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Wikipedia

Osteoporosis

April 08, 2023

Not to be confused with Osteosclerosis.

Osteoporosis is a systemic skeletal disorder characterized by low bone mass, micro-architectural deterioration of bone tissue leading to bone fragility, and consequent increase in fracture risk. It is the most common reason for a broken bone among the elderly.[3] Bones that commonly break include the vertebrae in the spine, the bones of the forearm, and the hip.[8] 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, the person may have chronic pain and a decreased ability to carry out normal activities.[3]

Osteoporosis
Elderly woman with osteoporosis showing a curved back from compression fractures of her back bones.
Pronunciation
SpecialtyRheumatology, Endocrinology, orthopedics
SymptomsIncreased risk of a broken bone[3]
ComplicationsChronic pain[3]
Usual onsetOlder age[3]
Risk factorsAlcoholism, anorexia, European or Asian ethnicity, hyperthyroidism, gastrointestinal diseases, surgical removal of the ovaries, kidney disease, smoking, certain medications[3]
Diagnostic methodDexa Scan( Bone density scan[4])
TreatmentGood diet, exercise, fall prevention, stopping smoking[3]
MedicationBisphosphonates[5][6]
Frequency15% (50 year olds), 70% (over 80 year olds)[7]

Osteoporosis may be due to lower-than-normal maximum bone mass and greater-than-normal bone loss. Bone loss increases after the menopause due to lower levels of estrogen, and after 'andropause' due to lower levels of testosterone.[9][10] 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 too little exercise are also risk factors.[3] Osteoporosis 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).[4]

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 a good diet, exercise, and fall prevention. Lifestyle changes such as stopping smoking and not drinking alcohol may help.[3] 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.[5][6][needs update][11] They do not appear to affect the risk of death.[12]

Osteoporosis becomes more common with age. About 15% of Caucasians in their 50s and 70% of those over 80 are affected.[7] It is more common in women than men.[3] In the developed world, depending on the method of diagnosis, 2% to 8% of males and 9% to 38% of females are affected.[13] Rates of disease in the developing world are unclear.[14] About 22 million women and 5.5 million men in the European Union had osteoporosis in 2010.[15] In the United States in 2010, about 8 million women and between 1 and 2 million men had osteoporosis.[13][16] White and Asian people are at greater risk.[3] The word "osteoporosis" is from the Greek terms for "porous bones".[17]

Signs and symptoms

 
Illustration depicting normal standing posture and osteoporosis

Osteoporosis itself has no symptoms; its main consequence is the increased risk of bone fractures. 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.

Fractures

Fractures are a common symptom of osteoporosis and can result in disability.[18] Acute and chronic pain in the elderly is often attributed to fractures from osteoporosis and can lead to further disability and early mortality.[19] These fractures may also be asymptomatic.[20] The most common osteoporotic fractures are of 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.[21]

Fractures of 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 hip surgery, with the mean average mortality rate for Europe being 23.3%, for Asia 17.9%, United States 21% and Australia 24.9%.[22]

Fracture risk calculators assess the risk of fracture based upon several criteria, including bone mineral density, age, smoking, alcohol usage, weight, and gender. Recognized calculators include FRAX,[23] the Garvan FRC calculator and QFracture as well as the open access FREM tool.[24] The FRAX tool can also be applied in a modification adapted to routinely collected health data.[25]

The term "established osteoporosis" is used when a broken bone due to osteoporosis has occurred.[26] Osteoporosis is a part of frailty syndrome.

Risk of falls

 
Progression of the shape of vertebral column with age in osteoporosis

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 the living environment may substantially reduce falls. Those with previous falls, as well as those with gait or balance disorders, are most at risk.[27]

Complication

As well as susceptibility to breaks and fractures, osteoporosis can lead to other complications. Bone fractures which are results from osteoporosis can lead to disability and even an increased chance of death after the injury.[28]

Depression is considered to be a complication of osteoporosis.[29] People with osteoporosis lose independence and risk being isolated due to less physical activity. This will further hinder the ability to manage health issues.[29]

Osteoporosis is also linked to respiratory and cardiovascular health issues, such as loss of lung capacity. Multiple fractures lead to a collapsed thoracic spine, which makes less air being able to move into the lungs. Every thoracic vertebral body collapsed results in the loss of nearly 10% of lung volume.[30]

Risk factors

Risk factors for osteoporotic fracture can be split between nonmodifiable and (potentially) modifiable. In addition, osteoporosis is a recognized complication of specific diseases and disorders. Medication use 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.[31]

Nonmodifiable

 
Bone density peaks at about 30 years of age. Women lose bone mass more rapidly than men.[32]
  • The most important risk factors for osteoporosis are advanced age (in both men and women) and female sex; estrogen deficiency following menopause or surgical removal of the ovaries is correlated with a rapid reduction in bone mineral density, while in men, a decrease in testosterone levels has a comparable (but less pronounced) effect.[33][34]
  • Ethnicity: While osteoporosis occurs in people from all ethnic groups, European or Asian ancestry predisposes for osteoporosis.[35]
  • Heredity: Those with a family history of fracture or osteoporosis are at an increased risk; the heritability of the fracture, as well as low bone mineral density, is relatively high, ranging from 25 to 80%. At least 30 genes are associated with the development of osteoporosis.[36]
  • Those who have already had a fracture are at least twice as likely to have another fracture compared to someone of the same age and sex.[37]
  • Build: A small stature is also a nonmodifiable risk factor associated with the development of osteoporosis.[38]

Potentially modifiable

  • Excessive alcohol: Although small amounts of alcohol might be beneficial (bone density increases with increasing alcohol intake, although the link has not been conclusively shown as causal), chronic heavy drinking (alcohol intake greater than three units/day) probably increases fracture risk despite any beneficial effects on bone density.[39][40]
  • Vitamin D deficiency:[41][42] Low circulating Vitamin D is common among the elderly worldwide.[4] Mild vitamin D insufficiency is associated with increased parathyroid hormone (PTH) production.[4] PTH increases bone resorption, leading to bone loss. A positive association exists between serum 1,25-dihydroxycholecalciferol levels and bone mineral density, while PTH is negatively associated with bone mineral density.[4]
  • Tobacco smoking: Many studies have associated smoking with decreased bone health, but the mechanisms are unclear.[43][44][45] Tobacco smoking has been proposed to inhibit the activity of osteoblasts, and is an independent risk factor for osteoporosis.[39][46] Smoking also results in increased breakdown of exogenous estrogen, lower body weight and earlier menopause, all of which contribute to lower bone mineral density.[4]
  • Malnutrition: Nutrition has an important and complex role in maintenance of good bone. Identified risk factors include low dietary calcium and/or phosphorus, magnesium, zinc, boron, iron, fluoride, copper, vitamins A, K, E and C (and D where skin exposure to sunlight provides an inadequate supply). Excess sodium is a risk factor. High blood acidity may be diet-related, and is a known antagonist of bone.[47] Some have identified low protein intake as associated with lower peak bone mass during adolescence and lower bone mineral density in elderly populations.[4] Conversely, some have identified low protein intake as a positive factor, protein is among the causes of dietary acidity. Imbalance of omega-6 to omega-3 polyunsaturated fats is yet another identified risk factor.[48]
  • A diet high in protein may be optimal for bone health, as higher protein diets tend to increase absorption of calcium from the diet and are associated with higher bone density.[49][50] No interventional trials have been performed on dietary protein in the prevention and treatment of osteoporosis [51] A meta-analysis of published medical studies shows that higher protein diet helps slightly with lower spine density but does not show significant improvement with other bones.[52]
  • Underweight/inactive: Bone remodeling occurs in response to physical stress, so physical inactivity can lead to significant bone loss.[4] Weight bearing exercise can increase peak bone mass achieved in adolescence,[4] and a highly significant correlation between bone strength and muscle strength has been determined.[53] The incidence of osteoporosis is lower in overweight people.[54]
  • Endurance training: In female endurance athletes, large volumes of training can lead to decreased bone density and an increased risk of osteoporosis.[55] This effect might be caused by intense training suppressing menstruation, producing amenorrhea, and it is part of the female athlete triad.[56] However, for male athletes, the situation is less clear, and although some studies have reported low bone density in elite male endurance athletes,[57] others have instead seen increased leg bone density.[58][59]
  • Heavy metals: A strong association between cadmium and lead with bone disease has been established. Low-level exposure to cadmium is associated with an increased loss of bone mineral density readily in both genders, leading to pain and increased risk of fractures, especially in the elderly and in females. Higher cadmium exposure results in osteomalacia (softening of the bone).[60]
  • Soft drinks: Some studies indicate soft drinks (many of which contain phosphoric acid) may increase risk of osteoporosis, at least in women.[61] Others suggest soft drinks may displace calcium-containing drinks from the diet rather than directly causing osteoporosis.[62]
  • Proton pump inhibitors (such as lansoprazole, esomeprazole, and omeprazole), which decrease the production of stomach acid, are a risk factor for bone fractures if taken for two or more years, due to decreased absorption of calcium in the stomach.[63]

