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==Overview==
==Overview==
[[Osteoporosis]] is a [[bone]] [[disease]], characterized by lowered [[bone mineral density]]; leads to increased risk of [[bone fracture|fracture]]. The pathology is negative balance between old bone resorption and new bone formation. Aging, female gender, thin and small stature, Asian or Caucasian races, [[alcoholism]], [[hypogonadism]], and [[steroid]] abuse are among the primary risk factors associated with osteoporosis. It can be prevented with lifestyle modification, or [[calcium]] and [[vitamin D]] supplementation. Preventing falls in people with known or suspected osteoporosis is an established way to prevent fractures. [[Bisphosphonate]]s, [[calcium]], and [[vitamin D]] supplementation form the main stay of treatment.
[[Osteoporosis]] is a [[bone]] [[disease]], characterized by lowered [[bone mineral density]]; leads to increased risk of [[bone fracture|fracture]]. The pathology is negative balance between old [[bone]] resorption and new [[bone]] formation. Aging, female gender, thin and short stature, Asian or Caucasian races, [[alcoholism]], [[hypogonadism]], and [[steroid]] abuse are among the primary risk factors associated with [[osteoporosis]]. It can be prevented with [[lifestyle]] modification, or [[calcium]] and [[vitamin D]] supplementation. Preventing falls in people with known or suspected [[osteoporosis]] is an established way to prevent [[fractures]]. [[Bisphosphonate]]s, [[calcium]], and [[vitamin D]] supplementation form the main stay of treatment.


==Historical Perspective==
==Historical Perspective==

Revision as of 12:35, 16 August 2017

Osteoporosis Microchapters

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Patient Information

Overview

Historical Perspective

Classification

Pathophysiology

Causes

Differentiating Osteoporosis from other Diseases

Epidemiology and Demographics

Risk Factors

Screening

Natural History, Complications and Prognosis

Diagnosis

History and Symptoms

Physical Examination

Laboratory Findings

Electrocardiogram

X-ray

CT

MRI

Echocardiography or Ultrasound

Other Imaging Findings

Other Diagnostic Studies

Treatment

Medical Therapy

Life Style Modification
Pharmacotherapy

Surgery

Primary Prevention

Secondary Prevention

Cost-Effectiveness of Therapy

Future or Investigational Therapies

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Eiman Ghaffarpasand, M.D. [2]

Overview

Osteoporosis is a bone disease, characterized by lowered bone mineral density; leads to increased risk of fracture. The pathology is negative balance between old bone resorption and new bone formation. Aging, female gender, thin and short stature, Asian or Caucasian races, alcoholism, hypogonadism, and steroid abuse are among the primary risk factors associated with osteoporosis. It can be prevented with lifestyle modification, or calcium and vitamin D supplementation. Preventing falls in people with known or suspected osteoporosis is an established way to prevent fractures. Bisphosphonates, calcium, and vitamin D supplementation form the main stay of treatment.

Historical Perspective

Osteoporosis was first discovered by John Hunter, British surgeon, in 1800's. He found that bones in human body are turning over, continuously; when some old or dysfunctioned bone tissue become eroded and eliminated, the new fully functioned one being substituted. Nowadays, the process is called remodeling, the most important issue in osteoporosis pathophysiology. Jean Lobstein, a French pathologist of 1830's, found that there are normal holes in every bones; but some people's bones from specific age and diseases may have larger holes than normal ones. He eventually named theses kinds of bones as porous; thus the diseasebecame called osteoporosis.

Classification

Osteoporosis may be classified into several subtypes based on disease origin and disease severity. Osteoporosis divided to primary and secondary diseases, upon classification based on disease origin. While, it becomes divided to osteopenia, osteoporosis, and severe osteoporosis, upon classification based on disease severity.

Pathophysiology

The pathophysiology of osteoporosis basically involves an imbalance between bone resorption and bone formation. Major factors that contribute to the development of osteoporosis include estrogen deficit and aging. The main pathway, through which these factors might lead to osteoporosis is reactive oxygen species (ROS) damage to osteocytes. Decreasing the capability of autophagy in osteocytes is another important issue; which make them vulnerable to oxidative stresses. Genes involved in the pathogenesis of osteoporosis are many genes that majorly can categorized in four main groups, include the osteoblast regulatory genes, osteoclast regulatory genes, bone matrix elements genes, and hormone/receptor genes.  

