Osteoporosis Explained

Osteoporosis
Field:Rheumatology, Endocrinology, orthopedics
Symptoms:Increased risk of a broken bone
Complications:Chronic pain
Onset:Older age
Risks:Alcoholism, anorexia, European or Asian ethnicity, hyperthyroidism, gastrointestinal diseases, surgical removal of the ovaries, kidney disease, smoking, certain medications
Diagnosis:Dexa Scan (Bone density scan)
Treatment:Good diet, exercise, fall prevention, stopping smoking
Medication:Bisphosphonates
Frequency:15% (50 year olds), 70% (over 80 year olds)

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.[1] Bones that commonly break include the vertebrae in the spine, the bones of the forearm, the wrist, and the hip.[2] [3] 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.

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.[4] Osteoporosis may also occur due to a number of diseases or treatments, including alcoholism, anorexia, hyperthyroidism, kidney disease, and surgical removal of the ovaries. Certain medications increase the rate of bone loss, including some antiseizure medications, chemotherapy, proton pump inhibitors, selective serotonin reuptake inhibitors, and glucocorticosteroids. Smoking and getting an inadequate amount of exercise are also risk factors. Osteoporosis 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).[5]

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.[1] 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.[6] [7] [8] They do not appear to affect the risk of death.[9]

Osteoporosis becomes more common with age. About 15% of Caucasians in their 50s and 70% of those over 80 are affected.[10] It is more common in women than men.[1] In the developed world, depending on the method of diagnosis, 2% to 8% of males and 9% to 38% of females are affected. Rates of disease in the developing world are unclear.[11] About 22 million women and 5.5 million men in the European Union had osteoporosis in 2010.[12] In the United States in 2010, about 8 million women and between 1 and 2 million men had osteoporosis.[13] [14] White and Asian people are at greater risk.[1] The word "osteoporosis" is from the Greek terms for "porous bones".

Signs and symptoms

Osteoporosis has no symptoms and the person usually does not know that they have osteoporosis until a bone is broken. Osteoporotic fractures occur in situations where healthy people would not normally break a bone; they are therefore regarded as fragility fractures. Typical fragility fractures occur in the vertebral column, rib, hip and wrist. Examples of situations where people would not normally break a bone include a fall from standing height, normal day-to-day activities such as lifting, bending, or coughing.[15]

Fractures

Fractures are a common symptom of osteoporosis and can result in disability.[16] Acute and chronic pain in the elderly is often attributed to fractures from osteoporosis and can lead to further disability and early mortality.[17] These fractures may also be asymptomatic.[18] 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.[19]

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%.[20]

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,[21] the Garvan FRC calculator and QFracture as well as the open access FREM tool.[22] The FRAX tool can also be applied in a modification adapted to routinely collected health data.[23]

The term "established osteoporosis" is used when a broken bone due to osteoporosis has occurred.[24] Osteoporosis is a part of frailty syndrome.

Risk of falls

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.[25]

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.[26] Osteoporosis can decrease the quality of life, increase disabilities, and increase the financial costs to health care systems.[27]

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.[28]

Nonmodifiable

Potentially modifiable

Medical disorders

Many diseases and disorders have been associated with osteoporosis.[58] 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.

Pregnancy-associated osteoporosis

Osteoporosis due to pregnancy and lactation is a rare condition of unknown cause.[78] [79] [80] [81] [82]

Evolutionary

Age-related bone loss is common among humans due to exhibiting less dense bones than other primate species.[83] Because of the more porous bones of humans, frequency of severe osteoporosis and osteoporosis related fractures is higher.[84] 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.[84] 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.[83] In addition, the porosity allows for more flexibility and a lighter skeleton that is easier to support.[84] 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.[85]

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.[86] Fractures occur when the force acting on a bone is greater than the strength of the bone.[87] 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.[88] Mechanical properties of a material depend on the geometry and inherent structure of the materials.[89] Bone as a material is very complex because of its hierarchal structure in which characteristics vary across length scales.[90] At the basic scale, bone is composed of an organic matrix of collagen type-I. Collagen type-I molecules form a composite material with hydroxyapatite to make up collagen fibrils. The hierarchal structure continuous with the fibrils being arranged into different patterns such as lamellae. The microstructure of bone then forms vascular channels, called osteons, which are surrounded by lamellae. At the subsequent scale of bones, there are different types of bone based on morphology: cortical (solid), cancellous (sponge), or trabecular (thin plates).  

A basic picture of the hierarchical structure of bones 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.[91] In another study, osteoporosis in human cancellous bone led to 3-27% variability in the stiffness and strength compared to health bone.[92] Additionally, bone mineral density (BMD) is a parameter used to evaluate fracture risk in bones and is used as a predictor of osteoporosis. A lower BMD value correlates to decreased bone and a higher bone fragility. Furthermore, bone diseases, such as osteoporosis, are known to alter the composition of collagen and other proteins that make up the bone matrix.[93] These alterations in composition contribute to how bone can handle mechanical loading. Thus, osteoporosis-induced changes at the macroscopic and microscopic levels significantly impact the mechanical properties of bone, predisposing individuals to fractures even under relatively low mechanical loads. Understanding these structural alterations is vital for developing effective diagnostic and therapeutic strategies for osteoporosis.

Pathogenesis

The underlying mechanism in all cases of osteoporosis is an imbalance between bone resorption and bone formation.[94] [95] 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.[96] 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.[94] [97]

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.[98] An interplay of these three mechanisms underlies the development of fragile bone tissue.[32] 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.[32] 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.[32]

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.[95] 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.[32] Osteoclast maturation and activity is also regulated by activation of colony stimulating factor 1 receptor (CSF1R).[99] 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.[100]

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. Around the ages of 30–35, cancellous or trabecular bone loss begins. Women may lose as much as 50%, while men lose about 30%.

Diagnosis

Osteoporosis can be diagnosed using conventional radiography and by measuring the bone mineral density (BMD).[101] The most popular method of measuring BMD is dual-energy X-ray absorptiometry.

In addition to the detection of abnormal BMD, the diagnosis of osteoporosis requires investigations into potentially modifiable underlying causes; this may be done with blood tests. Depending on the likelihood of an underlying problem, investigations for cancer with metastasis to the bone, multiple myeloma, Cushing's disease and other above-mentioned causes may be performed.[102]

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.[103] [104]

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.[105] [106]

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[5] :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.[5] :58 The World Health Organization has established the following diagnostic guidelines:[5] [24]

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

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.[107]

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.[108] Increased urinary excretion of C-telopeptides, a type-I collagen breakdown product, also serves as a biomarker for osteoporosis.[109]

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.[101]

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.[101] Some ultrasound devices can be used on the tibia.[110]

Screening

The U.S. Preventive Services Task Force (USPSTF) recommend that all women 65 years of age or older be screened by bone densitometry. Additionally they recommend screening younger women with risk factors.[111] There is insufficient evidence to make recommendations about the intervals for repeated screening and the appropriate age to stop screening.[112]

In men the harm versus benefit of screening for osteoporosis is unknown.[111] Prescrire states that the need to test for osteoporosis in those who have not had a previous bone fracture is unclear.[113] 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.[114] A number of tools exist to help determine who is reasonable to test.[115]

Prevention

Lifestyle prevention of osteoporosis is in many aspects the inverse of the potentially modifiable risk factors.[116] As tobacco smoking and high alcohol intake have been linked with osteoporosis, smoking cessation and moderation of alcohol intake are commonly recommended as ways to help prevent it.

In people with coeliac disease adherence to a gluten-free diet decreases the risk of developing osteoporosis[117] and increases bone density. The diet must ensure optimal calcium intake (of at least one gram daily) and measuring vitamin D levels is recommended, and to take specific supplements if necessary.

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.[118] 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.[119] 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.[120] A 2015 review found little data that supplementation of calcium decreases the risk of fractures.[121] 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.[122] [123] While supplementation does not appear to affect the risk of death, an increased risk of myocardial infarctions [124] [125] kidney stones, and stomach problems is associated with calcium supplementation.