Medical disorders

 
The body regulates calcium homeostasis with two pathways; one is signaled to turn on when blood calcium levels drop below normal and one is the pathway that is signaled to turn on when blood calcium levels are elevated.

Many diseases and disorders have been associated with osteoporosis.[64] For some, the underlying mechanism influencing the bone metabolism is straightforward, whereas for others the causes are multiple or unknown.

Medication

Certain medications have been associated with an increase in osteoporosis risk; only glucocorticosteroids and anticonvulsants are classically associated, but evidence is emerging with regard to other drugs.

Evolutionary

Age-related bone loss is common among humans due to exhibiting less dense bones than other primate species.[85] Because of the more porous bones of humans, frequency of severe osteoporosis and osteoporosis related fractures is higher.[86] The human vulnerability to osteoporosis is an obvious cost but it can be justified by the advantage of bipedalism inferring that this vulnerability is the byproduct of such.[86] 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.[85] In addition, the porosity allows for more flexibility and a lighter skeleton that is easier to support.[86] 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.[87]

Fracture risk assessment

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 a clinical FRAX is advised at age 50.

Pathogenesis

 
Osteoporosis locations

The underlying mechanism in all cases of osteoporosis is an imbalance between bone resorption and bone formation.[88][89] 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.[90] Osteoclasts are assisted by transcription factor PU.1 to degrade the bone matrix, while osteoblasts rebuild 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.[88][91]

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 the osteoblast and toward the marrow adipocyte lineage.[92] An interplay of these three mechanisms underlies the development of fragile bone tissue.[36] 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 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.[36] 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 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.[36]

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.[89] 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 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.[36] Osteoclast maturation and activity is also regulated by activation of colony stimulating factor 1 receptor (CSF1R).[93] 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.[94]

Trabecular bone (or cancellous bone) 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, 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.[citation needed] Around the ages of 30–35, cancellous or trabecular bone loss begins. Women may lose as much as 50%, while men lose about 30%.[38]

Diagnosis

 
Multiple osteoporotic wedge fractures demonstrated on a lateral thoraco-lumbar spine X-ray

Osteoporosis can be diagnosed using conventional radiography and by measuring the bone mineral density (BMD).[95] The most popular method of measuring BMD is dual-energy X-ray absorptiometry.[citation needed]

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 the bone, multiple myeloma, Cushing's disease and other above-mentioned causes may be performed.[96]

Conventional radiography

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 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.[97][98]

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 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.[99][100]

Dual-energy X-ray

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 a young (30–40-year-old[4]:58), 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.[4]:58 The World Health Organization has established the following diagnostic guidelines:[4][26]

Category T-score range % young women
Normal T-score ≥ −1.0 85%
Osteopenia −2.5 < T-score < −1.0 14%
Osteoporosis T-score ≤ −2.5 0.6%
Severe osteoporosis T-score ≤ −2.5 with fragility fracture[26]

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 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.[101]

Biomarkers

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 the resulting fragment, called a neoepitope, as a way to diagnose osteoporosis.[102] Increased urinary excretion of C-telopeptides, a type-I collagen breakdown product, also serves as a biomarker for osteoporosis.[103]

Comparison of bone pathology
Condition 		Calcium Phosphate Alkaline phosphatase Parathyroid hormone Comments
Osteopenia unaffected unaffected normal unaffected decreased bone mass
Osteopetrosis unaffected unaffected elevated unaffected[citation needed] thick dense bones also known as marble bone
Osteomalacia and rickets decreased decreased elevated elevated soft bones
Osteitis fibrosa cystica elevated decreased elevated elevated brown tumors
Paget's disease of bone unaffected unaffected variable (depending on stage of disease) unaffected abnormal bone architecture

Other measuring tools

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/cm3 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 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 the limitations of DXA and QCT.[95]

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 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.[95] Some ultrasound devices can be used on the tibia.[104]

Screening

The U.S. Preventive Services Task Force (USPSTF) recommend that all women 65 years of age or older be screened by bone densitometry.[105] Additionally they recommend screening younger women with risk factors.[105] There is insufficient evidence to make recommendations about the intervals for repeated screening and the appropriate age to stop screening.[106]

In men the harm versus benefit of screening for osteoporosis is unknown.[105] Prescrire states that the need to test for osteoporosis in those who have not had a previous bone fracture is unclear.[107] 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 a 70‑year‑old.[108] A number of tools exist to help determine who is reasonable to test.[109]

Prevention

Lifestyle prevention of osteoporosis is in many aspects the inverse of the potentially modifiable risk factors.[110] 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.[111]

In people with coeliac disease adherence to a gluten-free diet decreases the risk of developing osteoporosis[112] and increases bone density.[67] 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.[112]

Nutrition

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.[113] 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 the community who had no known history of vitamin D deficiency, osteoporosis, or a fracture.[114] 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.[115] A 2015 review found little data that supplementation of calcium decreases the risk of fractures.[116] While some meta-analyses have found a benefit of vitamin D supplements combined with calcium for fractures, they did not find a benefit of vitamin D supplements (800 IU/day or less) alone.[117][118] While supplementation does not appear to affect the risk of death,[114][118] an increased risk of myocardial infarctions [119][120] kidney stones,[114] and stomach problems[118] is associated with calcium supplementation.

