Choroba pageta kości
Rokowania, prognozy i postęp choroby
Choroba Pageta kości jest przewlekłym schorzeniem metabolicznym szkieletu, dotykającym 2-3% populacji powyżej 55 roku życia, charakteryzującym się ogniskową, nieprawidłową przebudową kości. Dysfunkcja osteoklastów, nadmierna resorpcja kości oraz nieprawidłowa regulacja szlaków sygnałowych, takich jak Akt/NFATC1, odgrywają kluczową rolę w patogenezie. Genetyczne uwarunkowania obejmują mutacje w genach SQSTM1, TNFSF11A, TNFRSF11B, VCP, OPTN, CSF1, DCSTAMP oraz nowo zidentyfikowaną mutację c.163GC w genie FKBP5, która sprzyja osteoklastogenezie. Badania GWAS wykazały, że kombinacja alleli ryzyka zwiększa zasięg i ciężkość choroby, a mutacje SQSTM1 korelują z bardziej zaawansowanym przebiegiem i większą liczbą terapii. Epigenetyczne zmiany metylacji DNA stanowią potencjalne markery diagnostyczne i prognostyczne, umożliwiając wczesną identyfikację pacjentów z rodzinnym wywiadem choroby.
Prognoza w chorobie Pageta kości
Choroba Pageta kości (Paget’s disease of bone) jest przewlekłym schorzeniem szkieletu, będącym drugą co do częstości występowania metaboliczną chorobą kości, zaraz po osteoporozie. Dotyka około 2-3% populacji powyżej 55 roku życia i charakteryzuje się ogniskowym nasileniem nieprawidłowej przebudowy kości. 12
Ogólna prognoza
Prognoza dla pacjentów leczonych z powodu choroby Pageta kości jest dobra, szczególnie jeśli choroba została rozpoznana we wczesnym stadium. Choć choroba Pageta kości nie ma leczenia przyczynowego, można ją skutecznie kontrolować poprzez spowolnienie lub nawet zatrzymanie jej progresji. 3
Pacjenci z postacią wieloogniskową (polyostotic) mają gorsze rokowanie niż pacjenci z postacią jednoogniskową (monostotic). Chorobowość wynika głównie z występowania złamań, przewlekłego bólu, deformacji kości i powikłań neurologicznych. 4
U większości pacjentów, u których leczenie rozpoczęto przed wystąpieniem znaczących zmian w kościach, możliwe jest prowadzenie normalnego, aktywnego życia. Natomiast gdy rozwiną się powikłania, leczenie chirurgiczne jest zwykle skuteczne w łagodzeniu bólu i poprawie funkcji. 5
Predyktory przebiegu choroby
Czynniki genetyczne
Czynniki genetyczne odgrywają kluczową rolę w patogenezie choroby Pageta kości. Zidentyfikowano kilka genów podatności, w tym SQSTM1, TNFSF11A, TNFRSF11B, VCP, OPTN, CSF1 i DCSTAMP. 6
Wyniki badań asocjacyjnych całego genomu (GWAS) pozwoliły na opracowanie skali oceny ryzyka ciężkości choroby. U pacjentów bez mutacji SQSTM1, kombinacja alleli ryzyka w najwyższym tercylu była związana z 27% wzrostem zasięgu choroby (definiowanym jako liczba zajętych kości) oraz 25% wzrostem punktacji ciężkości choroby, uwzględniającej powikłania wtórne. Pacjenci z mutacjami SQSTM1 wykazywali znacząco większy zasięg i ciężkość choroby oraz zwiększoną liczbę wcześniejszych terapii. 7
W niedawno opisanym przypadku rodzinnej choroby Pageta w północnochińskiej rodzinie zidentyfikowano nową mutację punktową c.163GC w genie FKBP5. Badania wykazały, że mutacja FKBP51V55L sprzyja różnicowaniu osteoklastów i resorpcji kości poprzez zwiększenie aktywności szlaku Akt/NFATC1, co może przyczyniać się do rozwoju choroby Pageta. 89
Czynniki epigenetyczne
Badania epigenetyczne wykazały, że czynniki epigenetyczne przyczyniają się do patogenezy choroby Pageta kości i mogą stanowić markery diagnostyczne do przewidywania choroby. Regiony z częstymi, ale niezależnymi zmianami metylacji w chorobie Pageta pozwalają odróżnić przypadki od kontroli z dużą dokładnością. 1011