Vitamin K deficiency is also a risk factor for osteoporotic fractures.[126] 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.[127] 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.[128]

Dietary sources of calcium include dairy products, leafy greens, legumes, and beans.[129] 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.[130] A review of the evidence shows no adverse effect of higher protein intake on bone health.[131]

Physical exercise

There is limited evidence indicating that exercise is helpful in promoting bone health.[132] 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%).[133] Weight bearing exercise has been found to cause an adaptive response in the skeleton.[134] Weight bearing exercise promotes osteoblast activity, protecting bone density.[135] A position statement concluded that increased bone activity and weight-bearing exercises at a young age prevent bone fragility in adults.[136] 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.[137]

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.[138]

Physical therapy

People with osteoporosis are at higher risk of falls due to poor postural control, muscle weakness, and overall deconditioning.[139] 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. The goal of these interventions are to regain normal spine curvatures, increase spine stability, and improve functional performance. Physical therapy interventions were also designed to slow the rate of bone loss through home exercise programs.[139]

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.[140] There are conflicting reviews as to whether vibration therapy improves bone mineral density.[141]

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.[142]

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.[143] Aerobics, weight bearing, and resistance exercises all maintain or increase BMD in postmenopausal women. [144] Daily intake of calcium and vitamin D is recommended for postmenopausal women. Fall prevention can help prevent osteoporosis complications. There is some evidence for hip protectors specifically among those who are in care homes.[145]

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%.[146] Bisphosphonates are useful in decreasing the risk of future fractures in those who have already sustained a fracture due to osteoporosis.[147] This benefit is present when taken for three to four years.[148] [149] They do not appear to change the overall risk of death. Tentative evidence does not support the use of bisphosphonates as a standard treatment for secondary osteoporosis in children. Different bisphosphonates have not been directly compared, therefore it is unknown if one is better than another. Fracture risk reduction is between 25 and 70% depending on the bone involved. There are concerns of atypical femoral fractures and osteonecrosis of the jaw with long-term use, but these risks are low.[150] 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. 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. In those at higher risk they recommend up to ten years of medication by mouth or six years of intravenous treatment.[151]

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.[152] That is because patients with a fracture are more likely to experience a recurrent fracture, with marked increase in morbidity and mortality compared.[152] Among the five bisphosphonates, no significant differences were found for a secondary fracture for all fracture endpoints combined.[152] 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.[152] There is concern that many people do not receive appropriate pharmacological therapy after a low-impact fracture.[153]

For those with osteoporosis but who have not had a fracture, evidence does not support a reduction in fracture risk with risedronate[7] or etidronate.[8] Alendronate decreases fractures of the spine but does not have any effect on other types of fractures.[6] Half stop their medications within a year.[154] When on treatment with bisphosphonates rechecking bone mineral density is not needed. There is tentative evidence of benefit in males with osteoporosis.[155]

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.[156] [157]

Teriparatide (a recombinant parathyroid hormone) has been shown to be effective in treatment of women with postmenopausal osteoporosis.[158] [147] Some evidence also indicates strontium ranelate is effective in decreasing the risk of vertebral and nonvertebral fractures in postmenopausal women with osteoporosis.[159] Hormone replacement therapy, while effective for osteoporosis, is only recommended in women who also have menopausal symptoms.[160] It is not recommended for osteoporosis by itself.[161] Raloxifene, while effective in decreasing vertebral fractures, does not affect the risk of nonvertebral fracture.[160] And while it reduces the risk of breast cancer, it increases the risk of blood clots and strokes.[160] While denosumab is effective at preventing fractures in women,[160] there is not clear evidence of benefit in males.[155] 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.[59] Calcitonin while once recommended is no longer recommended due to the associated risk of cancer and questionable effect on fracture risk.[162] Alendronic acid/colecalciferol can be taken to treat this condition in post-menopausal women.[163]

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.[164] [165]

Certain medications like alendronate, etidronate, risedronate, raloxifene, and strontium ranelate can help to prevent osteoporotic fragility fractures in postmenopausal women with osteoporosis.[166] Tentative evidence suggests that Chinese herbal medicines may have potential benefits on bone mineral density.[167]

Prognosis

Overall
Normal 5.3 9.4 6.6
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.[168]

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.[169]

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.[170] 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.

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.[171]

In the United States, 250,000 wrist fractures annually are attributable to osteoporosis.[170] 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.[172]

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

It is estimated that 200 million people have osteoporosis.[173] Osteoporosis becomes more common with age.[1] About 15% of Caucasians in their 50s and 70% of those over 80 are affected.[10] It is more common in women than men.[1] 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.[11]

Postmenopausal women have a higher rate of osteoporosis and fractures than older men.[174] Postmenopausal women have decreased estrogen which contributes to their higher rates of osteoporosis. A 60-year-old woman has a 44% risk of fracture while a 60-year-old man has a 25% risk of fracture.

There are 8.9 million fractures worldwide per year due to osteoporosis.[175] Globally, 1 in 3 women and 1 in 5 men over the age of 50 will have an osteoporotic fracture.[175] 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.[176] White and Asian people are at greater risk. 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.[176]

It has been shown that latitude affects risk of osteoporotic fracture.[177] 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.[177] 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.[176] 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.[178]

There is also an association between Celiac Disease and increased risk of osteoporosis.[179] In studies with premenopausal females and males, there was a correlation between Celiac Disease and osteoporosis and osteopenia.[179] 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.[180]

About 22 million women and 5.5 million men in the European Union had osteoporosis in 2010.[12] In the United States in 2010 about 8 million women and one to 2 million men had osteoporosis.[13] [14] 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.[175]

History

The link between age-related reductions in bone density goes back to the early 1800s. French pathologist Jean Lobstein coined the term osteoporosis.[181] The American endocrinologist Fuller Albright linked osteoporosis with the postmenopausal state.[182]

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.[183]

