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109-607: Werner syndrome is named after the German scientist Otto Werner . He identified the syndrome in four siblings observed with premature aging, which he explored as the subject of his dissertation of 1904. It has a global incidence rate of less than 1 in 100,000 live births (although incidence in Japan and Sardinia is higher, affecting 1 in 20,000–40,000 and 1 in 50,000, respectively). 1,300 cases had been reported as of 2006. Affected individuals typically grow and develop normally until puberty;

218-838: A broken bone due to osteoporosis has occurred. Osteoporosis is a part of frailty syndrome . There is an increased risk of falls associated with aging. These falls can lead to skeletal damage at the wrist, spine, hip, knee, foot, and ankle. Part of the fall risk is because of impaired eyesight due to many causes, (e.g. glaucoma , macular degeneration ), balance disorder , movement disorders (e.g. Parkinson's disease ), dementia , and sarcopenia (age-related loss of skeletal muscle ). Collapse (transient loss of postural tone with or without loss of consciousness). Causes of syncope are manifold, but may include cardiac arrhythmias (irregular heart beat), vasovagal syncope , orthostatic hypotension (abnormal drop in blood pressure on standing up), and seizures . Removal of obstacles and loose carpets in

327-474: A founder effect has caused a higher incidence rate than in other populations. The incidence rate of Werner syndrome in Japan is approximately 1 case per 100 thousand people (1:100,000), a large contrast with the rate of incidence for the rest of the world, which is between 1:1,000,000 and 1:10,000,000. A founder effect is also apparent in Sardinia, where there have been 18 recorded cases of Werner syndrome. In

436-460: A gluten-free diet decreases the risk of developing osteoporosis and increases bone density. The diet must ensure optimal calcium intake (of at least one gram daily) and measuring vitamin D levels is recommended, and to take specific supplements if necessary. Osteoporosis can affect nearly 1 in 3 women and the bone loss is the most rapid within the first 2-3 years after menopause. This can be prevented by menopause hormone therapy or MHT, which

545-543: A 2.27 decrease in TUG times in their experimental group. The overall thing to note when prescribing exercise for individuals with osteoporosis is to evaluate the individual's needs and then individualize their program with multiple exercise modalities that work for them, emphasizing increasing muscle strength as well as maintaining bone mass. People with osteoporosis are at higher risk of falls due to poor postural control, muscle weakness, and overall deconditioning. Postural control

654-432: A 70‑year‑old. A number of tools exist to help determine who is reasonable to test. Lifestyle prevention of osteoporosis is in many aspects the inverse of the potentially modifiable risk factors. As tobacco smoking and high alcohol intake have been linked with osteoporosis, smoking cessation and moderation of alcohol intake are commonly recommended as ways to help prevent it. In people with coeliac disease adherence to

763-449: A benefit of vitamin D supplements combined with calcium for prevention of fractures, they did not find a benefit of vitamin D supplements (800 IU/day or less) alone. Regarding adverse effects, supplementation does not appear to affect overall risk of death, although calcium supplementation could potentially be associated with some increased risk of myocardial infarctions , stroke , kidney stones , and gastrointestinal symptoms. There

872-432: A bone include a fall from standing height, normal day-to-day activities such as lifting, bending, or coughing. Fractures are a common complication of osteoporosis and can result in disability. Acute and chronic pain in the elderly is often attributed to fractures from osteoporosis and can lead to further disability and early mortality. These fractures may also be asymptomatic. The most common osteoporotic fractures are of

981-462: A clinical FRAX is advised at age 50. Osteoporosis occurs when reduction in bone mass surpasses a critical threshold with greater susceptibility to fracturing. Fractures occur when the force acting on a bone is greater than the strength of the bone. To understand the pathology of osteoporosis and skeletal degradation, studying the mechanical properties and behavior of bone is crucial, due to the under-diagnosing of osteoporosis. Mechanical properties of

1090-544: A connection between the loss of the WRN helicase activity and telomere and cell instability. While evidence shows that telomere dysfunction is consistent with the premature aging in WS, it has yet to be determined if it is the actual cause of the genomic instability observed in cells and the high rate of cancer in WS patients. Without the WRN protein, the interwoven pathways of DNA repair and telomere maintenance fail to suppress cancer and

1199-558: A form of DNA damage that results in a break of both strands of DNA. Thus, RecQ helicases are important for maintaining DNA stability, and loss of function of these helicases has important implications in the development of Werner syndrome. In addition to the central domain, there are three exonuclease domains at the N-terminus and a Helicase and Ribonuclease D C-terminal (HRDC) domain at the C-terminus . When functioning normally,

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1308-514: A good diet, exercise, and fall prevention . Lifestyle changes such as stopping smoking and not drinking alcohol may help. Bisphosphonate medications are useful to decrease future broken bones in those with previous broken bones due to osteoporosis. In those with osteoporosis but no previous broken bones, they are less effective. They do not appear to affect the risk of death. Osteoporosis becomes more common with age. About 15% of Caucasians in their 50s and 70% of those over 80 are affected. It

1417-422: A material depend on the geometry and inherent structure of the materials. Bone as a material is very complex because of its hierarchal structure in which characteristics vary across length scales. At the basic scale, bone is composed of an organic matrix of collagen type-I. Collagen type-I molecules form a composite material with hydroxyapatite to make up collagen fibrils. The hierarchal structure continuous with