Istnieje możliwość, że markery epigenetyczne, w połączeniu z profilowaniem genetycznym, mogłyby być wykorzystane do oceny ryzyka rozwoju choroby Pageta u osób z rodzinnym wywiadem tego schorzenia, umożliwiając wczesną interwencję w klinicznie uzasadnionych przypadkach. 12
Czynniki środowiskowe
Coraz więcej dowodów sugeruje, że czynniki środowiskowe i styl życia mogą wpływać na ekspresję genów i fenotyp kliniczny w różnych chorobach poprzez mechanizmy epigenetyczne, takie jak zmiany w metylacji DNA. Badana była również możliwa rola przetrwałej infekcji wirusowej, w tym wirusem odry i nosówki. 13
Powikłania wpływające na rokowanie
- Złamania patologiczne – osłabione, kruche kości są bardziej podatne na złamania
- Deformacje kostne – prowadzące do ograniczenia sprawności i bólu
- Powikłania neurologiczne – wynikające z ucisku struktur nerwowych przez zmienione kości
- Konieczność wymiany stawu – w przypadku znacznego zniszczenia stawu przez chorobę
- Kostniakomięsak (osteosarcoma) – rzadkie, ale poważne powikłanie
W przypadku rozwoju zezłośliwienia mięsaka (kostniakomięsaka) wskaźnik przeżycia może być bardzo niski. To rzadkie, ale bardzo poważne powikłanie znacząco pogarsza rokowanie. 16
Wczesna diagnostyka a rokowanie
Istotnym problemem klinicznym jest fakt, że wielu pacjentów z chorobą Pageta kości nie ma żadnych objawów i nie są świadomi choroby, dopóki nie wykonają zdjęć rentgenowskich z innego powodu. U większości pacjentów objawy pojawiają się dopiero w zaawansowanym stadium, gdy doszło już do nieodwracalnych uszkodzeń szkieletu. 1718
Badania nad markerami genetycznymi i epigenetycznymi mogą w przyszłości pozwolić na identyfikację pacjentów przed wystąpieniem nieodwracalnych i upośledzających uszkodzeń, co mogłoby znacząco poprawić rokowanie poprzez wczesne wdrożenie leczenia. 19
Odpowiedź na leczenie a rokowanie
W większości przypadków choroba Pageta kości może być kontrolowana za pomocą leków, które pomagają spowolnić lub zatrzymać postęp choroby. Leczenie skupia się na łagodzeniu objawów i zapobieganiu przyszłym powikłaniom, ponieważ nie ma lekarstwa na chorobę Pageta ani sposobu na odwrócenie jej wpływu na kości. 2021
U pacjentów z powikłaniami może być konieczne leczenie chirurgiczne w celu wyrównania zdeformowanych kości lub wspomagania gojenia złamań. Interwencja chirurgiczna jest zwykle skuteczna w łagodzeniu bólu i poprawie funkcji. 22
Dysfunkcja osteoklastów a przebieg choroby
Dysfunkcja osteoklastów jest pierwotnym defektem w chorobie Pageta kości. Osteoklasty pochodzące z monocytów krwi obwodowej pacjentów z chorobą Pageta są bardziej wrażliwe niż osteoklasty od pacjentów bez tej choroby na czynniki indukujące resorpcję kości, w tym 1,25-dihydroksywitaminę D3 i ligand receptora aktywatora czynnika jądrowego κB (RANKL). 23
Nieprawidłowa regulacja określonych szlaków sygnałowych jest ważnym elementem etiologii choroby Pageta, który może przyczyniać się do dysfunkcji osteoklastów i rozwoju choroby. Osteoklasty odpowiadają za nadmierną resorpcję kości, co prowadzi do charakterystycznego obrazu choroby i jej powikłań. 2425
Badania na mysich komórkach szpiku kostnego wykazały, że cząsteczki specyficzne dla osteoklastów, takie jak kwaśna fosfataza oporna na winian, receptor związany z osteoklastami i czynnik transkrypcyjny NFATC1, wykazują zwiększoną ekspresję w komórkach pochodzących od myszy z mutacją FKBP51V55L podczas różnicowania osteoklastów, co może mieć znaczenie dla przebiegu choroby u ludzi. 26