See also

External links

Notes and References

  1. Web site: Handout on Health: Osteoporosis . . 16 May 2015. August 2014. live. https://web.archive.org/web/20150518091922/http://www.niams.nih.gov/health_info/Osteoporosis/default.asp. 18 May 2015.
  2. Golob AL, Laya MB . Osteoporosis: screening, prevention, and management . The Medical Clinics of North America . 99 . 3 . 587–606 . May 2015 . 25841602 . 10.1016/j.mcna.2015.01.010 .
  3. Web site: NIAMS Science Communications and Outreach Branch . 2017-04-07 . Osteoporosis . 2023-09-16 . National Institute of Arthritis and Musculoskeletal and Skin Diseases . en.
  4. Web site: 2018-06-04 . Clinical Challenges: Managing Osteoporosis in Male Hypogonadism . 2022-03-22 . www.medpagetoday.com . en.
  5. Book: Prevention and management of osteoporosis . World Health Organization Technical Report Series . 2003 . 921 . 1-164, back cover . World Health Organization . 978-92-4-120921-2 . 10665/42841 . 15293701 .
  6. Wells GA, Cranney A, Peterson J, Boucher M, Shea B, Robinson V, Coyle D, Tugwell P . Alendronate for the primary and secondary prevention of osteoporotic fractures in postmenopausal women . The Cochrane Database of Systematic Reviews . 1 . CD001155 . January 2008 . 18253985 . 10.1002/14651858.CD001155.pub2 .
  7. Wells GA, Hsieh SC, Zheng C, Peterson J, Tugwell P, Liu W . May 2022 . Risedronate for the primary and secondary prevention of osteoporotic fractures in postmenopausal women . The Cochrane Database of Systematic Reviews . 2022 . 7. CD004523. 10.1002/14651858.CD004523.pub4 . 35502787. 9062986 .
  8. Wells GA, Cranney A, Peterson J, Boucher M, Shea B, Robinson V, Coyle D, Tugwell P . Etidronate for the primary and secondary prevention of osteoporotic fractures in postmenopausal women . The Cochrane Database of Systematic Reviews . 1 . CD003376 . January 2008 . 2008 . 18254018 . 10.1002/14651858.CD003376.pub3 . 6999803 .
  9. Cummings SR, Lui LY, Eastell R, Allen IE . Association Between Drug Treatments for Patients With Osteoporosis and Overall Mortality Rates: A Meta-analysis . JAMA Internal Medicine . August 2019 . 179 . 11 . 1491–1500 . 31424486 . 6704731 . 10.1001/jamainternmed.2019.2779 .
  10. Web site: Chronic rheumatic conditions. World Health Organization. 18 May 2015. https://web.archive.org/web/20150427154245/http://www.who.int/chp/topics/rheumatic/en. 27 April 2015.
  11. Handa R, Ali Kalla A, Maalouf G . Osteoporosis in developing countries . Best Practice & Research. Clinical Rheumatology . 22 . 4 . 693–708 . August 2008 . 18783745 . 10.1016/j.berh.2008.04.002 .
  12. Svedbom A, Hernlund E, Ivergård M, Compston J, Cooper C, Stenmark J, McCloskey EV, Jönsson B, Kanis JA . Osteoporosis in the European Union: a compendium of country-specific reports . Archives of Osteoporosis . 8 . 1–2 . 137 . 2013 . 24113838 . 3880492 . 10.1007/s11657-013-0137-0 .
  13. Wade SW, Strader C, Fitzpatrick LA, Anthony MS, O'Malley CD . 19534928 . Estimating prevalence of osteoporosis: examples from industrialized countries . Archives of Osteoporosis . 9 . 1 . 182 . 2014 . 24847682 . 10.1007/s11657-014-0182-3 .
  14. Willson T, Nelson SD, Newbold J, Nelson RE, LaFleur J . The clinical epidemiology of male osteoporosis: a review of the recent literature . Clinical Epidemiology . 7 . 65–76 . 2015 . 25657593 . 4295898 . 10.2147/CLEP.S40966 . free .
  15. Web site: 1 December 2022 . Osteoporosis . 16 September 2023 . National Institute of Arthritis and Musculoskeletal and Skin Diseases, US National Institutes of Health . en.
  16. Book: Harrison's principles of internal medicine.. Jameson JL, Kasper DL, Longo DL, Fauci AS, Hauser SL, Loscalzo J . 9781259644047. Twentieth. McGraw-Hill Education. New York. 990065894 . 2018-02-06.
  17. Old JL, Calvert M . Vertebral compression fractures in the elderly . American Family Physician . 69 . 1 . 111–116 . January 2004 . 14727827 . 31 March 2011 . live . https://web.archive.org/web/20110805184810/http://www.aafp.org/afp/2004/0101/p111.html . 5 August 2011 .
  18. Yang J, Mao Y, Nieves JW . Identification of prevalent vertebral fractures using Vertebral Fracture Assessment (VFA) in asymptomatic postmenopausal women: A systematic review and meta-analysis . Bone . 136 . 115358 . July 2020 . 32268210 . 10.1016/j.bone.2020.115358 . 215620114 .
  19. Kim DH, Vaccaro AR . Osteoporotic compression fractures of the spine; current options and considerations for treatment . The Spine Journal . 6 . 5 . 479–487 . 2006 . 16934715 . 10.1016/j.spinee.2006.04.013 . 28448924 .
  20. Downey C, Kelly M, Quinlan JF . Changing trends in the mortality rate at 1-year post hip fracture - a systematic review . World Journal of Orthopedics . 10 . 3 . 166–175 . March 2019 . 30918799 . 6428998 . 10.5312/wjo.v10.i3.166 . free .
  21. Web site: Fracture Risk Calculator. Susan Ott. https://web.archive.org/web/20091014090245/http://courses.washington.edu/bonephys/FxRiskCalculator.html. 2009-10-14. October 2009.
  22. Rubin KH, Möller S, Holmberg T, Bliddal M, Søndergaard J, Abrahamsen B . A New Fracture Risk Assessment Tool (FREM) Based on Public Health Registries . Journal of Bone and Mineral Research . 33 . 11 . 1967–1979 . November 2018 . 29924428 . 10.1002/jbmr.3528 . 49312906 . free .
  23. Yang S, Leslie WD, Morin SN, Lix LM . Administrative healthcare data applied to fracture risk assessment . Osteoporosis International . 30 . 3 . 565–571 . March 2019 . 30554259 . 10.1007/s00198-018-4780-6 . 54632462 .
  24. Book: Assessment of fracture risk and its application to screening for postmenopausal osteoporosis . World Health Organization Technical Report Series . 1994 . 843 . 1–129 . World Health Organization . 978-92-4-120843-7 . 10665/39142 . 7941614 .
  25. Ganz DA, Bao Y, Shekelle PG, Rubenstein LZ . Will my patient fall? . JAMA . 297 . 1 . 77–86 . 2007 . 17200478 . 10.1001/jama.297.1.77 .
  26. Web site: Osteoporosis - Symptoms and causes . 2022-03-25 . Mayo Clinic . en.
  27. Sözen T, Özışık L, Başaran NÇ . An overview and management of osteoporosis . European Journal of Rheumatology . 4 . 1 . 46–56 . March 2017 . 28293453 . 5335887 . 10.5152/eurjrheum.2016.048.
  28. Waugh EJ, Lam MA, Hawker GA, McGowan J, Papaioannou A, Cheung AM, Hodsman AB, Leslie WD, Siminoski K, Jamal SA . Risk factors for low bone mass in healthy 40–60 year old women: a systematic review of the literature . Osteoporosis International . 20 . 1 . 1–21 . January 2009 . 18523710 . 10.1007/s00198-008-0643-x . 5110317 .
  29. Sinnesael M, Claessens F, Boonen S, Vanderschueren D . 1637184 . Novel insights in the regulation and mechanism of androgen action on bone . Current Opinion in Endocrinology, Diabetes and Obesity . 20 . 3 . 240–44 . 2013 . 23449008 . 10.1097/MED.0b013e32835f7d04 .
  30. Sinnesael M, Boonen S, Claessens F, Gielen E, Vanderschueren D . Testosterone and the male skeleton: a dual mode of action . Journal of Osteoporosis . 2011 . 1–7 . 2011 . 21941679 . 10.4061/2011/240328 . 3173882 . free .
  31. Melton LJ . Epidemiology worldwide . Endocrinol. Metab. Clin. North Am. . 32 . 1 . v, 1–13 . 2003 . 12699289 . 10.1016/S0889-8529(02)00061-0 .
  32. Raisz . L. G. . Pathogenesis of osteoporosis: concepts, conflicts, and prospects . Journal of Clinical Investigation . December 2005 . 115 . 12 . 3318–3325 . 10.1172/JCI27071 . 16322775 . 1297264 .
  33. Ojo F, Al Snih S, Ray LA, Raji MA, Markides KS . History of fractures as predictor of subsequent hip and nonhip fractures among older Mexican Americans . Journal of the National Medical Association . 99 . 4 . 412–418 . 2007 . 17444431 . 2569658 .
