The Funen County Hip Fracture Study

Transcription

1 Ph.D thesis The Funen County Hip Fracture Study Incidence, recurrence, mortality, and projection Tine Nymark Department of Orthopaedics Odense University Hospital Institute of Clinical Research Faculty of Health Sciences University of Southern Denmark 2008

2

3 Contents Contents...1 List of abbreviations...3 English summary...4 Danish summary (dansk resumé)...7 Supervisors Preface Acknowledgement List of papers Background Hip fracture incidence Previous studies on hip fracture incidence Danish studies International studies Studies on accuracy of medical records Summary of previous studies on hip fracture incidence The second hip fracture Previous studies on subsequent hip fracture Danish studies International studies Summary of previous studies on the second hip fracture Hip fracture mortality Previous studies on hip fracture mortality Danish studies International studies Summary of previous studies on hip fracture mortality Projection of hip fractures Previous studies on the projection of hip fractures Danish studies International studies Summary of previous studies on the projection of hip fractures Literature search Aim of thesis Material and Method Demography and area The Danish Office of Civil Registration The Funen County The orthopaedic departments on Funen Data sources and establishment of the updated hip fracture register The Funen County Hip Fracture Register (HFR) The Hospital Patient Administrative System (PAS) Overview of the complete process of the data validation procedure Merging HFR and PAS to the updated hip fracture register for Funen County, (uhfr) The four studies Study 1 Hip fracture incidence in Funen County

4 6.3.2 Study 2 Second hip fracture: Study 3 Mortality rates Study 4: Demographic Projection of hip fractures Results Study 1: Hip fracture incidence (summary of paper I) Study 2: Second hip fracture (summary of paper II) Study 3: Mortality (summary of paper III) Analysis based on hip fracture cases and non-fracture controls Analysis of effect of control selection on mortality rates among controls Study 4: Demographic projection (summary), paper IV Model 1: decreasing trend Model 2: constant incidence rate Discussion of results Selection bias - Considerations of estimating hip fracture incidence rate based on ascertainment level Comparison with the previous study from Funen County from Comparison with other studies Ascertainment of hip fracture sequence High mortality following hip fracture Predicting the future number of hip fractures Conclusions and perspectives Conclusions Perspectives Incidence The second hip fracture Mortality Projection References Papers I-IV Appendix

5 List of abbreviations SAHFE HFR PAS uhfr ICD-8/ICD-10 NOMESCO NPR CPR UAG OUH SDU WHO CI PY Standardised Audit of Hip Fractures in Europe Funen County Hip Fracture Register Hospital Patient Administrative System Complete, validated and updated HFR International Classification of Diseases Nordic Medico Statistical Committee National Patient Registry Danish Civil Person Registration Number Accident Analysis Group Odense University Hospital University of Southern Denmark World Health Organisation Confidence Interval Person Years 3

6 English summary Introduction: This thesis is based on 4 studies conducted in cooperation with the Accident Analysis Group at Odense University Hospital, the Department of Orthopaedics at Odense University Hospital, and the Institute of Clinical Research at the Faculty of Health Sciences at University of Southern Denmark. Aim: The aims of the thesis were to 1: estimate the incidence rate of hip fractures in Funen County 2: estimate the frequency and risk of a second hip fracture 3: estimate mortality following a hip fracture with comparison to a frequency matched population group 4: estimate the future number of hip fractures Material and method: For the period 1994 to 2005 the Funen County Hip Fracture Register was validated and completed through a thorough validation procedure combining the already existing Register with hip fracture records from the National Health Register. In the validation procedure diagnoses and surgical codes if any were used. Additionally, the period from 1975 until the 1994 was checked for previous fractures in order to correctly sequence several fractures within the same patient. For the estimation of hip fracture incidence rate, the number of hip fractures at three levels of ascertainment was used. All hip fractures based on the number retrieved from the national health register, all hip fractures included in the completed hip fracture register and all first hip fractures included in the completed hip fracture register. Based on January 1 st population counts age and sex specific annual incidence rates were estimated and Poisson regression was used to analyse changes within the study period. For the estimation of second hip fractures all hip fractures in the completed hip fracture register were included. The population at risk was hip fracture patients, who came at risk on the date of their 4

7 first fracture. All were followed to death or the end of the study period. Failure occurred on the date of a second hip fracture. Poisson regression was used in the estimation of time and age stratified incidence rate developments of the second hip fracture during the study period. Poisson regression analysis was used to estimate the changes in the incidence rate of second hip fracture over time following the first hip fracture. In the estimation of mortality all patients from the hip fracture register came at risk at the time of the first hip fracture and then followed until death or end of study period. The mortality rate was then compared to a population based control who were randomly selected based on the population registry for Funen for the whole study period. To allow for frequency matching on age and sex eligible control subjects were assigned a random date within the study period as their index date. For each combination of age and sex four controls were selected per case, but for the ages 80+ scarcity of persons in the population resulted in fewer than four eligible persons per case. Kaplan Meier analysis principles were used for time estimates of survival among cases and population-based controls based on exact dates of death and tabulated at fixed time points. To test for differences in survival log rank test and Cox regression analysis was applied. Based on the estimations of the first hip fracture incidence in the study period, as well as Statistics Denmark s projection of the Funen County population until 2040, the future number of primary hip fractures was predicted. Two models were designed. Model one assumed a continued decreasing incidence rate of the first hip fracture as seen throughout the study period, whereas model two assumed a constant incidence rate of the first hip fracture. Results: For the period 1996 through 2003 a decreasing trend in the incidence of the first hip fracture was found. Based on Poisson regression the incidence rate of the first hip fracture decreased significantly during the period, in men by 2.4% per year (p=0.017) from 3.4/1,000 person years (95% CI: ) to 2.5 ( ). For women by 1.8% per year (p=0.004) from 7.5 ( ) to 6.5 ( ). The overall incidence rate of sustaining a second hip fracture was 2.37 per 1,000 person years (py) in men and 2.93 per 1,000 py in women. Adjusted estimates of the incidence rate by age group at 5