Zmienność populacyjna przebiegu choroby
Pomimo znacznych postępów genetycznych, konieczne są dalsze badania w celu wyjaśnienia innych aspektów choroby, w tym jej ogniskowego charakteru oraz zmian w ciężkości i częstości występowania obserwowanych w niektórych populacjach. Zmienność w przebiegu i nasileniu choroby Pageta kości pomiędzy różnymi grupami etnicznymi sugeruje złożone interakcje między czynnikami genetycznymi i środowiskowymi. 27
Kolejne rozdziały
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Materiały źródłowe
- #1https://link.springer.com/article/10.1007/s12018-016-9226-0
Pagets disease of bone (PDB) is the second most common metabolic bone disorder, after osteoporosis. […] A combination of risk alleles identified by genome-wide association studies led to the development of a score to predict disease severity, which could improve the management of the disease. […] Results from the genome-wide association analysis helped to build up a risk allele score for severity of disease. In patients without SQSTM1 mutations, a combination of risk GWAS alleles in the highest tertile was associated with a 27% increase in disease extent, defined by the number of affected bones, and 25% increase in disease severity score, which includes complications secondary to the disease. SQSTM1+ve patients showed a highly significant increase in disease extent, severity and number of previous treatments received. […] However, despite the great genetic advances, further research is needed to elucidate other aspects of the disease, including its focal nature, and the changes in severity and prevalence observed in some populations.
- #2 Paget’s Disease of Bone – OrthoInfo – AAOShttps://orthoinfo.aaos.org/en/diseases–conditions/pagets-disease-of-bone
Paget’s disease of bone is a chronic disease of the skeleton. Pagets disease causes this process to shift out of balance, resulting in new bone that is abnormally shaped, weak, and brittle. Pagets disease most often affects older people, occurring in approximately 2 to 3% of the population over the age of 55. […] Many patients with Pagets disease have no symptoms at all and are unaware they have the disease until X-rays are taken for some other reason. […] In most cases, treatment for Pagets disease involves taking medications to help slow or stop the progress of the disease. […] For patients who have complications, surgery may be needed to realign deformed bones or to help fractures heal. […] There is no cure for Pagets disease and no way to reverse its effects on bone. Treatment focuses on relieving symptoms and preventing future complications. […] If treatment occurs before major changes in bone occur, the majority of patients with Pagets disease are able to live a normal, active life. When complications do develop, surgical treatment is usually effective in relieving pain and improving function.
- #3 Paget Bone Disease – StatPearls – NCBI Bookshelfhttps://www.ncbi.nlm.nih.gov/books/NBK430805/
The prognosis for treated patients is good, especially if the disease is in its early stages. Paget disease of the bone has no cure, but the disorder can be controlled by slowing down or even stopping its progression. Patients with polyostotic disease have poorer outcomes than those with monostotic disease. The morbidity is usually due to fractures, chronic pain, bone deformity, and neurological complications. Once the patient develops sarcomatous degeneration, the survival rate may be very poor.