Vitamin K deficiency is also a risk factor for osteoporotic fractures.[121] 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.[122] Vitamin K2 is also used as a means of treatment for osteoporosis and the polymorphisms of GGCX could explain the individual variation in the response to treatment of vitamin K.[123]

Dietary sources of calcium include dairy products, leafy greens, legumes, and beans.[124] 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.[125] A review of the evidence shows no adverse effect of higher protein intake on bone health.[126]

Physical exercise

There is limited evidence indicating that exercise is helpful in promoting bone health.[127] There is some evidence that physical exercise may be beneficial for bone density in postmenopausal women and lead to a slightly reduced risk of a bone fracture (absolute difference 4%).[128] Weight bearing exercise has been found to cause an adaptive response in the skeleton.[129] Weight bearing exercise promotes osteoblast activity, protecting bone density.[130] A position statement concluded that increased bone activity and weight-bearing exercises at a young age prevent bone fragility in adults.[131] Bicycling and swimming are not considered weight-bearing exercise. Neither contribute to slowing bone loss with age, and professional bicycle racing has a negative effect on bone density.[132]

Low-quality evidence suggests that exercise may reduce pain and improve quality of life of people with vertebral fractures and there is moderate-quality evidence that exercise will likely improve physical performance in individuals with vertebral fractures.[133]

Physical therapy

People with osteoporosis are at higher risk of falls due to poor postural control, muscle weakness, and overall deconditioning.[134] Postural control 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.[133] The goal of these interventions are to regain normal spine curvatures, increase spine stability, and improve functional performance.[133] Physical therapy interventions were also designed to slow the rate of bone loss through home exercise programs.[134]

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.[135] There are conflicting reviews as to whether vibration therapy improves bone mineral density.[135][136]

Physical therapy can aid in overall prevention in 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.[137]

Hormone therapy

Reduced oestrogen levels increase the risk of osteoporosis, so hormone replacement therapy when women reach the menopause may reduce the incidence of osteoporosis.

Management

Lifestyle

Weight-bearing endurance exercise and/or exercises to strengthen muscles improve bone strength in those with osteoporosis.[128][138] Aerobics, weight bearing, and resistance exercises all maintain or increase BMD in postmenopausal women.[128] Fall prevention can help prevent osteoporosis complications. There is some evidence for hip protectors specifically among those who are in care homes.[139]

Pharmacologic therapy

The US National Osteoporosis Foundation recommends pharmacologic treatment for patients with hip of spine fracture thought to be related to osteoporosis, those with BMD 2.5 SD or more below the young normal mean (T-score -2.5 or below), and those with BMD between 1 and 2.5 SD below normal mean whose 10-year risk, using FRAX, for hip fracture is equal or more than 3%.[140]Bisphosphonates are useful in decreasing the risk of future fractures in those who have already sustained a fracture due to osteoporosis.[5][6][111][141] This benefit is present when taken for three to four years.[142][143] They do not appear to change the overall risk of death.[12] Tentative evidence does not support the use of bisphosphonates as a standard treatment for secondary osteoporosis in children.[143] Different bisphosphonates have not been directly compared, therefore it is unknown if one is better than another.[111] Fracture risk reduction is between 25 and 70% depending on the bone involved.[111] There are concerns of atypical femoral fractures and osteonecrosis of the jaw with long-term use, but these risks are low.[111][144] With evidence of little benefit when used for more than three to five years and in light of the potential adverse events, it may be appropriate to stop treatment after this time.[142] One medical organization recommends that after five years of medications by mouth or three years of intravenous medication among those at low risk, bisphosphonate treatment can be stopped.[145][146] In those at higher risk they recommend up to ten years of medication by mouth or six years of intravenous treatment.[145]

The goal of osteoporosis management is to prevent osteoporotic fractures, but for those who have sustained one already it is more urgent to prevent a secondary fracture.[147] That is because patients with a fracture are more likely to experience a recurrent fracture, with marker increase in morbidity and mortality compared.[147] Among the five bisphosphonates, no significant differences were found for a secondary fracture for all fracture endpoints combined.[147] That being said, alendronate was identified as the most efficacious for secondary prevention of vertebral and hip fractures while zoledronate showed better performance for nonvertebral non-hip fracture prevention.[147] There is concern that many people do not receive appropriate pharmacological therapy after a low-impact fracture.[148]

For those with osteoporosis but who have not had a fracture, evidence does not support a reduction in fracture risk with risedronate[6] or etidronate.[11] Alendronate decreases fractures of the spine but does not have any effect on other types of fractures.[5] Half stop their medications within a year.[149] When on treatment with bisphosphonates rechecking bone mineral density is not needed.[146] There is tentative evidence of benefit in males with osteoporosis.[150]

Fluoride supplementation does not appear to be effective in postmenopausal osteoporosis, as even though it increases bone density, it does not decrease the risk of fractures.[151][152]

Teriparatide (a recombinant parathyroid hormone) has been shown to be effective in treatment of women with postmenopausal osteoporosis.[153][141] Some evidence also indicates strontium ranelate is effective in decreasing the risk of vertebral and nonvertebral fractures in postmenopausal women with osteoporosis.[154] Hormone replacement therapy, while effective for osteoporosis, is only recommended in women who also have menopausal symptoms.[111] It is not recommended for osteoporosis by itself.[146] Raloxifene, while effective in decreasing vertebral fractures, does not affect the risk of nonvertebral fracture.[111] And while it reduces the risk of breast cancer, it increases the risk of blood clots and strokes.[111] While denosumab is effective at preventing fractures in women,[111] there is not clear evidence of benefit in males.[150] In hypogonadal men, testosterone has been shown to improve bone quantity and quality, but, as of 2008, no studies evaluated its effect on fracture risk or in men with a normal testosterone levels.[66] Calcitonin while once recommended is no longer due to the associated risk of cancer and questionable effect on fracture risk.[155] Alendronic acid/colecalciferol can be taken to treat this condition in post-menopausal women.[156]

Romosozumab (sold under the brand name Evenity) is a monoclonal antibody against sclerostin. Romosozumab is usually reserved for patients with very high fracture risk and is the only available drug therapy for osteoporosis that leads to simultaneous inhibition of bone resorption together with an anabolic effect.[157][158]

Certain medications like alendronate, etidronate, risedronate, raloxifene, and strontium ranelate can help to prevent osteoporotic fragility fractures in postmenopausal women with osteoporosis.[159] Tentative evidence suggests that Chinese herbal medicines may have potential benefits on bone mineral density.[160]

Prognosis

Hip fractures per 1000 person-years[161]
WHO category Age 50–64 Age > 64 Overall
Normal 5.3 9.4 6.6
Osteopenia 11.4 19.6 15.7
Osteoporosis 22.4 46.6 40.6

Although people with osteoporosis have increased mortality due to the complications of fracture, the fracture itself is rarely lethal.

Hip fractures can lead to decreased mobility and additional risks of numerous complications (such as deep venous thrombosis and/or pulmonary embolism, and pneumonia). The six-month mortality rate for those aged 50 and above following hip fracture was found to be around 13.5%, with a substantial proportion (almost 13%) needing total assistance to mobilize after a hip fracture.[162]

Vertebral fractures, while having a smaller impact on mortality, can lead to severe chronic pain of neurogenic origin, which can be hard to control, as well as deformity. Though rare, multiple vertebral fractures can lead to such severe hunchback (kyphosis), the resulting pressure on internal organs can impair one's ability to breathe.

Apart from risk of death and other complications, osteoporotic fractures are associated with a reduced health-related quality of life.[163]

The condition is responsible for millions of fractures annually, mostly involving the lumbar vertebrae, hip, and wrist. Fragility fractures of ribs are also common in men.

