Osteoporosis

Template:Short description Template:Distinguish Template:Cs1 config Template:Use dmy dates Template:Infobox medical condition (new) Osteoporosis is a systemic skeletal disorder characterized by low bone mass, micro-architectural deterioration of bone tissue leading to more porous bone, and consequent increase in fracture risk.

It is the most common reason for a broken bone among the elderly.<ref name="NIH2014">Template:Cite web</ref> Bones that commonly break include the vertebrae in the spine, the bones of the forearm, the wrist, and the hip.<ref name="Gol2015">Template:Cite journal</ref><ref>Template:Cite web</ref>

Until a broken bone occurs there are typically no symptoms. Bones may weaken to such a degree that a break may occur with minor stress or spontaneously. After the broken bone heals, some people may have chronic pain and a decreased ability to carry out normal activities.<ref name="NIH2014" />

Osteoporosis may be due to lower-than-normal maximum bone mass and greater-than-normal bone loss. Bone loss increases after menopause in women due to lower levels of estrogen, and after andropause in older men due to lower levels of testosterone.<ref>Template:Cite web</ref> Osteoporosis may also occur due to a number of diseases or treatments, including alcoholism, anorexia, hyperthyroidism, kidney disease, and after oophorectomy (surgical removal of the ovaries). Certain medications increase the rate of bone loss, including some antiseizure medications, chemotherapy, proton pump inhibitors, selective serotonin reuptake inhibitors, and glucocorticosteroids. Smoking and getting an inadequate amount of exercise are also risk factors.<ref name="NIH2014" /> 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).<ref name="WHOcriteria">Template:Cite bookTemplate:Page needed</ref>

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.<ref name=NIH2014/> 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.<ref name=Wells2008>Template:Cite journal</ref>Template:Update inline<ref name="Wells2008a">Template:Cite journal</ref><ref name="Wells-2024">Template:Cite journal</ref> They do not appear to affect the risk of death.<ref name="ABDTJAMA2019">Template:Cite journal</ref>

Osteoporosis becomes more common with age. About 15% of Caucasians in their 50s and 70% of those over 80 are affected.<ref name=WHOEpi>Template:Cite web</ref> It is more common in women than men.<ref name=NIH2014/> In the developed world, depending on the method of diagnosis, 2% to 8% of males and 9% to 38% of females are affected.<ref name=Wade2014/> Rates of disease in the developing world are unclear.<ref name=Han2008>Template:Cite journal</ref> About 22 million women and 5.5 million men in the European Union had osteoporosis in 2010.<ref name=Sve2013>Template:Cite journal</ref> In the United States in 2010, about 8 million women and between 1 and 2 million men had osteoporosis.<ref name=Wade2014>Template:Cite journal</ref><ref name=Will2015>Template:Cite journal</ref> White and Asian people are at greater risk.<ref name=NIH2014/> The word "osteoporosis" is from the Greek terms for "porous bones".<ref name=Grob2014 />

Signs and symptoms

File:Blausen 0686 Osteoporosis 01.png

Illustration depicting normal standing posture and osteoporosis

Osteoporosis has no symptoms and the person usually does not know that they have osteoporosis until a bone is broken. Osteoporotic fractures occur in situations where healthy people would not normally break a bone; they are therefore regarded as fragility fractures. Typical fragility fractures occur in the vertebral column, rib, hip and wrist.<ref name=niams/> Examples of situations where people would not normally break a bone include a fall from standing height, normal day-to-day activities such as lifting, bending, or coughing.<ref name="niams">Template:Cite web</ref>

Fractures

Fractures are a common complication of osteoporosis and can result in disability.<ref>Template:Cite book</ref> Acute and chronic pain in the elderly is often attributed to fractures from osteoporosis and can lead to further disability and early mortality.<ref>Template:Cite journal</ref> These fractures may also be asymptomatic.<ref>Template:Cite journal</ref> 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.<ref>Template:Cite journal</ref>

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 osteoporosis-related hip fracture, with the mean average mortality rate within one year for Europe being 23.3%, for Asia 17.9%, United States 21% and Australia 24.9%.<ref>Template:Cite journal</ref>

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,<ref>Template:Cite web</ref> the Garvan FRC calculator and QFracture as well as the open access FREM tool.<ref>Template:Cite journal</ref> The FRAX tool can also be applied in a modification adapted to routinely collected health data.<ref>Template:Cite journal</ref>

The term "established osteoporosis" is used when a broken bone due to osteoporosis has occurred.<ref name=WHO1994>Template:Cite bookTemplate:Page needed</ref> Osteoporosis is a part of frailty syndrome.