  34. Book: Brian K Alldredge . Koda-Kimble, Mary Anne . Young, Lloyd Y. . Wayne A Kradjan . B. Joseph Guglielmo . Applied therapeutics: the clinical use of drugs . Wolters Kluwer Health/Lippincott Williams & Wilkins . Philadelphia . 2009 . 101–103 . 978-0-7817-6555-8.
  35. Poole KE, Compston JE . Osteoporosis and its management . BMJ . 333 . 7581 . 1251–1256 . December 2006 . 17170416 . 1702459 . 10.1136/bmj.39050.597350.47 .
  36. Berg KM, Kunins HV, Jackson JL, Nahvi S, Chaudhry A, Harris KA, Malik R, Arnsten JH . Association between alcohol consumption and both osteoporotic fracture and bone density . Am J Med . 121 . 5 . 406–418 . 2008 . 18456037 . 2692368 . 10.1016/j.amjmed.2007.12.012 .
  37. Nieves JW . Osteoporosis: the role of micronutrients . Am J Clin Nutr . 81 . 5 . 1232S–1239S . 2005 . 15883457 . 10.1093/ajcn/81.5.1232. free .
  38. Gielen E, Boonen S, Vanderschueren D, Sinnesael M, Verstuyf A, Claessens F, Milisen K, Verschueren S . Calcium and vitamin d supplementation in men . Journal of Osteoporosis . 2011 . 1–6 . 2011 . 21876835 . 10.4061/2011/875249 . 3163142 . free .
  39. Agoons DD, Agoons BB, Emmanuel KE, Matawalle FA, Cunningham JM . January 2021 . Association between electronic cigarette use and fragility fractures among US adults . American Journal of Medicine Open . en . 1-6 . 100002 . 10.1016/j.ajmo.2021.100002 . 244502249 . 2667-0364. free . 39036626 . 11256257 .
  40. Hollenbach KA, Barrett-Connor E, Edelstein SL, Holbrook T . Cigarette smoking and bone mineral density in older men and women . American Journal of Public Health . 83 . 9 . 1265–1270 . September 1993 . 8363002 . 1694953 . 10.2105/AJPH.83.9.1265 .
  41. Kanis JA, Johnell O, Oden A, Johansson H, De Laet C, Eisman JA, Fujiwara S, Kroger H, McCloskey EV, Mellstrom D, Melton LJ, Pols H, Reeve J, Silman A, Tenenhouse A . Smoking and fracture risk: a meta-analysis . Osteoporosis International . 16 . 2 . 155–162 . February 2005 . 15175845 . 10.1007/s00198-004-1640-3 . 19890259 .
  42. Wong . Peter K. K. . Christie . Jemma J. . Wark . John D. . The effects of smoking on bone health . Clinical Science . September 2007 . 113 . 5 . 233–241 . 10.1042/CS20060173 . 17663660 .
  43. Ilich . Jasminka Z. . Kerstetter . Jane E. . Nutrition in Bone Health Revisited: A Story Beyond Calcium . Journal of the American College of Nutrition . December 2000 . 19 . 6 . 715–737 . 10.1080/07315724.2000.10718070 . 11194525 .
  44. Weiss LA, Barrett-Connor E, von Mühlen D . Ratio of n−6 to n−3 fatty acids and bone mineral density in older adults: the Rancho Bernardo Study . Am J Clin Nutr . 81 . 4 . 934–38 . 2005 . 15817874 . 10.1093/ajcn/81.4.934. free .
  45. Shams-White MM, Chung M, Du M, Fu Z, Insogna KL, Karlsen MC, LeBoff MS, Shapses SA, Sackey J, Wallace TC, Weaver CM . Dietary protein and bone health: a systematic review and meta-analysis from the National Osteoporosis Foundation . The American Journal of Clinical Nutrition . 105 . 6 . 1528–1543 . June 2017 . 28404575 . 10.3945/ajcn.116.145110 . free .
  46. Zittermann A, Schmidt A, Haardt J, Kalotai N, Lehmann A, Egert S, Ellinger S, Kroke A, Lorkowski S, Louis S, Schulze MB, Schwingshackl L, Siener R, Stangl GI, Volkert D, Watzl B, Bischoff-Ferrari HA . Protein intake and bone health: an umbrella review of systematic reviews for the evidence-based guideline of the German Nutrition Society . Osteoporosis International . 34 . 8 . 1335–1353 . August 2023 . 37126148 . 10382330 . 10.1007/s00198-023-06709-7 .
  47. Schönau E, Werhahn E, Schiedermaier U, Mokow E, Schiessl H, Scheidhauer K, Michalk D . Influence of muscle strength on bone strength during childhood and adolescence . Hormone Research . 45 . Suppl. 1 . 63–66 . 1996 . 8805035 . 10.1159/000184834 .
  48. Shapses SA, Riedt CS . Bone, body weight, and weight reduction: what are the concerns? . J. Nutr. . 136 . 6 . 1453–1456 . 1 June 2006 . 16702302 . 4016235 . 10.1093/jn/136.6.1453.
  49. Pollock . Noel . Grogan . Claire . Perry . Mark . Pedlar . Charles . Cooke . Karl . Morrissey . Dylan . Dimitriou . Lygeri . Bone-Mineral Density and Other Features of the Female Athlete Triad in Elite Endurance Runners: A Longitudinal and Cross-Sectional Observational Study . International Journal of Sport Nutrition and Exercise Metabolism . October 2010 . 20 . 5 . 418–426 . 10.1123/ijsnem.20.5.418 . 20975110 .
  50. Gibson JH, Mitchell A, Harries MG, Reeve J . 42115482 . Nutritional and exercise-related determinants of bone density in elite female runners . Osteoporosis International . 15 . 8 . 611–618 . 2004 . 15048548 . 10.1007/s00198-004-1589-2 .
  51. Hetland ML, Haarbo J, Christiansen C . Low bone mass and high bone turnover in male long distance runners . The Journal of Clinical Endocrinology and Metabolism . 77 . 3 . 770–775 . 1993 . 8370698 . 10.1210/jcem.77.3.8370698.
  52. Brahm H, Ström H, Piehl-Aulin K, Mallmin H, Ljunghall S . 32005973 . Bone metabolism in endurance trained athletes: A comparison to population-based controls based on DXA, SXA, quantitative ultrasound, and biochemical markers . Calcified Tissue International . 61 . 6 . 448–454 . 1997 . 9383270 . 10.1007/s002239900366 .
  53. MacKelvie KJ, Taunton JE, McKay HA, Khan KM . Bone mineral density and serum testosterone in chronically trained, high mileage 40–55 year old male runners . British Journal of Sports Medicine . 34 . 4 . 273–278 . 2000 . 10953900 . 1724199 . 10.1136/bjsm.34.4.273.
  54. Staessen JA, Roels HA, Emelianov D, Kuznetsova T, Thijs L, Vangronsveld J, Fagard R . 33697569 . Environmental exposure to cadmium, forearm bone density, and risk of fractures: prospective population study. Public Health and Environmental Exposure to Cadmium (PheeCad) Study Group . Lancet . 353 . 9159 . 1140–1144 . 1999 . 10209978 . 10.1016/S0140-6736(98)09356-8 .
  55. Tucker KL, Morita K, Qiao N, Hannan MT, Cupples LA, Kiel DP . Colas, but not other carbonated beverages, are associated with low bone mineral density in older women: The Framingham Osteoporosis Study . Am. J. Clin. Nutr. . 84 . 4 . 936–942 . 2006 . 17023723 . 10.1093/ajcn/84.4.936 . free .
  56. Soft drinks in schools . Pediatrics . 113 . 1 Pt 1 . 152–54 . 2004 . 14702469 . 10.1542/peds.113.1.152 . American Academy of Pediatrics Committee on School Health . free .
  57. Zhou B, Huang Y, Li H, Sun W, Liu J . 13532091 . Proton-pump inhibitors and risk of fractures: an update meta-analysis . Osteoporosis International . 27 . 1 . 339–347 . January 2016 . 26462494 . 10.1007/s00198-015-3365-x .
  58. Web site: ICSI Health Care Guideline: Diagnosis and Treatment of Osteoporosis, 5th edition . 2008-04-08 . Simonelli, C . July 2006 . PDF . Institute for Clinical Systems Improvement . etal . dead . https://web.archive.org/web/20070718014056/http://www.icsi.org/osteoporosis/diagnosis_and_treatment_of_osteoporosis__3.html . 18 July 2007 .
  59. Ebeling PR . Clinical practice. Osteoporosis in men . N Engl J Med . 358 . 14 . 1474–1482 . 2008 . 18385499 . 10.1056/NEJMcp0707217 .
  60. Mirza F, Canalis E. Management of endocrine disease: Secondary osteoporosis: pathophysiology and management. Eur J Endocrinol. 173. 3. R131–151. Sep 2015. 25971649. 4534332. 10.1530/EJE-15-0118. Review.
  61. Henwood . Maria J. . Binkovitz . Larry . Update on pediatric bone health . The Journal of the American Osteopathic Association . January 2009 . 109 . 1 . 5–12 . 19193819 .
