Osteoporosis overview: Difference between revisions
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==Overview== | ==Overview== | ||
[[Osteoporosis]] | [[Osteoporosis]] was first discovered by John Hunter, British [[surgeon]], in 1800's. [[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. 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|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]]. [[Osteoporosis]] must be differentiated from other [[diseases]] that cause decreasing in [[Bone mineral density|bone mineral density (BMD)]], such as idiopathic transient osteoporosis of [[hip]], [[osteomalacia]], [[scurvy]], [[osteogenesis imperfecta]], [[multiple myeloma]], [[homocystinuria]], and [[hypermetabolic]] resorptive [[osteoporosis]]. [[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 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|alcohol consumption]], [[immobility]], [[glucocorticoid]] abuse, and [[Proton pump inhibitor|proton pump inhibitor (PPI)]]. 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 [[United states preventive services task force recommendations scheme|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]], include [[Dual energy X-ray absorptiometry|dual energy x-ray absorptiometry (DXA)]] of both [[hip]] and [[lumbar spine]] [[bones]], and quantitative [[ultrasonography]] of the [[calcaneus]]. 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 [[immobility]]; [[emotional]] 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]]. 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]]. The mainstays of treatment in primary [[osteoporosis]] [[disease]] are based on in [[lifestyle]] modifications. Most of the time in high risk patients and people with past history of [[Osteoporosis|osteoporotic]] [[fracture]], [[Medical therapy template|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 (biology)|signal]] for [[bone]] removal. It is used to treat [[Osteoporosis]] in elder men and [[postmenopausal]] women. [[Teriparatide]] and Abaloparatide are human [[recombinant]] [[parathyroid hormone]]<nowiki/>s used to treat [[postmenopausal]] woman with [[osteoporosis]] at high risk of [[fracture]] or to increase [[bone]] mass in men with [[osteoporosis]]. | ||
==Historical Perspective== | ==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 [[disease]]<nowiki/>became called ''[[osteoporosis]]''. | [[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 [[disease]] <nowiki/>became called "''[[osteoporosis]]"''. | ||
==Classification== | ==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. | [[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== | ==Pathophysiology== | ||
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==Differentiating Osteoporosis from other Diseases== | ==Differentiating Osteoporosis from other Diseases== | ||
[[Osteoporosis]] must be differentiated from other [[diseases]] that cause decreasing in [[Bone mineral density|bone mineral density (BMD)]], such as idiopathic transient osteoporosis of [[hip]], [[osteomalacia]], [[scurvy]], [[osteogenesis imperfecta]], [[multiple myeloma]], [[homocystinuria]], and hypermetabolic resorptive osteoporosis. | [[Osteoporosis]] must be differentiated from other [[diseases]] that cause decreasing in [[Bone mineral density|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== | ==Epidemiology and Demographics== | ||
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==Diagnosis== | ==Diagnosis== | ||
===History and symptoms=== | ===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. | [[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=== | ===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|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]]. | [[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|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=== | ===Laboratory findings=== | ||
There is a limited role for [[Laboratory techniques|laboratory tests]] in diagnosis of [[osteoporosis]]; however, they may be used for differentiating primary versus secondary causes of the disease. [[Laboratory techniques|Lab tests]] for the [[diagnosis]] of [[osteoporosis]] include some baseline tests like [[complete blood count | There is a limited role for [[Laboratory techniques|laboratory tests]] in [[diagnosis]] of [[osteoporosis]]; however, they may be used for differentiating primary versus secondary causes of the [[disease]]. [[Laboratory techniques|Lab tests]] for the [[diagnosis]] of [[osteoporosis]] include some baseline tests like [[Complete blood count|complete blood count (CBC)]], [[Calcium|serum calcium]], [[phosphate]], [[alkaline phosphatase]], and [[Vitamin D|25-(OH)-vitamin D]]. There are also tests for diagnosing secondary [[osteoporosis]], which include 24 hr [[Calcium|serum calcium]], [[serum]] [[protein electrophoresis]], and [[serum]] [[Thyroid hormone|thyroid hormones]]. | ||
