is accompanied by, but does not entirely cause, increased fat mass, decreased muscle mass and decreased bone mineral density. Decreased androgen status often is seen particularly in patients with diabetes and is a common feature of poorly controlled diabetes, even in the young. The decline in testosterone status with aging and obesity is due partly to loss of function and number of Leydig cells. There is also a central component with reduced hypothalamic release of gonadotrophin releasing hormone (GnRH), Bone health leading to a decrease in the frequency and amplitude of...


In terms of available evidence, the best treatment for elderly obese patients is exercise. Cardio-respiratory fitness is an important determinant of health status in the elderly and can be improved by exercise. The majority of elderly women actually achieve the currently recommended levels of exercise during activities of daily living, including housework. However, this level of activity does not appear to be protective against obesity and its consequences. There is now evidence from a large number of studies that exercise in the elderly is beneficial in terms of glucose tolerance, cardiac and respiratory function, improved function and quality of life. Patients have traditionally been instructed that aerobic exercise is most beneficial. Meaningful amounts of aerobic exercise may not be achievable in many with functional limitation and severe obesity. Furthermore, there is often a worsening of symptoms and well-being in the short term, and this may decrease adherence to programs of...


Nutrients and aging genes If genes that convey longevity could be discovered, then these will be relevant to aging. This possibility rests on the likelihood that (1) especially in extreme old age, these genes may reduce rates of aging, and (2) these genes may modify cellular and biochemical pathways involved in gene-nutrient determined mechanisms of aging and age-related disease. The best-known example of such a gene is the s4 allele of the apolipoprotein E gene that decreases markedly in frequency with advancing age, whereas the much rarer e2 allele becomes more frequent. These findings are attributed to increased mortality in Alzheimer's and cardiovascular diseases associated with the fi4 allele and the slight protection afforded by the s2 allele. The siblings and children of centenarians show reduced rates of age-related cardiovascular diseases, hypertension, diabetes, and stroke but not osteoporosis, cancers, and thyroid disease, suggesting that genetic effects are greater in the...


Glucocorticosteroids have activity against prostate cancer. Their use as sole therapy is limited by long-term side effects including proximal myopathy, osteoporosis, and diabetes mellitus. While one study suggests they are as efficacious as flutamide in patients failing castration,140 in practice glucocorticosteroids are most often used as an adjunct to other therapy, such as aminoglutethimide or mitoxantrone. When used with aminoglutethimide, their primary role is to compensate for suppression of essential gluco-corticoid production by the adrenals.


Ventricular tachycardia, algorithms 121,122 Vermiculation 370 Verrucous carcinoma 404 Vertebral artery disease 295 Vertebral column carcinoma 423 infections 423 intervertebral discs 473-4 osteoporosis 480-1 pathological fractures 470 spinal cord compression 430-2 see also Cervical spine Vertebral column injury 429 dens fracture 429 fracture dislocations 429 Hangman's fracture 429 Jefferson fracture 429 stable unstable 429 Vesicoureteric junction obstruction 519 reflux 518-19 Vesicoureteric reflux 518-19 diagnosis 519 management 519 STING injection 519 Vestibular fistula 504 bucket handle deformity 504 VACTERL association 504 Video-assisted thoracopic surgery (VATS) 357-8 biopsy 358

Clinical Cohorts

The MINOS Study The MINOS Study was started in 1995 as a prospective study of osteoporosis and its determinants in men (Szulc et al., 2000). The participants are 840 men between 45 and 85 years of age who live in Montceau les Mines, France, which is a town of 21,000 inhabitants near Lyon.


The role of dyslipidemia in atherosclerosis has been clearly established. Both elevated LDL-cholesterol and reduced HDL-C are risk factors for atherosclerosis. This dyslipidemia has been shown to be related to bone mass and bone fragility and might represent a common underlying factor for both osteoporosis and atherosclerotic disease (Yamagushi et al., 2002). In a study of 214 postmenopausal Japanese women, plasma LDL-cholesterol levels were inversely correlated with bone mineral density at the forearm and the lumbar spine (Yamagushi et al., 2002). In this study, plasma HDL-C was positively correlated with BMD at the lumbar spine and at the forearm. Triglyceride (TG) predicted the presence of vertebral fractures in this cohort of post-menopausal women. This indicates that dyslipidemia is common to both atherosclerosis and osteoporosis. Consistent with these findings, the administration of high-fat diet reduced bone mineralization in mouse models (Parhami et al., 2001), suggesting that...