1526-408: A middle-aged man in his only appearance in the sequel Metal Gear Solid 2: Sons of Liberty . This article incorporates public domain text from The U.S. National Library of Medicine Otto Werner Carl Wilhelm Otto Werner (1 February 1879 – 5 June 1936) was a German physician , after whom Werner syndrome , a form of progeria , was named. As a medical student in 1903, Werner observed

1635-509: A need for supervision and precautionary measures. Studies of the benefits of supplementation with calcium and vitamin D are conflicting, possibly because most studies did not have people with low dietary intakes. A 2018 review by the USPSTF found low-quality evidence that the routine use of calcium and vitamin D supplements (or both supplements together) did not reduce the risk of having an osteoporotic fracture in male and female adults living in

1744-493: A negative effect on bone density). Risk of adverse events from the types of exercise usually considered appropriate for people with osteoporosis is generally low (though repeated forceful forward spinal bends are discouraged). For people who have had vertebral fractures, there is moderate-quality evidence that exercise is likely to improve physical performance, as well as some low-quality evidence suggesting that exercise may reduce pain and improve quality of life. Osteoporosis

1853-493: A normal cell, the telomeres (the ends of chromosomes) undergo repeated shortening during the cell cycle , which can prevent the cell from dividing and multiplying. This event can be counteracted by telomerase , an enzyme that extends the ends of the chromosomes by copying the telomeres and synthesizing an identical, but new end that can be added to the existing chromosome. However, patients with Werner syndrome often exhibit accelerated telomere shortening, indicating that there may be

1962-501: A range of mutations in the gene, WRN , the only gene currently attributed to cause Werner syndrome. WRN , which lies on chromosome 8 in humans, encodes the WRNp protein, a 1432 amino acid protein with a central domain resembling members of the RecQ helicases. RecQ helicases are a special type of helicase that function at unique times during DNA repair of doubled stranded breaks, which are

2071-687: A result, WS cells show a drastic reduction in replicative lifespan and enter into a stage of aging prematurely. The accumulation of these damaged cells due to telomere shortening over many years may be indicative of why Werner syndrome symptoms only appear after an individual is about twenty years old. WRN protein was found to have a specific role in preventing or repairing DNA damages resulting from chronic oxidative stress , particularly in slowly replicating cells. This finding suggested that WRN may be important in dealing with oxidative DNA damage that underlies normal aging (see DNA damage theory of aging ). A cure for Werner syndrome has not yet been discovered. It

2180-634: A separate radiation dose, is sensitive to change over time, can analyze a region of any size or shape, excludes irrelevant tissue such as fat, muscle, and air, and does not require knowledge of the patient's subpopulation in order to create a clinical score (e.g. the Z-score of all females of a certain age). Among QCT's disadvantages: it requires a high radiation dose compared to DXA, CT scanners are large and expensive, and because its practice has been less standardized than BMD, its results are more operator-dependent. Peripheral QCT has been introduced to improve upon

2289-450: A spinal fracture index that takes into account the number of vertebrae involved. Involvement of multiple vertebral bodies leads to kyphosis of the thoracic spine, leading to what is known as dowager's hump . Dual-energy X-ray absorptiometry (DEXA scan) is considered the gold standard for the diagnosis of osteoporosis. Osteoporosis is diagnosed when the bone mineral density is less than or equal to 2.5 standard deviations below that of

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2398-642: A week, moderate to high intensity, activities should be multidirectional, and load should be more than typical everyday load on bones. Some examples of exercises are jumping, skipping, hopping, depth jumps, etc.  Recommended dosage for progressive resistance training is 2 or more days a week, intensity (load) should start low and increase gradually. Resistance training should focus on major muscle groups used for functional movements as well as muscles that have direct stress on bones susceptible to fracture. Considerations for resistance training are to teach proper lifting techniques and be careful with lifting weights above

2507-446: A young (30–40-year-old ), healthy adult women reference population. This is translated as a T-score . But because bone density decreases with age, more people become osteoporotic with increasing age. The World Health Organization has established the following diagnostic guidelines: The International Society for Clinical Densitometry takes the position that a diagnosis of osteoporosis in men under 50 years of age should not be made on

2616-413: Is a stub . You can help Misplaced Pages by expanding it . Osteoporosis Osteoporosis is a systemic skeletal disorder characterized by low bone mass , micro-architectural deterioration of bone tissue leading to more porous bone, and consequent increase in fracture risk. It is the most common reason for a broken bone among the elderly . Bones that commonly break include the vertebrae in

2725-399: Is a very prevalent disease in the elderly population but not much is known about the optimal prescription and dosage of physical exercise to help prevent bone mineral loss. A lot of the focus around osteoporosis is also prevention and not so much maintenance which should be the front runner when considering what approach to take. When prescribing exercise, an aspect to take into consideration is

2834-734: Is also generally the earliest observed symptom, with hair loss occurring first on the scalp and the eyebrows. Werner syndrome patients often have skin that appears shiny and tight, and may also be thin or hardened. This is due to atrophy of the subcutaneous tissue and dermal fibrosis. Over time, the characteristic facial features may be more apparent due to these skin conditions. Other associated skin conditions include ulcers, which are very difficult to treat in Werner syndrome patients, and are caused in part by decreased potential of skin cells for replication. WS cataracts are distinctly different from those of normal aging. They are associated with problems in

2943-422: Is an imbalance between bone resorption and bone formation . In normal bone, matrix remodeling of bone is constant; up to 10% of all bone mass may be undergoing remodeling at any point in time. The process takes place in bone multicellular units (BMUs) as first described by Frost & Thomas in 1963. Osteoclasts are assisted by transcription factor PU.1 to degrade the bone matrix, while osteoblasts rebuild

