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Osteoarthritis. Epidemiologic and genetic aspects.

Franklin, Jonas LU (2010) In Lund University, Faculty of Medicine Doctoral Dissertation Series 2010:71.
Abstract (Swedish)
Popular Abstract in Swedish

Syftet med denna studie var att (I) utvärdera sambandet mellan övervikt mätt med det s.k. body mass index (BMI) och operation med höftleds- eller knäledsprotes (konstgjord led) på grund av artros, (II) utvärdera sambandet mellan mekanisk belastning på grund av yrke och operation med höftleds- eller knäledsprotes på grund av artros, (III) utvärdera naturalförloppet för en person med artros i sin höft påvisad vid röntgenundersökning med hänsyn till risken för senare operation med höftledsprotes eller risken för höftfraktur, (IV) undersöka förekomsten av höftartros påvisad vid röntgenundersökning hos patienter med höftfraktur och (V) utforska och jämföra ärftlighet för operation med höftledsprotes... (More)
Popular Abstract in Swedish

Syftet med denna studie var att (I) utvärdera sambandet mellan övervikt mätt med det s.k. body mass index (BMI) och operation med höftleds- eller knäledsprotes (konstgjord led) på grund av artros, (II) utvärdera sambandet mellan mekanisk belastning på grund av yrke och operation med höftleds- eller knäledsprotes på grund av artros, (III) utvärdera naturalförloppet för en person med artros i sin höft påvisad vid röntgenundersökning med hänsyn till risken för senare operation med höftledsprotes eller risken för höftfraktur, (IV) undersöka förekomsten av höftartros påvisad vid röntgenundersökning hos patienter med höftfraktur och (V) utforska och jämföra ärftlighet för operation med höftledsprotes och höftfraktur.

Man har tidigare ansett att artros främst är orsakad av mekanisk förslitning av lederna. Vid millenniumskiftet var det dock ärftligheten av artros som fångade störst intresse i forskningsvärlden. De senaste åren har emellertid betydelsen av fysisk belastning på lederna åter uppmärksammats som orsak till artros. I Delarbete I fann vi ett starkt samband mellan övervikt (BMI 25.0–29.9 kg/m2) och risken för operation med knäledsprotes hos både män och kvinnor. Detta samband var ännu starkare för kraftigt överviktiga (BMI 30.0 kg/m2 eller mer). Sambandet var svagare för operation med höftledsprotes och detta stämmer med en nylig stor svensk studie som visade att effekten av BMI är mindre för operation med höftledsprotes än för knäledsprotes. Det finns sannolikt flera faktorer som samverkar med effekten av kroppsvikt för risk för artros. Till exempel har vinkelfelställning i knäleden en kumulativ effekt tillsammans med kroppsvikt för att öka risken för artros i knäna. Effekten kan till viss del vara mekanisk, dvs. ökad vikt ger ökad belastning på lederna, men det har också visats att vissa molekyler (cytokiner) som har sitt ursprung i fettvävnad påverkar omsättning i broskvävnad.

I Delarbete II utforskade vi sambandet mellan yrke och operation med höft- eller knäledsprotes. Vi fann ett starkt samband mellan att vara manlig lantbrukare och konstgjord led i både höft och knä. Lantbrukare var också det yrket som visade sig ha mest ärftlighet. Detta kan påverka den risk för artros som yrket i sig medför. En möjlighet är att lantbrukare, som är uppväxta på en gård, i ung ålder blir utsatta för tungt fysiskt arbete och det kan möjligen vara skadligt för lederna.

I Delarbete III följde vi en grupp individer, som hade varit på röntgenundersökning av tjocktarmen mellan 11 och 28 år tillbaka i tiden. Vi studerade röntgenbilderna av deras höfter med avseende på förekomst av artros (eftersom dessa leder är synliga på översiktsbilden av nedre delen av magen). Mest slående var att endast 17% av de som hade artros påvisad på röntgenbilderna redan vid detta undersökningstillfälle hade fått konstgjord höftled under observationstiden på upp till 28 år.