8 the first fracture showed no difference between men and women. In both sexes, the rate increased with age. Adjusted for age group, the incidence rate of the second fracture was excessively high during the first twelve months following the first hip fracture. The median time from first to second hip fracture was 12 months in men and 19 months in women. The overall mortality rate was significantly higher among cases; males 297 per 1,000 person years (py) (95% CI ) and females 192 per 1000 py (95% CI ) compared to population based non-fracture controls; males 98 per 1,000 py (95% CI ) and females 81 per 1,000 py (95% CI 79-83). Males sustaining a hip fracture had a three times higher overall mortality compared to the population based non-fracture controls, whereas females had two times higher overall mortality. The 30 days and 12 months cumulative mortality remained the same throughout the study period. In the projection of model one the decreasing trend in sex and age specific incidence rates would result in an overall increase in the number of primary hip fractures from 826 fractures in 2005 to 1,016 fractures in If however model two was assumed (constant incidence rate) the number of primary hip fractures would increase from 826 to in Conclusions: A significant decrease in the incidence of the first hip fracture was seen in the period 1996 through The number of patients who sustain a second hip fracture was low, less than 10 %. The median time from first to second hip fracture was 12 months in men and 19 months in women. Mortality following the first hip fracture was high compared to the population controls. The median survival following the first hip fracture was 1.9 years in men and 3.7 years in women. Despite the decreasing trend in the incidence of the first hip fracture, the future number of primary hip fractures is expected to increase due to the much larger increases in the elderly population. 6

9 Danish summary (dansk resumé) Introduktion: Denne PhD afhandling er udført i samarbejde med Ulykkes Analyse Gruppen ved Odense Universitets Hospital, Ortopædkirurgisk afdeling ved Odense Universitets Hospital samt Klinisk Institut ved det Sundhedsvidenskabelige Fakultet ved Syddansk Universitet. Formålet var at: 1: beskrive udviklingen i forekomsten af hoftenære frakturer i Fyns Amt. 2: estimere forekomsten af og risikoen for at få hoftefraktur nr 2. 3: estimere dødelighed efter en hoftenær fraktur sammenlignet med en køns og alders matchet befolkningsgruppe fra Fyns Amt. 4: estimere det fremtidige antal af hoftefrakturer. Materiale og metode: For perioden 1994 til og med 2005 er det Fynske Hoftefraktur Register blev valideret og kompletteret ved en grundig validerings metode med udtræk fra Landspatientregisteret (LPR) kombineret med udtræk fra registeret. I udtrækket fra LPR blev anvendt både diagnose og operationskoder. Ligeledes er perioden 1975 til og med 1994 undersøgt for forudgående hoftenære frakturer hos patienter allerede inkluderet i det Fynske Hoftefraktur Register, med henblik på at identificere frakturrækkefølgen hos den enkelte. Antallet af hoftenære frakturer blev bestemt på tre niveauer for at beskrive forekomsten. Alle frakturer udtrukket på basis af diagnoser fra LPR, alle frakturer verificeret i det Fynske Hoftefraktur Register, samt alle primære hoftenære frakturer i det Fynske Hoftefraktur Register. Baseret på befolkningstal for Fyns Amt blev årlige alders- og køns specifikke incidens rater for hoftenære frakturer beregnet og ændringer i årlige incidens rater blev evalueret ved hjælp af Poisson regression. I estimeringen af fraktur nr. to blev alle hoftenære frakturer fra det Fynske Hoftefraktur Register inkluderet. Risikopopulationen var patienter med den første hoftenære fraktur. Alle blev fulgt til død eller afslutningen af studiet. I tilfælde af fraktur nr 2 blev patienten bortcensureret. Udviklingen 7

10 i tid og aldersstratificeret incidens blev estimeret ved hjælp af Poisson regression, på samme måde som ændringen over tid efter den første hoftefraktur blev estimeret. Alle patienter blev inkluderet i mortalitetsberegningerne på tidspunktet for deres første hoftefraktur og fulgt frem til død eller afslutningen af studiet. Dødeligheden blev sammenlignet med en tilfældig udtrukket befolknings gruppe fra Fyns Amt. Denne var frekvens matchet på køn og alder og kontrollerne blev herefter tildelt en tilfældig dato i studieperioden som index dato. Der blev udtrukket fire kontroller per case, dog færre i aldersgrupperne over 80, da der ikke var nok tilgængelige kontroller. Kaplan Meier overlevelsesanalyse blev gennemført for overlevelse blandt cases og de befolkningsbaserede kontroller, baseret på den nøjagtige dødsdato og efterfølgende tabuleret ved specifikke tidsintervaller. Forskelle overlevelse blev testet med log rank test og Cox regressions analyse. Ud fra incidens beregningerne i studieperioden, samt Danmarks Statistiks befolkningsprojektion frem til 2040, blev det fremtidige antal af primære hoftefrakturer forsøgt beregnet. To modeller blev designet. Beregningen i model ét var baseret på en forsat faldende incidens, mens model to var baseret på en konstant incidensrate for den primære hoftefraktur. Resultater: I perioden 1996 til og med 2003 fandtes en faldende forekomst antallet af primære hoftenære frakturer. Baseret på Poisson regression var faldet signifikant i perioden, hos mænd med 2.4% om året (p=0.017) fra 3.4/1,000 person år (95% CI: ) til 2.5 ( ). Og hos kvinder med 1.8% om året (p=0.004) fra 7.5 ( ) til 6.5 ( ). Den samlede forekomst af fraktur nr to var 2.37 per 1,000 person år hos mænd og 2.93 per 1,000 person år hos kvinder. Justeret for alder fandtes ingen køns specifikke forskelle. Hos både mænd og kvinder steg forekomsten med stigende alder. Justeret for alder var forekomsten meget høj inden for de første 12 måneder. Median tiden fra første til anden hoftenære fraktur var 12 måneder hos mænd og 19 måneder hos kvinder. Den samlede dødelighed var signifikant højere hos hoftefrakturpatienten; mænd 297 per 1,000 person år (95% CI ) og kvinder 192 per 1000 person år (95% CI ) sammenlignet med 8