Risk of falls

File:Menopause - Osteoporosis -- Smart-Servier (cropped).jpg

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 (e.g. glaucoma, macular degeneration), balance disorder, movement disorders (e.g. Parkinson's disease), dementia, sarcopenia (age-related loss of skeletal muscle), and 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.<ref>Template:Cite journal</ref>

Complications

As well as susceptibility to breaks and fractures, osteoporosis can lead to other complications. Bone fractures from osteoporosis can lead to disability and an increased risk of death after the injury in elderly people.<ref name="mayo">Template:Cite web</ref> Osteoporosis can decrease the quality of life, increase disabilities, and increase the financial costs to health care systems.<ref name="sozen">Template:Cite journal</ref>

Risk factors

The risk of having osteoporosis includes age and sex. Risk factors include both nonmodifiable (for example, age and some medications that may be necessary to treat a different condition) and modifiable (for example, alcohol use, smoking, vitamin deficiency). In addition, osteoporosis is a recognized complication of specific diseases and disorders. Medication use 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.<ref>Template:Cite journal</ref> White people have a higher risk for the disease.<ref>Template:Cite web</ref>

Nonmodifiable

File:615 Age and Bone Mass.jpg

Bone density peaks at about 30 years of age. Women lose bone mass more rapidly than men.<ref>Template:Cite book</ref>

• 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.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref>
• Ethnicity: While osteoporosis occurs in people from all ethnic groups, European or Asian ancestry predisposes for osteoporosis.<ref>Template:Cite journal</ref>
• Heredity: Those with a family history of fracture or osteoporosis are at an increased risk; the heritability of fracture risk, 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.<ref name="Raisz">Template:Cite journal</ref>
• 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.<ref>Template:Cite journal</ref>
• Build: A small stature is also a nonmodifiable risk factor associated with the development of osteoporosis.<ref name=AppTher>Template:Cite book</ref>

Potentially modifiable

• Alcohol: Alcohol intake greater than three units/day may increase the risk of osteoporosis, and people who consumed 0.5-1 drinks a day may have 1.38 times the risk compared to people who do not consume alcohol.<ref name="BMJosteoporosis">Template:Cite journal</ref><ref>Template:Cite journal</ref>
• Vitamin D deficiency:<ref name=micronutrients>Template:Cite journal</ref><ref>Template:Cite journal</ref> Low circulating Vitamin D is common among the elderly worldwide.<ref name="WHOcriteria"/> Mild vitamin D insufficiency is associated with increased parathyroid hormone (PTH) production.<ref name="WHOcriteria"/> 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.<ref name="WHOcriteria"/>
• Tobacco smoking: Many studies have associated smoking with decreased bone health, but the mechanisms are unclear.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref><ref>Template:Cite journal</ref> Tobacco smoking has been proposed to inhibit the activity of osteoblasts, and is an independent risk factor for osteoporosis.<ref name="BMJosteoporosis"/><ref>Template:Cite journal</ref> Smoking also results in increased breakdown of exogenous estrogen, lower body weight and earlier menopause, all of which contribute to lower bone mineral density.<ref name="WHOcriteria"/>
• Malnutrition: Nutrition has an important and complex role in maintenance of good bone. Identified risk factors include low dietary calcium or phosphorus, magnesium, zinc, boron, iron, fluoride, copper, vitamins A, K, E, and C (and vitamin 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.<ref name="pmid11194525">Template:Cite journal</ref> Imbalance of omega-6 to omega-3 polyunsaturated fats is yet another identified risk factor.<ref>Template:Cite journal</ref>
• A 2017 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.<ref name="pmid28404575"/> A 2023 meta-analysis sees no evidence for the relation between protein intake and bone health.<ref>Template:Cite journal</ref>
• Underweight/inactive: Bone remodeling occurs in response to physical stress, so physical inactivity can lead to significant bone loss.<ref name="WHOcriteria"/> Weight bearing exercise can increase peak bone mass achieved in adolescence,<ref name="WHOcriteria"/> and a highly significant correlation between bone strength and muscle strength has been determined.<ref>Template:Cite journal</ref> The incidence of osteoporosis is lower in overweight people.<ref>Template:Cite journal</ref>
• Endurance training: In female endurance athletes, large volumes of training can lead to decreased bone density and an increased risk of osteoporosis.<ref>Template:Cite journal</ref> This effect might be caused by intense training suppressing menstruation, producing amenorrhea, and it is part of the female athlete triad.<ref>Template:Cite journal</ref> However, for male athletes, the situation is less clear, and although some studies have reported low bone density in elite male endurance athletes,<ref>Template:Cite journal</ref> others have instead seen increased leg bone density.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref>
• 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).<ref>Template:Cite journal</ref>
• Soft drinks: Some studies indicate soft drinks (many of which contain phosphoric acid) may increase risk of osteoporosis, at least in women.<ref>Template:Cite journal</ref> Others suggest soft drinks may displace calcium-containing drinks from the diet rather than directly causing osteoporosis.<ref>Template:Cite journal</ref>
• 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.<ref>Template:Cite journal</ref>