  62. Beto JA. The role of calcium in human aging. Clin Nutr Res. 4. 1. 1–8. Jan 2015. 25713787. 4337919. 10.7762/cnr.2015.4.1.1. Review.
  63. Web site: Chronic Kidney Disease. The Lecturio Medical Concept Library . 24 August 2021.
  64. Park PG, Kim KH, Hyun HS, Lee CH, Park JS, Kie JH, Choi YH, Moon KC, Cheong HI . Three cases of multicentric carpotarsal osteolysis syndrome: a case series . BMC Medical Genetics . 19 . 1 . 164 . September 2018 . 30208859 . 6134760 . 10.1186/s12881-018-0682-x . free .
  65. Elsebaie H, Mansour MA, Elsayed SM, Mahmoud S, El-Sobky TA . Multicentric Osteolysis, Nodulosis, and Arthropathy in two unrelated children with matrix metalloproteinase 2 variants: Genetic-skeletal correlations . Bone Reports . 15 . 101106 . December 2021 . 34307793 . 8283316 . 10.1016/j.bonr.2021.101106 .
  66. Book: Nunes . Mark E. . GeneReviews® . 1993 . University of Washington, Seattle . https://www.ncbi.nlm.nih.gov/books/NBK1150/ . Hypophosphatasia . 20301329 .
  67. Web site: Hypophosphatasia Case Studies: Dangers of Misdiagnosis. Hypophosphatasia.com. 5 August 2014. live. https://web.archive.org/web/20140808054019/http://www.hypophosphatasia.com/hcp/dangers-of-misdiagnosis. 8 August 2014.
  68. Invernizzi M, Carda S, Viscontini GS, Cisari C . Osteoporosis in Parkinson's disease . Parkinsonism & Related Disorders . 15 . 5 . 339–346 . 2009 . 19346153 . 10.1016/j.parkreldis.2009.02.009 .
  69. Celsi F, Pizzo P, Brini M, Leo S, Fotino C, Pinton P, Rizzuto R . Mitochondria, calcium and cell death: A deadly triad in neurodegeneration . Biochimica et Biophysica Acta (BBA) - Bioenergetics . 1787 . 5 . 335–344 . 2009 . 19268425 . 2696196 . 10.1016/j.bbabio.2009.02.021 .
  70. Book: Bone and Tooth Society of Great Britain . National Osteoporosis Society . Royal College of Physicians . Glucocorticoid-induced Osteoporosis . 2003 . Royal College of Physicians of London . London . 978-1-86016-173-5 . dead . https://web.archive.org/web/20120114134537/http://bookshop.rcplondon.ac.uk/contents/pub89-a953a6c0-06c0-46d8-b79a-e951536d9070.pdf . 14 January 2012 . dmy-all . 3 October 2011 . National Osteoporosis Society .
  71. Homik J, Suarez-Almazor ME, Shea B, Cranney A, Wells G, Tugwell P . Calcium and vitamin D for corticosteroid-induced osteoporosis . The Cochrane Database of Systematic Reviews . 2 . CD000952 . 1998-04-27 . 1998 . 10796394 . 10.1002/14651858.cd000952 . 7046131 .
  72. Gourlay M, Franceschini N, Sheyn Y . 26017061 . Prevention and treatment strategies for glucocorticoid-induced osteoporotic fractures . Clinical Rheumatology . 26 . 2 . 144–153 . February 2007 . 16670825 . 10.1007/s10067-006-0315-1 .
  73. Petty SJ, O'Brien TJ, Wark JD . 2953573 . Anti-epileptic medication and bone health . Osteoporosis International . 18 . 2 . 129–142 . 2007 . 17091219 . 10.1007/s00198-006-0185-z .
  74. Ruiz-Irastorza G, Khamashta MA, Hughes GR . 2922860 . Heparin and osteoporosis during pregnancy: 2002 update . Lupus . 11 . 10 . 680–682 . 2002 . 12413068 . 10.1191/0961203302lu262oa .
  75. Gage BF, Birman-Deych E, Radford MJ, Nilasena DS, Binder EF . Risk of osteoporotic fracture in elderly patients taking warfarin: results from the National Registry of Atrial Fibrillation 2 . Arch. Intern. Med. . 166 . 2 . 241–246 . 2006 . 16432096 . 10.1001/archinte.166.2.241 . free .
  76. Yang YX, Lewis JD, Epstein S, Metz DC . Long-term proton pump inhibitor therapy and risk of hip fracture . JAMA . 296 . 24 . 2947–2953 . 2006 . 17190895 . 10.1001/jama.296.24.2947 . free .
  77. Murphy CE, Rodgers PT . 21577063 . Effects of thiazolidinediones on bone loss and fracture . Annals of Pharmacotherapy . 41 . 12 . 2014–2018 . 2007 . 17940125 . 10.1345/aph.1K286 .
  78. Hardcastle . Sarah A. . Pregnancy and Lactation Associated Osteoporosis . Calcified Tissue International . May 2022 . 110 . 5 . 531–545 . 10.1007/s00223-021-00815-6 . 33620518 .
  79. Lujano-Negrete . Abraham Yair . Rodríguez-Ruiz . Martha Cecilia . Skinner-Taylor . Cassandra Michele . Perez-Barbosa . Lorena . Cardenas de la Garza . Jesus Alberto . García-Hernández . Pedro Alberto . Espinosa-Banuelos . Luis Gerardo . Gutierrez-Leal . Luz Fernanda . Jezzini-Martínez . Sofia . Galarza-Delgado . Dionicio Ángel . Bone metabolism and osteoporosis during pregnancy and lactation . Archives of Osteoporosis . December 2022 . 17 . 1 . 36 . 10.1007/s11657-022-01077-x . 35182221 .
  80. Phillips . A. J. . Ostlere . S. J. . Smith . R. . Pregnancy-Associated Osteoporosis: Does the Skeleton Recover? . Osteoporosis International . May 2000 . 11 . 5 . 449–454 . 10.1007/s001980070113 . 10912848 .
  81. Gestational osteoporosis: Myth or true? . International Journal of Biology and Pharmacy Research Updates . 30 January 2024 . 3 . 1 . 001–011 . 10.53430/ijbpru.2024.3.1.0040 . George A. . Komnos . Dionyssios . Paridis . Christos . Donoudis . Sotirios . Sotiriou . free .
  82. Rizzoli . R . Bonjour . JP . Pregnancy-associated osteoporosis . The Lancet . August 1996 . 348 . 9024 . 403 . 10.1016/S0140-6736(05)65018-0 .
  83. Latimer B . 43294733 . The perils of being bipedal . Ann Biomed Eng . 33 . 1 . 3–6 . 2005 . 15709701 . 10.1007/s10439-005-8957-8 .
  84. Cotter M . et al . 2011 . Human evolution and osteoporosis-related spinal fractures . PLOS ONE . 6 . 10. 10.1371/journal.pone.0026658 . e26658 . 22028933 . 3197574. 2011PLoSO...626658C . free .
  85. Eaton SB, Nelson DA . Calcium in evolutionary perspective . Am. J. Clin. Nutr. . 54 . 1 Suppl . 281S–287S . 1991 . 2053574 . 10.1093/ajcn/54.1.281S. free .
  86. Book: 10.1007/3-540-27376-X_3 . Overview of osteoporosis: Pathophysiology and determinants of bone strength . The Aging Spine . 2005 . Bono . Christopher M. . Einhorn . Thomas A. . European Spine Journal . 12 . Suppl 2 . 8–14 . 978-3-540-24408-0 . 13680312 . 3591823 .
  87. Chen H, Kubo KY . Bone three-dimensional microstructural features of the common osteoporotic fracture sites . World Journal of Orthopedics . 5 . 4 . 486–495 . September 2014 . 25232524 . 10.5312/wjo.v5.i4.486 . free . 4133454 .
  88. Osterhoff G, Morgan EF, Shefelbine SJ, Karim L, McNamara LM, Augat P . Bone mechanical properties and changes with osteoporosis . Injury . 47 . Suppl 2 . S11–S20 . June 2016 . 27338221 . 4955555 . 10.1016/s0020-1383(16)47003-8 .
  89. Sharir A, Barak MM, Shahar R . Whole bone mechanics and mechanical testing . Veterinary Journal . 177 . 1 . 8–17 . July 2008 . 17986396 . 10.1016/j.tvjl.2007.09.012 .
  90. Zimmermann EA, Busse B, Ritchie RO . The fracture mechanics of human bone: influence of disease and treatment . BoneKEy Reports . 4 . 743 . 2015-09-02 . 26380080 . 4562496 . 10.1038/bonekey.2015.112 .
  91. Boskey AL, Imbert L . Bone quality changes associated with aging and disease: a review . Annals of the New York Academy of Sciences . 1410 . 1 . 93–106 . December 2017 . 29265417 . 10.1111/nyas.13572 . 5774017 . 2017NYASA1410...93B .
  92. Kim G, Cole JH, Boskey AL, Baker SP, van der Meulen MC . Reduced tissue-level stiffness and mineralization in osteoporotic cancellous bone . Calcified Tissue International . 95 . 2 . 125–131 . August 2014 . 24888692 . 4104238 . 10.1007/s00223-014-9873-4 .
  93. Sroga GE, Vashishth D . Effects of bone matrix proteins on fracture and fragility in osteoporosis . Current Osteoporosis Reports . 10 . 2 . 141–150 . June 2012 . 22535528 . 10.1007/s11914-012-0103-6 . 3375270 .
  94. Dance . Amber . Fun facts about bones: More than just scaffolding . Knowable Magazine . 23 February 2022 . 10.1146/knowable-022222-1 . free .