11 kontrolgruppen; mænd 98 per 1,000 person år (95% CI ) og kvinder 81 per 1,000 person år (95% CI 79-83). Efter en hoftenær fraktur havde mænd samlet set tre gange højere dødelighed end mænd fra kontrolgruppen, kvinder havde to gange højere dødelighed. Den kumulative dødelighed efter 30 dage og 12 måneder forblev uændret igennem perioden. Ved fremskrivningen af model ét resulterede den faldende tendens i den køns og alders specifikke incidens i en forventet stigning i antallet af primære hoftenære frakturer fra 826 frakturer til 1,016 frakturer i I model to medførte den konstante incidens rate en stigning fra 826 frakturer til frakturer i Konklusioner: Der fandtes et signifikant fald i antallet af primære hoftenære frakturer i perioden fra 1996 til og med Antallet af patienter der pådrog sig hoftefraktur nr to var lavt, mindre end 10%. Median tiden fra første til anden hoftefraktur var 12 måneder hos mænd og 19 måneder hos kvinder. Dødeligheden efter den første hoftenære fraktur var høj sammenlignet med kontroller. Median overlevelsen efter den første hoftenære fraktur fra 1.9 år hos mænd og 3.7 år hos kvinder. På trods af faldet i forekomsten af hoftenære frakturer, kan der forventes en stigning i fremtiden på grund af den hastigt voksende ældre befolkningsgruppe. 9

12 Supervisors Ole Ovesen, associate professor, senior consultant. Department of Orthopaedics, Odense University Hospital, Denmark Jens M. Lauritsen, associate professor, senior consultant. Department of Orthopaedics, Odense University Hospital, Denmark Statistics, Institute of Public Health, University of Southern Denmark, Denmark Niels Dieter Röck, senior consultant, head of department of Orthopaedics. Department of Orthopaedics, Odense University Hospital, Denmark Bernard Jeune, associate professor, Epidemiology, Institute of Public Health, University of Southern Denmark, Denmark 10

13 1 Preface My interest in hip fractures was started in medical school, where I during a summer holiday in 1997 worked at a local hospital. The orthopaedic surgeon whom I assisted at the osteosyntesis of a pertrochanteric fracture suddenly handed me the drill and told me to position the drill hole. That was my first encounter with a hip fracture. In my final year in medical school I was introduced to the validation of diagnoses as well as setting up a small research project. I performed a validation study on the accuracy of diagnoses and surgical procedure codes in relation to the DRG-values which resulted in the publication of my first original article. My interest into the epidemiology of elderly people was laid during a six month rotation at the department of geriatrics. The foundation for this thesis was laid in the spring of Senior consultant at the department of Orthopaedics at Odense University Hospital Ole Ovesen created the basic idea behind this thesis together with the head of the department of Orthopaedics Niels Dieter Röck, who had been one of the initiators of the register. They encouraged me to take on this PhDproject. The Funen County Hip Fracture Register had then existed in 5 years and it was believed that the data would be sufficient enough to support a PhD thesis. The University of Southern Denmark approved the study as a PhDstudy by March 2003 It is my hope that this thesis will lead to a better understanding of the importance of validated clinical databases. This thesis shows clearly that national health data should be analysed with caution. Furthermore, I hope that the thesis will give new and further insight into the epidemiology of hip fractures. Not only as an overall figure, but also insight into the importance of being able to clearly distinguish among first and second hip fractures. It is important to be aware of the sequence of fractures when estimating not only incidence rates, but also when discussion mortality following a hip fracture. Is a patient with two fractures included as two separate units, and what time unit is included into the period of risk? Odense 2008 Tine Nymark 11

14 2 Acknowledgement I am grateful to many people for their contributions. My thanks go to: - My main supervisor, senior consultant Ole Ovesen at the department of Orthopaedics, Odense University Hospital, for his constant interest and safe guidance. For his ability to manoeuvre the epidemiologic discussions back on track and to clarify texts. - My second main supervisor, associate professor and senior consultant Jens Martin Lauritsen at the Accident Analysis Group at the department of Orthopaedics, Odense University Hospital, for his never ending interest and capability of guidance regarding the analytical processes. For his constant encouragement and safe guidance throughout the many pitfalls of a research project. - My co-supervisor, senior consultant Niels Dieter Röck, at the department of Orthopaedics, Odense University Hospital, for ideas regarding the outline of the project and insight into the administrative implications of my findings. - My co-supervisor, associate professor Bernard Jeune, at Epidemiology, Institute of Public Health, University of Southern Denmark, for his overwhelming insight into the epidemiology of elderly people. For his ability to clarify texts. - The hospital medical director, Peter Frandsen, at Odense University Hospital for granting me access to his original data from his thesis regarding hip fractures in Funen County. - Doctors employed at orthopaedic departments in Funen County for filling out the Funen County Hip Fracture Register questionnaire throughout the years. - The dedicated secretaries at the orthopaedic departments in Funen County for entering the data into a computerised database. 12