===Electrocardiogram=== | ===Electrocardiogram=== | ||
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===CT scan=== | ===CT scan=== | ||
Despite that [[Bone mineral density|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 absorptiometry|dual energy X-ray absorbtiometery (DXA)]] and [[Computed tomography|CT scan]] (especially volumetric quantitative CT (vQCT)). [[Modality|Modalities]] for assessing osteoporotic [[fracture]] risk, without any destruction or invasion, include [[High resolution CT|high resolution CT (hrCT)]] and micro CT (μCT). The only tests that is possible ''[[in vivo]]'' are hrCT and vQCT. | [[High resolution CT|High resolution CT (hrCT)]] and micro [[CT-scans|CT]] (μCT) may be helpful in the [[diagnosis]] of [[osteoporosis]]. Despite that [[Bone mineral density|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 absorptiometry|dual energy X-ray absorbtiometery (DXA)]] and [[Computed tomography|CT scan]] (especially volumetric quantitative [[CT-scans|CT]] (vQCT)). [[Modality|Modalities]] for assessing osteoporotic [[fracture]] risk, without any destruction or invasion, include [[High resolution CT|high resolution CT (hrCT)]] and micro [[CT-scans|CT]] (μCT). The only tests that is possible ''[[in vivo]]'' are hrCT and vQCT. | ||
===MRI=== | ===MRI=== | ||
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Regarding that [[Magnetic resonance imaging|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 bone|trabecular bones]], but they have highest impression from [[metabolic]] stimuli; thus, in contrast with [[Dual energy X-ray absorptiometry|DXA]] which is measure both [[Trabecular bone|trabecular]] and [[Cortical bone|cortical]] at the same time, [[Magnetic resonance imaging|MRI]] would be better choice. The most impressing aspect of [[Magnetic resonance imaging|MRI]] in diagnosing [[osteoporosis]] is the ability to take ''[[in vivo]]'' images of [[Trabecular bone|trabecular bones]]. The plain [[resolution]] starts at about 150 μm and slice thickness starts at 300 μm; measuring [[Trabecular bone|trabecular bones]] precisely. | Regarding that [[Magnetic resonance imaging|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 bone|trabecular bones]], but they have highest impression from [[metabolic]] stimuli; thus, in contrast with [[Dual energy X-ray absorptiometry|DXA]] which is measure both [[Trabecular bone|trabecular]] and [[Cortical bone|cortical]] at the same time, [[Magnetic resonance imaging|MRI]] would be better choice. The most impressing aspect of [[Magnetic resonance imaging|MRI]] in diagnosing [[osteoporosis]] is the ability to take ''[[in vivo]]'' images of [[Trabecular bone|trabecular bones]]. The plain [[resolution]] starts at about 150 μm and slice thickness starts at 300 μm; measuring [[Trabecular bone|trabecular bones]] precisely. | ||
===Echocardiography/Ultrasound=== | ===Echocardiography/Ultrasound=== | ||
[[Quantitative]] [[ultrasound]] may be helpful in the [[diagnosis]] of [[osteoporosis]]. | There are no echocardiography findings associated with [[osteoporosis]]. [[Quantitative]] [[ultrasound]] may be helpful in the [[diagnosis]] of [[osteoporosis]]. The main finding on an [[ultrasound]] that may be diagnostic of [[osteoporosis]] is [[Bone loss|bone mass loss]], mainly [[trabecular bone]] that is the major [[bone]] type involving in [[osteoporosis]]. Problems with [[Dual energy X-ray absorptiometry|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 [[Phalanx|phalanges]]. | ||
===Other imaging findings=== | ===Other imaging findings=== | ||