Medical disorders

File:625 Calcium Homeostasis.jpg

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.<ref name=ICSI>Template:Cite web</ref> 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. 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.Template:Citation needed
• Hypogonadal states can cause secondary osteoporosis. These include Turner syndrome, Klinefelter syndrome, Kallmann syndrome, anorexia nervosa, andropause,<ref name='medscapeosteoporosis'/> hypothalamic amenorrhea or hyperprolactinemia.<ref name='medscapeosteoporosis'/> In females, the effect of hypogonadism is mediated by estrogen deficiency. It can appear as early menopause (<45 years) or from prolonged premenopausal amenorrhea (>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,<ref name="WHOcriteria"/> hyperparathyroidism,<ref name="WHOcriteria"/> hyperthyroidism,<ref name="WHOcriteria"/> hypothyroidism, diabetes mellitus type 1 and 2,<ref name=OsteoporosisMen>Template:Cite journal</ref> acromegaly, and adrenal insufficiency.<ref name="ICSI" />
• Malnutrition, parenteral nutrition<ref name="WHOcriteria"/> 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),<ref name="WHOcriteria"/><ref name=MirzaCanalis2015>Template:Cite journal</ref> Crohn's disease,<ref name="Pediatric">Template:Cite journal</ref> ulcerative colitis,<ref name="Pediatric"/> cystic fibrosis,<ref name="Pediatric"/> surgery<ref name='medscapeosteoporosis'/> (after gastrectomy, intestinal bypass surgery or bowel resection) and severe liver disease (especially primary biliary cirrhosis).<ref name='medscapeosteoporosis'/> People with lactose intolerance or milk allergy may develop osteoporosis due to restrictions of calcium-containing foods.<ref name=Beto2015>Template:Cite journal</ref> 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,<ref name='medscapeosteoporosis'/> ankylosing spondylitis,<ref name='medscapeosteoporosis'>Template:EMedicine</ref> 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.<ref>Template:Cite web</ref>
• Hematologic disorders linked to osteoporosis are multiple myeloma<ref name='medscapeosteoporosis'/> and other monoclonal gammopathies,<ref name=OsteoporosisMen/> lymphoma, leukemia, mastocytosis,<ref name="medscapeosteoporosis" /> hemophilia, sickle-cell disease and thalassemia.
• Immune disorders: Osteoporosis can be a symptom of mast cell activation syndrome.<ref name="PMID27012973">Template:Cite journal</ref><ref name="PMID38948000">Template:Cite journal</ref><ref name="PMID24801454">Template:Cite journal</ref>
• Several inherited or genetic disorders have been linked to osteoporosis. These include osteogenesis imperfecta,<ref name='medscapeosteoporosis'/> Multicentric carpotarsal osteolysis syndrome,<ref>Template:Cite journal</ref> Multicentric Osteolysis, Nodulosis, and Arthropathy,<ref>Template:Cite journal</ref> Marfan syndrome,<ref name='medscapeosteoporosis'/> hemochromatosis,<ref name="WHOcriteria"/> hypophosphatasia<ref>Template:Cite book</ref> (for which it is often misdiagnosed),<ref>Template:Cite web</ref> glycogen storage diseases, homocystinuria,<ref name='medscapeosteoporosis'/> Ehlers–Danlos syndrome,<ref name='medscapeosteoporosis'/> 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.<ref>Template:Cite journal</ref> In Parkinson's disease there may be a link between the loss of dopaminergic neurons and altered calcium metabolism<ref>Template:Cite journal</ref> (and iron metabolism) causing a stiffening of the skeleton and kyphosis.

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.

• 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.<ref>Template:Cite book</ref> It is recommended to use calcium or Vitamin D as prevention.<ref>Template:Cite journal</ref> Alternate day use may not prevent this complication.<ref name=GIOP>Template:Cite journal</ref>
• Barbiturates, phenytoin and some other enzyme-inducing antiepileptics – these probably accelerate the metabolism of vitamin D.<ref>Template:Cite journal</ref>
• L-Thyroxine over-replacement may contribute to osteoporosis, in a similar fashion as thyrotoxicosis does.<ref name="ICSI"/> 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,<ref>Template:Cite journal</ref> and warfarin (and related coumarins) have been linked with an increased risk in osteoporotic fracture in long-term use.<ref>Template:Cite journal</ref>
• Proton pump inhibitors – these drugs inhibit the production of stomach acid; this is thought to interfere with calcium absorption.<ref>Template:Cite journal</ref> Chronic phosphate binding may also occur with aluminium-containing antacids.<ref name="ICSI"/>
• Thiazolidinediones (used for diabetes) – rosiglitazone and possibly pioglitazone, inhibitors of PPARγ, have been linked with an increased risk of osteoporosis and fracture.<ref>Template:Cite journal</ref>
• Chronic lithium therapy has been associated with osteoporosis.<ref name="ICSI"/>

Pregnancy-associated osteoporosis

Template:Expand section Osteoporosis due to pregnancy and lactation is a rare condition of unknown cause.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref><ref>Template:Cite journal</ref><ref>Template:Cite journal</ref><ref>Template:Cite journal</ref>

Evolutionary

Age-related bone loss is common among humans due to exhibiting less dense bones than other primate species.<ref name="Latimer_2005">Template:Cite journal</ref> Because of the more porous bones of humans, frequency of severe osteoporosis and osteoporosis related fractures is higher.<ref name=Cot2011>Template:Cite journal</ref> 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.<ref name=Cot2011/> 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.<ref name="Latimer_2005"/> In addition, the porosity allows for more flexibility and a lighter skeleton that is easier to support.<ref name=Cot2011/> 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.<ref name="pmid2053574">Template:Cite journal</ref>

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.