15 - Secretary Birte Landorph, at the Accident Analysis Group, who meticulously kept track of the hip fracture patients. - The staff at the Accident Analysis Group, secretary Marianne Fur-Poulsen and programmer Anni Ellegard-Hansen, who were exceptionally helpful throughout my study. - Statistician Jacob Hjelmborg, department of Statistics, University of Southern Denmark, for statistical aid with the projection analyses. - The institute of Clinical Research at University of Southern Denmark. - My family, especially Henrik and Thor, for their love, support, patience and interest. - Funen County, The Guildal Foundation and the Danish Orthopaedic Society Foundation for financial support. 13

16 3 List of papers The thesis is based on the following papers that will be referred to in the text by their Roman numerals. I. Nymark T, Lauritsen JM, Ovesen O, Röck ND, Jeune B. Decreasing incidence of hip fracture in the Funen County Denmark. Acta Orthopaedica, 2006, 77(1) II. Nymark T, Lauritsen JM, Ovesen O, Röck ND, Jeune B. Short time frame from first to second hip fracture in the Funen County Hip Fracture Study. Osteoporosis International, 2006, 17: III. Nymark T, Lauritsen JM, Ovesen O, Röck ND, Jeune B. Ten year follow-up mortality estimates in hip fracture patients remains high compared to age- and sex matched population based controls. In review Age and Ageing IV. Nymark T, Lauritsen JM, Hjelmborg J, Ovesen O, Röck ND, Jeune B. Demografic projection of the future proportions of hip fractures in Funen. Manuscript 14

17 4 Background 4.1 Hip fracture incidence In Denmark a hip fracture is the most frequent admission diagnosis among the elderly. Despite accelerated focused clinical pathway programmes hip fracture is the diagnosis ranking highest on total number of in-patient days. The burden may increase as the number of 65+ year old people is expected to increase rapidly over the coming decades. The estimation of hip fracture incidence rates relies on the practice of counting hip fractures. There are no standards on how to count. Some studies rely on national health registers including all hip fracture diagnoses; others rely on specific registers including all incident hip fractures. A few distinguish between the first and the second hip fracture. 4.2 Previous studies on hip fracture incidence For simplicity Figure 4-1 summarises the changes in incidence rates found in the literature. Only studies with specific year and incidence rates are included. Each line represents the rates from a specific paper, referred to by name, gender and country, ie. Frandsen, male, DK Danish studies In the period from 1973 to 1979, Frandsen et al [1] found an increasing number of hip fractures in Funen County. The annual number of fractures increased from 436 to 603. The period included all hip fractures, verified by x-ray, occurring in patients aged 40 and older, N=3,069. This resulted in an overall hip fracture incidence rate in Funen County increasing from 1.18 to 1.60 per 1,000 person years (py) in men and 3.35 to 4.51 per 1,000 py in women. The female age specific incidence rate was approximately twice as high as for males (five year age groups). In Århus municipality, Schroder et al [2] found that the number of fractures tripled from 134 hip fractures in 1970 to 390 in Within the period the incidence rate increased from 0.9 to 2.1 per 15

18 1,000 py in men and 2.1 to 5.4 per 1,000 py in women. The female age specific incidence rate was twice as high as for males (ten year age groups). From 1976 to 1988 the incidence of hip fractures in Aalborg increased from 3.31 per 1,000 py (men 1.88, women 4.51) to 7.15 per 1,000 py (men 3.51, women 10.06) [3] based on patients admitted to hospital with a hip fracture diagnosis. From 1986 to 1991 all patients from the county of Southern Jutland [4] who were discharged with a hip fracture diagnosis were registered. In men the overall incidence rate increased from 2.95 per 1,000 py in 1986 to 3.10 per 1,000 py in 1991, in women it increased from 9.20 per 1,000 py to 9.80 per 1,000 py. Based on data from NPR a recent study from Viborg County covering the period from 1987 to 1997 Giversen [5] found the age adjusted incidence rate of the first hip fracture in men had increased from 1.27 per 1,000 py (95% CI ) to 2.95 per 1,000 py ( ). In women the age adjusted rate increased from 4.06 per 1,000 py ( ) to 5.72 per 1,000 py ( ) International studies As most studies on hip fracture incidence rates originate from Scandinavia, focus has been on these. The development in hip fracture incidence rates resembles that seen in Denmark. In 1989 Falch et al [6] compared the incidence rate of all new hip fractures from seven urban populations departments throughout Scandinavia. The incidence rate was highest among women in all cities and for both sexes an increase with age was found. They found significant differences in the incidence of hip fractures between the cities. From Sweden several studies[7-13] have reported on the incidence rate of hip fractures. In a large study from Stockholm, Sweden Hedlund et al [7], included 20,583 first admissions for hip fractures in a 10 year period from 1972 to They found a nearly constant increasing rate, exponentially increasing with age for both men and women. The incidence rate doubled every 7 to 7.8 year in men and every 5.6 years in women. 16