The most important [[modality]] for measuring [[Bone mineral density|bone mineral density (BMD)]], that every [[osteoporosis]] diagnostic and [[therapeutic]] decision are based on, is [[Dual energy X-ray absorptiometry|dual energy X-ray absorptiometry (DEXA)]]. [[Dual energy X-ray absorptiometry|DEXA]] is a 2-dimensional image of a 3- | The most important [[modality]] for measuring [[Bone mineral density|bone mineral density (BMD)]], that every [[osteoporosis]] diagnostic and [[therapeutic]] decision are based on, is [[Dual energy X-ray absorptiometry|dual energy X-ray absorptiometry (DEXA)]]. [[Dual energy X-ray absorptiometry|DEXA]] is a 2-dimensional image of a 3-dimensional subject, mainly depends on size of the [[bone]] which is studied. Regarding the vast advantages of [[Dual energy X-ray absorptiometry|DEXA]], it seems that [[Dual energy X-ray absorptiometry|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. [[Bone mineral density|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 [[Dual energy X-ray absorptiometry|DEXA]]. | ||
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. | |||
[[Bone mineral density|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 [[Dual energy X-ray absorptiometry|DEXA]]. | |||
===Other diagnostic studies=== | ===Other diagnostic studies=== | ||
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==== Life style modification ==== | ==== 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. | 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 cessation|smoking quit]], [[alcohol consumption]], and also fall prevention. | ||
==== Pharmacotherapy ==== | ==== Pharmacotherapy ==== | ||
The mainstays of treatment in primary [[osteoporosis]] [[disease]] are based on in | The mainstays of treatment in primary [[osteoporosis]] [[disease]] are based on in [[lifestyle]] modifications. Most of the time in high risk patients and people with past history of [[Osteoporosis|osteoporotic]] [[fracture]], [[Medical therapy template|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 (biology)|signal]] for [[bone]] removal. It is used to treat [[Osteoporosis]] in elder men and [[postmenopausal]] women. [[Teriparatide]] and Abaloparatide are human [[recombinant]] [[parathyroid hormone]]<nowiki/>s used to treat [[postmenopausal]] woman with [[osteoporosis]] at high risk of [[fracture]] or to increase [[bone]] mass in men with [[osteoporosis]]. | ||
===Surgery=== | ===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 | [[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 [[Osteoporosis|osteoporotic]] [[vertebral]] [[fracture]]<nowiki/>s in patients, refractory to [[Medical therapy template|medical therapy]]. [[Surgery]] options for [[osteoporosis]] are very limited. In case of [[hip fracture]], [[open reduction internal fixation]] or in rare cases [[Hip replacement surgery|total hip replacement]] [[surgery]] are the options. | ||
===Primary Prevention=== | ===Primary Prevention=== | ||
In [[osteoporosis]], some of | In [[osteoporosis]], some of [[lifestyle]] 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=== | ===Secondary Prevention=== | ||
Effective measures for the [[secondary prevention]] of [[osteoporosis]] include [[pharmacological]] therapy and also | Effective measures for the [[secondary prevention]] of [[osteoporosis]] include [[pharmacological]] therapy and also [[lifestyle]] modification as soon as [[osteoporosis]] is diagnosed. | ||
===Cost-Effectiveness of Therapy=== | ===Cost-Effectiveness of Therapy=== | ||
44 million people of more than 50 years old in US are suffering from [[osteoporosis]], more than half of over 50 years people. Remaining the current conditions and utilities, it is estimated that more than 61 million people in 2020 will involved in [[osteoporosis]]. Women are 80% of the osteoporotic population. [[PTH]] analogues ([[teriparatide]] and abaloparatide) have more prices and QALYs in contrast with [[zoledronate]]. [[Teriparatide]] and abaloparatide are $43,440 and $22,061 more costly than [[zoledronate]]. In Europe the whole cost of medical therapies for [[osteoporosis]] in 2010 was €37 billion, in which 66% was for acute [[fractures]] management, 29% was for long-term [[fracture]] outcome management, and 5% was for medical prevention. On the other hand, holistic burden of [[osteoporosis]] in Europe assumed to be loss of 1,180,000 life years (quality adjusted (QALY)), most of them because of prior osteoporotic [[fractures]]. Regarding that one QALY is equal value of 2xGDP, it is assumed that the total burden of [[osteoporosis]] become €60.4 billion, in 2010. Surprisingly, the QALY number will raise from 1.2 million in 2010 to about 1.4 million years in 2025, with 20% increase. | 44 million people of more than 50 years old in US are suffering from [[osteoporosis]], more than half of over 50 years people. Remaining the current conditions and utilities, it is estimated that more than 61 million people in 2020 will involved in [[osteoporosis]]. Women are 80% of the