3052-405: Is an obvious cost but it can be justified by the advantage of bipedalism inferring that this vulnerability is the byproduct of such. It has been suggested that porous bones help to absorb the increased stress that we have on two surfaces compared to our primate counterparts who have four surfaces to disperse the force. In addition, the porosity allows for more flexibility and a lighter skeleton that

3161-540: Is available to be translated into the WRNp protein. Mutations may also lead to the truncation (shortening) of the WRNp protein, leading to the loss of its nuclear localization signal sequence , thus it is no longer transported into the nucleus where it interacts with the DNA. This leads to a reduction in DNA repair. Furthermore, mutated proteins are more likely to be degraded than normal WRNp. Apart from causing defects in DNA repair, its aberrant association with p53 down-regulates

3270-430: Is based on six cardinal symptoms: premature graying of the hair or hair loss, presence of bilateral cataracts, atrophied or tight skin, soft tissue calcification, sharp facial features, and an abnormal, high-pitched voice. Patients are generally short-statured due to absence of the adolescent growth spurt. Patients also display decreased fertility. The most common symptom of the six is premature graying and loss of hair. This

3379-428: Is defined as a bone density of 2.5 standard deviations below that of a young adult. This is typically measured by dual-energy X-ray absorptiometry (DXA or DEXA). Prevention of osteoporosis includes a proper diet during childhood, hormone replacement therapy for menopausal women, and efforts to avoid medications that increase the rate of bone loss. Efforts to prevent broken bones in those with osteoporosis include

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3488-427: Is easier to support. One other consideration may be that diets today have much lower amounts of calcium than the diets of other primates or the tetrapedal ancestors to humans which may lead to higher likelihood to show signs of osteoporosis. In the absence of risk factors other than sex and age a BMD measurement using dual-energy X-ray absorptiometry (DXA) is recommended for women at age 65. For women with risk factors

3597-403: Is emerging with regard to other drugs. Osteoporosis due to pregnancy and lactation is a rare condition of unknown cause. Age-related bone loss is common among humans due to exhibiting less dense bones than other primate species. Because of the more porous bones of humans, frequency of severe osteoporosis and osteoporosis related fractures is higher. The human vulnerability to osteoporosis

3706-440: Is essential because the structure will translate to the mechanical behavior of bones. Previous work indicates that osteoporotic bones undergo specific structural changes that contribute to altered mechanical behavior. For instance, a study demonstrated that osteoporotic bone exhibits reduced bone volume fraction, trabecular thickness, and connectivity. In another study, osteoporosis in human cancellous bone led to 3-27% variability in

3815-518: Is from the Greek terms for "porous bones". Osteoporosis has no symptoms and the person usually does not know that they have osteoporosis until a bone is broken. Osteoporotic fractures occur in situations where healthy people would not normally break a bone; they are therefore regarded as fragility fractures . Typical fragility fractures occur in the vertebral column , rib , hip and wrist . Examples of situations where people would not normally break

3924-653: Is important to maintaining functional movements such as walking and standing. Physical therapy may be an effective way to address postural weakness that may result from vertebral fractures, which are common in people with osteoporosis. Physical therapy treatment plans for people with vertebral fractures include balance training, postural correction, trunk and lower extremity muscle strengthening exercises, and moderate-intensity aerobic physical activity. The goal of these interventions are to regain normal spine curvatures, increase spine stability, and improve functional performance. Physical therapy interventions were also designed to slow

4033-479: Is insufficient evidence to make recommendations about the intervals for repeated screening and the appropriate age to stop screening. In men the harm versus benefit of screening for osteoporosis is unknown. Prescrire states that the need to test for osteoporosis in those who have not had a previous bone fracture is unclear. The International Society for Clinical Densitometry suggest BMD testing for men 70 or older, or those who are indicated for risk equal to that of

4142-529: Is lower than that normally needed to stimulate the uterus and breast gland . The α-form of the estrogen receptor appears to be the most important in regulating bone turnover. In addition to estrogen, calcium metabolism plays a significant role in bone turnover, and deficiency of calcium and vitamin D leads to impaired bone deposition; in addition, the parathyroid glands react to low calcium levels by secreting parathyroid hormone (parathormone, PTH), which increases bone resorption to ensure sufficient calcium in

4251-418: Is meant to prevent bone loss and the degradation of the bone microarchitecture and is noted to reduce the risk of fractures in bones by 20-30%. However, MHT has been linked to safety concerns, so it is not generally recommended. As far as management goes with this potentially limiting disease, there are practices that can and should be implemented within the daily lifestyle. For example, it would be beneficial if

4360-608: Is more common in women than men. In the developed world , depending on the method of diagnosis, 2% to 8% of males and 9% to 38% of females are affected. Rates of disease in the developing world are unclear. About 22 million women and 5.5 million men in the European Union had osteoporosis in 2010. In the United States in 2010, about 8 million women and between 1 and 2 million men had osteoporosis. White and Asian people are at greater risk. The word "osteoporosis"

4469-449: Is no evidence that supplementation before menopause can enhance bone mineral density. Vitamin K deficiency is also a risk factor for osteoporotic fractures. The gene gamma-glutamyl carboxylase (GGCX) is dependent on vitamin K. Functional polymorphisms in the gene could attribute to variation in bone metabolism and BMD. Vitamin K2 is also used as a means of treatment for osteoporosis and