19 Based on the first recorded admission with a hip fracture Naessen et al [8] included patients from 1965 to 1983 in the Uppsala Health Care Region. Per year the number of admissions for first hip fracture increased by 2.9 % in men and 1.1 % in women. In the age group a decrease was seen in women. During the period 1940 to 1986 Nilsson et al [9] found an increase of 500 per cent in the number of hip fractures among people aged 50 and older in Östergötland. The overall incidence rate tripled during the period in both males and females. In Uppsala Nungu et al [10] included all hip fractures from 1980 to 1991 and confirmed the decreasing tendency of hip fracture incidence in women younger than 85 which was also seen by Naessen et al [8] From Malmö Gullberg et al [11] included all hip fracture patients based on x-ray registration rather than a discharge register. In men the overall incidence rate increased from 0.76 per 1,000 py in 1950 to 3.87 per 1,000 py in 1991, whereas the rate in women increased from 3.21 per 1,000 py to 9.11 per 1,000. The increase in age specific incidence rate was more pronounced in men than in women. Rogmark et al[12] continued the study from Malmö to include all patients 50 years and older with hip fracture in the years 1992 to The overall incidence rate was 3.6 per 1,000 py in men and 8.5 per 1,000 py in women. Compared to the previous period from Malmö reported by Gullberg et al [11] a trend-break was seen as no increase was found in the hip fracture incidence rate. The hip fracture incidence rate was estimated for the period 1992 to 1997 among 65+years for the city of Malmö and a rural area in the south of Sweden by Billsten et al [13]. The overall incidence rate for the period in Malmö was 0.69 per 1,000 py in men and 1.38 per 1,000 py in women. The corresponding rates from the rural area were 0.62 per 1,000 py in men and 1.25 per 1,000 py in women. Women from the rural area had a significantly lower rate compared to women from Malmö. Four Norwegian studies[14-17] compared the differences in hip fracture incidence with previous reports as well as between cities and rural areas. 17

20 In the study by Falch et al [14] all new hip fractures in a two year period from 1988 to 1989 were included. Differences in hip fracture incidence rate between Oslo and the rural county of Sogn og Fjordane was found. In Oslo the incidence rate of femoral neck and intertrochanteric fracture per 1,000 py was 1.05 and 0.71 in men and 3.22 and 2.31 in women, whereas the rate for the rural county was 1.05 and 1.01 in men and 2.15 and 1.38 in women respectively. Both in Oslo and in the rural county, the same pattern of a sex and age dependent increase in hip fracture incidence was found. In Oslo an increase in the sex and age specific incidence rate was found compared to a previous report from 1978/1979 by Falch et al [17]. For the year 1989 Kaastad et al [15] compared hip fracture incidence rate within six defined areas of Oslo and the rural county of Sogn og Fjordane by including all new hip fractures occurring in residents of the defined areas 50 years and older. The overall hip fracture incidence rate for Oslo was 4.6 in men and 11.2 in women per 1,000 py, and for Sogn og Fjordane 3.8 in men and 7.7 in women per 1,000 py. The eastern parts of Oslo had higher sex and age specific hip fracture incidence rates compared to the western parts. All of the areas within Oslo had higher incidences compared to the rural county. Finsen et al [16] compared hip fracture incidence rates from 1972/1973 and 1983/1984 to 1992/1993 and 1997/1998 from central Norway. An overall increase of 80% in the number of fractures was seen between the first two periods, 18% within the following two, and a 10% increase in the overall number of fractures were seen from 1992/1993 to 1997/1998. However the incidence rates only increased significantly from 1972/1973 to 1983/1984. Four studies from Finland [18-21] reported on hip fracture incidence rates from the catchment area of one central hospital as well as all of Finland. Huusko et al [18] included all new hip fracture patients admitted to one central hospital in the central part of Finland in 1982/1983 and 1992/1993. During the ten year period the total number of hip fractures increased by 11%. In 1982/1983 the overall hip fracture incidence rate was 1.8 per 1,000 py (95% CI ) in men and 3.8 per py ( ) in women. By 1992/1993 this had increased to 2.0 per 1,000 py ( ) in men and 3.9 per 1,000 py ( ) in women. No significant increase was found in any age group. 18

21 Lonnroos et al [19] continued the study above to cover the years 2002 and The overall hip fracture incidence rate in men was 2.14 per 1,000 py (95% CI ) and in women 4.49 per 1,000 py ( ). Even though the overall incidence rate did not increase a significant increase was seen in the oldest age groups. The total number of hip fractures increased from 351 in 1992/1993 to 597 in 2002/2003. In the period from 1970 to 1997 Kannus et al [20] included all patients 50 years and older who were admitted to a hospital for the primary treatment of a hip fracture. From 1970 to 1997 the total number of hip fractures increased by 10.5% per year, from 1,857 to 7,122. This resulted in an increase in the overall incidence from 1.63 to 4.38 per 1,000 py. The age adjusted incidence rate increased from 1.12 to 2.33 per 1,000 py in men and from 2.92 to 4.67 per 1,000 py in women. In women as well as men the age specific incidence rate rose in all age groups throughout the study period. Kannus et al [21] concluded in a recent study that the alarming rise in hip fracture incidence had levelled off in 50+ year old Finns. The overall incidence rate declined from 4.38 per 1,000 py in 1997 to 3.74 per 1,000 py in The age adjusted incidence in men had declined to 2.23 per 1,000 py and 4.12 per 1,000 py in women. In a 65 year study covering the period 1928 to 1992 from Rochester, Minnesota Melton et al [22]found a steady increasing trend in the hip fracture incidence in men from 1928 to 1980, and in women from 1928 to Then declining incidence rates were seen. They found that the mean age at the first fracture increased by 13.7 years during the study period. 19

