Paget’s disease of bone: a review of epidemiology, pathophysiology and management

Shaker, Joseph L.

doi:10.1177/1759720x09351779

Cited by 74 publications

(69 citation statements)

References 173 publications

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“…However, mutations in SQSTM1 frequently exist in patients with PDB, which is characterized by extensive bone remodeling with enlarged and weakened bone tissue, affecting mostly individuals >50 years of age [51]. PDB is the second most common metabolic bone disease after osteoporosis, and about 1% of affected individuals will subsequently develop OS [52, 53]. One remaining question is whether SQSTM1 can serve as a driver for PDB-induced OS.…”

Section: The Genomic Landscape Of Osteosarcomamentioning

confidence: 99%

Molecular genetics of osteosarcoma

Rickel

Fang

Tao

2017

Bone

204

179

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Osteosarcoma is the predominant form of bone cancer, affecting mostly adolescents. Recent progress made in molecular genetic studies of osteosarcoma has changed our view on the cause of the disease and ongoing therapeutic approaches for patients. As we draw closer to gaining more complete catalogues of candidate cancer driver genes in common forms of cancer, the landscape of somatic mutations in osteosarcoma is emerging from its first phase. In this review, we summarize recent whole genome and/or whole exome genomic studies, and then put these findings in the context of genetic hallmarks of somatic mutations and mutational processes in human osteosarcoma. One of the lessons learned here is that the extent of somatic mutations and complexity of the osteosarcoma genome are similar to that of common forms of adult cancer. Thus, a much higher number of samples than those currently obtained are needed to complete the catalogue of driver mutations in human osteosarcoma. In parallel, genetic studies in other species have revealed candidate driver genes and their roles in the genesis of osteosarcoma. This review also summarizes newly identified drivers in genetically engineered mouse models (GEMMs) and discusses our understanding of the impact of nature and number of drivers on tumor latency, subtypes, and metastatic potentials of osteosarcoma. It is becoming apparent that a synergistic team composed of three drivers (one ‘first driver’ and two ‘synergistic drivers’) may be required to generate an animal model that recapitulates aggressive osteosarcoma with a short latency. Finally, new cancer therapies are urgently needed to improve survival rate and quality of life for osteosarcoma patients. Several vulnerabilities in osteosarcoma are illustrated in this review to exemplify the opportunities for next generation molecularly targeted therapies. However, much work remains in order to complete our understanding of the somatic mutation basis of osteosarcoma, to develop reliable animal models of human disease, and to apply this information to guide new therapeutic approaches for reducing morbidity and mortality of this rare disease.

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Section: The Genomic Landscape Of Osteosarcomamentioning

confidence: 99%

Molecular genetics of osteosarcoma

Rickel

Fang

Tao

2017

Bone

204

179

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“…Það getur því varla útskýrt fótkulda Egils, því samfara djúpum verkjum í fótleggjum hjá Pagetssjúklingum verður aukinn húðhiti vegna aukins blóð flaeðis. 44 Þessi þráláti sjúkdómur getur einnig leitt til heyrnarleys is, blindu, erfiðleika með hreyfingu útlima vegna fergingar heila tauga auk utanhöfuðkúputaugaþrengsla. 45,46 Heyrnarskerðingu er þó óvanalegt að sjá koma fyrst fram í kringum níraeðisaldur hjá Pagetssjúklingum.…”