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4578-520: Is often treated by managing the associated diseases and relieving symptoms to improve quality of life. The skin ulcers that accompany WS can be treated in several ways, depending on the severity. Topical treatments can be used for minor ulcers, but are not effective in preventing new ulcers from occurring. In the most severe cases, surgery may be required to implant a skin graft or amputate a limb if necessary. Diseases commonly associated with Werner syndrome such as diabetes and cancer are treated in generally

4687-448: Is only functional when localized to the nucleus. The finding that WRN protein interacts with DNA-PKcs and the Ku protein complex, combined with evidence that WRN deficient cells produce extensive deletions at sites of joining of non-homologous DNA ends, suggests a role for WRN protein in the DNA repair process of non-homologous end joining (NHEJ). WRN protein also physically interacts with

4796-682: Is relatively insensitive to detection of early disease and requires a substantial amount of bone loss (about 30%) to be apparent on X-ray images. The main radiographic features of generalized osteoporosis are cortical thinning and increased radiolucency. Frequent complications of osteoporosis are vertebral fractures for which spinal radiography can help considerably in diagnosis and follow-up. Vertebral height measurements can objectively be made using plain-film X-rays by using several methods such as height loss together with area reduction, particularly when looking at vertical deformity in T4-L4, or by determining

4905-542: Is replaced more often than cortical bone, providing early evidence of metabolic change. Also, the calcaneus is fairly flat and parallel, reducing repositioning errors. The method can be applied to children, neonates, and preterm infants, just as well as to adults. Some ultrasound devices can be used on the tibia . The U.S. Preventive Services Task Force (USPSTF) recommend that all women 65 years of age or older be screened by bone densitometry . Additionally they recommend screening younger women with risk factors. There

5014-422: Is sometimes the best medicine. Resistance training is the most recommended method of physical activity but that can come in multiple forms. High intensity and high impact training is shown to be extremely beneficial in improving bone health and the most effective in improving, maintaining, bone density in the lower spine and femur. Although these types of exercises are safe for postmenopausal women, there still may be

5123-513: Is the sponge-like bone in the ends of long bones and vertebrae. Cortical bone is the hard outer shell of bones and the middle of long bones. Because osteoblasts and osteoclasts inhabit the surface of bones, trabecular bone is more active and is more subject to bone turnover and remodeling. Not only is bone density decreased, but the microarchitecture of bone is also disrupted. The weaker spicules of trabecular bone break ("microcracks"), and are replaced by weaker bone. Common osteoporotic fracture sites,

5232-560: Is theoretically modifiable, although in many cases, the use of medication that increases osteoporosis risk may be unavoidable. Caffeine is not a risk factor for osteoporosis. Many diseases and disorders have been associated with osteoporosis. For some, the underlying mechanism influencing the bone metabolism is straightforward, whereas for others the causes are multiple or unknown. Certain medications have been associated with an increase in osteoporosis risk; only glucocorticosteroids and anticonvulsants are classically associated, but evidence

5341-755: The Achilles tendon and malleoli (around ankles). Other symptoms include change in voice (weak, hoarse, high-pitched), atrophy of gonads leading to reduced fertility , bilateral cataracts (clouding of lens), premature arteriosclerosis (thickening and loss of elasticity of arteries), calcinosis (calcium deposits in blood vessels), atherosclerosis (blockage of blood vessels), type 2 diabetes , osteoporosis (loss of bone mass), telangiectasia , and malignancies . The prevalence of rare cancers, such as meningiomas , are increased in individuals with Werner syndrome. Gene transcription changes found in WS cells are strikingly similar to those observed in normal aging. At

5450-509: The Metal Gear franchise, several characters visually suffer from the effects of Werner Syndrome. The first character is Solid Snake , who suffers from rapidly accelerated aging, despite being a young man. By the time of his early 40s, he appears to be in his early 70s. This is revealed to be the side effect of being a genetically engineered "test-tube baby", specifically made to be a clone of Big Boss (Metal Gear) . Solid Snake's genetic code

5559-525: The WRN gene and its associated protein (WRNp) are important for maintaining genome stability. WRNp is active in unwinding DNA, a step necessary in DNA repair and DNA replication . Specifically, it has an important role in responding to replication malfunctions, particularly double-stranded breaks , and stalled replication machinery. WRNp may reactivate replication by preventing unwanted recombination processes from occurring or by promoting recombination, depending on

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5668-686: The Wnt signaling pathway is recognized, but less well understood. Local production of eicosanoids and interleukins is thought to participate in the regulation of bone turnover, and excess or reduced production of these mediators may underlie the development of osteoporosis. Osteoclast maturation and activity is also regulated by activation of colony stimulating factor 1 receptor (CSF1R). Menopause -associated increase production of TNF-α stimulates stromal cells to produce colony stimulating factor 1 (CSF-1) which activates CSF1R and stimulates osteoclasts to reabsorb bone. Trabecular bone (or cancellous bone)

5777-404: The bone mineral density (BMD). The most popular method of measuring BMD is dual-energy X-ray absorptiometry . In addition to the detection of abnormal BMD, the diagnosis of osteoporosis requires investigations into potentially modifiable underlying causes; this may be done with blood tests . Depending on the likelihood of an underlying problem, investigations for cancer with metastasis to

5886-542: The lens posterior cortex and subcapsular regions. These cataracts are generally treatable with cataract surgery , which should restore normal vision. Symptoms become apparent in the late teens and early twenties and continue to progress. Most patients live to about fifty years of age. The most common causes of death for people are associated diseases and complications, especially atherosclerosis and cancer. Werner syndrome patients are at increased risk for several other diseases, many associated with aging. Atherosclerosis ,