  95. Robling AG, Bonewald LF . The Osteocyte: New Insights . Annual Review of Physiology . 82 . 1 . 485–506 . February 2020 . 32040934 . 8274561 . 10.1146/annurev-physiol-021119-034332 .
  96. Frost HM, Thomas CC. Bone Remodeling Dynamics. Springfield, IL: 1963.
  97. Wu S, Liu Y, Zhang L, Han Y, Lin Y, Deng HW . Genome-wide approaches for identifying genetic risk factors for osteoporosis . Genome Medicine . 5 . 5 . 44 . 2013 . 23731620 . 3706967 . 10.1186/gm448 . free .
  98. Paccou J, Hardouin P, Cotten A, Penel G, Cortet B . The Role of Bone Marrow Fat in Skeletal Health: Usefulness and Perspectives for Clinicians . The Journal of Clinical Endocrinology and Metabolism . 100 . 10 . 3613–21 . October 2015 . 26244490 . 10.1210/jc.2015-2338 . free .
  99. El-Gamal MI, Al-Ameen SK, Al-Koumi DM, Hamad MG, Jalal NA, Oh CH . Recent Advances of Colony-Stimulating Factor-1 Receptor (CSF-1R) Kinase and Its Inhibitors . Journal of Medicinal Chemistry . 61 . 13 . 5450–5466 . July 2018 . 29293000 . 10.1021/acs.jmedchem.7b00873 .
  100. Zhao R . Immune regulation of osteoclast function in postmenopausal osteoporosis: a critical interdisciplinary perspective . International Journal of Medical Sciences . 9 . 9 . 825–832 . 2012 . 23136547 . 3491443 . 10.7150/ijms.5180 .
  101. Guglielmi . Giuseppe . Scalzo . Giacomo . Imaging tools transform diagnosis of osteoporosis . Diagnostic Imaging Europe . 6 May 2010 . 26 . 3 .
  102. Sheu A, Diamond T . Secondary osteoporosis . Australian Prescriber . 39 . 3 . 85–87 . June 2016 . 27346916 . 4919174 . 10.18773/austprescr.2016.038 .
  103. Brunader R, Shelton DK . Radiologic bone assessment in the evaluation of osteoporosis . American Family Physician . 65 . 7 . 1357–1364 . April 2002 . 11996418 .
  104. Grampp S, Steiner E, Imhof H . Radiological diagnosis of osteoporosis . European Radiology . 7 . Suppl 2 . S11–S19 . 1997 . 10.1007/PL00006859 . 9126455 . 10799509 .
  105. Fon GT, Pitt MJ, Thies AC . Thoracic kyphosis: range in normal subjects . AJR. American Journal of Roentgenology . 134 . 5 . 979–983 . May 1980 . 6768276 . 10.2214/ajr.134.5.979 .
  106. Voutsinas SA, MacEwen GD . Sagittal profiles of the spine . Clinical Orthopaedics and Related Research . 210 . 235–242 . September 1986 . 3757369 .
  107. Leib ES, Lewiecki EM, Binkley N, Hamdy RC . Official positions of the International Society for Clinical Densitometry . J Clin Densitom . 7 . 1 . 2004 . 14742881 . 10.1385/JCD:7:1:1 . 1–5. 32856123 . quoted in: "Diagnosis of osteoporosis in men, premenopausal women, and children"
  108. . The role of cathepsins in osteoporosis and arthritis: rationale for the design of new therapeutics . Adv. Drug Deliv. Rev. . 57 . 7 . 973–993 . 2005 . 15876399 . 10.1016/j.addr.2004.12.013 .
  109. Book: Meunier P . Osteoporosis: Diagnosis and Management. 1998. Taylor and Francis. London. 978-1-85317-412-4.
  110. Web site: Bindex, a Radiation-Free Device for Osteoporosis Screening, FDA Cleared. https://web.archive.org/web/20160615042358/http://www.medgadget.com/2016/05/bindex-a-radiation-free-device-for-osteoporosis-screening-fda-cleared.html. live. 27 May 2016. Medgadget. 15 June 2016.
  111. Curry SJ, Krist AH, Owens DK, Barry MJ, Caughey AB, Davidson KW, Doubeni CA, Epling JW, Kemper AR, Kubik M, Landefeld CS, Mangione CM, Phipps MG, Pignone M, Silverstein M, Simon MA, Tseng CW, Wong JB . Screening for Osteoporosis to Prevent Fractures: US Preventive Services Task Force Recommendation Statement . JAMA . 319 . 24 . 2521–2531 . June 2018 . 29946735 . 10.1001/jama.2018.7498 . free .
  112. Screening for osteoporosis: U.S. preventive services task force recommendation statement . Annals of Internal Medicine . 154 . 5 . 356–364 . March 2011 . 21242341 . 10.7326/0003-4819-154-5-201103010-00307 . U.S. Preventive Services Task Force . free .
  113. 100 most recent Archives 2017 2016 2015 2014 2013 2012 2011 2010 2009 2008 2007 2006 2005 Bone fragility: preventing fractures. Prescrire International. April 2017. 26. 181. 103–106. live. https://web.archive.org/web/20170908174355/http://english.prescrire.org/en/81/168/52990/0/2017/ArchiveNewsDetails.aspx?page=1. 8 September 2017.
  114. International Society for Clinical Densitometry (ISCD). 2013 ISCD Official Positions – Adult. (2013). at Web site: 2013 ISCD Official Positions – Adult – International Society for Clinical Densitometry (ISCD) . 2015-05-04 . live . https://web.archive.org/web/20150505080031/http://www.iscd.org/official-positions/2013-iscd-official-positions-adult/ . 5 May 2015 .
  115. Rud B, Hilden J, Hyldstrup L, Hróbjartsson A . 13641749 . The Osteoporosis Self-Assessment Tool versus alternative tests for selecting postmenopausal women for bone mineral density assessment: a comparative systematic review of accuracy . Osteoporosis International . 20 . 4 . 599–607 . April 2009 . 18716823 . 10.1007/s00198-008-0713-0 .
  116. Ebeling PR, Daly RM, Kerr DA, Kimlin MG . Building healthy bones throughout life: an evidence-informed strategy to prevent osteoporosis in Australia . The Medical Journal of Australia . 199 . 7 Suppl . 90–91 . October 2013 . 25370432 . 10.5694/mja12.11363. 10536/DRO/DU:30060407 . 29255357 .
  117. Ludvigsson JF, Bai JC, Biagi F, Card TR, Ciacci C, Ciclitira PJ, Green PH, Hadjivassiliou M, Holdoway A, van Heel DA, Kaukinen K, Leffler DA, Leonard JN, Lundin KE, McGough N, Davidson M, Murray JA, Swift GL, Walker MM, Zingone F, Sanders DS, ((BSG Coeliac Disease Guidelines Development Group)), ((British Society of Gastroenterology)). Diagnosis and management of adult coeliac disease: guidelines from the British Society of Gastroenterology. Gut. 63. 8. 1210–1228. Aug 2014. 24917550. 4112432. 10.1136/gutjnl-2013-306578. Review.
  118. Drugs for Postmenopausal Osteoporosis. The Medical Letter on Drugs and Therapeutics . 29 September 2014 . 56. 1452. 91–96. 25247344.
  119. Kahwati LC, Weber RP, Pan H, Gourlay M, LeBlanc E, Coker-Schwimmer M, Viswanathan M . 205090176 . Vitamin D, Calcium, or Combined Supplementation for the Primary Prevention of Fractures in Community-Dwelling Adults: Evidence Report and Systematic Review for the US Preventive Services Task Force . JAMA . 319 . 15 . 1600–1612 . April 2018 . 29677308 . 10.1001/jama.2017.21640 . Systematic Review & Meta-Analysis . free .
  120. Web site: Final Recommendation Statement Vitamin D, Calcium, or Combined Supplementation for the Primary Prevention of Fractures in Community-Dwelling Adults: Preventive Medication. www.uspreventiveservicestaskforce.org. USPSTF Program Office.
  121. Bolland MJ, Leung W, Tai V, Bastin S, Gamble GD, Grey A, Reid IR . Calcium intake and risk of fracture: systematic review . BMJ . 351 . h4580 . September 2015 . 26420387 . 4784799 . 10.1136/bmj.h4580 .
  122. ((DIPART Group)) . Patient level pooled analysis of 68 500 patients from seven major vitamin D fracture trials in US and Europe . BMJ . 340 . b5463 . January 2010 . 20068257 . 2806633 . 10.1136/bmj.b5463 .
  123. Avenell A, Mak JC, O'Connell D . Vitamin D and vitamin D analogues for preventing fractures in post-menopausal women and older men . The Cochrane Database of Systematic Reviews . 4 . 4 . CD000227 . April 2014 . 24729336 . 10.1002/14651858.CD000227.pub4 . 7032685 .
  124. Bolland MJ, Avenell A, Baron JA, Grey A, MacLennan GS, Gamble GD, Reid IR . Effect of calcium supplements on risk of myocardial infarction and cardiovascular events: meta-analysis . BMJ (Clinical Research Ed.) . 341 . c3691 . 2010 . 20671013 . 2912459 . 10.1136/bmj.c3691 .