Mechanics

Osteoporosis occurs when reduction in bone mass surpasses a critical threshold with greater susceptibility to fracturing.<ref>Template:Cite book</ref> Fractures occur when the force acting on a bone is greater than the strength of the bone.<ref name="Chen-2014">Template:Cite journal</ref> To understand the pathology of osteoporosis and skeletal degradation, studying the mechanical properties and behavior of bone is crucial, due to the under-diagnosing of osteoporosis.<ref>Template:Cite journal</ref> Mechanical properties of a material depend on the geometry and inherent structure of the materials.<ref name = "Sharir_2008">Template:Cite journal</ref> Bone as a material is very complex because of its hierarchal structure in which characteristics vary across length scales.<ref name = "Sharir_2008" /><ref name="Zimmermann-2015">Template:Cite journal</ref> At the basic scale, bone is composed of an organic matrix of collagen type-I.<ref name="Sharir_2008" /> Collagen type-I molecules form a composite material with hydroxyapatite to make up collagen fibrils.<ref name="Zimmermann-2015" /> The hierarchal structure continuous with the fibrils being arranged into different patterns such as lamellae.<ref name="Zimmermann-2015" /> The microstructure of bone then forms vascular channels, called osteons, which are surrounded by lamellae.<ref name="Zimmermann-2015" /> At the subsequent scale of bones, there are different types of bone based on morphology: cortical (solid), cancellous (sponge), or trabecular (thin plates).<ref name="Zimmermann-2015" />  

A basic picture of the hierarchical structure of bones is essential because the structure will translate to the mechanical behavior of bones. Previous work indicates that osteoporotic bones undergo specific structural changes that contribute to altered mechanical behavior. For instance, a study demonstrated that osteoporotic bone exhibits reduced bone volume fraction, trabecular thickness, and connectivity.<ref>Template:Cite journal</ref> In another study, osteoporosis in human cancellous bone led to 3-27% variability in the stiffness and strength compared to health bone.<ref>Template:Cite journal</ref> Additionally, bone mineral density (BMD) is a parameter used to evaluate fracture risk in bones and is used as a predictor of osteoporosis.<ref name="Chen-2014" /> A lower BMD value correlates to decreased bone and a higher bone fragility.<ref name="Chen-2014" /> Furthermore, bone diseases, such as osteoporosis, are known to alter the composition of collagen and other proteins that make up the bone matrix.<ref name = "Sroga_2012">Template:Cite journal</ref> These alterations in composition contribute to how bone can handle mechanical loading.<ref name = "Sroga_2012" /> Thus, osteoporosis-induced changes at the macroscopic and microscopic levels significantly impact the mechanical properties of bone, predisposing individuals to fractures even under relatively low mechanical loads. Understanding these structural alterations is vital for developing effective diagnostic and therapeutic strategies for osteoporosis.

Pathogenesis

File:Osteoporosis Locations.png

Osteoporosis locations

The underlying mechanism in all cases of osteoporosis is an imbalance between bone resorption and bone formation.<ref name="Dance">Template:Cite journal</ref><ref name="Robling">Template:Cite journal</ref> 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.<ref>Frost HM, Thomas CC. Bone Remodeling Dynamics. Springfield, IL: 1963.</ref> 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.<ref name="Dance"/><ref>Template:Cite journal</ref>

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.<ref>Template:Cite journal</ref> An interplay of these three mechanisms underlies the development of fragile bone tissue.<ref name=Raisz/> 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.<ref name=Raisz/> 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.<ref name=Raisz/>

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.<ref name="Robling"/> 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.<ref name=Raisz/> Osteoclast maturation and activity is also regulated by activation of colony stimulating factor 1 receptor (CSF1R).<ref>Template:Cite journal</ref> 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.<ref>Template:Cite journal</ref>

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.Template: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%.<ref name=AppTher />

• Light micrograph of an osteoclast displaying typical distinguishing characteristics: a large cell with multiple nuclei and a "foamy" cytosol.
  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.
  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 left
  Collapse of vertebra on the right, normal on the left

Diagnosis

File:L1 2 vertebral fracture.jpg

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

Osteoporosis often has no clear symptoms<ref>Template:Cite journal</ref> in the early stages, making it difficult to detect without screening. However, you may experience signs such as unexplained back pain, loss of height, or a stooped posture as the condition progresses.[1] <ref>Template:Cite journal</ref> Osteoporosis can be diagnosed using conventional radiography and by measuring the bone mineral density (BMD).<ref name="Guglielmi Scalzo 2010 Imaging tools">Template:Cite journal</ref> The most popular method of measuring BMD is dual-energy X-ray absorptiometry.<ref>Template:Cite journal</ref>

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.<ref>Template:Cite journal</ref>

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.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref>

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.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref>

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<ref name="WHOcriteria"/>^: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.<ref name="WHOcriteria"/>^:58 The World Health Organization has established the following diagnostic guidelines:<ref name="WHOcriteria"/><ref name=WHO1994/>

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<ref name=WHO1994/>

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.<ref name="pmid14742881">Template:Cite journal quoted in: "Diagnosis of osteoporosis in men, premenopausal women, and children" Template:Webarchive</ref>

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.<ref name="pmid15876399">Template:Cite journal</ref> Increased urinary excretion of C-telopeptides, a type-I collagen breakdown product, also serves as a biomarker for osteoporosis.<ref>Template:Cite book</ref>