I en artikel som publicerades för fyra decennier sedan hävdades att där finns ett omvänt samband mellan artros och höftfraktur. Sedan dess har det publicerats flera artiklar som stödjer denna hypotes och andra som vederlägger den. I Delarbete IV undersökte vi förekomsten av artros påvisad vid röntgenundersökning hos patienter med höftfraktur. Risken att ha artros hos patienter med höftfraktur var en tredjedel av den som vi fann hos kontrollgruppen. Vi undersökte även förekomsten av riskfaktorer för sekundär benskörhet (orsakat av t.ex vissa läkemedel). Vi fann att hos patienter med både artros i höftleden och höftfraktur var det tre gånger mer sannolikt att hitta riskfaktor för sekundär benskörhet än hos patienter med höftfraktur, men utan höftledsartros.

Baserat på dessa fynd antog vi att det omvända sambandet mellan artros i höftleden och höftfraktur eventuellt kunde förklaras av ärftlighet. Tidigare artiklar har visat att patienter med konstgjord höftled på grund av artros är mer i släkt med varandra än befolkningen på Island i allmänhet. Hypotesen var att både operation med höftledsprotes och höftfrakturer gick i släkt, men i olika släkter. I Delarbete V utforskade vi om patienter med konstgjord höftled är mindre släkt med patienter med höftfraktur än man kan förvänta sig i bakgrundsbefolkningen. Vad vi fann var dock att patienter med höftfraktur var mer besläktade med varandra, liksom att patienter med höftprotes på grund av artros var mer släkt med varandra än befolkningen i allmänhet. Vår studie kunde dock inte bekräfta att dessa familjetyper var mindre släkt med varandra än förväntat. Vi tolkar detta resultat som att det omvända sambandet mellan höftledsartros och höftfraktur inte kan förklaras av ärftlighet.



Popular Abstract in Icelandic

Markmiðið með þessari rannsókn var að: (I) Kanna tengsl milli líkamsþyngdar mældri með s.k. „body mass index“ (BMI) og gerviliðaaðgerða í mjöðm og hné vegna slitgigtar. (II) Athuga hvort tengsl eru á milli starfsgreina og gerviliðaaðgerða í mjöðm og hné vegna slitgigtar. (III) Kanna hvernig einstaklingum með slitgigt í mjöðm samkvæmt röntgenrannsókn vegnaði með tilliti til áhættu á gerviliðaaðgerð síðar meir eða áhættu á mjaðmarbroti. (IV) Kanna tíðni slitgigtar við röntgenrannsókn hjá einstaklingum með mjaðmarbrot. (V) Bera saman erfðir slitgigtar í mjöðm sem leitt hefur til gerviliðaaðgerðar annars vegar og mjaðmarbrots hins vegar.

Áður var talið að slitgigt væri fyrst og fremst afleiðing álags á liðina eins og nafnið gefur til kynna. Um aldamótin var mestur áhugi á erfðum slitgigtar og talið að þær lægju til grundvallar í flestum tilvikum, en hin síðari ár hefur hins vegar vægi álags á liðina aftur lent í sviðsljósinu. Í grein I fundum við sterk tengsl á milli ofþyngdar (BMI 25.0–29.9 kg/m2) og hættu á að þurfa gervilið í hné, bæði hjá körlum og konum. Þessi tengsl voru enn sterkari hjá þeim sem voru mjög þungir (BMI 30.0 kg/m2 eða hærra), en tengslin voru ekki eins sterk við hættu á að þurfa gervilið í mjöðm. Líklegt má telja að það séu margir þættir, sem samhliða líkamsþyngd, geta haft áhrif á hvort einstaklingar fái slitgigt. Til dæmis hefur verið sýnt fram á að öxulskekkja í hnélið (kiðfættir og hjólbeinóttir) eykur áhrif líkamsþyngdar á slitgigt í hné. Þessi áhrif eru að hluta bein áhrif þyngdarinnar sem eykur álagið á liðinn, en einnig hefur verið sýnt fram á að efni sem upprunnin eru í fituvef hafa áhrif á niðurbrot brjósks við slitgigt.

