The clinical presentation of osteoporosis in its early stages is asymptomatic and fractures developing as a result of bone fragility are the first manifestation of the disease [1]. Fractures in osteoporosis are seen after low-energy trauma that would otherwise be a minor injury in healthy adults, such as falling from standing height or even smaller exposure of the skeletal system to stress [2]. Fracture of the vertebral body is the most common type of fracture in this patient population, often preceded or accompanied by a progressing kyphosis of the spine [1] [2]. Fractures of the humerus, forearm, femur, and hip are also encountered [1] [2]. They are almost always accompanied by pain, which can be acute when the fracture has occurred, but chronic pain is also reported [1] [2] In addition to fractures, several physical characteristics may be observed. Shortening of the trunk, loss of height (from four to 10 or more centimeters), protrusion of the abdomen, and very long limbs compared to the trunk are some of the main findings [1] [2]. The Thannenbaum or "fir tree phenomenon" is a sign observed in osteoporosis and denotes the presence of skin folds that stretch from the back laterally to the flanks in a "hanging" fashion, resembling a fir tree [2]. Gait abnormalities are also frequent [2].

• Pain

  Osteoporosis itself is does not cause pain. But broken bones caused by osteoporosis can be painful, and sometimes lead to long-term difficulties. Spinal compression fractures can cause a change in body shape and ongoing, chronic back pain. [nos.org.uk]

  This is the first report in the literature of complex regional pain syndrome and musculoskeletal co-morbidities in an athlete, and is the first to focus on dual-energy X-ray absorptiometry for the clinical assessment of complex regional pain syndrome. [ncbi.nlm.nih.gov]

  People who have bone pain from metastatic cancer also often receive these drugs. [cancer.net]

• Falling

  Fall prevention Preventing falls is a special concern for men and women with osteoporosis. Falls can increase the likelihood of fracturing a bone in the hip, wrist, spine, or other part of the skeleton. [niams.nih.gov]

  Falls prevention and osteoporosis A third of people aged over 65 years fall every year and six per cent of those falls lead to a fracture. Reducing the risk of falls is important. [betterhealth.vic.gov.au]

  Fall Prevention Preventing falls is a special concern for men and women with osteoporosis. Falls can increase the likelihood of fracturing a bone in the hip, wrist, spine, or other part of the skeleton. [bones.nih.gov]

• Asymptomatic

  Denosumab-induced hypocalcemia is a rare but important adverse event, which is usually asymptomatic in patients with osteoporosis. It is also known that hypocalcemia is common in patients with bone metastases and severe renal impairment. [ncbi.nlm.nih.gov]

  A 65-year-old asymptomatic man is concerned about his risk of osteoporosis. His mother died after a hip fracture at 74 years of age. [doi.org]

• Underweight

  Severely restricting food intake and being underweight weakens bone in both men and women. Gastrointestinal surgery. [mayoclinic.org]

  Not smoking cigarettes Eating foods with plenty of calcium and vitamin D, including dairy products, kale, broccoli, canned salmon, and sardines Regular weight-bearing exercise such as walking, dancing, or climbing stairs Eating enough to avoid being underweight [jamanetwork.com]

• Severe Pain

  Common complaints announced by patients are severe pain in the lower back, hips and the joints of the lower extremities with a reduced and less mobility status in general. [ncbi.nlm.nih.gov]

  Sufferers of these serious yet largely preventable injuries often experience severe pain, long-term disability and even early death. The burden to health systems, economies and society is also huge – and on the increase. [iofbonehealth.org]

• Dysphagia

  Possible side effects include upper gastrointestinal disorders such as dysphagia, esophagitis, and esophageal or gastric ulcer. To reduce the risk of side effects, take these medications on an empty stomach with 8 oz. of tap water. [web.archive.org]

  Caution often is advised for people with dysphagia (trouble swallowing) because the dysphagia may be a manifestation of a problem in the esophagus that will cause the bisphosphonate tablets to get stuck. [medicinenet.com]

  The main side effects associated with bisphosphonates include: irritation to the oesophagus (the tube that food passes through from the mouth to the stomach) swallowing problems (dysphagia) stomach pain Not everyone will experience these side effects. [nhsinform.scot]