- #4 Paget Bone Disease – StatPearls – NCBI Bookshelfhttps://www.ncbi.nlm.nih.gov/books/NBK430805/
The prognosis for treated patients is good, especially if the disease is in its early stages. Paget disease of the bone has no cure, but the disorder can be controlled by slowing down or even stopping its progression. Patients with polyostotic disease have poorer outcomes than those with monostotic disease. The morbidity is usually due to fractures, chronic pain, bone deformity, and neurological complications. Once the patient develops sarcomatous degeneration, the survival rate may be very poor.
- #5 Paget’s Disease of Bone – OrthoInfo – AAOShttps://orthoinfo.aaos.org/en/diseases–conditions/pagets-disease-of-bone
Paget’s disease of bone is a chronic disease of the skeleton. Pagets disease causes this process to shift out of balance, resulting in new bone that is abnormally shaped, weak, and brittle. Pagets disease most often affects older people, occurring in approximately 2 to 3% of the population over the age of 55. […] Many patients with Pagets disease have no symptoms at all and are unaware they have the disease until X-rays are taken for some other reason. […] In most cases, treatment for Pagets disease involves taking medications to help slow or stop the progress of the disease. […] For patients who have complications, surgery may be needed to realign deformed bones or to help fractures heal. […] There is no cure for Pagets disease and no way to reverse its effects on bone. Treatment focuses on relieving symptoms and preventing future complications. […] If treatment occurs before major changes in bone occur, the majority of patients with Pagets disease are able to live a normal, active life. When complications do develop, surgical treatment is usually effective in relieving pain and improving function.
- #6 A FKBP5 mutation is associated with Pagetâs disease of bone and enhances osteoclastogenesis | Experimental & Molecular Medicinehttps://www.nature.com/articles/emm201764
Pagets disease of bone (PDB) is a common metabolic bone disease that is characterized by aberrant focal bone remodeling, which is caused by excessive osteoclastic bone resorption followed by disorganized osteoblastic bone formation. […] Genetic factors are a critical determinant of PDB pathogenesis, and several susceptibility genes and loci have been reported, including SQSTM1, TNFSF11A, TNFRSF11B, VCP, OPTN, CSF1 and DCSTAMP. […] The osteoclast-specific molecules tartrate-resistant acid phosphatase, osteoclast-associated receptor and transcription factor NFATC1 were increased in bone marrow-derived monocyte/macrophage cells (BMMs) from FKBP51V55L mice during osteoclast differentiation. […] These results demonstrate that the mutant FKBP51V55L promotes osteoclastogenesis and function, which could subsequently participate in PDB development.
- #7https://link.springer.com/article/10.1007/s12018-016-9226-0
Pagets disease of bone (PDB) is the second most common metabolic bone disorder, after osteoporosis. […] A combination of risk alleles identified by genome-wide association studies led to the development of a score to predict disease severity, which could improve the management of the disease. […] Results from the genome-wide association analysis helped to build up a risk allele score for severity of disease. In patients without SQSTM1 mutations, a combination of risk GWAS alleles in the highest tertile was associated with a 27% increase in disease extent, defined by the number of affected bones, and 25% increase in disease severity score, which includes complications secondary to the disease. SQSTM1+ve patients showed a highly significant increase in disease extent, severity and number of previous treatments received. […] However, despite the great genetic advances, further research is needed to elucidate other aspects of the disease, including its focal nature, and the changes in severity and prevalence observed in some populations.
- #8 A FKBP5 mutation is associated with Pagetâs disease of bone and enhances osteoclastogenesis | Experimental & Molecular Medicinehttps://www.nature.com/articles/emm201764
Although the exact pathogenesis of PDB is still unclear, genetic factors are known to be important in PDB development. […] Osteoclast dysfunction is the primary defect in PDB. […] Osteoclasts derived from the peripheral blood monocytes of patients with PDB are more sensitive than osteoclasts from non-PDB patients to factors that induce bone resorption, including the 1,25-dihydroxyvitamin D3 and receptor activator for nuclear factor B (NFB) ligand (RANKL). […] Thus, aberrant regulation of specific signaling pathways is an important component of PDB etiology that may contribute to osteoclast dysfunction and disease development. […] In this study, we report an extremely rare case of familial PDB found in a northern Han Chinese family. […] The results of our research proved that the FKBP5 mutation, which co-segregated with patients, enhances osteoclast differentiation and bone resorption activity, both of which are primary defects in PDB development.