Fractures

Hip fractures are responsible for the most serious consequences of osteoporosis. In the United States, more than 250,000 hip fractures annually are attributable to osteoporosis.[164] A 50-year-old white woman is estimated to have a 17.5% lifetime risk of fracture of the proximal femur. The incidence of hip fractures increases each decade from the sixth through the ninth for both women and men for all populations. The highest incidence is found among men and women ages 80 or older.[165]

Between 35 and 50% of all women over 50 had at least one vertebral fracture. In the United States, 700,000 vertebral fractures occur annually, but only about a third are recognized. In a series of 9704 women aged 68.8 on average studied for 15 years, 324 had already sustained a vertebral fracture at entry into the study and 18.2% developed a vertebral fracture, but that risk rose to 41.4% in women who had a previous vertebral fracture.[166]

In the United States, 250,000 wrist fractures annually are attributable to osteoporosis.[164] Wrist fractures are the third most common type of osteoporotic fractures. The lifetime risk of sustaining a Colles' fracture is about 16% for white women. By the time women reach age 70, about 20% have had at least one wrist fracture.[165]

Fragility fractures of the ribs are common in men as young as age 35.[citation needed] These are often overlooked as signs of osteoporosis, as these men are often physically active and develop the fracture in the course of physical activity, such as falling while water skiing or jet skiing.

Epidemiology

 
Age-standardised hip fracture rates in 2012.[167]
  Low (< 150 / 100 000)
  Medium (150–250 / 100 000)
  High (> 250 / 100 000)

It is estimated that 200 million people have osteoporosis.[168] Osteoporosis becomes more common with age.[3] About 15% of Caucasians in their 50s and 70% of those over 80 are affected.[7] It is more common in women than men.[3] In the developed world, depending on the method of diagnosis, 2% to 8% of males and 9% to 38% of females are affected.[13] Rates of disease in the developing world are unclear.[14]

Postmenopausal women have a higher rate of osteoporosis and fractures than older men.[169] Postmenopausal women have decreased estrogen which contributes to their higher rates of osteoporosis.[169] A 60-year-old woman has a 44% risk of fracture while a 60-year-old man has a 25% risk of fracture.[169]

There are 8.9 million fractures worldwide per year due to osteoporosis.[170] Globally, 1 in 3 women and 1 in 5 men over the age of 50 will have an osteoporotic fracture.[170] Data from the United States shows a decrease in osteoporosis within the general population and in white women, from 18% in 1994 to 10% in 2006.[171] White and Asian people are at greater risk.[3] People of African descent are at a decreased risk of fractures due to osteoporosis, although they have the highest risk of death following an osteoporotic fracture.[171]

It has been shown that latitude affects risk of osteoporotic fracture.[167] Areas of higher latitude such as Northern Europe receive less Vitamin D through sunlight compared to regions closer to the equator, and consequently have higher fracture rates in comparison to lower latitudes.[167] For example, Swedish men and women have a 13% and 28.5% risk of hip fracture by age 50, respectively, whereas this risk is only 1.9% and 2.4% in Chinese men and women.[171] Diet may also be a factor that is responsible for this difference, as vitamin D, calcium, magnesium, and folate are all linked to bone mineral density.[172]

There is also an association between Celiac Disease and increased risk of osteoporosis.[173] In studies with premenopausal females and males, there was a correlation between Celiac Disease and osteoporosis and osteopenia.[173] Celiac Disease can decrease absorption of nutrients in the small intestine such as calcium, and a gluten-free diet can help people with Celiac Disease to revert to normal absorption in the gut.[174]

About 22 million women and 5.5 million men in the European Union had osteoporosis in 2010.[15] In the United States in 2010 about 8 million women and one to 2 million men had osteoporosis.[13][16] This places a large economic burden on the healthcare system due to costs of treatment, long-term disability, and loss of productivity in the working population. The EU spends 37 billion euros per year in healthcare costs related to osteoporosis, and the US spends an estimated US$19 billion annually for related healthcare costs.[170]

History

The link between age-related reductions in bone density goes back to the early 1800s. French pathologist Jean Lobstein coined the term osteoporosis.[17] The American endocrinologist Fuller Albright linked osteoporosis with the postmenopausal state.[175]

Anthropologists have studied skeletal remains that showed loss of bone density and associated structural changes that were linked to a chronic malnutrition in the agricultural area in which these individuals lived. "It follows that the skeletal deformation may be attributed to their heavy labor in agriculture as well as to their chronic malnutrition", causing the osteoporosis seen when radiographs of the remains were made.[176]

See also

References

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External links

  • Handout on Health: Osteoporosis  – US National Institute of Arthritis and Musculoskeletal and Skin Diseases
  • Osteoporosis  – l NIH Osteoporosis and Related Bone Diseases – National Resource Center
  • Office of the Surgeon General (2004). Bone Health and Osteoporosis: A Report of the Surgeon General. Rockville, MD: U.S. Department of Health and Human Services. PMID 20945569. Retrieved 18 July 2016.
  • "Osteoporosis". MedlinePlus. U.S. National Library of Medicine.