Causes

Osteoporosis may be caused by any condition, which could lead to disturb the balance between bone formation and bone resorption. The most common conditions include but not limited to agingmenopausenutritional deficiency of calciumand/or vitamin Dchronic renal failure, immobility, hyperparathyroidism, and chronic glucocorticoid abuse.

Differentiating Osteoporosis from other Diseases

Osteoporosis must be differentiated from other diseases that cause decreasing in bone mineral density (BMD), such as idiopathic transient osteoporosis of hip, osteomalacia, scurvy, osteogenesis imperfecta, multiple myeloma, homocystinuria, and hypermetabolic resorptive osteoporosis.

Epidemiology and Demographics

Osteoporosis is a major health problem involving 43.9% (43.4 million) of male and female population in the United States. The disease rate increased as people's age raised. The most prevalent age group of patients is 80 years and older. White females and African-American males have the highest frequency among the other races.

Risk Factors

Risk factors for osteoporosis disease are of two types, including non-modifiable and modifiable (potentially) factors. Non-modifiable risk factors are age, sex, menopause, and family history. Modifiable (potentially) factors are smoking, alcohol consumption, immobility, glucocorticoid abuse, and proton pump inhibitor (PPI).

Screening

Today, risk of fracture due to osteoporosis is threatening one out of two postmenopausal women and also one out of five older men. The 10-year risk for any osteoporosis-related fractures in 65-year-old white woman with no other risk factor is 9.3%. Upon the guidelines of USPSTF, all women ≥ 65 years old along with women < 65 years old with high risk of fracture are target of screening for osteoporosis; but there is not any recommendation to screen men for the disease. There are two major methods, that is suggested to use for screening osteoporosis: dual energy x-ray absorptiometry (DXA) of both hip and lumbar spine bones, and quantitative ultrasonography of the calcaneus.

Natural History, Complications and Prognosis

If left untreated, most of patients with Osteoporosis may progress to develop fracture. With appropriate and timely usage of medications along with calcium and/or vitamin D supplementation, the outcome of osteoporosis is usually good. Apart from risk of death and other complications, osteoporotic fractures are associated with a reduced quality of life due to immobilityemotional problems may also raised as a consequence. As studies suggested, the impact of osteoporosis and also osteoporotic fractures on public life would be worse than lots of life threatening diseases; especially with aging.

Diagnosis

History and symptoms

Osteoporosis, actually has not any acute symptoms, especially in early stages. The hallmark of osteoporosis is bone pain.Gradually, when bone mineral density loss is intensified (i.e., postmenopausal or elderly), the main symptoms could be seen; which are usually consisted of bone pain and weakness. After a while, when osteoporosis become severed, the fractures happen. Then, the major signs of fractures appeared; which include bone pain and tenderness, shortness of height, and stooped posture.

Physical examination

Osteoporosis is generally asymptomatic during initial years; until the bone mass loss rich to the point that fractures occur. These fractures could be divided to acute and chronic ones; mostly involve femoral neck and vertebral bones, respectively. The main feature of femoral fracture is immobilization and the main feature of vertebral fracture is Dowager's hump appearance. Any other secondary causes of the disease (e.g., chronic corticosteroid use or hyperthyroidism) may have their own symptoms; signifying a risk factor for osteoporosis.

Laboratory findings

There is a limited role for laboratory tests in diagnosis of osteoporosis; however, they may be used for differentiating primary versus secondary causes of the disease. Lab tests for the diagnosis of osteoporosis include some baseline tests like complete blood count (CBC), serum calcium, phosphate, alkaline phosphatase, and 25-(OH)-vitamin D. There are also tests for diagnosing secondary osteoporosis, which include 24 hr serum calcium, serum protein electrophoresis, and serum thyroid hormones.

Electrocardiogram

There are no electrocardiogram (ECG) findings associated with osteoporosis.

X-ray

X-ray may be helpful in the diagnosis of osteoporosis. The main finding on x-ray suggestive of osteoporosis is bone mass loss, identified with decreased bony trabecula in primary stages and then decreased cortical thickness. The most common bones monitored for osteoporosis evidences are femoral neck, lumbar vertebrae, and calcaneus. Plain radiography needs at least 30-50% of bone loss to demonstrate decreased bone density; therefore, it is not a very sensitive modality.