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.<ref name="Guglielmi Scalzo 2010 Imaging tools"/>

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.<ref name="Guglielmi Scalzo 2010 Imaging tools"/> Some ultrasound devices can be used on the tibia.<ref>Template:Cite web</ref>

Screening

The U.S. Preventive Services Task Force (USPSTF) recommend that all women 65 years of age or older be screened by bone densitometry.<ref name=USPSTF2018b/> Additionally they recommend screening younger women with risk factors.<ref name="USPSTF2018b">Template:Cite journal</ref> There is insufficient evidence to make recommendations about the intervals for repeated screening and the appropriate age to stop screening.<ref name=USP2011>Template:Cite journal</ref>

In men the harm versus benefit of screening for osteoporosis is unknown.<ref name=USPSTF2018b/> Prescrire states that the need to test for osteoporosis in those who have not had a previous bone fracture is unclear.<ref>Template:Cite journal</ref> 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.<ref>International Society for Clinical Densitometry (ISCD). 2013 ISCD Official Positions – Adult. (2013). at Template:Cite web</ref> A number of tools exist to help determine who is reasonable to test.<ref name="pmid18716823">Template:Cite journal</ref>

Prevention

Lifestyle prevention of osteoporosis is in many aspects the inverse of the potentially modifiable risk factors.<ref name="pmid25370432">Template:Cite journal</ref> 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.<ref name=Review2011/>

In people with coeliac disease adherence to a gluten-free diet decreases the risk of developing osteoporosis<ref name=LudvigssonBai2014>Template:Cite journal</ref> and increases bone density.<ref name=MirzaCanalis2015 /> 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.<ref name=LudvigssonBai2014 />

Osteoporosis can affect nearly 1 in 3 women and the bone loss is the most rapid within the first 2–3 years after menopause. This can be prevented by menopause hormone therapy or MHT, which is meant to prevent bone loss and the degradation of the bone microarchitecture and is noted to reduce the risk of fractures in bones by 20-30%. However, MHT has been linked to safety concerns, so it is not generally recommended.<ref>Template:Cite journal</ref> As far as management goes with this potentially limiting disease, there are practices that can and should be implemented within the daily lifestyle. For example, it would be beneficial if the individual with osteoporosis refrained from consuming excess alcohol and to avoid smoking.<ref>Template:Cite journal</ref> These individuals should also be intentional about intaking an adequate amount of protein, calcium, and vitamin D. If the woman has an even higher risk of fracture, managing this may require therapy. Generally, the recommended treatment of prevention for a decrease in bone mineral density is physical activity. Exercise is sometimes the best medicine. Resistance training is the most recommended method of physical activity but that can come in multiple forms. High intensity and high impact training is shown to be extremely beneficial in improving bone health and the most effective in improving, maintaining, bone density in the lower spine and femur. Although these types of exercises are safe for postmenopausal women, there still may be a need for supervision and precautionary measures.<ref>Template:Cite journal</ref>

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.<ref name="MedicalLetter">Template:Cite journal</ref> 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.<ref name=USPSTF2018>Template:Cite journal</ref> 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.<ref name="USPSTF2018Recs">Template:Cite web</ref> A 2015 review found little data that supplementation of calcium decreases the risk of fractures.<ref>Template:Cite journal</ref> While some meta-analyses have found a benefit of vitamin D supplements combined with calcium for prevention of fractures, they did not find a benefit of vitamin D supplements (800 IU/day or less) alone.<ref>Template:Cite journal</ref><ref name="Ave2014">Template:Cite journal</ref> Regarding adverse effects, supplementation does not appear to affect overall risk of death,<ref name="USPSTF2018" /><ref name="Ave2014" /> although calcium supplementation could potentially be associated with some increased risk of myocardial infarctions, stroke, kidney stones,<ref name="USPSTF2018" /> and gastrointestinal symptoms.<ref name="Ave2014"/> There is no evidence that supplementation before menopause can enhance bone mineral density.<ref>Template:Cite journal</ref>

Vitamin K deficiency is also a risk factor for osteoporotic fractures.<ref>Template:Cite journal</ref> 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.<ref>Template:Cite journal</ref> 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.<ref>Template:Cite journal</ref>

Dietary sources of calcium include dairy products, leafy greens, legumes, and beans.<ref>Template:Cite web</ref> 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.<ref>Template:Cite web</ref> A review of the evidence shows no adverse effect of higher protein intake on bone health.<ref name="pmid28404575">Template:Cite journal</ref>