  125. Bolland MJ, Grey A, Avenell A, Gamble GD, Reid IR . Calcium supplements with or without vitamin D and risk of cardiovascular events: reanalysis of the Women's Health Initiative limited access dataset and meta-analysis . BMJ . 342 . d2040 . 2011 . apr19 1 . 21505219 . 3079822 . 10.1136/bmj.d2040 .
  126. Rodríguez-Olleros Rodríguez C, Díaz Curiel M . Vitamin K and Bone Health: A Review on the Effects of Vitamin K Deficiency and Supplementation and the Effect of Non-Vitamin K Antagonist Oral Anticoagulants on Different Bone Parameters . Journal of Osteoporosis . 2019 . 2069176 . 2019-12-31 . 31976057 . 6955144 . 10.1155/2019/2069176 . free .
  127. De Vilder EY, Debacker J, Vanakker OM . GGCX-Associated Phenotypes: An Overview in Search of Genotype-Phenotype Correlations . International Journal of Molecular Sciences . 18 . 2 . 240 . January 2017 . 28125048 . 5343777 . 10.3390/ijms18020240 . free .
  128. Hosoi T . Genetic aspects of osteoporosis . Journal of Bone and Mineral Metabolism . 28 . 6 . 601–607 . November 2010 . 20697753 . 10.1007/s00774-010-0217-9 . 35412918 .
  129. Web site: Preventing and Reversing Osteoporosis. Physicians Committee for Responsible Medicine. en. 2019-08-05.
  130. Web site: Dietary Reference Intakes for Adequacy: Calcium and Vitamin D – Dietary Reference Intakes for Calcium and Vitamin D – NCBI Bookshelf . 18 December 2020.
  131. Shams-White MM, Chung M, Du M, Fu Z, Insogna KL, Karlsen MC, LeBoff MS, Shapses SA, Sackey J, Wallace TC, Weaver CM . Dietary protein and bone health: a systematic review and meta-analysis from the National Osteoporosis Foundation . The American Journal of Clinical Nutrition . 105 . 6 . 1528–1543 . June 2017 . 28404575 . 10.3945/ajcn.116.145110 . free .
  132. Laskou F, Dennison E . Interaction of Nutrition and Exercise on Bone and Muscle . en-GB . European Endocrinology . 15 . 1 . 11–12 . April 2019 . 31244903 . 6587895 . 10.17925/ee.2019.15.1.11 .
  133. Howe TE, Shea B, Dawson LJ, Downie F, Murray A, Ross C, Harbour RT, Caldwell LM, Creed G . Exercise for preventing and treating osteoporosis in postmenopausal women . The Cochrane Database of Systematic Reviews . Art. No.: CD000333 . 7 . CD000333 . July 2011 . 21735380 . 10.1002/14651858.CD000333.pub2 .
  134. Giangregorio L, Blimkie CJ . Skeletal adaptations to alterations in weight-bearing activity: a comparison of models of disuse osteoporosis . Sports Medicine . 32 . 7 . 459–476 . 2002 . 12015807 . 10.2165/00007256-200232070-00005 . 25835205 .
  135. Uda Y, Azab E, Sun N, Shi C, Pajevic PD . Osteocyte Mechanobiology . Current Osteoporosis Reports . 15 . 4 . 318–325 . August 2017 . 28612339 . 5656287 . 10.1007/s11914-017-0373-0 .
  136. Weaver CM, Gordon CM, Janz KF, Kalkwarf HJ, Lappe JM, Lewis R, O'Karma M, Wallace TC, Zemel BS . The National Osteoporosis Foundation's position statement on peak bone mass development and lifestyle factors: a systematic review and implementation recommendations . Osteoporosis International . 27 . 4 . 1281–1386 . April 2016 . 26856587 . 4791473 . 10.1007/s00198-015-3440-3 .
  137. Abrahin O, Rodrigues RP, Marçal AC, Alves EA, Figueiredo RC, de Sousa EC . Swimming and cycling do not cause positive effects on bone mineral density: a systematic review . Revista Brasileira de Reumatologia . 56 . 4 . 345–351 . 2016 . 27476628 . 10.1016/j.rbre.2016.02.013 . free .
  138. Gibbs JC, MacIntyre NJ, Ponzano M, Templeton JA, Thabane L, Papaioannou A, Giangregorio LM . Exercise for improving outcomes after osteoporotic vertebral fracture . The Cochrane Database of Systematic Reviews . 7 . CD008618 . July 2019 . 7 . 31273764 . 6609547 . 10.1002/14651858.CD008618.pub3 . Cochrane Musculoskeletal Group .
  139. Zhou X, Deng H, Shen X, Lei Q . Effect of balance training on falls in patients with osteoporosis: A systematic review and meta-analysis . Journal of Rehabilitation Medicine . 50 . 7 . 577–581 . July 2018 . 29767225 . 10.2340/16501977-2334 . free .
  140. Jepsen DB, Thomsen K, Hansen S, Jørgensen NR, Masud T, Ryg J . Effect of whole-body vibration exercise in preventing falls and fractures: a systematic review and meta-analysis . BMJ Open . 7 . 12 . e018342 . December 2017 . 29289937 . 6027066 . 10.1136/bmjopen-2017-018342 .
  141. Marín-Cascales E, Alcaraz PE, Ramos-Campo DJ, Martinez-Rodriguez A, Chung LH, Rubio-Arias JÁ . Whole-body vibration training and bone health in postmenopausal women: A systematic review and meta-analysis . Medicine . 97 . 34 . e11918 . August 2018 . 30142802 . 6112924 . 10.1097/MD.0000000000011918 .
  142. Tong X, Chen X, Zhang S, Huang M, Shen X, Xu J, Zou J . The Effect of Exercise on the Prevention of Osteoporosis and Bone Angiogenesis . BioMed Research International . 2019 . 8171897 . 2019-04-18 . 31139653 . 6500645 . 10.1155/2019/8171897 . free .
  143. Body JJ, Bergmann P, Boonen S, Boutsen Y, Bruyere O, Devogelaer JP, Goemaere S, Hollevoet N, Kaufman JM, Milisen K, Rozenberg S, Reginster JY . Non-pharmacological management of osteoporosis: a consensus of the Belgian Bone Club . Osteoporosis International . 22 . 11 . 2769–2788 . November 2011 . 21360219 . 3186889 . 10.1007/s00198-011-1545-x .
  144. Kanis JA, Cooper C, Rizzoli R, Reginster JY . European guidance for the diagnosis and management of osteoporosis in postmenopausal women . Osteoporosis International . 30 . 1 . 3–44 . January 2019 . 30324412 . 7026233 . 10.1007/s00198-018-4704-5 .
  145. Kasturi GC, Adler RA . Osteoporosis: nonpharmacologic management . PM&R . 3 . 6 . 562–572 . June 2011 . 21478069 . 10.1016/j.pmrj.2010.12.014 . 45409462 . free .
  146. Watts NB . Postmenopausal Osteoporosis: A Clinical Review . Journal of Women's Health . 27 . 9 . 1093–1096 . September 2018 . 29583083 . 10.1089/jwh.2017.6706 . 4795899 .
  147. Cheng C, Wentworth K, Shoback DM . New Frontiers in Osteoporosis Therapy . Annual Review of Medicine . 71 . 1 . 277–288 . January 2020 . 31509477 . 10.1146/annurev-med-052218-020620 . 202564164 .
  148. Whitaker M, Guo J, Kehoe T, Benson G . Bisphosphonates for osteoporosis--where do we go from here? . The New England Journal of Medicine . 366 . 22 . 2048–2051 . May 2012 . 22571168 . 10.1056/NEJMp1202619 . 27821662 . free .
  149. Ward L, Tricco AC, Phuong P, Cranney A, Barrowman N, Gaboury I, Rauch F, Tugwell P, Moher D . Bisphosphonate therapy for children and adolescents with secondary osteoporosis . The Cochrane Database of Systematic Reviews . 2010 . 4 . CD005324 . October 2007 . 17943849 . 8884163 . 10.1002/14651858.cd005324.pub2 .
  150. Suresh E, Pazianas M, Abrahamsen B . Safety issues with bisphosphonate therapy for osteoporosis . Rheumatology . 53 . 1 . 19–31 . January 2014 . 23838024 . 10.1093/rheumatology/ket236 . free .
  151. Adler RA, El-Hajj Fuleihan G, Bauer DC, Camacho PM, Clarke BL, Clines GA, Compston JE, Drake MT, Edwards BJ, Favus MJ, Greenspan SL, McKinney R, Pignolo RJ, Sellmeyer DE . Managing Osteoporosis in Patients on Long-Term Bisphosphonate Treatment: Report of a Task Force of the American Society for Bone and Mineral Research . Journal of Bone and Mineral Research . 31 . 1 . 16–35 . January 2016 . 26350171 . 4906542 . 10.1002/jbmr.2708 .
  152. Shi L, Min N, Wang F, Xue QY . Bisphosphonates for Secondary Prevention of Osteoporotic Fractures: A Bayesian Network Meta-Analysis of Randomized Controlled Trials . BioMed Research International . 2019 . 2594149 . 2019-11-19 . 31828096 . 6885847 . 10.1155/2019/2594149 . free . Text was copied from this source, which is available under a Creative Commons Attribution 4.0 International License.