CT scan

Despite that bone mineral density (BMD) measurement may provide so much information about osteoporosis and also osteoporotic fracture risk, but some researchers suggest that it has a limited role in bone strength description. In order to describe the bone strength more precisely, it seems necessary to do quantitative assays such as dual energy X-ray absorbtiometery (DXA) and CT scan (especially volumetric quantitative CT (vQCT)). Modalities for assessing osteoporotic fracture risk, without any destruction or invasion, include high resolution CT (hrCT) and micro CT (μCT). The only tests that is possible in vivo are hrCT and vQCT.

MRI

Regarding that magnetic resonance imaging (MRI) technique is very precise in measuring trabecular bone structure, it could be a suitable surrogate for multiple sites bone biopsy. On the other hand, although 20% of skeleton consist of trabecular bones, but they have highest impression from metabolic stimuli; thus, in contrast with DXA which is measure both trabecular and cortical at the same time, MRI would be better choice. The most impressing aspect of MRI in diagnosing osteoporosis is the ability to take in vivo images of trabecular bones. The plain resolution starts at about 150 μm and slice thickness starts at 300 μm; measuring trabecular bones precisely.

Echocardiography/Ultrasound

Quantitative ultrasound may be helpful in the diagnosis of osteoporosis. Findings on an ultrasound diagnostic of osteoporosis include bone mass loss, mainly trabecular bone that is the major bone type involving in osteoporosis. Problems with DXA method have led to choose some methods with less harms and limitations, such as ultrasound (especially quantitative), which could diagnose osteoporosis with lower radiation, lower price, and also higher availability. Most common site of ultrasound application is peripheral parts, such as calcaneus and phalanges.

Other imaging findings

The most important modality for measuring bone mineral density (BMD), that every osteoporosis diagnostic and therapeutic decision are based on, is dual energy X-ray absorptiometry (DEXA). DEXA is a 2-dimensional image of a 3-demensional subject, mainly depends on size of the bone which is studied. Regarding the vast advantages of DEXA, it seems that DEXA will remain the masterpiece of fracture risk assessment and also osteoporosis diagnosis in the future.

Finite element modeling (FEM) is basically an engineering computer-based simulation software. FEM typically simulate the physical loading effects on materials. The effects may be strain or compression, while the subject determined as net-like elements connected to each other.

BMD is focused on density and does not imply for microstructure or architecture of bones. One of the most powerful methods to determine the microstructure is trabecular bone score (TBS) as a complementary method for DEXA.

Other diagnostic studies

There are no additional diagnostic findings for osteoporosis.

Treatment

Medical therapy

Life style modification

There are various lifestyle modifications that can be implemented to help prevent the development or even treatment of osteoporosis. They are including calcium and vitamin D supplementation, diet, exercise, smoking quit, alcohol consumption, and also fall prevention.

Pharmacotherapy

The mainstays of treatment in primary osteoporosis disease are based on in life style modifications. Most of the time in high risk patients and people with past history of osteoporotic fracture, medical therapy is necessary. Bisphosphonates are the first line treatment for osteoporosis disease. Raloxifene is the second line treatment of osteoporosis in postmenopausal women, for both treatment and prevention. Denosumab is a human monoclonal antibody designed to inhibit RANKL (RANK ligand), a protein that acts as the primary signal for bone removal. It is used to treat Osteoporosis in elder men and postmenopausal women. Teriparatide and Abaloparatide are human recombinant parathyroid hormones used to treat postmenopausal woman with osteoporosis at high risk of fracture or to increase bone mass in men with osteoporosis.

Surgery

Surgery is not the first-line treatment option for patients with osteoporosis. Vertebroplasty, kyphoplasty, lordoplasty, and vesselplasty are procedures that usually reserved for patients with either pathological or osteoporotic vertebral fractures in patients, refractory to medical therapy. Surgery options for osteoporosis are very limited. In case of hip fracture open reduction internal fixation or in rare cases total hip replacement surgery are the options.

Primary Prevention

In osteoporosis, some of life style modification strategies would be beneficial for both primary prevention and also initial treatment; because osteoporosis is majorly depends on life style, in every stages of the disease. Lifestyle modification, as well as calcium supplementation, are the best early and long-term measures for the prevention of osteoporosis. There are also medications available that can be used to prevent worsening of osteoporosis. The primary prevention of osteoporosis is particularly important because the micro-architectural changes that occur in osteoporosis are largely irreversible.

Secondary Prevention

Effective measures for the secondary prevention of osteoporosis include pharmacological therapy and also life style modification as soon as osteoporosis is diagnosed.

Cost-Effectiveness of Therapy

Future or Investigational Therapies

References

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