  […] ulcerations, perforations, bleeding events, muscular and joint pains Contraindications: abnormalities of the esophagus; inability to stand or sit upright for at least 30 minutes; hypersensitivity to any product component; increased risk of aspiration or dysphagia [aafp.org]

• Visual Impairment

  Clinically identifiable risk factors were identified across 6 domains: orthostatic hypotension, visual impairment, impairment of gait or balance, medication use, limitations in basic or instrumental activities of daily living, and cognitive impairment [doi.org]

  Other risk factors have been identified in the elderly, such as visual impairment, urinary incontinence, functional disability, orthostatic hypotension and alcohol consumption. [english.prescrire.org]

  epileptic seizure, cognitive impairment, visual impairment, balance impairment Cardiovascular disease Drugs - Levodopa induced dyskinesia Multiple sclerosis[edit] Evidence show that there is high prevalence of falls among people with multiple sclerosis [en.wikipedia.org]

  Falls and conditions increasing the risk of falls, such as: Visual impairment. Lack of neuromuscular co-ordination or strength. Cognitive impairment. Sedative medication and alcohol. [patient.info]

• Alopecia

  Celiac disease and alopecia areata: report of a new association. Gastroenterology 109, 1333–1337 (1995). 68. Bardella, M. T. et al. Alopecia areata and coeliac disease: no effect of a gluten-free diet on hair growth. [dx.doi.org]

• Osteoporosis

  Osteoporosis and fragility fractures Every year, on October 20, the world comes together to highlight World Osteoporosis Day; a day dedicated to raising global awareness of the prevention, diagnosis and treatment of osteoporosis and fragility fractures [ucb.com]

  Secondary Osteoporosis There are several well known risk factors for osteoporosis and osteoporotic fractures. Men and Osteoporosis Think only women are at risk of osteoporosis? Think again. [osteoporosis.ca]

  What is osteoporosis and what does it do? Osteoporosis is a condition in which bones lose their strength and are more likely to break. Osteoporosis doesn't show any outward symptoms and the first sign of osteoporosis is often a broken bone. [nos.org.uk]

  Unchangeable risks Some risk factors for osteoporosis are out of your control, including: Your sex. Women are much more likely to develop osteoporosis than are men. Age. The older you get, the greater your risk of osteoporosis. Race. [mayoclinic.org]

  Defining Osteoporosis Osteoporosis is a disease marked by loss of bone tissue and low bone mass. Osteoporosis can lead to bone weakness and fragile bones. [disabled-world.com]

• Osteopenia

  Most fractures in postmenopausal women occur in those with osteopenia, so therapies that are effective in women with osteopenia are needed. [doi.org]

  Osteopenia is the early stage of Osteoporosis. Having osteopenia places a person at risk of developing Osteoporosis. [irishosteoporosis.ie]

  Osteopenia, if it happens at all, usually occurs after age 50. The exact age depends how strong your bones are when you're young. If they're hardy, you may never get osteopenia. If your bones aren't naturally dense, you may get it earlier. [webmd.com]

  Osteopenia is a condition where bone mineral density is lower than normal. It is considered a precursor to osteoporosis. [mag365.co.uk]

• Back Pain

  Pregnancy and lactation-associated osteoporosis (PLO) is very rare, but it can cause severe vertebral compression fractures with disabling back pain. [ncbi.nlm.nih.gov]

  Back pain is the most common cause of disability among young adults. Many factors, physical, psychological and occupational, contribute to the occurrence of back pain. [web.archive.org]

• Bone Pain

  Another huge advantage is that these patients often have bone pain and joint pain ... which will be relieved almost immediately after a successful parathyroid operation in about 90-95% of patients. Most claim their bone pain is completely gone. [parathyroid.com]

  Transient osteoporosis of the hip (TOH) is characterized by bone pain, osteopenia, and bone marrow edema in the absence of trauma. We present a 59-year-old man with chronic lymphocytic leukemia who underwent F-FDG PET/CT. [ncbi.nlm.nih.gov]

  Talk with your doctor about an earlier scan if you have any warning signs or risk factors for osteoporosis: a bone fracture after age 50 sudden back pain loss of height or increasingly stooped posture use of medications that can thin bones a bone-threatening [hopkinsmedicine.org]

  Higher and more frequent dosing of these agents is given as part of cancer therapy to reduce bone pain and hypercalcemia of malignancy (abnormally high calcium levels in the blood) associated with metastatic breast cancer, prostate cancer and multiple [mouthhealthy.org]