Physical exercise

Evidence suggests that exercise can help promote bone health in older people.<ref name=Pinheiro2020>Template:Cite journal</ref> In particular, physical exercise can be beneficial for bone density in postmenopausal women,<ref name=Mohebbi2023/> and lead to a slightly reduced risk of a bone fracture (absolute difference 4%).<ref name=":Howe2011">Template:Cite journal</ref> Weight bearing exercise has been found to cause an adaptive response in the skeleton,<ref>Template:Cite journal</ref> promoting osteoblast activity and protecting bone density.<ref>Template:Cite journal</ref> A position statement concluded that increased bone activity and weight-bearing exercises at a young age prevent bone fragility in adults.<ref>Template:Cite journal</ref> Limitations in the available evidence hinder the production of detailed evidence-based exercise recommendations.<ref name=Mohebbi2023>Template:Cite journal</ref> Some expert consensus guidance does exist.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref> International guidelines recommend multicomponent exercise tailored to individual needs that includes "balance and mobility training, paired with weight bearing exercise, progressive resistance training, and posture exercises" (generally accompanied by optimal nutrition).<ref>Template:Cite journal</ref> Cycling and swimming are not considered weight-bearing exercise, and neither helps slow age-related bone loss (professional bicycle racing has a negative effect on bone density).<ref>Template:Cite journal</ref> Risk of adverse events from the types of exercise usually considered appropriate for people with osteoporosis is generally low (though repeated forceful forward spinal bends are discouraged).<ref name="NOGG2019-5">Template:Cite web</ref>

For people who have had vertebral fractures, there is moderate-quality evidence that exercise is likely to improve physical performance, as well as some low-quality evidence suggesting that exercise may reduce pain and improve quality of life.<ref name = "Gibbs_2019">Template:Cite journal</ref>

Physical exercise prescription

Osteoporosis is a very prevalent disease in the elderly population but not much is known about the optimal prescription and dosage of physical exercise to help prevent bone mineral loss. A lot of the focus around osteoporosis is prevention oriented, rather than maintenance focused, which should be the front runner when considering what approach to take. When prescribing exercise, an aspect to take into consideration is the individual’s need this can be attained by conducting a pre-exercise evaluation or screening, exercise should also be tailored to the individual and what works for them. Important things often overlooked when treating osteoporosis are muscle strength and maintenance of BMD, which should be incorporated into the program to optimize the benefits of exercise. This entails including exercises that focus on and improve muscle strength and exercises that focus on and improve skeletal strength or BMD as these go hand in hand for reducing fall and fracture risk.<ref name="Daly-2019">Template:Cite journal</ref> It’s also important to reference the ACSM general training principle to better design a program for the individual. Which mode of exercise and dosage has been a recurring question for treating osteoporosis, many articles have found that multimodal exercise programs have had findings of significant improvement in factors related to osteoporosis. Factors include lower limb strength, balance, flexibility, and risk of falls.<ref>Template:Cite journal</ref> Other modes of exercise have also proven to improve individuals with osteoporosis, some of these modes include weight-bearing, resistance specifically progressive resistance, and aerobic exercise. The recommendations for these types of exercises are as follows, weight-bearing exercise should be done 4–7 days a week, moderate to high intensity, activities should be multidirectional, and load should be more than typical everyday load on bones.<ref name="Daly-2019" /> Some examples of exercises are jumping, skipping, hopping, depth jumps, etc.  Recommended dosage for progressive resistance training is 2 or more days a week, intensity (load) should start low and increase gradually.<ref name="Daly-2019" /> Resistance training should focus on major muscle groups used for functional movements as well as muscles that have direct stress on bones susceptible to fracture. Considerations for resistance training are to teach proper lifting techniques and be careful with lifting weights above the head.<ref name="Daly-2019" /> Lastly, aerobic exercise has minimal effect on preventing BMD loss unless done at a higher intensity or with a load like a weighted vest. Considerations with this mode are that this may cause a higher risk of fall or fracture.<ref name="Daly-2019" /> Improvements can also be observed in other ways, such as decreased Timed-Up-and-Go, increased Sit-To-Stand, and increased One-Leg-Stance-Test. A study with a 12-week exercise intervention on postmenopausal osteoporotic women observed a 2.27 decrease in TUG times in their experimental group.<ref>Template:Cite journal</ref> The overall thing to note when prescribing exercise for individuals with osteoporosis is to evaluate the individual's needs and then individualize their program with multiple exercise modalities that work for them, emphasizing increasing muscle strength as well as maintaining bone mass.

Physical therapy

People with osteoporosis are at higher risk of falls due to poor postural control, muscle weakness, and overall deconditioning.<ref name="Effect of balance training on falls">Template:Cite journal</ref> 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.<ref name = "Gibbs_2019" /> The goal of these interventions are to regain normal spine curvatures, increase spine stability, and improve functional performance.<ref name = "Gibbs_2019" /> Physical therapy interventions were also designed to slow the rate of bone loss through home exercise programs.<ref name="Effect of balance training on falls"/>

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.<ref name=Jepsen2017>Template:Cite journal</ref> There are conflicting reviews as to whether vibration therapy improves bone mineral density.<ref name=Jepsen2017 /><ref name=MarinCascales2018>Template:Cite journal</ref>

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.<ref>Template:Cite journal</ref>