22 Figure 4-1: The changes in incidence rates based on findings in previous studies see section 4.2 for detail Incidence per 1,000 py Gullberg men S Gullberg women S Schroder men DK Schroder women DK Kannus men F Kannus women F Frandsen men DK Frandsen women DK Rasmussen men DK Rasmussen women DK Huusko - Lonross men F Huusko - Lonroos women F Laursen men DK Laursen women DK Giversen men DK Giversen women DK Rogmark men S Rogmark women S Nymark men DK Nymark women DK Kannus overall F Year

23 4.2.3 Studies on accuracy of medical records In a Swedish study from 1989 Carl Zetterberg pointed out [23] the pitfalls of relying on only one source of data when carrying out epidemiological studies. Comparing ICD-8 codes of hip fracture (ICD 820,xx) to a manually validated register based on surgical logbooks and radiographs he found an overestimation of hip fractures of more than 100%. In a study from Baltimore in 1990 and 1991 regarding accuracy of medical records in hip fracture patients, Fox et al [24] included 151 verified hip fracture patients 65 years and older. Discrepancy was found between the final diagnoses on the hospital facesheet and the diagnoses found in the entire medical record (12%), as well as between the abstracted surgical procedure and radiographs where 15% of the patients who received a hemiarthroplasty were coded with a total hip arthroplasty. Furthermore postoperative complications were noted in the chart but not carried on to the facesheet in 17%. Thus, patients appear healthier, but may still have a poor outcome. In a study from New Zealand, Langley et al [25] pointed out the importance of considering the biases in estimating incidence rates when an admission period crossed the reference period. A Norwegian study, Lofthus et al [26] found discrepancies in the number of hip fracture patients in three local electronic discharge registers compared to a defined golden standard (review of medical records) of verifying hip fracture patients. One register underestimated 46% (95% CI -56 to -37), whereas the two other overestimated 19% (95% CI 10-28) and 17% (95% 8-26) the number of patients. The national register overestimated the number by 19% (95% CI 13-24). From New Zealand two studies [27;28] involving the same patient foundation resulted in two different estimates based on the definition of case selection. Fielden et al [27] included patients 65 years and older admitted with a diagnosis of femoral neck fracture. They found a significantly (p<0.002) declining age specific incidence rate in women in the period 1989 to In men a constant rate was seen during the period. Stephenson et al [28] re-examined the population paying particular attention to the case selection, thereby excluding 28 % due to readmissions or day patients. This resulted in a lower estimate of the incidence per year but a stronger upward trend over the period than found by Fielden et al [27]. 21

24 4.3 Summary of previous studies on hip fracture incidence Worldwide there has been a significant rise in overall as well as age-standardised hip fracture incidence during the second half of the 20th century, the rise has been most pronounced in Northern and Western Europe. The highest incidence rates have also been found in Northern and Western Europe. At the end of the last century a few reports have shown a trend break as the incidence rates started to decrease. 4.4 The second hip fracture Previous studies on subsequent hip fracture Prior to the first hip fracture, falls among elderly are frequent [29]. A Cochrane review indicates Interventions to prevent falls that are likely to be effective are now available; less is known about their effectiveness in preventing fall-related injury. Even upon presentation with a fall-related injury to the emergency department, falls assessment is not implemented [30;31]. In addition, only a limited number of hip fracture patients receive preventive fracture treatment [32]. In most cases no or insufficient preventive treatment is offered after the first fracture [33;34] Danish studies During a 16 year period Schroder et al [35] found 256 (6.2%) second hip fractures in 3,898 patients in the Århus municipality. The mean interval from the first to the second hip fracture was 3.3 years (range five days to 14 years). Twenty percent occurred within the first twelve months and 55% within three years. They found an incidence of the first fracture of 1.6 per 1,000 py in men and 3.6 per 1,000 py in women, whereas the incidence of the second hip fracture was 15 per 1,000 py in men and 22 per 1,000 py in women International studies From Trondheim, Norway Finsen et al [36] studied patients 50 years and older admitted with a fracture during a 25 months period. Patients were asked if they had suffered a previous hip fracture, which 151 reported they had. Of these 151 patients 76 were admitted with a second hip fracture. 22

25 The mean interval from first to second hip fracture was 7 years (SD 8). In a survey from 1943 to 1977 from Rochester, Minnesota, Melton et al [37] included 1,145 hip fracture patients of whom 106 subsequently suffered a second hip fracture (femoral neck and intertrochanteric fractures). During a five year period Chiu et al [38] found 35 (2.3%) subsequent hip fractures in hip fracture patients. The mean time from first to second was 23.9 months (range 1 to 60). During an eight year follow up period Wolinsky et al [39] found 7.3% with a second hip fracture in 368 hip fracture patients. Dretakis et al [40] identified 106 second hip fractures in 1685 hip fracture patients during a follow up of 4 years. They found that older patients sustained the second hip fracture in shorter time and that the occurrence rate of the second hip fracture increased by 3% by every one more year of age at the first hip fracture. Weatherall et al [41] included 462 hip fracture patients during a three year period in New Zealand. Within two years 11 patients suffered a second hip fracture. The mean time from first to second hip fracture was 372 days (median 368, range 67 to 651 days). The overall incidence of suffering a second hip fracture was 2.38 % (95% CI ) In a retrospective study by Shabat et al [42] 84 patients, who had sustained the second hip fracture within a period of 22 months, were included. They reported a frequency of second hip fracture of 9.5%, as 802 patients were admitted with the first fracture within the same period of 22 months. However the interval from the first to the second hip fracture ranged from 2 to 297 months. Pearse et al [43] included patients admitted with a second hip fracture from 1999 to Within this period 42 second hip fractures were included. They represented 12% of the total number of hip fractures within the period. The median time from first to second hip fracture was 31 months (range months). 23