Í grein II könnuðum við tengslin milli starfsgreinar og gerviliðaaðgerða í mjöðm og hné. Þar kom í ljós að karlkyns bændur eru í langmestri hættu á að þurfa gervilið í mjöðm eða hné. Bóndastarfið var einnig sú starfsgrein sem gekk mest í arf. Þetta getur haft áhrif á þá hættu sem bóndastarfið felur í sér. Ein hugsanleg skýring er að bændur, sem sjálfir alast upp í sveit, byrji á unga aldri í þungri líkamlegri vinnu og það geti mögulega verið skaðlegt fyrir liðina.

Í grein III fylgdum við hópi einstaklinga, sem höfðu farið í röntgenrannsókn á ristlinum, 11-28 árum áður en rannsókn okkar var gerð. Röntgenmyndir frá ristilrannsókninni voru skoðaðar en þær má nota til að meta slit í mjöðm. Það sem kom mest á óvart í þeirri rannsókn var að einungis 17% þeirra sem voru með slit í mjöðm í ristilrannsókninni fengu gervilið í mjöðmina á þessu tímabili sem einstaklingunum var fylgt eftir.

Fyrir um fjórum áratugum var birt grein þar sem því var haldið fram að einstaklingar með slit í mjöðm fengju sjaldan mjaðmarbrot og öfugt, þ.e. einstaklingar með mjaðmarbrot væru sjaldan með slit í mjöðminni. Síðan þá hefur birst fjöldi greina sem hafa ýmist stutt þetta eða andmælt þessu. Í grein IV könnuðum við tíðni slitgigtar hjá einstaklingum með mjaðmarbrot. Hættan á slitgigt var einn þriðji hjá einstaklingum með mjaðmarbrot miðað við samanburðarhópinn. Einnig var könnuð tíðni áhættuþátta á lágri beinþéttni hjá einstaklingum með mjaðmarbrot. Það kom í ljós að einstaklingar með mjaðmarbrot og slitgigt í mjöðm voru þrisvar sinnum líklegri til að hafa slíka áhættuþætti en einstaklingar með mjaðmarbrot en ekki með slit í mjöðm.

Með tilliti til lágrar tíðni slitgigtar hjá einstaklingum með mjaðmarbrot töldum við að þetta gæti hugsanlega skýrst af erfðum. Áður hefur verið sýnt fram á að einstaklingar með gervilið í mjöðm vegna slitgigtar eru náskyldari en Íslendingar almennt, m.ö.o. slitgigt sem leiðir til gerviliðaaðgerðar gengur í arf. Við vildum því athuga hvort eins væri farið með mjaðmarbrot og hvort mjaðmarbrot og slitgigt lægju í mismunandi ættum. Í grein V könnuðum við því hvort einstaklingar með gervilið í mjöðm vegna slitgigtar væru fjarskyldari einstaklingum með mjaðmarbrot en öðrum Íslendingum almennt. Niðurstaðan var sú að einstaklingar með mjaðmarbrot voru náskyldari en Íslendingar almennt og sama gilti um einstaklinga með gervilið í mjöðm vegna slitgigtar. Það var þó ekki hægt að sýna fram á að einstaklingar með mjaðmarbrot væru fjarskyldari einstaklingum með gervilið í mjöðm en öðrum Íslendingum almennt. Þetta táknar að þessi lága tíðni slitgigtar hjá einstaklingum með mjaðmarbrot skýrist ekki af erfðum. (Less)
Abstract
The purpose of this study was to (I) assess the association between body mass index (BMI) and total hip replacement (THR) and total knee replacement (TKR) due to osteoarthritis (OA), (II) assess the association between the mechanical load of work and THR and TKR due to OA, (III) evaluate the natural history of radiographic hip OA with regards to THR and hip fracture, (IV) to determine the prevalence of radiographic OA in patients with hip fracture, and (V) to examine and compare the inheritance patterns of THR for OA and hip fracture.

OA was previously regarded as a consequence of the wear and tear the joint is subjected to during one’s lifetime. At the turn of the century the genetics of OA were of high interest. In recent years... (More)
The purpose of this study was to (I) assess the association between body mass index (BMI) and total hip replacement (THR) and total knee replacement (TKR) due to osteoarthritis (OA), (II) assess the association between the mechanical load of work and THR and TKR due to OA, (III) evaluate the natural history of radiographic hip OA with regards to THR and hip fracture, (IV) to determine the prevalence of radiographic OA in patients with hip fracture, and (V) to examine and compare the inheritance patterns of THR for OA and hip fracture.