5995-446: The osteoblast and toward the marrow adipocyte lineage. An interplay of these three mechanisms underlies the development of fragile bone tissue. Hormonal factors strongly determine the rate of bone resorption; lack of estrogen (e.g. as a result of menopause) increases bone resorption, as well as decreasing the deposition of new bone that normally takes place in weight-bearing bones. The amount of estrogen needed to suppress this process

6104-495: The p38 signaling pathway, which may become activated as a result of genomic instability and stalled replication forks that are characteristic mutations in WS. This activation of p38 may play a role in the onset of premature cell aging, skin aging, cataracts, and graying of the hair. The p38 pathway has also been implicated in the inflammatory response that causes atherosclerosis, diabetes, and osteoporosis, all of which are associated with Werner's syndrome. This drug has shown to revert

6213-474: The spine , the bones of the forearm , the wrist , and the hip . Until a broken bone occurs there are typically no symptoms. Bones may weaken to such a degree that a break may occur with minor stress or spontaneously. After the broken bone heals, some people may have chronic pain and a decreased ability to carry out normal activities. Osteoporosis may be due to lower-than-normal maximum bone mass and greater-than-normal bone loss. Bone loss increases after

6322-753: The ACSM general training principle to better design a program for the individual. Which mode of exercise and dosage has been a recurring question for treating osteoporosis, many articles have found that multimodal exercise programs have had findings of significant improvement in factors related to osteoporosis. Factors include lower limb strength, balance, flexibility, and risk of falls. Other modes of exercise have also proven to improve individuals with osteoporosis, some of these modes include weight-bearing, resistance specifically progressive resistance, and aerobic exercise. The recommendations for these types of exercises are as follows, weight-bearing exercise should be done 4-7 days

6431-490: The aged characteristics of young WS cells to those seen in normal, young cells and improve the lifespan of WS cells in vitro . SB203580 is in the clinical trial stages, and the same results have not yet been seen in vivo . In 2010, vitamin C supplementation was found to reverse the premature aging and several tissue dysfunctions in a genetically modified mouse model of the disease. Vitamin C supplementation also appeared to normalize several age-related molecular markers such as

6540-434: The aging symptoms seen in patients with WS. Events such as rapid telomere shortening cause Werner syndrome cells to exhibit low responses to overall cellular stress. In addition to telomere dysfunction, over-expression of oncogenes and oxidation can induce this type of response. High stress causes a synergistic effect, where WS cells become even more sensitive to agents that increase cell stress and agents that damage DNA. As

6649-501: The basis of densitometric criteria alone. It also states, for premenopausal women, Z-scores (comparison with age group rather than peak bone mass) rather than T-scores should be used, and the diagnosis of osteoporosis in such women also should not be made on the basis of densitometric criteria alone. Chemical biomarkers are a useful tool in detecting bone degradation. The enzyme cathepsin K breaks down type-I collagen , an important constituent in bones. Prepared antibodies can recognize

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6758-732: The blood. The role of calcitonin , a hormone generated by the thyroid that increases bone deposition, is less clear and probably not as significant as that of PTH. The activation of osteoclasts is regulated by various molecular signals, of which RANKL (receptor activator of nuclear factor kappa-B ligand) is one of the best-studied. This molecule is produced by osteoblasts and other cells (e.g. lymphocytes ), and stimulates RANK (receptor activator of nuclear factor κB). Osteoprotegerin (OPG) binds RANKL before it has an opportunity to bind to RANK, and hence suppresses its ability to increase bone resorption. RANKL, RANK, and OPG are closely related to tumor necrosis factor and its receptors. The role of

6867-509: The bone matrix. These alterations in composition contribute to how bone can handle mechanical loading. Thus, osteoporosis-induced changes at the macroscopic and microscopic levels significantly impact the mechanical properties of bone, predisposing individuals to fractures even under relatively low mechanical loads. Understanding these structural alterations is vital for developing effective diagnostic and therapeutic strategies for osteoporosis. The underlying mechanism in all cases of osteoporosis

6976-455: The bone matrix. Low bone mass density can then occur when osteoclasts are degrading the bone matrix faster than the osteoblasts are rebuilding the bone. The three main mechanisms by which osteoporosis develops are an inadequate peak bone mass (the skeleton develops insufficient mass and strength during growth), excessive bone resorption, and inadequate formation of new bone during remodeling, likely due to mesenchymal stem cells biasing away from

7085-521: The bone, multiple myeloma, Cushing's disease and other above-mentioned causes may be performed. Conventional radiography is useful, both by itself and in conjunction with CT or MRI, for detecting complications of osteopenia (reduced bone mass; pre-osteoporosis), such as fractures; for differential diagnosis of osteopenia; or for follow-up examinations in specific clinical settings, such as soft tissue calcifications, secondary hyperparathyroidism, or osteomalacia in renal osteodystrophy. However, radiography

7194-479: The community who had no known history of vitamin D deficiency, osteoporosis, or a fracture. The USPSTF does not recommend low dose supplementation (less than 1 g of calcium and 400 IU of vitamin D) in postmenopausal women as there does not appear to be a difference in fracture risk. A 2015 review found little data that supplementation of calcium decreases the risk of fractures. While some meta-analyses have found

7303-566: The daughter of a physician. He then began a rural medical practice based in Eddelak , a small German town near the Danish border. There, he remained for the rest of his life, except for his service as a medical officer with the German Navy during World War I . He died of liver cancer a few months after his 57th birthday. This article about a German person in the field of medicine