26 Among 501 patients admitted with a first hip fracture during 2002 and 2003, Lönroos et al[44] found that 6.8% had sustained a second hip fracture at the end of From the original Framingham Heart Study Berry et al[45] included 481 patients with a first hip fracture between 1952 and They found 71 patients (14.8%) subsequently admitted with a second hip fracture. The median time from first to second hip fracture was 4.2 years (range 1 month to 33.3 years). The incidence of the second hip fracture was 0.13 per 1,000 py in men and 0.25 per 1,000 py in women. Within the first year 2.5% had experience a second hip fracture. In contrast the one year mortality following the first hip fracture was 15.9% (one year mortality following the second hip fracture was 24.1%). 4.5 Summary of previous studies on the second hip fracture A few studies have been published focusing on the second hip fracture. Reported frequencies range from 2.3% to 9.5% [35;37-43]. The studies report mean, median and/or range for time distributions, but none have analysed the distribution of time from the first to the second hip fracture. This information could be important in order to determine which kind of intervention will be the most beneficial. 4.6 Hip fracture mortality It is well known that mortality in hip fracture patients as a group is excessively high compared to the general population. 4.7 Previous studies on hip fracture mortality Tabel 4-1 summarises cumulative mortality after specific time intervals following a hip fracture as found in the literature. 24

27 4.7.1 Danish studies From April 1 st 1971 to March 31 st 1977 the mortality following hip fracture was estimated by Jensen et al [46]. In 1,592 patients the mean age in men were 74 years (range 51-98), and in women 78 years (range 51-99). All patients were followed until death or February 1 st There was no information about patients admitted with a second hip fracture. The in-hospital mortality was 8.6%, with a mean length of stay of 24 days (range 20-28). Throughout the period men in all age groups had a higher mortality compared to women. The three months cumulative mortality was 21.5 % in men and 15.2 % in women. At six months 25.0% in men and 20.0 % in women. They point out the importance of knowing the length of stay when referring to in-hospital mortality. The three and six month mortality had not changed during the past 15 years although the mean age had increased. Between 1970 and 1985 Schroder et al [47] included all patients with a hip fracture from Aarhus County, all were followed until June 1988 or death. If a patient was included with more than one fracture (6.2%), the time of the last fracture was used for the survival estimate. The cumulative mortality after one month was 9.5%, after three months 16.8%, after six months 21%, and after 12 months 27%. Men had the highest mortality in all age groups. The mortality rate increased with increasing age in both men and women. The mortality rates of hip fracture patients were then compared to the survival of an age and sex matched Danish background population. The relative survival decreased within the first year, but did not normalise until after 5-10 years. In a recent register based study by Giversen [48] 2,674 first hip fractures in patients 50 years and older occurred from 1987 to 1996 in Viborg County. All were followed until December 31 st 1996 or death. The mean age increased in both men and women throughout the period. In 1987 the mean age was 77.8 in men and 79.3 in women, increasing to 80.3 in men and 80.7 in women in The cumulative mortality after one month was 14.1% in men and 7.0 in women, after three months 21.9% in men and 12.8% in women, after twelve months 35.8% in men and 23.2% in women, and after two years 45.7% in men and 32.7% in women. Overall the cumulative mortality was 9.0%, 15.5%, 26.5% and 36.2% respectively. The mortality over time did not change even though the mean age increased. A change in the age distribution was seen. 25

28 4.7.2 International studies Studies on mortality following hip fracture in general In New Zealand Walker et al [49] estimated 35 day and one year mortality among 10,684 individuals aged 60 years or older admitted with a hip fracture from 1988 to The 35 day mortality was 12% among men and 7% among women, whereas the one year mortality was 33% among men and 22% among women. The mortality increased exponentially with age in both men and women. Billsten et al [13] compared mortality following hip fracture among 65+years in two regions of southern Sweden from 1992 to If a patient (6%) had been admitted with two hip fractures the time of death was calculated from the last fracture. In men from Malmö and the rural area the one month mortality was 10.6% and 9.1%, the six months mortality was 25% and 23.1%, and the one year mortality was 31.6% and 28.9% respectively. Women from Malmö had a higher mortality at one and six months compared to women from the rural area, 5.6% and 3.2% at one, and 15.9% and 12.8% at six months. Within one year after the last fracture 33% were deceased. The differences in mortality between the two regions were also found in the general population. From Edmonton, Canada, Cree et al [50] included 558 first hip fracture patients during July 1996 to August Mortality after three months was of 8% (13% of men, and 6% of women). Among those alive after three months, who before the fracture had lived independently, 13% of men and 18% of women were institutionalised. Male gender and cognitive impairment were identified as significantly related to an increased risk of mortality within 3 months, whereas mental status, age and postfracture physical function were related to the risk of being institutionalised within 3 months. Keene et al [51] included 1,000 hip fracture patients during 1989 to 1992 from two British trauma centres. The one year mortality was related to age, with the lowest (3%) in patients less than 60 years and highest (51%) among 90+ year old. Heikkinen et al [52] compared one year mortality among hip fracture patients 50 years and older included from 1989 to 1997 from Peterborough, England and Oulu, Finland. The one year mortality 26