Hormone therapy

Reduced estrogen levels increase the risk of osteoporosis, so hormone replacement therapy when women reach the menopause may reduce the incidence of osteoporosis. A more natural way of restoring hormone levels in postmenopausal women include participating in specific forms of exercise. Weight-bearing exercises and resistance training exercises such as squats with weights, step-ups, lunges, stair climbing, and even jogging can elicit hormone responses that are advantageous for post-menopausal women living with osteoporosis. These exercises result in the release of growth hormone and Insulin-like growth factor-1 or IGF-1 that participate in bone remodeling.<ref>Template:Cite journal</ref> Stress is applied to the bones, thus activating osteoblast, which are cells that form new bones and grow and heal existing bones<ref>Template:Citation</ref> while restoring hormones that increase bone density. Resistance training exercises, like weight lifting, can lead to brief increased in anabolic hormones, like testosterone, which aid in muscle and bone strength.<ref>Template:Cite journal</ref> The increase in mechanical tension during resistance exercise will likely help stimulate the production of Insulin-like growth factors in the bone, but at a greater extent. Post-menopausal women experience a reduction of estrogen, which is essential for density, so these exercise-induced hormonal enhancements can counteract the loss of bone mineral density in the most critical area, like the lumbar spine and the femoral neck.<ref>Template:Cite journal</ref> Research suggest that regular resistance training accompanied with weight-bearing activities help reduce the progression of osteoporosis and risk of fracture.

Management

Lifestyle Changes

Weight-bearing endurance exercise and/or exercises to strengthen muscles improve bone strength in those with osteoporosis.<ref name=":Howe2011" /><ref name="pmid21360219">Template:Cite journal</ref> Aerobics, weight bearing, and resistance exercises all maintain or increase BMD in postmenopausal women.<ref name=":Howe2011" /><ref name="Kanis-2019">Template:Cite journal</ref> Daily intake of calcium and vitamin D is recommended for postmenopausal women.<ref name="Kanis-2019" /> Fall prevention can help prevent osteoporosis complications. There is some evidence for hip protectors specifically among those who are in care homes.<ref name="pmid21478069">Template:Cite journal</ref>

Pharmacologic therapy

The US National Osteoporosis Foundation recommends pharmacologic treatment for patients with hip or 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%.<ref>Template:Cite journal</ref> Bisphosphonates are useful in decreasing the risk of future fractures in those who have already sustained a fracture due to osteoporosis.<ref name="Wells2008" /><ref name="Wells2008a" /><ref name="Review2011" /><ref name="Cheng">Template:Cite journal</ref> This benefit is present when taken for three to four years.<ref name="FDA2012">Template:Cite journal</ref><ref name="Ward-2007">Template:Cite journal</ref> They do not appear to change the overall risk of death.<ref name="ABDTJAMA2019" /> Tentative evidence does not support the use of bisphosphonates as a standard treatment for secondary osteoporosis in children.<ref name="Ward-2007" /> Different bisphosphonates have not been directly compared, therefore it is unknown if one is better than another.<ref name="Review2011" /> Fracture risk reduction is between 25 and 70% depending on the bone involved.<ref name="Review2011" /> There are concerns of atypical femoral fractures and osteonecrosis of the jaw with long-term use, but these risks are low.<ref name="Review2011" /><ref>Template:Cite journal</ref> 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.<ref name="FDA2012" /> 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.<ref name="Ad2016" /><ref name="Qa2017" /> In those at higher risk they recommend up to ten years of medication by mouth or six years of intravenous treatment.<ref name="Ad2016">Template:Cite journal</ref>

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.<ref name="Shi 2594149">Template:Cite journal File:CC-BY icon.svg Text was copied from this source, which is available under a Creative Commons Attribution 4.0 International License.</ref> That is because patients with a fracture are more likely to experience a recurrent fracture, with marked increase in morbidity and mortality compared.<ref name="Shi 2594149"/> Among the five bisphosphonates, no significant differences were found for a secondary fracture for all fracture endpoints combined.<ref name="Shi 2594149"/> 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.<ref name="Shi 2594149"/> There is concern that many people do not receive appropriate pharmacological therapy after a low-impact fracture.<ref>Template:Cite journal</ref>

For those with osteoporosis but who have not had a fracture, evidence does not support a reduction in fracture risk with risedronate<ref name=Wells2008a/> or etidronate.<ref name="Wells-2024" /> Alendronate decreases fractures of the spine but does not have any effect on other types of fractures.<ref name=Wells2008/> Half stop their medications within a year.<ref>Template:Cite journal</ref> When on treatment with bisphosphonates rechecking bone mineral density is not needed.<ref name=Qa2017/> There is tentative evidence of benefit in males with osteoporosis.<ref name=Males2017>Template:Cite journal</ref>

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.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref>

Teriparatide (a recombinant parathyroid hormone) has been shown to be effective in treatment of women with postmenopausal osteoporosis.<ref>Template:Cite journal</ref><ref name="Cheng"/> Some evidence also indicates strontium ranelate is effective in decreasing the risk of vertebral and nonvertebral fractures in postmenopausal women with osteoporosis.<ref>Template:Cite journal</ref> Hormone replacement therapy, while effective for osteoporosis, is only recommended in women who also have menopausal symptoms.<ref name=Review2011>Template:Cite journal</ref> It is not recommended for osteoporosis by itself.<ref name=Qa2017>Template:Cite journal</ref> Raloxifene, while effective in decreasing vertebral fractures, does not affect the risk of nonvertebral fracture.<ref name=Review2011/> And while it reduces the risk of breast cancer, it increases the risk of blood clots and strokes.<ref name=Review2011/> While denosumab is effective at preventing fractures in women,<ref name=Review2011/> there is not clear evidence of benefit in males.<ref name=Males2017/> 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 normal testosterone levels.<ref name="OsteoporosisMen"/> Calcitonin while once recommended is no longer recommended due to the associated risk of cancer and questionable effect on fracture risk.<ref>Template:Cite web</ref> Alendronic acid/colecalciferol can be taken to treat this condition in post-menopausal women.<ref>Template:Cite web</ref>