7412-437: The development of osteoporosis through therapeutic exercise. Prescribed amounts of mechanical loading or increased forces on the bones promote bone formation and vascularization in various ways, therefore offering a preventative measure that is not reliant on drugs. Specific exercise interacts with the body's hormones and signaling pathways which encourages the maintenance of a healthy skeleton. Reduced estrogen levels increase

7521-432: The discovery of the gene, it has become clear that the premature aging displayed in Werner syndrome is not the same, on a cellular level, as normal aging. The role of WRN in DNA repair and its exonuclease and helicase activities have been the subject of many studies in recent years. Since the initial discovery in 1904, several other cases of Werner syndrome have been recorded. Many of these cases have occurred in Japan, where

7630-436: The effects of Werner's Syndrome, he is injected with a nanomachine-borne virus named "FOXDIE" that, over a long enough period of time, will cause rapid aging and premature death in the victim. However, FOXDIE causes Liquid Snake to suffer from a fatal heart attack before he can live long enough to see the apparent effects of Werner's Syndrome. Solidus Snake, never having been injected with FOXDIE, but ages naturally, and appears as

7739-407: The evidence shows no adverse effect of higher protein intake on bone health. Evidence suggests that exercise can help promote bone health in older people. In particular, physical exercise can be beneficial for bone density in postmenopausal women, and lead to a slightly reduced risk of a bone fracture (absolute difference 4%). Weight bearing exercise has been found to cause an adaptive response in

7848-399: The fibrils being arranged into different patterns such as lamellae. The microstructure of bone then forms vascular channels, called osteons, which are surrounded by lamellae. At the subsequent scale of bones, there are different types of bone based on morphology: cortical (solid), cancellous (sponge), or trabecular (thin plates).   A basic picture of the hierarchical structure of bones

7957-411: The financial costs to health care systems. The risk of having osteoporosis includes age and sex. Risk factors include both nonmodifiable (for example, age and some medications that may be necessary to treat a different condition) and modifiable (for example, alcohol use, smoking, vitamin deficiency). In addition, osteoporosis is a recognized complication of specific diseases and disorders. Medication use

8066-462: The function of p53, leading to a reduction in p53-dependent apoptosis and increasing the survival of these dysfunctional cells. Cells of affected individuals also have reduced lifespan in culture , have more chromosome breaks and translocations and have extensive deletions. Patients with Werner syndrome lose the RecQ helicase activity in the WRN protein because of the loss of its C-terminus region, but

8175-472: The head. Lastly, aerobic exercise has minimal effect on preventing BMD loss unless done at a higher intensity or with a load like a weighted vest. Considerations with this mode are that this may cause a higher risk of fall or fracture. Improvements can also be observed in other ways, such as decreased Timed-Up-and-Go, increased Sit-To-Stand, and increased One-Leg-Stance-Test. A study with a 12-week exercise intervention on postmenopausal osteoporotic women observed

8284-412: The increased levels of the transcription factor NF-κB . In addition, it decreases activity of genes activated in human Werner syndrome and increases gene activity involved in tissue repair. Supplementation of vitamin C is suspected to be beneficial in the treatment of human Werner syndrome, although there was no evidence of anti-aging activity in nonmutant mice. In general, treatments are available for only

8393-416: The individual with osteoporosis refrained from consuming excess alcohol and to avoid smoking. These individuals should also be intentional about intaking an adequate amount of protein, calcium, and vitamin D. If the woman has an even higher risk of fracture, managing this may require therapy. Generally, the recommended treatment of prevention for a decrease in bone mineral density is physical activity. Exercise

8502-597: The individual’s need this can be attained by conducting a pre-exercise evaluation or screening, exercise should also be tailored to the individual and what works for them. Important things often overlooked when treating osteoporosis are muscle strength and maintenance of BMD, which should be incorporated into the program to optimize the benefits of exercise. This entails including exercises that focus on and improve muscle strength and exercises that focus on and improve skeletal strength or BMD as these go hand in hand for reducing fall and fracture risk. It’s also important to reference

8611-431: The level of gene expression, WRN protein deficiency causes changes in the pattern of gene expression that markedly resemble those of normal old age. The mutation in the WRN gene that causes Werner syndrome is autosomal and recessive, meaning that affected people must inherit a copy of the gene from each parent. Patients display rapid premature aging beginning in young adulthood, usually in their early twenties. Diagnosis

8720-424: The limitations of DXA and QCT. Quantitative ultrasound has many advantages in assessing osteoporosis. The modality is small, no ionizing radiation is involved, measurements can be made quickly and easily, and the cost of the device is low compared with DXA and QCT devices. The calcaneus is the most common skeletal site for quantitative ultrasound assessment because it has a high percentage of trabecular bone that

8829-455: The living environment may substantially reduce falls. Those with previous falls, as well as those with gait or balance disorders, are most at risk. As well as susceptibility to breaks and fractures, osteoporosis can lead to other complications. Bone fractures from osteoporosis can lead to disability and an increased risk of death after the injury in elderly people. Osteoporosis can decrease the quality of life, increase disabilities, and increase

8938-491: The long bones acutely impair mobility and may require surgery . Hip fracture , in particular, usually requires prompt surgery, as serious risks are associated with it, such as deep vein thrombosis and pulmonary embolism . There is also an increased risk of mortality associated with osteoporosis-related hip fracture, with the mean average mortality rate within one year for Europe being 23.3%, for Asia 17.9%, United States 21% and Australia 24.9%. Fracture risk calculators assess