April 08, 2023
osteoporosis, confused, with, osteosclerosis, systemic, skeletal, disorder, characterized, bone, mass, micro, architectural, deterioration, bone, tissue, leading, bone, fragility, consequent, increase, fracture, risk, most, common, reason, broken, bone, among,. Not to be confused with Osteosclerosis Osteoporosis is a systemic skeletal disorder characterized by low bone mass micro architectural deterioration of bone tissue leading to bone fragility and consequent increase in fracture risk It is the most common reason for a broken bone among the elderly 3 Bones that commonly break include the vertebrae in the spine the bones of the forearm and the hip 8 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 the person may have chronic pain and a decreased ability to carry out normal activities 3 OsteoporosisElderly woman with osteoporosis showing a curved back from compression fractures of her back bones Pronunciation ˌ ɒ s t i oʊ p e ˈ r oʊ s ɪ s 1 2 SpecialtyRheumatology Endocrinology orthopedicsSymptomsIncreased risk of a broken bone 3 ComplicationsChronic pain 3 Usual onsetOlder age 3 Risk factorsAlcoholism anorexia European or Asian ethnicity hyperthyroidism gastrointestinal diseases surgical removal of the ovaries kidney disease smoking certain medications 3 Diagnostic methodDexa Scan Bone density scan 4 TreatmentGood diet exercise fall prevention stopping smoking 3 MedicationBisphosphonates 5 6 Frequency15 50 year olds 70 over 80 year olds 7 Osteoporosis may be due to lower than normal maximum bone mass and greater than normal bone loss Bone loss increases after the menopause due to lower levels of estrogen and after andropause due to lower levels of testosterone 9 10 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 too little exercise are also risk factors 3 Osteoporosis 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 4 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 a good diet exercise and fall prevention Lifestyle changes such as stopping smoking and not drinking alcohol may help 3 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 5 6 needs update 11 They do not appear to affect the risk of death 12 Osteoporosis becomes more common with age About 15 of Caucasians in their 50s and 70 of those over 80 are affected 7 It is more common in women than men 3 In the developed world depending on the method of diagnosis 2 to 8 of males and 9 to 38 of females are affected 13 Rates of disease in the developing world are unclear 14 About 22 million women and 5 5 million men in the European Union had osteoporosis in 2010 15 In the United States in 2010 about 8 million women and between 1 and 2 million men had osteoporosis 13 16 White and Asian people are at greater risk 3 The word osteoporosis is from the Greek terms for porous bones 17 Contents 1 Signs and symptoms 1 1 Fractures 1 2 Risk of falls 1 3 Complication 2 Risk factors 2 1 Nonmodifiable 2 2 Potentially modifiable 2 3 Medical disorders 2 4 Medication 2 5 Evolutionary 2 6 Fracture risk assessment 3 Pathogenesis 4 Diagnosis 4 1 Conventional radiography 4 2 Dual energy X ray 4 3 Biomarkers 4 4 Other measuring tools 5 Screening 6 Prevention 6 1 Nutrition 6 2 Physical exercise 6 3 Physical therapy 6 4 Hormone therapy 7 Management 7 1 Lifestyle 7 2 Pharmacologic therapy 8 Prognosis 8 1 Fractures 9 Epidemiology 10 History 11 See also 12 References 13 External linksSigns and symptoms Edit Illustration depicting normal standing posture and osteoporosis Osteoporosis itself has no symptoms its main consequence is the increased risk of bone fractures 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 Fractures Edit Fractures are a common symptom of osteoporosis and can result in disability 18 Acute and chronic pain in the elderly is often attributed to fractures from osteoporosis and can lead to further disability and early mortality 19 These fractures may also be asymptomatic 20 The most common osteoporotic fractures are of 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 21 Fractures of 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 hip surgery with the mean average mortality rate for Europe being 23 3 for Asia 17 9 United States 21 and Australia 24 9 22 Fracture risk calculators assess the risk of fracture based upon several criteria including bone mineral density age smoking alcohol usage weight and gender Recognized calculators include FRAX 23 the Garvan FRC calculator and QFracture as well as the open access FREM tool 24 The FRAX tool can also be applied in a modification adapted to routinely collected health data 25 The term established osteoporosis is used when a broken bone due to osteoporosis has occurred 26 Osteoporosis is a part of frailty syndrome Risk of falls Edit Progression of the shape of vertebral column with age in osteoporosis 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 the living environment may substantially reduce falls Those with previous falls as well as those with gait or balance disorders are most at risk 27 Complication Edit As well as susceptibility to breaks and fractures osteoporosis can lead to other complications Bone fractures which are results from osteoporosis can lead to disability and even an increased chance of death after the injury 28 Depression is considered to be a complication of osteoporosis 29 People with osteoporosis lose independence and risk being isolated due to less physical activity This will further hinder the ability to manage health issues 29 Osteoporosis is also linked to respiratory and cardiovascular health issues such as loss of lung capacity Multiple fractures lead to a collapsed thoracic spine which makes less air being able to move into the lungs Every thoracic vertebral body collapsed results in the loss of nearly 10 of lung volume 30 Risk factors EditRisk factors for osteoporotic fracture can be split between nonmodifiable and potentially modifiable In addition osteoporosis is a recognized complication of specific diseases and disorders Medication use 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 31 Nonmodifiable Edit Bone density peaks at about 30 years of age Women lose bone mass more rapidly than men 32 The most important risk factors for osteoporosis are advanced age in both men and women and female sex estrogen deficiency following menopause or surgical removal of the ovaries is correlated with a rapid reduction in bone mineral density while in men a decrease in testosterone levels has a comparable but less pronounced effect 33 34 Ethnicity While osteoporosis occurs in people from all ethnic groups European or Asian ancestry predisposes for osteoporosis 35 Heredity Those with a family history of fracture or osteoporosis are at an increased risk the heritability of the fracture as well as low bone mineral density is relatively high ranging from 25 to 80 At least 30 genes are associated with the development of osteoporosis 36 Those who have already had a fracture are at least twice as likely to have another fracture compared to someone of the same age and sex 37 Build A small stature is also a nonmodifiable risk factor associated with the development of osteoporosis 38 Potentially modifiable Edit Excessive alcohol Although small amounts of alcohol might be beneficial bone density increases with increasing alcohol intake although the link has not been conclusively shown as causal chronic heavy drinking alcohol intake greater than three units day probably increases fracture risk despite any beneficial effects on bone density 39 40 Vitamin D deficiency 41 42 Low circulating Vitamin D is common among the elderly worldwide 4 Mild vitamin D insufficiency is associated with increased parathyroid hormone PTH production 4 PTH increases bone resorption leading to bone loss A positive association exists between serum 1 25 dihydroxycholecalciferol levels and bone mineral density while PTH is negatively associated with bone mineral density 4 Tobacco smoking Many studies have associated smoking with decreased bone health but the mechanisms are unclear 43 44 45 Tobacco smoking has been proposed to inhibit the activity of osteoblasts and is an independent risk factor for osteoporosis 39 46 Smoking also results in increased breakdown of exogenous estrogen lower body weight and earlier menopause all of which contribute to lower bone mineral density 4 Malnutrition Nutrition has an important and complex role in maintenance of good bone Identified risk factors include low dietary calcium and or phosphorus magnesium zinc boron iron fluoride copper vitamins A K E and C and D where skin exposure to sunlight provides an inadequate supply Excess sodium is a risk factor High blood acidity may be diet related and is a known antagonist of bone 47 Some have identified low protein intake as associated with lower peak bone mass during adolescence and lower bone mineral density in elderly populations 4 Conversely some have identified low protein intake as a positive factor protein is among the causes of dietary acidity Imbalance of omega 6 to omega 3 polyunsaturated fats is yet another identified risk factor 48 A diet high in protein may be optimal for bone health as higher protein diets tend to increase absorption of calcium from the diet and are associated with higher bone density 49 50 No interventional trials have been performed on dietary protein in the prevention and treatment of osteoporosis 51 A meta analysis of published medical studies shows that higher protein diet helps slightly with lower spine density but does not show significant improvement with other bones 52 Underweight inactive Bone remodeling occurs in response to physical stress so physical inactivity can lead to significant bone loss 4 Weight bearing