- #9 A FKBP5 mutation is associated with Pagetâs disease of bone and enhances osteoclastogenesis | Experimental & Molecular Medicinehttps://www.nature.com/articles/emm201764
These studies indicate that the FKBP5 mutation that we identified is associated with PDB through enhancing osteoclastogenesis. […] The V55L mutation in FKBP51 was shown to influence the function of FKBP51 in regulating Akt phosphorylation in cells. […] In summary, the results of our experiments prove that the FKBP51V55L mutation increases osteoclast formation by enhancing the activity of the Akt/NFATC1 pathway in a mouse model in vitro. […] In conclusion, in seeking to identify gene disorders responsible for a Chinese familial PDB, we demonstrated that a novel c.163GC point mutation in the FKBP5 gene is associated with PDB.
- #10 Epigenetic analysis of Pagetâs disease of bone identifies differentially methylated loci that predict disease status | eLifehttps://elifesciences.org/articles/65715
Pagets disease of bone (PDB) is characterized by focal increases in disorganized bone remodeling. […] In conclusion, this study has shown for the first time that epigenetic factors contribute to the pathogenesis of PDB and may offer diagnostic markers for prediction of the disease. […] For most patients however, symptoms are only present at an advanced stage, when irreversible damage to the skeleton has already occurred. […] This research sheds light onto the underlying changes that trigger PDB. Future experiments should explore whether it may be possible to use these genetic changes to identify patients before the onset of irreversible and debilitating damage. […] The possible role of persistent viral infection with measles and distemper has been studied experimentally. […] Accumulating evidence suggests that environmental and lifestyle factors can influence gene expression and clinical phenotype in various diseases through epigenetic mechanisms such as changes in DNA methylation.
- #11 Epigenetic analysis of Pagetâs disease of bone identifies differentially methylated loci that predict disease status | eLifehttps://elifesciences.org/articles/65715
Our analysis was extended to identify regions with frequent but independent methylation changes in PDB amongst sites that are adjacent to each other. […] The Pooled sites identified from the discovery set were able to discriminate cases and controls with a considerable accuracy when tested on the cross-validation set. […] This study raises the possibility that epigenetic markers, possibly when combined with genetic profiling, would be worth exploring as means of assessing the risk of developing PDB in people with a family history of the disorder so that early intervention can be considered where clinically appropriate.
- #12 Epigenetic analysis of Pagetâs disease of bone identifies differentially methylated loci that predict disease status | eLifehttps://elifesciences.org/articles/65715
Our analysis was extended to identify regions with frequent but independent methylation changes in PDB amongst sites that are adjacent to each other. […] The Pooled sites identified from the discovery set were able to discriminate cases and controls with a considerable accuracy when tested on the cross-validation set. […] This study raises the possibility that epigenetic markers, possibly when combined with genetic profiling, would be worth exploring as means of assessing the risk of developing PDB in people with a family history of the disorder so that early intervention can be considered where clinically appropriate.
- #13 Epigenetic analysis of Pagetâs disease of bone identifies differentially methylated loci that predict disease status | eLifehttps://elifesciences.org/articles/65715
Pagets disease of bone (PDB) is characterized by focal increases in disorganized bone remodeling. […] In conclusion, this study has shown for the first time that epigenetic factors contribute to the pathogenesis of PDB and may offer diagnostic markers for prediction of the disease. […] For most patients however, symptoms are only present at an advanced stage, when irreversible damage to the skeleton has already occurred. […] This research sheds light onto the underlying changes that trigger PDB. Future experiments should explore whether it may be possible to use these genetic changes to identify patients before the onset of irreversible and debilitating damage. […] The possible role of persistent viral infection with measles and distemper has been studied experimentally. […] Accumulating evidence suggests that environmental and lifestyle factors can influence gene expression and clinical phenotype in various diseases through epigenetic mechanisms such as changes in DNA methylation.