OA was previously regarded as a consequence of the wear and tear the joint is subjected to during one’s lifetime. At the turn of the century the genetics of OA were of high interest. In recent years there has been renewed interest in the effects of mechanical load on the joint. In Paper I it was found that there was a strong association between being overweight (BMI 25.0–29.9 kg/m2) and the risk for TKR for both genders. This was even stronger for obese individuals (BMI 30.0 kg/m2 or above). This association was weaker for THR and this is in agreement with another recently published study that showed that the effect of BMI is less in THR than TKR. There are probably several factors that influence the effect of body weight on the risk for OA. For example malalignment has an additive effect of body weight on the development of knee OA. The effect may to an extent be purely mechanical, i.e. the increased weight putting more strain on the joint, but it has also been shown that cytokines originating from adipose tissue have an effect on cartilage metabolism.

In Paper II the association between profession and total joint replacement in the knee and hip was explored. It was found that male farmers have greatly increased odds for total joint replacement, in both hip and knee, compared to other professions. It is not clear why farming has much greater odds for joint replacement due to OA than other physical labour professions. Farming was also the profession that showed the greatest degree of inheritance, so it is possible that it has a interacting effect. One possibility is that farmers, being raised on a farm, are exposed to heavy physical labour at a young age and it has been hypothesised that this can be detrimental for the joints. In epidemiologic studies, definition of OA can be based on a set of questions, purely radiographic grading or a clinical definition, which may be presence of a TJR or a combination of radiographic changes and clinical symptoms and signs. Previous studies have shown discrepancies between these definitions.

In Paper III a cohort of subjects that had undergone a colon radiography were followed for 11-28 years. Their radiographic hip status was registered at baseline. The most striking finding was that after 11-28 years, only 17% of those with radiographic OA at baseline had undergone THR. The individuals with radiographic hip OA that were subject to a hip fracture were so few, that no strong conclusions could be drawn based on that group.

In a publication four decades ago it was claimed that there was an inverse relationship between hip OA and hip fracture. Since then there have been publications both supporting and refuting this claim. In Paper IV the prevalence of radiographic hip OA in a cohort of patients with hip fracture was examined. The odds for having radiographic hip OA were one third in patients with hip fracture, compared to controls. The prevalence of risk factors for secondary osteoporosis was further examined and revealed that patients with hip OA and hip fracture were three times more likely to have a risk factor for secondary osteoporosis than patients with hip fracture, but without hip OA. This suggests that secondary osteoporosis needs to be accounted for and adjusted for when studying the relationship between OA and osteoporosis.