9047-448: The major NHEJ factor X4L4 ( XRCC4 - DNA ligase 4 complex). X4L4 stimulates WRN exonuclease activity that likely facilitates DNA end processing prior to final ligation by X4L4. WRN protein appears to play a role in resolving recombination intermediate structures during homologous recombinational repair (HRR) of DNA double-strand breaks. WRN protein participates in a complex with RAD51 , RAD54, RAD54B and ATR proteins in carrying out

9156-666: The mean age of diagnosis is twenty-four, often realized when the adolescent growth spurt is not observed. The youngest person diagnosed was six years old. The median and mean ages of death are 47–48 and 54 years, respectively. The main causes of death are cardiovascular disease and cancer. Werner syndrome patients exhibit growth retardation, short stature, premature graying of hair, alopecia (hair loss), wrinkling , prematurely aged faces with beaked noses , skin atrophy (wasting away) with scleroderma -like lesions , lipodystrophy (loss of fat tissues), abnormal fat deposition leading to thin legs and arms, and severe ulcerations around

9265-472: The mechanism by which this happens is unclear. The loss of the helicase activity can have far-reaching consequences in terms of cell stability and mutation. One instance of these consequences involves telomeres . It is thought that the WRN helicase activity is important not only for DNA repair and recombination, but also for maintaining telomere length and stability. Thus, WRN helicase is important for preventing catastrophic telomere loss during DNA replication. In

9374-598: The menopause due to lower levels of estrogen , and after " andropause " due to lower levels of testosterone . Osteoporosis may also occur due to a number of diseases or treatments, including alcoholism , anorexia , hyperthyroidism , kidney disease , and surgical removal of the ovaries . Certain medications increase the rate of bone loss, including some antiseizure medications , chemotherapy , proton pump inhibitors , selective serotonin reuptake inhibitors , and glucocorticosteroids . Smoking and getting an inadequate amount of exercise are also risk factors. Osteoporosis

9483-604: The most common cancer types. Other types of skin cancer, other epithelial cancers such as thyroid and liver cancers, MDS ( myelodysplastic syndrome ), and MFH ( malignant fibrous histiocytoma ) are also prevalent among. Mutations in the WRN gene, especially single-nucleotide polymorphisms (SNPs), are associated with many of the cancers and other associated diseases. WRN SNPs correlate with cancers such as sarcomas and non-Hodgkin lymphomas, as well as diabetes and cardiovascular problems including atherosclerosis. Approximately 90% of individuals presenting Werner syndrome have any of

9592-526: The normal population, the rate of osteoporosis is especially high for male patients. Diabetes mellitus is another common accompaniment. Skin ulcers occur in about 75% of patients – and can be difficult to treat. If skin ulcers become badly infected or develop gangrene , they often require amputation . Unlike most other related diseases and complications, these ulcers are not associated with normal aging. Patients are also at an increased risk of cancer, especially malignant melanoma . Soft-tissue sarcomas are

9701-466: The polymorphisms of GGCX could explain the individual variation in the response to treatment of vitamin K. Dietary sources of calcium include dairy products, leafy greens, legumes, and beans. There has been conflicting evidence about whether or not dairy is an adequate source of calcium to prevent fractures. The National Academy of Sciences recommends 1,000 mg of calcium for those aged 19–50, and 1,200 mg for those aged 50 and above. A review of

9810-446: The production of Insulin-like growth factors in the bone, but at a greater extent. Post-menopausal women experience a reduction of estrogen, which is essential for density, so these exercise-induced hormonal enhancements can counteract the loss of bone mineral density in the most critical area, like the lumbar spine and the femoral neck. Research suggest that regular resistance training accompanied with weight-bearing activities help reduce

9919-402: The rate of bone loss through home exercise programs. Whole body vibration therapy has also been suggested as a physical therapy intervention. Moderate to low-quality evidence indicates that whole body vibration therapy may reduce the risk of falls. There are conflicting reviews as to whether vibration therapy improves bone mineral density. Physical therapy can aid in overall prevention in

10028-410: The recombination step during inter-strand DNA cross-link repair. Evidence was presented that WRN protein plays a direct role in the repair of methylation induced DNA damage . This process likely involves the helicase and exonuclease activities of WRN protein that operate together with DNA polymerase beta in long patch base excision repair . Mutations which cause Werner syndrome all occur at

10137-429: The regions of the gene which encode for protein, and not at non-coding regions. There are 35 different known mutations of WRN , which correspond to stop codons , insertions , or deletions that result in a frameshift mutation. These mutations can have a range of effects. They may decrease the stability of the transcribed messenger RNA (mRNA), which increases the rate at which they are degraded. With less mRNA, less

10246-544: The release of growth hormone and Insulin-like growth factor-1 or IGF-1 that participate in bone remodeling. Stress is applied to the bones, thus activating osteoblast, which are cells that form new bones and grow and heal existing bones while restoring hormones that increase bone density. Resistance training exercises, like weight lifting, can lead to brief increased in anabolic hormones, like testosterone, which aid in muscle and bone strength. The increase in mechanical tension during resistance exercise will likely help stimulate

10355-567: The resulting fragment, called a neoepitope , as a way to diagnose osteoporosis. Increased urinary excretion of C-telopeptides , a type-I collagen breakdown product, also serves as a biomarker for osteoporosis. Quantitative computed tomography (QCT) differs from DXA in that it gives separate estimates of BMD for trabecular and cortical bone and reports precise volumetric mineral density in mg/cm rather than BMD's relative Z-score. Among QCT's advantages: it can be performed at axial and peripheral sites, can be calculated from existing CT scans without