  These drugs slow the rate of bone thinning. They may also reduce new bone damage and promote healing. People who have bone pain from metastatic cancer also often receive these drugs. [cancer.net]

• Low Back Pain

  CONCLUSIONS Thunder-fire moxibustion is an effective method for treating low back pain due to primary osteoporosis. KEYWORDS: Low Back Pain; Osteoporosis; SF-36; Thunder-Fire Moxibustion; VAS; Yang’s Modulus [ncbi.nlm.nih.gov]

  As Osteoporosis develops, it may cause dull pain in the bones or muscles, particularly low back pain or neck pain. Subsequently, sharp pains may come on. [thephysiocompany.com]

• Anger

  CHU d'Angers, 49933 Angers cedex, France. [ncbi.nlm.nih.gov]

  Angerer P, Stork S, Kothny W, Schmitt P, von Schacky C. Effect of oral postmenopausal hormone replacement on progression of atherosclerosis: a randomized, controlled trial. Arterioscler Thromb Vasc Biol. 2001;21:262-268. Google Scholar 30. [jama.ama-assn.org]

• Dizziness

  Everyone should pay attention to home safety and road safety, wear non-skid footwear, avoid medicines which cause dizziness and wear appropriate corrective eyeglasses. [elderly.gov.hk]

  A dizzying array of calcium supplements is available—so many, in fact, that choosing one can be tricky. You can choose from flavored chews, pills, chewable tablets, and liquids. [health.harvard.edu]

  Side effects include leg cramps and dizziness. Long-term safety is unknown, so use is limited to 2 years. [web.archive.org]

  […] and keeping eyewear up to date installing grab bars, for example, in the bathroom ensuring there is plenty of light in the home practicing exercise that helps with balance, such as tai chi asking the doctor to review medications, to reduce the risk of dizziness [medicalnewstoday.com]

• Unable to Walk

  Following a hip fracture, there is a 10%-20% mortality over the subsequent 6 months, 50% of sufferers will be unable to walk without assistance, and 25% will require long-term domiciliary care. [ncbi.nlm.nih.gov]

  Hip fractures are a frequent fracture and leave about half of those who break a hip unable to walk independently. Women who have a hip fracture are at fourfold greater risk for a second hip fracture. [emedicinehealth.com]

  Loss of function and independence among survivors is profound, with 40% unable to walk independently, 60% requiring assistance a year later (34). [iofbonehealth.org]

  […] to walk independently at 1 year, and 60% require assistance with at least 1 essential activity of daily living. 31 Hip fractures account for a large portion of the morbidity and mortality associated with osteoporotic fractures, with 21% to 30% of patients [doi.org]

• Insomnia

  "The comorbidity of insomnia, chronic pain, and depression: dopamine as a putative mechanism". Sleep Medicine Reviews. 17 (3): 173–83. doi:10.1016/j.smrv.2012.03.003. PMC 3519938. PMID 22748562. ^ Ji RR, Berta T, Nedergaard M (December 2013). [en.wikipedia.org]

• Vertigo

  Balance disorders – vertigo, Syncope, unsteadiness Visual, sensory, motor and cognitive impairment - affected reflexes Medications and alcohol consumption - taking medications for a long time can make one feel dizzy, confused, and slow. [en.wikipedia.org]

The diagnostic workup of patients in whom osteoporosis is the possible cause of fractures and associated symptoms must start with a detailed patient history [3]. Because so many disorders (in addition to age-related changes) can cause reduced bone mineral density, it is of essential importance to inquire about the presence of any diseases and identify if any of the drugs that are known induce this phenomenon are being used [3]. One of the key questions that should be asked should be about height loss (either prospective or historical) [3]. Additionally, lifestyle and demographic factors should be taken into account when being suspicious about osteoporosis. The initial workup should start with a detailed physical examination, followed by a complete laboratory assessment - renal and liver function tests (urea, creatinine, liver transaminases), serum electrolytes (calcium and phosphorus), inflammatory markers (C-reactive protein and erythrocyte sedimentation rate, or CRP and ESR, respectively), vitamin D levels, hormonal workup (thyroid stimulating hormone, PTH, gonadal hormones), serum glucose levels, urinary calcium excretion, and alkaline phosphatase (ALP) are some of the studies used to exclude secondary causes [3]. Plain radiography should be employed to assess reported fractures and to evaluate the overall state of the skeletal system, but the key component of the workup is the evaluation of bone mineral density (BMD) [1] [3] [4] [5] [6]. Using X-ray absorptiometry at the hip and spine is a definitive study that establishes the severity of bone fragility and thus determines what is the optimal therapeutic approach [1] [3] [4] [5] [6] [7]. The diagnosis is confirmed when BMD is > 2.5 SDs below the reference mean (T-score ≤ –2.5) of young adult females for both genders [8].