- #14 Paget disease of the bone: MedlinePlus Medical EncyclopediaLockhttps://medlineplus.gov/ency/article/000414.htm
Most of the time, the condition can be controlled with medicines. A small number of people may develop a cancer of the bone called osteosarcoma. Some people will need joint replacement surgery. […] Complications may include:
- #15 Paget Bone Disease – StatPearls – NCBI Bookshelfhttps://www.ncbi.nlm.nih.gov/books/NBK430805/
The prognosis for treated patients is good, especially if the disease is in its early stages. Paget disease of the bone has no cure, but the disorder can be controlled by slowing down or even stopping its progression. Patients with polyostotic disease have poorer outcomes than those with monostotic disease. The morbidity is usually due to fractures, chronic pain, bone deformity, and neurological complications. Once the patient develops sarcomatous degeneration, the survival rate may be very poor.
- #16 Paget Bone Disease – StatPearls – NCBI Bookshelfhttps://www.ncbi.nlm.nih.gov/books/NBK430805/
The prognosis for treated patients is good, especially if the disease is in its early stages. Paget disease of the bone has no cure, but the disorder can be controlled by slowing down or even stopping its progression. Patients with polyostotic disease have poorer outcomes than those with monostotic disease. The morbidity is usually due to fractures, chronic pain, bone deformity, and neurological complications. Once the patient develops sarcomatous degeneration, the survival rate may be very poor.
- #17 Paget’s Disease of Bone – OrthoInfo – AAOShttps://orthoinfo.aaos.org/en/diseases–conditions/pagets-disease-of-bone
Paget’s disease of bone is a chronic disease of the skeleton. Pagets disease causes this process to shift out of balance, resulting in new bone that is abnormally shaped, weak, and brittle. Pagets disease most often affects older people, occurring in approximately 2 to 3% of the population over the age of 55. […] Many patients with Pagets disease have no symptoms at all and are unaware they have the disease until X-rays are taken for some other reason. […] In most cases, treatment for Pagets disease involves taking medications to help slow or stop the progress of the disease. […] For patients who have complications, surgery may be needed to realign deformed bones or to help fractures heal. […] There is no cure for Pagets disease and no way to reverse its effects on bone. Treatment focuses on relieving symptoms and preventing future complications. […] If treatment occurs before major changes in bone occur, the majority of patients with Pagets disease are able to live a normal, active life. When complications do develop, surgical treatment is usually effective in relieving pain and improving function.
- #18 Epigenetic analysis of Pagetâs disease of bone identifies differentially methylated loci that predict disease status | eLifehttps://elifesciences.org/articles/65715
Pagets disease of bone (PDB) is characterized by focal increases in disorganized bone remodeling. […] In conclusion, this study has shown for the first time that epigenetic factors contribute to the pathogenesis of PDB and may offer diagnostic markers for prediction of the disease. […] For most patients however, symptoms are only present at an advanced stage, when irreversible damage to the skeleton has already occurred. […] This research sheds light onto the underlying changes that trigger PDB. Future experiments should explore whether it may be possible to use these genetic changes to identify patients before the onset of irreversible and debilitating damage. […] The possible role of persistent viral infection with measles and distemper has been studied experimentally. […] Accumulating evidence suggests that environmental and lifestyle factors can influence gene expression and clinical phenotype in various diseases through epigenetic mechanisms such as changes in DNA methylation.