exercise can increase peak bone mass achieved in adolescence 4 and a highly significant correlation between bone strength and muscle strength has been determined 53 The incidence of osteoporosis is lower in overweight people 54 Endurance training In female endurance athletes large volumes of training can lead to decreased bone density and an increased risk of osteoporosis 55 This effect might be caused by intense training suppressing menstruation producing amenorrhea and it is part of the female athlete triad 56 However for male athletes the situation is less clear and although some studies have reported low bone density in elite male endurance athletes 57 others have instead seen increased leg bone density 58 59 Heavy metals A strong association between cadmium and lead with bone disease has been established Low level exposure to cadmium is associated with an increased loss of bone mineral density readily in both genders leading to pain and increased risk of fractures especially in the elderly and in females Higher cadmium exposure results in osteomalacia softening of the bone 60 Soft drinks Some studies indicate soft drinks many of which contain phosphoric acid may increase risk of osteoporosis at least in women 61 Others suggest soft drinks may displace calcium containing drinks from the diet rather than directly causing osteoporosis 62 Proton pump inhibitors such as lansoprazole esomeprazole and omeprazole which decrease the production of stomach acid are a risk factor for bone fractures if taken for two or more years due to decreased absorption of calcium in the stomach 63 Medical disorders Edit The body regulates calcium homeostasis with two pathways one is signaled to turn on when blood calcium levels drop below normal and one is the pathway that is signaled to turn on when blood calcium levels are elevated Many diseases and disorders have been associated with osteoporosis 64 For some the underlying mechanism influencing the bone metabolism is straightforward whereas for others the causes are multiple or unknown In general immobilization causes bone loss following the use it or lose it rule For example localized osteoporosis can occur after prolonged immobilization of a fractured limb in a cast This is also more common in active people with a high bone turn over for example athletes Other examples include bone loss during space flight or in people who are bedridden or use wheelchairs for various reasons citation needed Hypogonadal states can cause secondary osteoporosis These include Turner syndrome Klinefelter syndrome Kallmann syndrome anorexia nervosa andropause 65 hypothalamic amenorrhea or hyperprolactinemia 65 In females the effect of hypogonadism is mediated by estrogen deficiency It can appear as early menopause lt 45 years or from prolonged premenopausal amenorrhea gt 1 year Bilateral oophorectomy surgical removal of the ovaries and premature ovarian failure cause deficient estrogen production In males testosterone deficiency is the cause for example andropause or after surgical removal of the testes Endocrine disorders that can induce bone loss include Cushing s syndrome 4 hyperparathyroidism 4 hyperthyroidism 4 hypothyroidism diabetes mellitus type 1 and 2 66 acromegaly and adrenal insufficiency 64 Malnutrition parenteral nutrition 4 and malabsorption can lead to osteoporosis Nutritional and gastrointestinal disorders that can predispose to osteoporosis include undiagnosed and untreated coeliac disease both symptomatic and asymptomatic people 4 67 Crohn s disease 68 ulcerative colitis 68 cystic fibrosis 68 surgery 65 after gastrectomy intestinal bypass surgery or bowel resection and severe liver disease especially primary biliary cirrhosis 65 People with lactose intolerance or milk allergy may develop osteoporosis due to restrictions of calcium containing foods 69 Individuals with bulimia can also develop osteoporosis Those with an otherwise adequate calcium intake can develop osteoporosis due to the inability to absorb calcium and or vitamin D Other micronutrients such as vitamin K or vitamin B12 deficiency may also contribute People with rheumatologic disorders such as rheumatoid arthritis 65 ankylosing spondylitis 65 systemic lupus erythematosus and polyarticular juvenile idiopathic arthritis are at increased risk of osteoporosis either as part of their disease or because of other risk factors notably corticosteroid therapy Systemic diseases such as amyloidosis and sarcoidosis can also lead to osteoporosis Chronic kidney disease can lead to renal osteodystrophy 70 Hematologic disorders linked to osteoporosis are multiple myeloma 65 and other monoclonal gammopathies 66 lymphoma leukemia mastocytosis 65 hemophilia sickle cell disease and thalassemia Several inherited or genetic disorders have been linked to osteoporosis These include osteogenesis imperfecta 65 Multicentric carpotarsal osteolysis syndrome 71 Multicentric Osteolysis Nodulosis and Arthropathy 72 Marfan syndrome 65 hemochromatosis 4 hypophosphatasia 73 for which it is often misdiagnosed 74 glycogen storage diseases homocystinuria 65 Ehlers Danlos syndrome 65 porphyria Menkes syndrome epidermolysis bullosa and Gaucher s disease People with scoliosis of unknown cause also have a higher risk of osteoporosis Bone loss can be a feature of complex regional pain syndrome It is also more frequent in people with Parkinson s disease and chronic obstructive pulmonary disease People with Parkinson s disease have a higher risk of broken bones This is related to poor balance and poor bone density 75 In Parkinson s disease there may be a link between the loss of dopaminergic neurons and altered calcium metabolism 76 and iron metabolism causing a stiffening of the skeleton and kyphosis Medication Edit Certain medications have been associated with an increase in osteoporosis risk only glucocorticosteroids and anticonvulsants are classically associated but evidence is emerging with regard to other drugs Steroid induced osteoporosis SIOP arises due to use of glucocorticoids analogous to Cushing s syndrome and involving mainly the axial skeleton The synthetic glucocorticoid prescription drug prednisone is a main candidate after prolonged intake Some professional guidelines recommend prophylaxis in patients who take the equivalent of more than 30 mg hydrocortisone 7 5 mg of prednisolone especially when this is in excess of three months 77 It is recommended to use calcium or Vitamin D as prevention 78 Alternate day use may not prevent this complication 79 Barbiturates phenytoin and some other enzyme inducing antiepileptics these probably accelerate the metabolism of vitamin D 80 L Thyroxine over replacement may contribute to osteoporosis in a similar fashion as thyrotoxicosis does 64 This can be relevant in subclinical hypothyroidism Several drugs induce hypogonadism for example aromatase inhibitors used in breast cancer methotrexate and other antimetabolite drugs depot progesterone and gonadotropin releasing hormone agonists Anticoagulants long term use of heparin is associated with a decrease in bone density 81 and warfarin and related coumarins have been linked with an increased risk in osteoporotic fracture in long term use 82 Proton pump inhibitors these drugs inhibit the production of stomach acid this is thought to interfere with calcium absorption 83 Chronic phosphate binding may also occur with aluminium containing antacids 64 Thiazolidinediones used for diabetes rosiglitazone and possibly pioglitazone inhibitors of PPARg have been linked with an increased risk of osteoporosis and fracture 84 Chronic lithium therapy has been associated with osteoporosis 64 Evolutionary Edit Age related bone loss is common among humans due to exhibiting less dense bones than other primate species 85 Because of the more porous bones of humans frequency of severe osteoporosis and osteoporosis related fractures is higher 86 The human vulnerability to osteoporosis is an obvious cost but it can be justified by the advantage of bipedalism inferring that this vulnerability is the byproduct of such 86 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 85 In addition the porosity allows for more flexibility and a lighter skeleton that is easier to support 86 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 87 Fracture risk assessment Edit 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 a clinical FRAX is advised at age 50 Pathogenesis Edit Osteoporosis locations The underlying mechanism in all cases of osteoporosis is an imbalance between bone resorption and bone formation 88 89 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 amp Thomas in 1963 90 Osteoclasts are assisted by transcription factor PU 1 to degrade the bone matrix while osteoblasts rebuild 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 88 91 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 the osteoblast and toward the marrow adipocyte lineage 92 An interplay of these three mechanisms underlies the development of fragile bone tissue 36 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 is lower than that normally needed to stimulate the uterus and breast gland The a form of the estrogen receptor appears to be the most important in regulating bone turnover 36 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 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 36 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 89 This molecule is produced by osteoblasts and other cells e g lymphocytes and stimulates RANK receptor activator of nuclear factor kB 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 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 36 Osteoclast maturation and activity is also regulated by activation