10464-459: The risk of fracture based upon several criteria, including bone mineral density , age, smoking, alcohol usage, weight, and gender. Recognized calculators include FRAX , the Garvan FRC calculator and QFracture as well as the open access FREM tool. The FRAX tool can also be applied in a modification adapted to routinely collected health data. The term "established osteoporosis" is used when

10573-525: The risk of osteoporosis, so hormone replacement therapy when women reach the menopause may reduce the incidence of osteoporosis. A more natural way of restoring hormone levels in postmenopausal women include participating in specific forms of exercise. Weight-bearing exercises and resistance training exercises such as squats with weights, step-ups, lunges, stair climbing, and even jogging can elicit hormone responses that are advantageous for post-menopausal women living with osteoporosis. These exercises result in

10682-408: The same ways as they would be for a non-Werner syndrome individual. A change in diet and exercise can help prevent and control arteriosclerosis, and regular cancer screenings can allow for early detection of cancer. There is evidence that suggests that the cytokine -suppressive anti-inflammatory drug SB203580 may be a possible therapeutic option for patients with Werner's syndrome. This drug targets

10791-790: The skeleton, promoting osteoblast activity and protecting bone density. A position statement concluded that increased bone activity and weight-bearing exercises at a young age prevent bone fragility in adults. Limitations in the available evidence hinder the production of detailed evidence-based exercise recommendations. Some expert consensus guidance does exist. International guidelines recommend multicomponent exercise tailored to individual needs that includes "balance and mobility training, paired with weight bearing exercise, progressive resistance training, and posture exercises" (generally accompanied by optimal nutrition). Cycling and swimming are not considered weight-bearing exercise, and neither helps slow age-related bone loss (professional bicycle racing has

10900-399: The stiffness and strength compared to health bone. Additionally, bone mineral density (BMD) is a parameter used to evaluate fracture risk in bones and is used as a predictor of osteoporosis. A lower BMD value correlates to decreased bone and a higher bone fragility. Furthermore, bone diseases, such as osteoporosis, are known to alter the composition of collagen and other proteins that make up

11009-412: The symptoms or complications and not for the disease itself. Otto Werner was the first to observe Werner syndrome in 1904 as a part of his dissertation research. As a German ophthalmologist , Werner described several progeria-like features and juvenile cataracts in many of his patients. He noticed these symptoms particularly in a family with four sequential children who all showed the characteristics of

11118-426: The syndrome at around the same age. He assumed the cause to be genetic, though most of his evidence was clinical. Between 1934 and 1941, two internists from New York, Oppenheimer and Kugel, coined the term "Werner Syndrome", igniting a wave of interest and research on the disease. During that time, Agatson and Gartner suggested a possible link between Werner's syndrome and cancer. However, it was not until 1966 that there

11227-637: The syndrome in four siblings near the age of 30. He documented his observations in his inaugural dissertation in 1904. Werner was born in Flensburg , the son of a provincial councillor. He attended school in Kiel and qualified to practice medicine at Christian-Albrechts-Universität zu Kiel in 1904. He served as an army doctor with the Infantry Regiment at Holstein and, in 1906, in Kiel, he married

11336-432: The thickening of artery walls due to cholesterol buildup, is one common complication. While normal atherosclerosis generally involves the major arteries, smaller arterioles are more likely to be affected. It is possible nervous system disorders are associated. Brain atrophy is present in 40% of patients. Osteoporosis , the loss of bone mineral density common in post-menopausal women, is another common symptom. In contrast with

11445-441: The type of DNA damage. In addition, WRNp physically interacts with or binds to several other proteins that are involved in processing DNA. For example, when WRNp binds to RPA, its helicase activity is stimulated. WRNp also physically interacts with p53 , a tumor suppressor gene that stops the formation of tumors and the progression of cancers, which inhibits the exonuclease activity of the WRNp. Since WRNp's function depends on DNA, it

11554-412: The wrist, spine, shoulder and hip. The symptoms of a vertebral collapse (" compression fracture ") are sudden back pain , often with radicular pain (shooting pain due to nerve root compression) and rarely with spinal cord compression or cauda equina syndrome . Multiple vertebral fractures lead to a stooped posture, loss of height, and chronic pain with resultant reduction in mobility. Fractures of

11663-458: The wrist, the hip, and the spine, have a relatively high trabecular bone to cortical bone ratio. These areas rely on the trabecular bone for strength, so the intense remodeling causes these areas to degenerate most when the remodeling is imbalanced. Around the ages of 30–35, cancellous or trabecular bone loss begins. Women may lose as much as 50%, while men lose about 30%. Osteoporosis can be diagnosed using conventional radiography and by measuring

11772-400: Was a general consensus on the autosomal recessive mode of inheritance for the syndrome. By 1981, geneticists had located the WRN gene on chromosome 8, leading to its cloning in 1996. This cloning of the WRN was significant because it revealed the predicted WRN protein was made from a family of DNA helicases . Prior to 1996, Werner syndrome was thought to be a model for accelerated aging. Since

11881-445: Was deliberately modified to make him rapidly age and die prematurely, to ensure he could not turn rogue against a powerful Shadow government (conspiracy theory) named "The Patriots". Big Boss' genetic material was also used to create two other clone children, named Liquid Snake, and Solidus Snake. Liquid Snake is the main antagonist of the 1998 entry in the franchise, Metal Gear Solid (1998 video game) . While not visually suffering from

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