Based on these findings we hypothesised that this inverse relationship between hip OA and hip fracture might be explained by inheritance. The theory was that both THR and hip fracture run in the family, but in distinctly separate families. Previous publications have shown that patients with THR are more related to each other than the population in general. Paper V therefore examined if patients with THR were less related to patients with hip fracture than can be expected in the population. This hypothesis was found to be false. It was revealed that patients with hip fracture were more related to other patients with hip fracture, as expected, but the apparent inverse relationship between hip OA and hip fracture could not be explained by inheritance. (Less)
Please use this url to cite or link to this publication:
author
supervisor
opponent
  • Croft, Peter, Keele University, UK
organization
publishing date
type
Thesis
publication status
published
subject
keywords
body mass index, knee, hip, epidemiology, Osteoarthritis, occupation, hip fracture, inheritance, natural history
in
Lund University, Faculty of Medicine Doctoral Dissertation Series
volume
2010:71
pages
43 pages
publisher
Lund University
defense location
Föreläsningssal F1, Centralblocket, Skånes Universitetssjukhus i Lund
defense date
2010-06-11 09:15
ISSN
1652-8220
ISBN
978-91-86443-87-0
language
English
LU publication?
yes
id
42f7eada-8c08-45f3-8caf-ccb7660604f2 (old id 1604118)
date added to LUP
2010-05-19 08:56:24
date last changed
2018-05-29 11:49:15
@phdthesis{42f7eada-8c08-45f3-8caf-ccb7660604f2,
  abstract     = {The purpose of this study was to (I) assess the association between body mass index (BMI) and total hip replacement (THR) and total knee replacement (TKR) due to osteoarthritis (OA), (II) assess the association between the mechanical load of work and THR and TKR due to OA, (III) evaluate the natural history of radiographic hip OA with regards to THR and hip fracture, (IV) to determine the prevalence of radiographic OA in patients with hip fracture, and (V) to examine and compare the inheritance patterns of THR for OA and hip fracture. <br/><br>
OA was previously regarded as a consequence of the wear and tear the joint is subjected to during one’s lifetime. At the turn of the century the genetics of OA were of high interest. In recent years there has been renewed interest in the effects of mechanical load on the joint. In Paper I it was found that there was a strong association between being overweight (BMI 25.0–29.9 kg/m2) and the risk for TKR for both genders. This was even stronger for obese individuals (BMI 30.0 kg/m2 or above). This association was weaker for THR and this is in agreement with another recently published study that showed that the effect of BMI is less in THR than TKR. There are probably several factors that influence the effect of body weight on the risk for OA. For example malalignment has an additive effect of body weight on the development of knee OA. The effect may to an extent be purely mechanical, i.e. the increased weight putting more strain on the joint, but it has also been shown that cytokines originating from adipose tissue have an effect on cartilage metabolism. <br/><br>
In Paper II the association between profession and total joint replacement in the knee and hip was explored. It was found that male farmers have greatly increased odds for total joint replacement, in both hip and knee, compared to other professions. It is not clear why farming has much greater odds for joint replacement due to OA than other physical labour professions. Farming was also the profession that showed the greatest degree of inheritance, so it is possible that it has a interacting effect. One possibility is that farmers, being raised on a farm, are exposed to heavy physical labour at a young age and it has been hypothesised that this can be detrimental for the joints. In epidemiologic studies, definition of OA can be based on a set of questions, purely radiographic grading or a clinical definition, which may be presence of a TJR or a combination of radiographic changes and clinical symptoms and signs. Previous studies have shown discrepancies between these definitions. <br/><br>
In Paper III a cohort of subjects that had undergone a colon radiography were followed for 11-28 years. Their radiographic hip status was registered at baseline. The most striking finding was that after 11-28 years, only 17% of those with radiographic OA at baseline had undergone THR. The individuals with radiographic hip OA that were subject to a hip fracture were so few, that no strong conclusions could be drawn based on that group. <br/><br>
In a publication four decades ago it was claimed that there was an inverse relationship between hip OA and hip fracture. Since then there have been publications both supporting and refuting this claim. In Paper IV the prevalence of radiographic hip OA in a cohort of patients with hip fracture was examined. The odds for having radiographic hip OA were one third in patients with hip fracture, compared to controls. The prevalence of risk factors for secondary osteoporosis was further examined and revealed that patients with hip OA and hip fracture were three times more likely to have a risk factor for secondary osteoporosis than patients with hip fracture, but without hip OA. This suggests that secondary osteoporosis needs to be accounted for and adjusted for when studying the relationship between OA and osteoporosis. <br/><br>
Based on these findings we hypothesised that this inverse relationship between hip OA and hip fracture might be explained by inheritance. The theory was that both THR and hip fracture run in the family, but in distinctly separate families. Previous publications have shown that patients with THR are more related to each other than the population in general. Paper V therefore examined if patients with THR were less related to patients with hip fracture than can be expected in the population. This hypothesis was found to be false. It was revealed that patients with hip fracture were more related to other patients with hip fracture, as expected, but the apparent inverse relationship between hip OA and hip fracture could not be explained by inheritance.},
  author       = {Franklin, Jonas},
  isbn         = {978-91-86443-87-0},
  issn         = {1652-8220},
  keyword      = {body mass index,knee,hip,epidemiology,Osteoarthritis,occupation,hip fracture,inheritance,natural history},
  language     = {eng},
  pages        = {43},
  publisher    = {Lund University},
  school       = {Lund University},
  series       = {Lund University, Faculty of Medicine Doctoral Dissertation Series},
  title        = {Osteoarthritis. Epidemiologic and genetic aspects.},
  volume       = {2010:71},
  year         = {2010},
}