• Schmorl's Nodes

  In the final case, the centrally indented body of the 4th lumbar vertebra contained a Schmorl's node. [doi.org]

• Testosterone Increased

  Estrogen deficiency is associated with: Menopause Surgical removal of ovaries (oophorectomy) Eating disorders such as anorexia nervosa Men Low levels of testosterone increase osteoporosis risk. [mountsinai.org]

The therapeutic approach to patients with osteoporosis depends on several factors, such as the patient's age, the presence of comorbidities, and the severity of bone fragility. Hence, different modalities can be recommended to different populations [9] [10] [11] [12]:

• Lifestyle changes - Physical activity has a very influential effect on the skeletal system and any form of exercise is strongly recommended for individuals who are at risk or already have osteoporosis [10] [11]. Increasing or maintaining flexibility, muscle strength, and balance are of great benefit for the patient and sports that promote bone growth the most are basketball, gymnastics, dancing, tennis, impact-aerobic, and weight training [2] [10] [11]. Cessation of cigarette smoking, avoiding an underweight status, and sun exposure for at least 30 minutes every day (in order to facilitate vitamin D production) are additional factors that may be influenced by behavior [2].
• Calcium and vitamin D supplementation - Many patients will use calcium and vitamin D supplements either prophylactically or for therapeutic purposes and they have become engraved in the treatment protocol of osteoporosis. Typical doses of vitamin D should range between 400-1200 international units (IU)/day, whereas 1000-1300 mg/day is the usual dose of calcium [2] [9] [10]. If possible, dietary modification should be recommended prior to giving supplements, but many patients cannot reach the necessary daily intake of calcium [2] [10].
• Pharmacologic therapy - Various drugs are used to treat osteoporosis. Alendronate, ibandronate, and risedronate belong to the group of bisphosphonates that inhibit the activity of osteoclasts and thus inhibit bone resorption [2] [6] [11]. They are used as first-line therapy, and apart from mild gastrointestinal side-effects, they are safe to use, but are of limited efficacy in severe renal insufficiency [2] [6] [10] [11]. Denosumab is a recently approved monoclonal antibody that interferes with bone resorption by inhibiting the receptor activator of nuclear factor kappa B ligand and may be freely used in patients who developed renal failure [10]. If these drugs do not improve the status of the patient, raloxifene (only in women), teriparatide (recombinant human PTH), and strontium ranelate are effective alternatives [2] [6] [9] [10] [11].

In the absence of an early diagnosis, osteoporosis carries a significant risk for long-term disability. Studies have shown that up to 50% of all individuals who sustain hip fractures (regarded as the most severe type of injury) never regain previous physical function and mortality rates reach up to 36% within 1 year, according to some reports [1] [2]. Because of the effectiveness of screening procedures that are able to identify early osteoporotic changes, it is imperative to make an early diagnosis and thus prevent injuries that will profoundly decrease the quality of life.

Osteoporosis develops as a result of age-related bone mineral density loss and the term "primary osteoporosis" is often used as a synonym [2] [6] [7]. Many diseases and drugs have shown to either promote or directly influence this process as well and the term "secondary osteoporosis" is used when causes other than aging are involved in the pathogenesis [3] [4] [6] [7]:

• Diseases - A myriad of conditions affect the pathways involved in bone homeostasis and remodeling. Gastrointestinal (celiac disease, inflammatory bowel disease, malabsorptive syndromes, biliary cirrhosis, or previous surgical procedures), endocrine (hyperparathyroidism, Cushing's disease, thyrotoxicosis, diabetes mellitus), hematologic (sickle cell disease, multiple myeloma, leukemias, lymphomas, hemophilia), autoimmune (systemic lupus erythematosus, rheumatoid arthritis, and ankylosing spondylitis), are some of the examples [3] [4] [6] [7]. Furthermore, end-stage renal disease (ESRD), hypercalciuria, congestive heart failure, chronic obstructive lung disease, Parkinson's disease, muscular dystrophies, or injury to the spinal cord have also been included in this long list [3] [4] [6] [7].
• Drugs - Aromatase inhibitors (anastrozole, letrozole, exemestane), anticoagulants, long-term use of glucocorticoids (prednisolone), selective serotonin reuptake inhibitors (SSRIs), premenopausal use of tamoxifen, aromatase inhibitors, premenopausal contraceptives (medroxyprogesterone), aluminum-containing antacids, proton-pump inhibitors (omeprazole, pantoprazole), cyclosporin A, thiazolidinediones, cytotoxic chemotherapy drugs (methotrexate, ifosfamide), valproic acid, and gonadotropin-releasing hormone (GnRH) agonists have all been described as potential potential causes [3] [4] [6] [7].
• Genetic disorders - Marfan syndrome, osteogenesis imperfecta, hypophosphatasia, cystic fibrosis, glycogen storage diseases, hemochromatosis, and homocystinuria are examples of genetic diseases that either cause or contribute to osteoporosis [3] [4] [6] [7].

It is estimated that over 200 million people have osteoporosis worldwide and approximately 50% of women and 20% of men will eventually suffer from a fracture as a result of osteoporosis [2] [9]. The list of risk factors that contribute to the development of osteoporosis encompasses disorders of various systems, but also drugs and certain lifestyle actions [3] [4]. Older age, inadequate and insufficient physical activity, low intake of calcium, smoking, immobilization, vitamin D deficiency, low body mass index (BMI), abuse of alcohol, high intake of salt, and excessive falling are some of the main lifestyle factors that are strongly associated with osteoporosis [2] [3] [4] [7] [9]. As stated previously, women are significantly more affected than men, and it is shown that up to 70% of all fractures encountered in this patient population occurs among women over 65 years of age [1] [2]. Caucasians and Asian races seem to be at an increased risk for osteoporosis compared to black men and women [6].

Osteoporosis stems from abnormalities in the bone remodeling process. Under physiological circumstances, a constant balance between bone resorption (mediated by osteoclasts) and bone growth (mediated by osteoblasts) is being maintained [5] [12]. As humans reach older age, this process eventually decreases in efficiency, leading to excessive bone resorption that is not matched by the rate of bone remodeling [5] [12]. Calcium is the key element around which all hormones and other electrolytes revolve when it comes to the skeletal system. More than 99% of all body calcium is stored in bones and a tight regulatory system comprised of vitamin D, parathyroid hormone (PTH), calcitonin, estrogen, and several other elements, ensures that serum calcium levels are constantly within physiological limits, but also aid in maintaining the structural integrity of the skeleton [5] [7] [9] [11]. Deficiency of calcium intake or impaired absorption in the gastrointestinal system, vitamin D deficiency, hyperparathyroidism, or estrogen deficiency (all occuring in older age), lead to a shift of the bone remodeling process toward accelerated bone resorption [5] [7] [9] [11]. Estrogen, considered to be a crucial element for epiphyseal closure in both genders and vital for bone remodeling. Its deficiency, most evidently seen in postmenopausal women, is well-known to contribute to osteoporosis [5] [7] [9] [11]. The end-result is a loss of bone mass and fragility that predisposes patients to falls and pathological fractures, the hallmarks of osteoporosis.

Osteoporosis is a highly controllable disease if recognized in its early stages, which is why a plethora of studies and guidelines focus on screening methods and early detection [2] [3] [6] [11] [12] [13]. Some authors emphasize the need for risk factor evaluation as early as 50 years of age, whereas BMD testing should be performed in women who are older than 65 and in men who are older than 70 years [13]. Furthermore, postmenopausal women between 50-69 years with one or more risk factors (examples being height loss of ≥ 4 or long-term therapy with glucocorticoids) are advised to undergo screening for osteoporosis [6] [13] [14].