- #19 Epigenetic analysis of Pagetâs disease of bone identifies differentially methylated loci that predict disease status | eLifehttps://elifesciences.org/articles/65715
Pagets disease of bone (PDB) is characterized by focal increases in disorganized bone remodeling. […] In conclusion, this study has shown for the first time that epigenetic factors contribute to the pathogenesis of PDB and may offer diagnostic markers for prediction of the disease. […] For most patients however, symptoms are only present at an advanced stage, when irreversible damage to the skeleton has already occurred. […] This research sheds light onto the underlying changes that trigger PDB. Future experiments should explore whether it may be possible to use these genetic changes to identify patients before the onset of irreversible and debilitating damage. […] The possible role of persistent viral infection with measles and distemper has been studied experimentally. […] Accumulating evidence suggests that environmental and lifestyle factors can influence gene expression and clinical phenotype in various diseases through epigenetic mechanisms such as changes in DNA methylation.
- #20 Paget’s Disease of Bone – OrthoInfo – AAOShttps://orthoinfo.aaos.org/en/diseases–conditions/pagets-disease-of-bone
Paget’s disease of bone is a chronic disease of the skeleton. Pagets disease causes this process to shift out of balance, resulting in new bone that is abnormally shaped, weak, and brittle. Pagets disease most often affects older people, occurring in approximately 2 to 3% of the population over the age of 55. […] Many patients with Pagets disease have no symptoms at all and are unaware they have the disease until X-rays are taken for some other reason. […] In most cases, treatment for Pagets disease involves taking medications to help slow or stop the progress of the disease. […] For patients who have complications, surgery may be needed to realign deformed bones or to help fractures heal. […] There is no cure for Pagets disease and no way to reverse its effects on bone. Treatment focuses on relieving symptoms and preventing future complications. […] If treatment occurs before major changes in bone occur, the majority of patients with Pagets disease are able to live a normal, active life. When complications do develop, surgical treatment is usually effective in relieving pain and improving function.
- #21 Paget disease of the bone: MedlinePlus Medical EncyclopediaLockhttps://medlineplus.gov/ency/article/000414.htm
Most of the time, the condition can be controlled with medicines. A small number of people may develop a cancer of the bone called osteosarcoma. Some people will need joint replacement surgery. […] Complications may include:
- #22 Paget’s Disease of Bone – OrthoInfo – AAOShttps://orthoinfo.aaos.org/en/diseases–conditions/pagets-disease-of-bone
Paget’s disease of bone is a chronic disease of the skeleton. Pagets disease causes this process to shift out of balance, resulting in new bone that is abnormally shaped, weak, and brittle. Pagets disease most often affects older people, occurring in approximately 2 to 3% of the population over the age of 55. […] Many patients with Pagets disease have no symptoms at all and are unaware they have the disease until X-rays are taken for some other reason. […] In most cases, treatment for Pagets disease involves taking medications to help slow or stop the progress of the disease. […] For patients who have complications, surgery may be needed to realign deformed bones or to help fractures heal. […] There is no cure for Pagets disease and no way to reverse its effects on bone. Treatment focuses on relieving symptoms and preventing future complications. […] If treatment occurs before major changes in bone occur, the majority of patients with Pagets disease are able to live a normal, active life. When complications do develop, surgical treatment is usually effective in relieving pain and improving function.
- #23 A FKBP5 mutation is associated with Pagetâs disease of bone and enhances osteoclastogenesis | Experimental & Molecular Medicinehttps://www.nature.com/articles/emm201764
Although the exact pathogenesis of PDB is still unclear, genetic factors are known to be important in PDB development. […] Osteoclast dysfunction is the primary defect in PDB. […] Osteoclasts derived from the peripheral blood monocytes of patients with PDB are more sensitive than osteoclasts from non-PDB patients to factors that induce bone resorption, including the 1,25-dihydroxyvitamin D3 and receptor activator for nuclear factor B (NFB) ligand (RANKL). […] Thus, aberrant regulation of specific signaling pathways is an important component of PDB etiology that may contribute to osteoclast dysfunction and disease development. […] In this study, we report an extremely rare case of familial PDB found in a northern Han Chinese family. […] The results of our research proved that the FKBP5 mutation, which co-segregated with patients, enhances osteoclast differentiation and bone resorption activity, both of which are primary defects in PDB development.