of colony stimulating factor 1 receptor CSF1R 93 Menopause associated increase production of TNF a stimulates stromal cells to produce colony stimulating factor 1 CSF 1 which activates CSF1R and stimulates osteoclasts to reabsorb bone 94 Trabecular bone or cancellous bone 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 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 citation needed Around the ages of 30 35 cancellous or trabecular bone loss begins Women may lose as much as 50 while men lose about 30 38 Light micrograph of an osteoclast displaying typical distinguishing characteristics a large cell with multiple nuclei and a foamy cytosol Light micrograph of osteoblasts several displaying a prominent Golgi apparatus actively synthesizing osteoid containing two osteocytes Collapse of vertebra on the right normal on the leftDiagnosis Edit Multiple osteoporotic wedge fractures demonstrated on a lateral thoraco lumbar spine X ray Osteoporosis can be diagnosed using conventional radiography and by measuring the bone mineral density BMD 95 The most popular method of measuring BMD is dual energy X ray absorptiometry citation needed 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 the bone multiple myeloma Cushing s disease and other above mentioned causes may be performed 96 Conventional radiography Edit 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 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 97 98 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 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 99 100 Dual energy X ray Edit 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 a young 30 40 year old 4 58 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 4 58 The World Health Organization has established the following diagnostic guidelines 4 26 Category T score range young womenNormal T score 1 0 85 Osteopenia 2 5 lt T score lt 1 0 14 Osteoporosis T score 2 5 0 6 Severe osteoporosis T score 2 5 with fragility fracture 26 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 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 101 Biomarkers Edit 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 the resulting fragment called a neoepitope as a way to diagnose osteoporosis 102 Increased urinary excretion of C telopeptides a type I collagen breakdown product also serves as a biomarker for osteoporosis 103 Comparison of bone pathology viewtalkeditCondition Calcium Phosphate Alkaline phosphatase Parathyroid hormone CommentsOsteopenia unaffected unaffected normal unaffected decreased bone massOsteopetrosis unaffected unaffected elevated unaffected citation needed thick dense bones also known as marble boneOsteomalacia and rickets decreased decreased elevated elevated soft bonesOsteitis fibrosa cystica elevated decreased elevated elevated brown tumorsPaget s disease of bone unaffected unaffected variable depending on stage of disease unaffected abnormal bone architectureOther measuring tools Edit 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 cm3 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 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 the limitations of DXA and QCT 95 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 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 95 Some ultrasound devices can be used on the tibia 104 Screening EditThe U S Preventive Services Task Force USPSTF recommend that all women 65 years of age or older be screened by bone densitometry 105 Additionally they recommend screening younger women with risk factors 105 There is insufficient evidence to make recommendations about the intervals for repeated screening and the appropriate age to stop screening 106 In men the harm versus benefit of screening for osteoporosis is unknown 105 Prescrire states that the need to test for osteoporosis in those who have not had a previous bone fracture is unclear 107 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 a 70 year old 108 A number of tools exist to help determine who is reasonable to test 109 Prevention EditLifestyle prevention of osteoporosis is in many aspects the inverse of the potentially modifiable risk factors 110 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 111 In people with coeliac disease adherence to a gluten free diet decreases the risk of developing osteoporosis 112 and increases bone density 67 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 112 Nutrition Edit 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 113 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 the community who had no known history of vitamin D deficiency osteoporosis or a fracture 114 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 115 A 2015 review found little data that supplementation of calcium decreases the risk of fractures 116 While some meta analyses have found a benefit of vitamin D supplements combined with calcium for fractures they did not find a benefit of vitamin D supplements 800 IU day or less alone 117 118 While supplementation does not appear to affect the risk of death 114 118 an increased risk of myocardial infarctions 119 120 kidney stones 114 and stomach problems 118 is associated with calcium supplementation Vitamin K deficiency is also a risk factor for osteoporotic fractures 121 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 122 Vitamin K2 is also used as a means of treatment for osteoporosis and the polymorphisms of GGCX could explain the individual variation in the response to treatment of vitamin K 123 Dietary sources of calcium include dairy products leafy greens legumes and beans 124 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 125 A review of the evidence shows no adverse effect of higher protein intake on bone health 126 Physical exercise Edit There is limited evidence indicating that exercise is helpful in promoting bone health 127 There is some evidence that physical exercise may be beneficial for bone density in postmenopausal women and lead to a slightly reduced risk of a bone fracture absolute difference 4 128 Weight bearing exercise has been found to cause an adaptive response in the skeleton 129 Weight bearing exercise promotes osteoblast activity protecting bone density 130 A position statement concluded that increased bone activity and weight bearing exercises at a young age prevent bone fragility in adults 131 Bicycling and swimming are not considered weight bearing exercise Neither contribute to slowing bone loss with age and professional bicycle racing has a negative effect on bone density 132 Low quality evidence suggests that exercise may reduce pain and improve quality of life of people with vertebral fractures and there is moderate quality evidence that exercise will likely improve physical performance in individuals with vertebral fractures 133 Physical therapy Edit People with osteoporosis are at higher risk of falls due to poor postural control muscle weakness and overall deconditioning 134 Postural control 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 133 The goal of these interventions are to regain normal spine curvatures increase spine stability and improve functional performance 133 Physical therapy interventions were also designed to slow the rate of bone loss through home exercise programs 134 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 135 There are conflicting reviews as to whether vibration therapy improves bone mineral density 135 136 Physical therapy can aid in overall prevention in 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 137 Hormone therapy Edit Reduced oestrogen levels increase the risk of osteoporosis so hormone replacement therapy when women reach the menopause may reduce the incidence of osteoporosis Management EditLifestyle Edit Weight bearing endurance exercise and or exercises to strengthen muscles improve bone strength in those with osteoporosis 128 138 Aerobics weight bearing and resistance exercises all maintain or increase BMD in postmenopausal women 128 Fall prevention can help prevent osteoporosis complications There is some evidence for hip protectors specifically among those who are in care homes 139 Pharmacologic therapy Edit The US National Osteoporosis Foundation recommends pharmacologic treatment for patients with hip of spine fracture thought to be related to osteoporosis those with BMD 2 5 SD or more below the young normal mean T score 2 5 or below and those with BMD between 1 and 2 5 SD below normal mean whose 10 year risk using FRAX for hip fracture is equal or more than 3 140 Bisphosphonates are useful in decreasing the risk of future fractures in those who have already sustained a fracture due to osteoporosis 5 6 111 141 This benefit is present when taken for three to four years 142 143 They do not appear to change the overall risk of death 12 Tentative evidence does not support the use of bisphosphonates as a standard treatment for secondary osteoporosis in children 143 Different bisphosphonates have not been directly compared therefore it is unknown if one is better than another 111 Fracture risk reduction is between 25 and 70 depending on the bone involved 111 There are concerns of atypical femoral fractures and osteonecrosis of the jaw with long term use but these risks are low 111 144 With evidence of little benefit when used for more than three to five years and in light of the potential adverse events it may be appropriate to stop treatment after this time 142 One medical organization recommends that after five years of medications by mouth or three years of intravenous medication among those at low risk bisphosphonate treatment can be stopped 145 146 In those at higher risk they recommend up to ten years of medication