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.<ref>Template:Cite journal</ref><ref>Template:Cite web</ref>

Certain medications like alendronate, etidronate, risedronate, raloxifene, and strontium ranelate can help to prevent osteoporotic fragility fractures in postmenopausal women with osteoporosis.<ref>Template:Cite web</ref> Tentative evidence suggests that Chinese herbal medicines may have potential benefits on bone mineral density.<ref name = "Liu_2014">Template:Cite journal</ref>

Prognosis

Hip fractures per 1000 person-years<ref name="pmid17846439">Template:Cite journal</ref>

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.<ref name="pmid11386929">Template:Cite journal</ref>

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.<ref>Template:Cite journal</ref>

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.<ref name=RiggsEtAl2005>Template:Cite journal</ref> 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.<ref name='Merkepid'/>

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.<ref name="pmid18165669">Template:Cite journal</ref>

In the United States, 250,000 wrist fractures annually are attributable to osteoporosis.<ref name=RiggsEtAl2005/> 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.<ref name='Merkepid'>Template:Cite web</ref>

Fragility fractures of the ribs are common in men as young as age 35.Template: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

File:Hip fracture incidence world map.svg

Age-standardised hip fracture rates in 2012.<ref name="Kanis 2239–2256"/>Template:LegendTemplate:LegendTemplate:Legend

Osteoporosis becomes more common with age, especially after 50 years (its prevalence rises from about 2% at 50 years to almost 50% by the age of 80).<ref name=cks-prevalence2023>Template:Cite web</ref> It affects women more than men due to the sharp fall in estrogen production that follows menopause.<ref name=cks-prevalence2023/> Globally, it is estimated that 21.2% of women and 6.3% of men over the age of 50 have osteoporosis, corresponding to a total of around 500 million people worldwide.<ref name=Found-epi2024>Template:Cite web</ref> About 15% of Caucasians in their 50s and 70% of those over 80 are affected.<ref name=WHOEpi/> In the developed world, depending on the method of diagnosis, 2% to 8% of males and 9% to 38% of females are affected.<ref name=Wade2014/> Rates of disease in the developing world are unclear.<ref name=Han2008/>

From the age of 50 onwards, fractures (including hip fractures) are roughly twice as common in women than in men.<ref name=Clynes2020>Template:Cite journal</ref> A 60-year-old woman has a 44% chance of experiencing a fracture in her lifetime, whereas the lifetime risk for a 60-year-old man is only 25%.<ref name="Ji-2015" /> Such differences can be attributed to the increased risk of osteoporosis due to decreased estrogen levels following menopause.<ref name="Ji-2015">Template:Cite journal</ref>

In 2019,<ref name=GBD2019>Template:Cite journal</ref> up to 37 million fragility fractures linked to osteoporosis were thought to occur in people over the age of 55 worldwide.<ref name=Found-epi2024/> Globally, 1 in 3 women and 1 in 5 men over the age of 50 will have an osteoporotic fracture.<ref name=Found-epi2024/> 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.<ref name="Cauley 1891–1899">Template:Cite journal</ref> White and Asian people are at greater risk.<ref name="NIH2014" /> 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.<ref name="Cauley 1891–1899"/>

It has been shown that latitude affects risk of osteoporotic fracture.<ref name="Kanis 2239–2256">Template:Cite journal</ref> 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.<ref name="Kanis 2239–2256"/> 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.<ref name="Cauley 1891–1899"/> 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.<ref>Template:Cite journal</ref>

There is also an association between Celiac Disease and increased risk of osteoporosis.<ref name="Prevalence of osteoporosis and oste">Template:Cite journal</ref> In studies with premenopausal females and males, there was a correlation between Celiac Disease and osteoporosis and osteopenia.<ref name="Prevalence of osteoporosis and oste"/> 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.<ref>Template:Cite web</ref>

About 22 million women and 5.5 million men in the European Union had osteoporosis in 2010.<ref name=Sve2013/> In the United States in 2010 about 8 million women and one to 2 million men had osteoporosis.<ref name=Wade2014/><ref name=Will2015/> 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.<ref name="iofbonehealth.org">Template:Cite web</ref>

History

Research on age-related reductions in bone density goes back to the early 1800s. French pathologist Jean Lobstein coined the term osteoporosis.<ref name=Grob2014>Template:Cite book</ref> The American endocrinologist Fuller Albright linked osteoporosis with the postmenopausal state.<ref>Template:Cite journal</ref>

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.<ref>Template:Cite journal</ref>

See also

• Fracture Risk Assessment Tool (FRAX)
• Spaceflight osteopenia
• World Osteoporosis Day

External links

• Template:Commons-inline
• 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
• Template:Cite book
• Template:Cite web