- #24 A FKBP5 mutation is associated with Pagetâs disease of bone and enhances osteoclastogenesis | Experimental & Molecular Medicinehttps://www.nature.com/articles/emm201764
Although the exact pathogenesis of PDB is still unclear, genetic factors are known to be important in PDB development. […] Osteoclast dysfunction is the primary defect in PDB. […] Osteoclasts derived from the peripheral blood monocytes of patients with PDB are more sensitive than osteoclasts from non-PDB patients to factors that induce bone resorption, including the 1,25-dihydroxyvitamin D3 and receptor activator for nuclear factor B (NFB) ligand (RANKL). […] Thus, aberrant regulation of specific signaling pathways is an important component of PDB etiology that may contribute to osteoclast dysfunction and disease development. […] In this study, we report an extremely rare case of familial PDB found in a northern Han Chinese family. […] The results of our research proved that the FKBP5 mutation, which co-segregated with patients, enhances osteoclast differentiation and bone resorption activity, both of which are primary defects in PDB development.
- #25 A FKBP5 mutation is associated with Pagetâs disease of bone and enhances osteoclastogenesis | Experimental & Molecular Medicinehttps://www.nature.com/articles/emm201764
Pagets disease of bone (PDB) is a common metabolic bone disease that is characterized by aberrant focal bone remodeling, which is caused by excessive osteoclastic bone resorption followed by disorganized osteoblastic bone formation. […] Genetic factors are a critical determinant of PDB pathogenesis, and several susceptibility genes and loci have been reported, including SQSTM1, TNFSF11A, TNFRSF11B, VCP, OPTN, CSF1 and DCSTAMP. […] The osteoclast-specific molecules tartrate-resistant acid phosphatase, osteoclast-associated receptor and transcription factor NFATC1 were increased in bone marrow-derived monocyte/macrophage cells (BMMs) from FKBP51V55L mice during osteoclast differentiation. […] These results demonstrate that the mutant FKBP51V55L promotes osteoclastogenesis and function, which could subsequently participate in PDB development.
- #26 A FKBP5 mutation is associated with Pagetâs disease of bone and enhances osteoclastogenesis | Experimental & Molecular Medicinehttps://www.nature.com/articles/emm201764
Pagets disease of bone (PDB) is a common metabolic bone disease that is characterized by aberrant focal bone remodeling, which is caused by excessive osteoclastic bone resorption followed by disorganized osteoblastic bone formation. […] Genetic factors are a critical determinant of PDB pathogenesis, and several susceptibility genes and loci have been reported, including SQSTM1, TNFSF11A, TNFRSF11B, VCP, OPTN, CSF1 and DCSTAMP. […] The osteoclast-specific molecules tartrate-resistant acid phosphatase, osteoclast-associated receptor and transcription factor NFATC1 were increased in bone marrow-derived monocyte/macrophage cells (BMMs) from FKBP51V55L mice during osteoclast differentiation. […] These results demonstrate that the mutant FKBP51V55L promotes osteoclastogenesis and function, which could subsequently participate in PDB development.
- #27https://link.springer.com/article/10.1007/s12018-016-9226-0
Pagets disease of bone (PDB) is the second most common metabolic bone disorder, after osteoporosis. […] A combination of risk alleles identified by genome-wide association studies led to the development of a score to predict disease severity, which could improve the management of the disease. […] Results from the genome-wide association analysis helped to build up a risk allele score for severity of disease. In patients without SQSTM1 mutations, a combination of risk GWAS alleles in the highest tertile was associated with a 27% increase in disease extent, defined by the number of affected bones, and 25% increase in disease severity score, which includes complications secondary to the disease. SQSTM1+ve patients showed a highly significant increase in disease extent, severity and number of previous treatments received. […] However, despite the great genetic advances, further research is needed to elucidate other aspects of the disease, including its focal nature, and the changes in severity and prevalence observed in some populations.