29 in England was 36.4% in men, and 26.5% in women, and in Finland 32.6% in men, and 21.8% in women. In New York, USA Richmond et al [53] included 836 hip fracture patients between July 1987 and December Patients were 65 years or older, previously ambulatory and home dwelling. All were followed for 24 months or until death. The one year mortality was 11.5%, and the two year mortality was 16.9%. They found a significantly increased mortality among year old patients in ASA group 3 and 4 [54]. In a large database study of hip fractures in 65 years and older patients occurring during 1968 to 1998 in southern England Roberts et al [55] included a total of 32,590 hip fractures based on ICD 9 and 10 diagnoses. In both men and women the age distribution increased significantly throughout the period. The mortality rated declined during the early part and levelled of from the early 1980s. Mortality rates increased with increasing age; however the age specific rates were higher from 1968 to 1983 than from 1984 to The one year mortality rate in men decreased from 43.4% from 1968 to 1983 to 30.7% from 1984 to In women it decreased from 40.9% to 28.4%. Between 1994 and 1998 in Finland Heinonen et al [56] included 243 consecutive communitydwelling patients aged 65 or older, who were able to walk unaided before the hip fracture. The one year mortality in men was 17%, and in women 15%. The aim was however to evaluate whether physical function two weeks after hip fracture could predict one year mortality. A patient not being able to stand up two weeks after the hip fracture was the best predictor of one year mortality, with a hazard ratio of 4.64 (95% CI ). The inability to sit down or walk unaided two weeks after a hip fracture was also major risk factors of one year mortality. Endo et al [57] included 983 patients admitted with a non pathologic hip fracture between July 1987 and June The patients were at least 65 years old, ambulatory prior to the fracture, cognitively intact, and living independently. Among these patients the one year mortality among men was 16.5% and women 9.4%. The mean length of stay was 23 days, with an inhospital mortality of four percent in men and two percent in women. They also found that the ambulatory status of half of both men and women declined as a result of the fracture. 27

30 Comparative mortality studies Between 1983 and 1989 Willig et al [58] included 200 consecutive trochanteric hip fracture patients from Oulu, Finland and 200 age and sex matched controls from the same area. All were followed to death or January 30 th 1994, with a mean follow-up of 7 years (range 4.5 to 10.5 years). The one month mortality was 7.0% among cases and 2.5% among controls, at six months 16% and 10%, at one year 19% and 16%, and at two years 32% and 27.5%. From 1984 to 1986 in Baltimore, USA Magaziner et al [59] compared 578 women 70 + year old with a hip fracture to women 70+ year included in the Longitudinal Study on Aging [60], of which 3773 subjects were selected who at baseline had not suffered a hip fracture and who did not suffer a hip fracture during the 6 years of follow-up. After adjusting for age, education, comorbidity and functional impairment hip fracture patients had greatest excess mortality within the first 6 months (observed to expected ratio 6.08) the excess then levelled off and had disappeared after 4 years. In a population based, prospective, matched-pair, cohort study from Norway Forsén et al [61] estimated sex and age specific short and long term excess mortality in hip fracture patients. Within the study period from March 1 st 1986 to December 31 st 1995 they included 1,825 hip fracture patients, and 19,277 non-fracture controls aged 50 and older. No information on the number of second hip fractures among cases. The one year mortality among cases was 31% in men, and 17% in women. Divided into three age groups the numbers were 16% and 7% in year old men and women, 30% and 18% in year old, and 48% and 27% in 85 years and older. There was an increased excess mortality within the first three to six months in all age groups. The excess mortality remained significantly higher for at least 5 years in men and 9 years in women, however the oldest women had no excess mortality after three months. From western Sydney, Australia Katelaris et al [62] compared survival among 211 hip fracture patients, 65 years and older from a defined area, to 201 non hip fracture control subjects living in the same area. Inclusion took place between March 1990 and August 1991 with a follow-up period until May In hip fracture patients the one month mortality was 4.7% and the one year mortality was 21.7%, compared to no deaths after one month in the control group and 4.7% after one year. 28

31 During July 1991 to February 1994 in Auckland, New Zealand, Fransen et al [63] included 565 community dwelling 60 years and older people discharged from the hospital after a hip fracture, and 782 randomly selected controls, frequency matched on age and sex from the same area. They estimated the two year mortality as well as the risk of being institutionalised. The two year mortality of cases and controls were 38% and 8.2% in men, and 20.7% and 10.3% in women. At the end of the two year follow-up 52.1% of the male cases and 12.4% male controls were either dead or institutionalised, in the women the frequencies were 39.2% of cases and 19.7% of controls. Men sustaining a hip fracture had seven fold increased odds of dying or being institutionalised compared to controls. In women the odds were one and a half fold increased. The results could suggest that the absolute burden of mortality and institutionalisation due to a hip fracture may be greater in men. Kirke et al [64] conducted a case control study among Irish women. They included 106 women above 50 years admitted with a hip fracture and 89 age and gender matched non-fracture controls from the same catchment area. All were followed for two years. The one year mortality was 16% in cases and 4.5% in controls, and the two year mortality was 23.6% in cases and 10.1% in controls. At inclusion there was no difference among the surviving cases and controls in the ability to walk 100 yards unaided, however after two years 58% of cases could not walk unaided whereas only 11.5% of controls needed aid (p<0.001). At follow up cases were significantly less independent and more likely to be institutionalised. 4.8 Summary of previous studies on hip fracture mortality A few studies have looked into details of the relationship btw. hip fracture status in comparison to the general population [46;47;65-67], but have not taken the relative high proportion of hip fracture patients in the older age groups in the population into account. Only two studies have looked at more than 1-2 years of follow-up [47;67] and few studies have examined hip fracture mortality in a case cohort or case control setting [59;61-63]. None of the studies attempted to assess the magnitude or direction of bias based on principle of control selection. Most applied the principle of only using non-fracture controls [59;61-63]. This would a priori give an overestimation of the difference in mortality between patients and controls, since the non-fracture controls would be expected to be healthier than the general population including those with hip-fracture. It could also be 29