Osteoporosis is defined as a disorder of the skeletal system that is distinguished by the loss of bone mass and disruption of the bone microarchitecture that predisposes individuals to fractures and injury [1] [2] [5]. Since its initial description in the 19th century much has been revealed about the pathogenesis, clinical presentation, etiology, diagnosis, and treatment. A rather long list of disorders affecting the hematologic, gastrointestinal, endocrine, autoimmune, and other systems that play a role in the development of osteoporosis has been established (the term secondary osteoporosis is sometimes used), but age is regarded as the most important (primary osteoporosis [3] [4] [6]. However, several lifestyle factors have shown to promote osteoporosis [2] [3] [4] [6] [9]. Insufficient physical activity, cigarette smoking, a very low body mass index (a BMI < 20 is said to double the risk of a femoral fracture in these patients), alcohol abuse, low calcium intake, and high salt intake are identified. The pathogenesis of this skeletal condition arises as a result of a disturbed balance in the bone remodeling process. To preserve the health of the skeletal system, a constant process of resorption and regrowth of the bones is taking place, but once humans reach older age, bone resorption outpaces bone regrowth, resulting in a decreased bone mass and fragility [5] [9] [12]. The clinical presentation of patients with osteoporosis is mainly asymptomatic in the initial stages of the disease, and patients are, unfortunately, recognized when pathological fractures already occur [1] [2]. Fractures of the vertebra, humerus, forearm, or hip can occur and result in severe disability [4]. A thorough diagnostic approach comprised of clinical, laboratory, and imaging studies is necessary to assess the extent and severity of osteoporosis, but also to design optimal therapeutic strategies [3] [4]. Treatment principles include lifestyle modifications (initiation of regular physical activity, cessation of smoking and alcohol abuse), adequate intake of calcium and vitamin D, and pharmacologic therapy with bisphosphonates, hormone therapy (estrogens, parathyroid hormone) or more advanced drugs that target receptor activator of nuclear factor kappa-B (RANK) ligand inhibitor (denosumab). Prevention of osteoporosis is key in reducing morbidity and mortality from fractures and all associated complications and screening guidelines suggest that all adults should be tested for early signs at 50-60 years of age [13].

Osteoporosis is a condition that affects millions of older adults and elderly individuals worldwide. This condition is defined as a progressive loss of bone strength and bone density, mainly as a result of old age (termed primary osteoporosis). In addition to age-related changes of the skeleton, a very large number of diseases (gastrointestinal, hormonal, autoimmune, or genetic) and different drugs (proton pump inhibitors, hormones, antiepileptics, chemotherapy drugs, glucocorticoids, etc.) can induce or promote bone loss. When a specific disorder is responsible for osteoporosis, the term "secondary osteoporosis" is used to denote that older age is not the main culprit. Several risk factors have been established - poor physical activity, high intake of salt, inadequate calcium/vitamin D intake (through food and sun exposure, respectively), cigarette smoking, low body weight and a low body mass index (BMI), female gender (postmenopausal women are substantially more prone to osteoporosis than men), and Caucasian/Asian race. Osteoporosis does not produce any symptoms in its initial stages. Fractures, particularly after falls or low energy trauma that wouldn't normally cause severe injury, are the first recognizable symptom. Unfortunately, these fractures cause marked disability - up to 50% of all patients who suffer from a hip fracture will not fully recover, and up to 36% of patients die within 1 year of this injury. Other frequently encountered fractures involve the spine, the arms and forearms, as well as the femur. Other signs include height loss, kyphosis, shortening of the trunk, and the "fir tree phenomenon", where skin folds extend from the back to the flanks and resemble a fir tree. Because these injuries pose a significant risk for the patient, an early diagnosis is of critical importance. Physicians should conduct a detailed interview during which the underlying cause should be revealed. After a physical examination and a full laboratory workup that aids in excluding other conditions, evaluation of bone mineral density (BMD) is the cornerstone for confirming osteoporosis. Based on the reduction in bone mineral density, different therapeutic approaches are implemented. In milder cases, dietary changes that support an increased intake of calcium through food and vitamin D by exposing the skin to the sun for at least 30 minutes every day, along with physical exercise, are the first steps. Vitamin D and calcium supplementation is often used, whereas bisphosphonates (alendronate, ibandronate, and risedronate) are first-line drugs that are the in patients who require pharmacological therapy. Raloxifene (only in women), teriparatide, strontium ranelate, and denosumab, are other drugs used in therapy. Screening for osteoporosis is advised in women over 65 and in men over 70 years of age, but screening may start as early as 50 years in the presence of one or more risk factors.

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