  153. Hopkins . Ria E. . Warner . Victoria . Sztal-Mazer . Shoshana . Poole . Susan . Page . Amy . The assessment and pharmacological management of osteoporosis after admission for minimal-trauma fracture at a major metropolitan centre . Journal of Pharmacy Practice and Research . December 2020 . 50 . 6 . 481–489 . 10.1002/jppr.1674 .
  154. Davis . Stacy . Sachdeva . Alok . Goeckeritz . Bruce . Oliver . Alyce . Approved treatments for osteoporosis and what's in the pipeline . Drug Benefit Trends . May 2010 . 22 . 4 . 121–124 .
  155. Nayak S, Greenspan SL . Osteoporosis Treatment Efficacy for Men: A Systematic Review and Meta-Analysis . Journal of the American Geriatrics Society . 65 . 3 . 490–495 . March 2017 . 28304090 . 5358515 . 10.1111/jgs.14668 .
  156. Haguenauer D, Welch V, Shea B, Tugwell P, Wells G . Fluoride for treating postmenopausal osteoporosis . The Cochrane Database of Systematic Reviews . 4 . CD002825 . 2000 . 2010 . 11034769 . 10.1002/14651858.CD002825 . 8453489 .
  157. Vestergaard P, Jorgensen NR, Schwarz P, Mosekilde L . 25890845 . Effects of treatment with fluoride on bone mineral density and fracture risk--a meta-analysis . Osteoporosis International . 19 . 3 . 257–268 . March 2008 . 17701094 . 10.1007/s00198-007-0437-6 .
  158. Han SL, Wan SL . Effect of teriparatide on bone mineral density and fracture in postmenopausal osteoporosis: meta-analysis of randomised controlled trials . International Journal of Clinical Practice . 66 . 2 . 199–209 . February 2012 . 22257045 . 10.1111/j.1742-1241.2011.02837.x . 44529401 . free .
  159. O'Donnell S, Cranney A, Wells GA, Adachi JD, Reginster JY . Strontium ranelate for preventing and treating postmenopausal osteoporosis . The Cochrane Database of Systematic Reviews . 4 . CD005326 . October 2006 . 2006 . 17054253 . 10.1002/14651858.CD005326.pub3 . 8092570 . Cranney A .
  160. Body JJ . How to manage postmenopausal osteoporosis? . Acta Clinica Belgica . 66 . 6 . 443–447 . 2011 . 22338309 . 10.1179/ACB.66.6.2062612 .
  161. Qaseem A, Forciea MA, McLean RM, Denberg TD . Treatment of Low Bone Density or Osteoporosis to Prevent Fractures in Men and Women: A Clinical Practice Guideline Update From the American College of Physicians . Annals of Internal Medicine . 166 . 11 . 818–839 . June 2017 . 28492856 . 10.7326/M15-1361 . free .
  162. Web site: Background Document for Meeting of Advisory Committee for Reproductive Health Drugs and Drug Safety and Risk Management Advisory Committee . FDA . Mar 2013 . live . https://web.archive.org/web/20130609063058/https://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/ReproductiveHealthDrugsAdvisoryCommittee/UCM341779.pdf . 9 June 2013 .
  163. Web site: Alendronic acid: medicine to treat and prevent osteoporosis . National Health Service (UK) . 8 March 2022 . en . 24 August 2018.
  164. McClung MR, Rothman MS, Lewiecki EM, Hanley DA, Harris ST, Miller PD, Kendler DL . The role of osteoanabolic agents in the management of patients with osteoporosis . Postgraduate Medicine . 134 . 6 . 541–551 . August 2022 . 35635798 . 10.1080/00325481.2022.2069582 . 249200643 . free .
  165. Web site: Office of the Commissioner. 2020-03-24 . FDA approves new treatment for osteoporosis in postmenopausal women at high risk of fracture . 2022-09-12 . FDA . en.
  166. Web site: Osteoporosis – primary prevention (TA160) : Alendronate, etidronate, risedronate, raloxifene and strontium ranelate for the primary prevention of osteoporotic fragility fractures in postmenopausal women. National Institute for Health and Care Excellence (NICE). UK. January 2011. live. https://web.archive.org/web/20131022170354/http://guidance.nice.org.uk/TA160. 22 October 2013.
  167. Liu Y, Liu JP, Xia Y . Chinese herbal medicines for treating osteoporosis . The Cochrane Database of Systematic Reviews . 3 . CD005467 . March 2014 . 2014 . 24599707 . 10.1002/14651858.cd005467.pub2 . 10638660 .
  168. Hannan EL, Magaziner J, Wang JJ, Eastwood EA, Silberzweig SB, Gilbert M, Morrison RS, McLaughlin MA, Orosz GM, Siu AL . Mortality and locomotion 6 months after hospitalization for hip fracture: risk factors and risk-adjusted hospital outcomes . JAMA . 285 . 21 . 2736–2742 . 2001 . 11386929 . 10.1001/jama.285.21.2736 . free .
  169. Brenneman SK, Barrett-Connor E, Sajjan S, Markson LE, Siris ES . Impact of recent fracture on health-related quality of life in postmenopausal women . J. Bone Miner. Res. . 21 . 6 . 809–816 . 2006 . 16753011 . 10.1359/jbmr.060301. 24283913 . free .
  170. Riggs BL, Melton LJ . The worldwide problem of osteoporosis: insights afforded by epidemiology . Bone . 17 . 5 Suppl . 505S–511S . 1995 . 8573428 . 10.1016/8756-3282(95)00258-4 .
  171. Cauley JA, Hochberg MC, Lui LY, Palermo L, Ensrud KE, Hillier TA, Nevitt MC, Cummings SR . Long-term risk of incident vertebral fractures . JAMA . 298 . 23 . 2761–2767 . 2007 . 18165669 . 10.1001/jama.298.23.2761 . free .
  172. Web site: MerckMedicus Modules: Osteoporosis – Epidemiology . 2008-06-13 . Merck & Co., Inc . https://web.archive.org/web/20071228030929/http://www.merckmedicus.com/pp/us/hcp/diseasemodules/osteoporosis/epidemiology.jsp . 28 December 2007.
  173. International Osteoporosis Foundation. Epidemiology .
  174. Ji MX, Yu Q . Primary osteoporosis in postmenopausal women . Chronic Diseases and Translational Medicine . 1 . 1 . 9–13 . March 2015 . 29062981 . 5643776 . 10.1016/j.cdtm.2015.02.006 .
  175. Web site: The Global Burden of Osteoporosis International Osteoporosis Foundation. www.iofbonehealth.org. 2016-02-09. live. https://web.archive.org/web/20160305005414/http://www.iofbonehealth.org/data-publications/fact-sheets/global-burden-osteoporosis. 5 March 2016.
  176. Cauley JA . Defining ethnic and racial differences in osteoporosis and fragility fractures . Clinical Orthopaedics and Related Research . 469 . 7 . 1891–1899 . July 2011 . 21431462 . 3111798 . 10.1007/s11999-011-1863-5 .
  177. Kanis JA, Odén A, McCloskey EV, Johansson H, Wahl DA, Cooper C . A systematic review of hip fracture incidence and probability of fracture worldwide . Osteoporosis International . 23 . 9 . 2239–2256 . September 2012 . 22419370 . 3421108 . 10.1007/s00198-012-1964-3 .
  178. Herrmann M, Peter Schmidt J, Umanskaya N, Wagner A, Taban-Shomal O, Widmann T, Colaianni G, Wildemann B, Herrmann W . The role of hyperhomocysteinemia as well as folate, vitamin B(6) and B(12) deficiencies in osteoporosis: a systematic review . Clinical Chemistry and Laboratory Medicine . 45 . 12 . 1621–1632 . 2007 . 18067447 . 10.1515/cclm.2007.362 . 7641257 .
  179. Ganji R, Moghbeli M, Sadeghi R, Bayat G, Ganji A . Prevalence of osteoporosis and osteopenia in men and premenopausal women with celiac disease: a systematic review . Nutrition Journal . 18 . 1 . 9 . February 2019 . 30732599 . 6504166 . 10.1186/s12937-019-0434-6 . free .
  180. Web site: What People With Celiac Disease Need To Know About Osteoporosis NIH Osteoporosis and Related Bone Diseases National Resource Center. www.bones.nih.gov. 2019-08-01.
  181. Book: Grob . Gerald N. . Aging Bones: A Short History of Osteoporosis . 2014 . JHU Press . 978-1-4214-1318-1 . 5 .
  182. Albright F, Bloomberg E, Smith PH . 1940 . Postmenopausal osteoporosis . Trans. Assoc. Am. Physicians . 55 . 298–305.
  183. Hirata K, Morimoto I . Vertebral Osteoporosis in Late Edo Japanese . 102 . 4 . 345–361 . 1994 . Anthropological Science . 10.1537/ase.102.345 . free .

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