Section: Einkenni Egils Og Pagets-sjúkdómurinnunclassified

Visna Egils Skallagrímssonar

Einarsson

Mikkelsen

Gylfason

et al. 2019

LBL

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Egils saga gerist á landnámsöld og er talin rituð af Snorra Sturlu syni í kringum 1230. Snemma kom í ljós að Agli svipaði mjög í útliti til Gríms (Skallagríms) föður síns og fáir voru jafn stórir sem Egill. Á einum stað segir að Skallagrímur og hans útvöldu vaeru heldur líkir þursum að vexti og sýn en mennskum mönnum. Ekki hafði Egill útlitið með sér; grófgerður í andliti og dökkur yfirlit um. Tekið skal fram að sú lýsing Snorra á útliti Egils þarf ekki að benda til afbrigðilegs beinvaxtarsjúkdóms (skeletal dysplasia). Egill gerðist þunglyndur eftir að Böðvar sonur hans drukknaði. Egill lagðist þá í lokrekkju, þáði hvorki vott né þurrt, og óskaði þess einfaldlega að deyja. Þorgerður dóttir hans sagðist þá vilja deyja með honum. Hún lagðist við hlið hans í aðra rekkju og kom þar á eftir í hann baeði sölvum og mjólk. Þegar Egill var orðinn aldraður maður gerðist hann hrumur með heyrnar og sjónskerðingu. Fyrir utan þá hnignun og hreyfiskerðingu -en Egill var þungfaer, fót stirður og fótkaldur -segir sagan að hann hafi átt það til að missa jafnvaegið og hrasa. Silfur EgilsEgill var berserkur mikill, gríðarlega fégjarn og varð snemma stór auðugur. Þegar hér er komið sögu var Egill kominn á níraeðisald ur. Þá faer hann þá hugdettu (á sama tíma og menn undirbjuggu sig til þings) að halda til Þingvalla með tvaer kistur fullar af ensku silfri. Þaer silfurkistur höfðu honum áskotnast hjá Aðalsteini kon ungi eftir sigurinn á Vínheiði, ungum að árum. Faerði hann aldrei föður sínum silfrið í sonargjöld eins og konungur hafði beðið hann að gera þegar hann kaemi heim til Íslands. Þess í stað dró Egill sér silfrið og bar það með sér allar götur síðan, fram á elliár. Þá var aetlun hans undir lokin að kasta silfrinu til mannfjöldans við Lögberg og fylgjast síðan með slagsmálum manna á milli um silfrið. Þess skal getið hér að Peter Hallberg, fyrrum dósent við Háskóla Íslands og síðar prófessor í bókmenntasögu við Gauta borgarháskóla, segir í bók sinni Den isländska sagan að Egill hafi lagt á ráðin um að sá silfrinu á Alþingi sér til skemmtunar eða daegrastyttingar. 1 Vísar það í ákveðna persónuleikatruflun. Fjöl skylda Egils kom þó í veg fyrir þessa fyriraetlun hans. Þess í stað, og eftir að hafa maelt "vil ég fara til laugar," hélt hann með aðstoð tveggja þraela Gríms til laugar Mosfellinga með kisturnar tvaer. Segir sagan að hvorki þraelarnir né silfrið hafi skilað sér til baka og er kenning höfundar Egils sögu sú að Egill hafi drepið þraelana tvo. En ber þetta vott um minnisleysi Egils eða er mögulegt að þraelarnir hafi platað veikan manninn og stungið af með silfrið? Hörpuskelin hans EgilsFlestir geta verið sammála um að með hjálp bókmenntarýni, forn leifa og sagnfraeði auk laeknisfraeði sé haegt (upp að vissu marki) að varpa ljósi á ákveðið heilsufarsástand manna fyrr á öldum. Í bók sinni Hetjur og hugarvíl bendir Óttar Guðmundsson geðlaekn ir á að engin persóna Íslendingasagnanna falli að eins mörgum greiningum geðsjúkdómafraeðinnar og Egill. 2 Fleiri mismuna greiningar má vissulega nefna en þaer byggjast á túlkun texta úr Eg...

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“…They include localized pain at lesion, neurological symptoms due to deformity of vertebrae compressing on the cord or nerves, Pagetic hearing loss, high output heart failure due to extensive skeletal involvement, and hypercalcemia related to immobilization. Bisphosphonates are also recommended to be used before orthopedic intervention to the involved bone to possibly reduce blood loss 25,26…”

Section: Controversy On the Use Of Bisphosphonates In Treating Paget’mentioning

confidence: 99%

Current perspectives on bisphosphonate treatment in Paget’s disease of bone

Wat¹

2014

TCRM

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Paget’s disease of bone is a chronic metabolic bone disease with focal increase in bone turnover. The exact etiology of the disease is uncertain, although genetic and environmental factors are believed to be important. Bisphosphonate is the main class of medication being used to control disease activity via its antiresorptive effect. This review discusses the controversies concerning the use of bisphosphonates in the treatment of Paget’s disease of bone, the efficacy of different bisphosphonates in controlling disease activity, and the possible rare side effects of bisphosphonates. Symptoms are the main indication for treatment in Paget’s disease of bone. As treatment benefits in asymptomatic individuals remain controversial and nonevidence based, the decision to treat these patients should be individualized to their risk and benefit profiles. There are several trials conducted to evaluate and compare the efficacy of different regimes of bisphosphonates for treating Paget’s disease of bone. Most trials used biochemical markers rather than clinical symptoms or outcomes as parameters for comparison. Zoledronate is an attractive option as it can achieve high rates of biochemical remission and sustain long duration of suppression by a single dose. Atypical femoral fracture and osteonecrosis of the jaw are two rare and severe side effects reported, possibly related to the use of bisphosphonates in patients with osteoporosis and malignancy-induced hypercalcemia. As the regimes of bisphosphonates used for treating Paget’s disease of bone are different from those two diseases, the risks of developing these two possible side effects are expected to be very low, although this remains unknown. Vitamin D and calcium supplement should be given to patients at risk of vitamin D insufficiency when given zoledronate, as symptomatic hypocalcemia may develop. For those intolerant of bisphosphonates, subcutaneous calcitonin can be used for a limited period due to its associated risk of malignancy.

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Paget’s disease of bone: a review of epidemiology, pathophysiology and management

Cited by 74 publications

References 173 publications

Molecular genetics of osteosarcoma

Molecular genetics of osteosarcoma

Visna Egils Skallagrímssonar

Current perspectives on bisphosphonate treatment in Paget’s disease of bone

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Paget’s disease of bone: a review of epidemiology, pathophysiology and management

Cited by 74 publications

References 173 publications

Molecular genetics of osteosarcoma

Molecular genetics of osteosarcoma

Visna Egils Skallagrímssonar

Current perspectives on bisphosphonate treatment in Paget&rsquo;s disease of bone

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Current perspectives on bisphosphonate treatment in Paget’s disease of bone