by mouth or six years of intravenous treatment 145 The goal of osteoporosis management is to prevent osteoporotic fractures but for those who have sustained one already it is more urgent to prevent a secondary fracture 147 That is because patients with a fracture are more likely to experience a recurrent fracture with marker increase in morbidity and mortality compared 147 Among the five bisphosphonates no significant differences were found for a secondary fracture for all fracture endpoints combined 147 That being said alendronate was identified as the most efficacious for secondary prevention of vertebral and hip fractures while zoledronate showed better performance for nonvertebral non hip fracture prevention 147 There is concern that many people do not receive appropriate pharmacological therapy after a low impact fracture 148 For those with osteoporosis but who have not had a fracture evidence does not support a reduction in fracture risk with risedronate 6 or etidronate 11 Alendronate decreases fractures of the spine but does not have any effect on other types of fractures 5 Half stop their medications within a year 149 When on treatment with bisphosphonates rechecking bone mineral density is not needed 146 There is tentative evidence of benefit in males with osteoporosis 150 Fluoride supplementation does not appear to be effective in postmenopausal osteoporosis as even though it increases bone density it does not decrease the risk of fractures 151 152 Teriparatide a recombinant parathyroid hormone has been shown to be effective in treatment of women with postmenopausal osteoporosis 153 141 Some evidence also indicates strontium ranelate is effective in decreasing the risk of vertebral and nonvertebral fractures in postmenopausal women with osteoporosis 154 Hormone replacement therapy while effective for osteoporosis is only recommended in women who also have menopausal symptoms 111 It is not recommended for osteoporosis by itself 146 Raloxifene while effective in decreasing vertebral fractures does not affect the risk of nonvertebral fracture 111 And while it reduces the risk of breast cancer it increases the risk of blood clots and strokes 111 While denosumab is effective at preventing fractures in women 111 there is not clear evidence of benefit in males 150 In hypogonadal men testosterone has been shown to improve bone quantity and quality but as of 2008 no studies evaluated its effect on fracture risk or in men with a normal testosterone levels 66 Calcitonin while once recommended is no longer due to the associated risk of cancer and questionable effect on fracture risk 155 Alendronic acid colecalciferol can be taken to treat this condition in post menopausal women 156 Romosozumab sold under the brand name Evenity is a monoclonal antibody against sclerostin Romosozumab is usually reserved for patients with very high fracture risk and is the only available drug therapy for osteoporosis that leads to simultaneous inhibition of bone resorption together with an anabolic effect 157 158 Certain medications like alendronate etidronate risedronate raloxifene and strontium ranelate can help to prevent osteoporotic fragility fractures in postmenopausal women with osteoporosis 159 Tentative evidence suggests that Chinese herbal medicines may have potential benefits on bone mineral density 160 Prognosis EditHip fractures per 1000 person years 161 WHO category Age 50 64 Age gt 64 OverallNormal 5 3 9 4 6 6Osteopenia 11 4 19 6 15 7Osteoporosis 22 4 46 6 40 6Although people with osteoporosis have increased mortality due to the complications of fracture the fracture itself is rarely lethal Hip fractures can lead to decreased mobility and additional risks of numerous complications such as deep venous thrombosis and or pulmonary embolism and pneumonia The six month mortality rate for those aged 50 and above following hip fracture was found to be around 13 5 with a substantial proportion almost 13 needing total assistance to mobilize after a hip fracture 162 Vertebral fractures while having a smaller impact on mortality can lead to severe chronic pain of neurogenic origin which can be hard to control as well as deformity Though rare multiple vertebral fractures can lead to such severe hunchback kyphosis the resulting pressure on internal organs can impair one s ability to breathe Apart from risk of death and other complications osteoporotic fractures are associated with a reduced health related quality of life 163 The condition is responsible for millions of fractures annually mostly involving the lumbar vertebrae hip and wrist Fragility fractures of ribs are also common in men Fractures Edit Hip fractures are responsible for the most serious consequences of osteoporosis In the United States more than 250 000 hip fractures annually are attributable to osteoporosis 164 A 50 year old white woman is estimated to have a 17 5 lifetime risk of fracture of the proximal femur The incidence of hip fractures increases each decade from the sixth through the ninth for both women and men for all populations The highest incidence is found among men and women ages 80 or older 165 Between 35 and 50 of all women over 50 had at least one vertebral fracture In the United States 700 000 vertebral fractures occur annually but only about a third are recognized In a series of 9704 women aged 68 8 on average studied for 15 years 324 had already sustained a vertebral fracture at entry into the study and 18 2 developed a vertebral fracture but that risk rose to 41 4 in women who had a previous vertebral fracture 166 In the United States 250 000 wrist fractures annually are attributable to osteoporosis 164 Wrist fractures are the third most common type of osteoporotic fractures The lifetime risk of sustaining a Colles fracture is about 16 for white women By the time women reach age 70 about 20 have had at least one wrist fracture 165 Fragility fractures of the ribs are common in men as young as age 35 citation needed These are often overlooked as signs of osteoporosis as these men are often physically active and develop the fracture in the course of physical activity such as falling while water skiing or jet skiing Epidemiology EditThis article needs to be updated Please help update this article to reflect recent events or newly available information December 2020 Age standardised hip fracture rates in 2012 167 Low lt 150 100 000 Medium 150 250 100 000 High gt 250 100 000 It is estimated that 200 million people have osteoporosis 168 Osteoporosis becomes more common with age 3 About 15 of Caucasians in their 50s and 70 of those over 80 are affected 7 It is more common in women than men 3 In the developed world depending on the method of diagnosis 2 to 8 of males and 9 to 38 of females are affected 13 Rates of disease in the developing world are unclear 14 Postmenopausal women have a higher rate of osteoporosis and fractures than older men 169 Postmenopausal women have decreased estrogen which contributes to their higher rates of osteoporosis 169 A 60 year old woman has a 44 risk of fracture while a 60 year old man has a 25 risk of fracture 169 There are 8 9 million fractures worldwide per year due to osteoporosis 170 Globally 1 in 3 women and 1 in 5 men over the age of 50 will have an osteoporotic fracture 170 Data from the United States shows a decrease in osteoporosis within the general population and in white women from 18 in 1994 to 10 in 2006 171 White and Asian people are at greater risk 3 People of African descent are at a decreased risk of fractures due to osteoporosis although they have the highest risk of death following an osteoporotic fracture 171 It has been shown that latitude affects risk of osteoporotic fracture 167 Areas of higher latitude such as Northern Europe receive less Vitamin D through sunlight compared to regions closer to the equator and consequently have higher fracture rates in comparison to lower latitudes 167 For example Swedish men and women have a 13 and 28 5 risk of hip fracture by age 50 respectively whereas this risk is only 1 9 and 2 4 in Chinese men and women 171 Diet may also be a factor that is responsible for this difference as vitamin D calcium magnesium and folate are all linked to bone mineral density 172 There is also an association between Celiac Disease and increased risk of osteoporosis 173 In studies with premenopausal females and males there was a correlation between Celiac Disease and osteoporosis and osteopenia 173 Celiac Disease can decrease absorption of nutrients in the small intestine such as calcium and a gluten free diet can help people with Celiac Disease to revert to normal absorption in the gut 174 About 22 million women and 5 5 million men in the European Union had osteoporosis in 2010 15 In the United States in 2010 about 8 million women and one to 2 million men had osteoporosis 13 16 This places a large economic burden on the healthcare system due to costs of treatment long term disability and loss of productivity in the working population The EU spends 37 billion euros per year in healthcare costs related to osteoporosis and the US spends an estimated US 19 billion annually for related healthcare costs 170 History EditThe link between age related reductions in bone density goes back to the early 1800s French pathologist Jean Lobstein coined the term osteoporosis 17 The American endocrinologist Fuller Albright linked osteoporosis with the postmenopausal state 175 Anthropologists have studied skeletal remains that showed loss of bone density and associated structural changes that were linked to a chronic malnutrition in the agricultural area in which these individuals lived It follows 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