osteoporotic population. [[PTH]] analogues ([[teriparatide]] and abaloparatide) have more prices and QALYs in contrast with [[zoledronate]]. [[Teriparatide]] and abaloparatide are $43,440 and $22,061 more costly than [[zoledronate]]. In Europe the whole cost of [[Medical therapy template|medical therapies]] for [[osteoporosis]] in 2010 was €37 billion, in which 66% was for acute [[fractures]] management, 29% was for long-term [[fracture]] outcome management, and 5% was for medical prevention. On the other hand, holistic burden of [[osteoporosis]] in Europe assumed to be loss of 1,180,000 life years (quality adjusted (QALY)), most of them because of prior osteoporotic [[fractures]]. Regarding that one QALY is equal value of 2xGDP, it is assumed that the total burden of [[osteoporosis]] become €60.4 billion, in 2010. Surprisingly, the QALY number will raise from 1.2 million in 2010 to about 1.4 million years in 2025, with 20% increase. | ||
===Future or Investigational Therapies=== | ===Future or Investigational Therapies=== | ||
Revision as of 14:46, 17 August 2017
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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 was first discovered by John Hunter, British surgeon, in 1800's. 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. 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. 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. 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 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). 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, include dual energy x-ray absorptiometry (DXA) of both hip and lumbar spine bones, and quantitative ultrasonography of the calcaneus. 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 immobility; emotional 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. 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. The mainstays of treatment in primary osteoporosis disease are based on in lifestyle 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.
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 disease became 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 aging, menopause, nutritional deficiency of calciumand/or vitamin D, chronic 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 immobility; emotional 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
High resolution CT (hrCT) and micro CT (μCT) may be helpful in the diagnosis of osteoporosis. 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
There are no echocardiography findings associated with osteoporosis. Quantitative ultrasound may be helpful in the diagnosis of osteoporosis. The main finding on an ultrasound that may be diagnostic of osteoporosis is 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-dimensional 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 lifestyle 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 lifestyle 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 lifestyle modification as soon as osteoporosis is diagnosed.
Cost-Effectiveness of Therapy
44 million people of more than 50 years old in US are suffering from osteoporosis, more than half of over 50 years people. Remaining the current conditions and utilities, it is estimated that more than 61 million people in 2020 will involved in osteoporosis. Women are 80% of the osteoporotic population. PTH analogues (teriparatide and abaloparatide) have more prices and QALYs in contrast with zoledronate. Teriparatide and abaloparatide are $43,440 and $22,061 more costly than zoledronate. In Europe the whole cost of medical therapies for osteoporosis in 2010 was €37 billion, in which 66% was for acute fractures management, 29% was for long-term fracture outcome management, and 5% was for medical prevention. On the other hand, holistic burden of osteoporosis in Europe assumed to be loss of 1,180,000 life years (quality adjusted (QALY)), most of them because of prior osteoporotic fractures. Regarding that one QALY is equal value of 2xGDP, it is assumed that the total burden of osteoporosis become €60.4 billion, in 2010. Surprisingly, the QALY number will raise from 1.2 million in 2010 to about 1.4 million years in 2025, with 20% increase.
Future or Investigational Therapies
Some future antiresorptive drugs that are not yet improved by FDA, include calcitriol, genistein, other bisphosphonates (etidronate, pamidronate, and tiludronate), PTH (1-84), sodium fluoride, strontium ranelate, and also tibolone.