1. Hip fracture in dialysis patients
Workshop on JSDT Registry (JRDR)
Hip fracture
in dialysis patients
Niigata ★
Minako Wakasugi, Junichiro James Kazama,
Kunitoshi Iseki, Yoshiharu Tsubakihara, Ichiei Narita
Center for Inter-organ Communication Research,
Division of Clinical Nephrology and Rheumatology,
Niigata University Graduate School of Medical and Dental Sciences.
Committee of Renal Data Registry, Japanese Society for Dialysis Therapy.
COI Disclosure Name of presenter : Minako Wakasugi
The authors have no financial conflicts of interest to disclose concerning the presentation.
Okinawa ★

2. Using data from JSDT registry (JRDR), we found and reported
Increased risk of hip fracture among Japanese hemodialysis patients.
Wakasugi M, et al. J Bone Miner Metab 2013
Regional variation in hip fracture incidence among Japanese hemodialysis patients.
Wakasugi M, et al. Ther Apher Dial 2014
Hip fracture

3. Dialysis patients have more risks of hip fracture compared with the general population.
Common risk factors
older age, female gender, etc.
Dialysis patient-specific factors
A beta-2M-amyloidosis and related osteopathy, secondary hyperparathyroidism, etc.

4. How much higher is the incidence of hip fracture in dialysis patients than that of the general population?
General population
Dialysis patients ?
Common risk factors
older age, female gender, etc.
Dialysis patient-specific factors
A beta-2M-amyloidosis and related osteopathy, secondary hyperparathyroidism, etc.

5. How much higher is the incidence of hip fracture in dialysis patients than that of the general population?
General population
Dialysis patients
USRDS
Rochester, Minesota
4 times
Hip fracture incidence among American Caucasian populations from 1983 to 1992.
Hip fracture incidence among
all Caucasian patients
who began dialysis
between 1989 and 1996
Alem AM, et al. Kidney Int 2000;58:396-9.

6. This study included only Caucasians.
Hip fracture incidence among dialysis patients was 4 times higher than that of the general population.
General population
Dialysis patients
USRDS
Rochester, Minesota
4 times
Hip fracture incidence among American Caucasian populations from 1983 to 1992.
Hip fracture incidence among
all Caucasian patients
who began dialysis
between 1989 and 1996
This study included only Caucasians.
How about Asians?
Alem AM, et al. Kidney Int 2000;58:396-9.

7. Race is an important risk factors for hip fractures in the general population
Is age-adjusted incidence of hip fracture
among Asian dialysis patients also higher than that of
the general Asian population?
Oslo ( )
Stockholm
( )
Rochester
( )
Okinawa (1987)
Japanese
Tottori ( ) ★
Niigata
Niigata (1985) ★
Tottori
Asians
Singapore
( )
Okinawa
Yamamoto K et al.
Osteoporosis Int 1993;Suppl. 1:S48-50 ★

8. This study included only Caucasians.
How much higher is the incidence of hip fracture in dialysis patients than that of the general population?
General population
Dialysis patients
USRDS
Rochester, Minesota
4 times
Hip fracture incidence among American Caucasian populations from 1983 to 1992.
Hip fracture incidence among
all Caucasian patients
who began dialysis
between 1989 and 1996
This study included only Caucasians.
How about Asians?
Alem AM, et al. Kidney Int 2000;58:396-9.

9. How much higher is the incidence of hip fracture in the Japanese dialysis patients than that of the general population?
General population
Dialysis patients ?
JRDR
Hip fracture incidence among Japanese general population
Hip fracture incidence among
Japanese HD patients

10. ? JRDR Data sources General population HD patients
Hip fracture incidence among Japanese general population in 2007
Hip fracture incidence among
Japanese dialysis patients

11. JRDR Data sources JRDR at the end of 2007 HD patients
Patients without a history of hip fracture who received HD three times per week
as of December 31, 2007, were included.
JRDR
Fracture event
Hip fracture incidence among
Japanese HD patients in 2008
JRDR at the end of 2008
A question regarding a history of hip fracture
Yes No

12. How to calculate incidence of hip fracture
Total number of fractures
JRDR at the end of 2007
Incidence ＝ Σ
(Patient time at risk)
Patient time
at risk
(ti) t2
Total number of fractures t1 t6 ＝ n t3 t4 tn Σ ti t5
Fracture event
died
i =1
died
JRDR at the end of 2008
Since exact dates of fracture incidents were not available, we applied the following assumption.
If a patient suffered a hip fracture, the patient’s time at risk was equal to half of the patient’s survival time during the study period.

13. This assumption is considered reasonableΣ ＝
(Patient time at risk)
i =1 n ti
; the average of patient’s time at risk n
; number of patients
No seasonal trends
A symmetrical seasonal trend
Hagino H et al, Bone 1999
J Orthop Sci 2004
Jan
Feb
Mar
Apr
June
July
Aug
Sep
Oct
Nov
Dec
Numbers of fracture patients
Numbers of fracture patients
is equal to half of the patients’ survival time during the study.

14. The total patient time at risk did not significantly change when this assumption was changed
If a patient suffered a hip fracture, the patient’s time at risk was equal to half of the patient’s survival time during the study period.

15. The total patient time at risk did not significantly change when this assumption was changed
JRDR at the end of 2007
JRDR at the end of 2007
Fracture event
died
died
Fracture event
JRDR at the end of 2008
JRDR at the end of 2008
When we assumed that
all fractured patients were suffered
on the first day,
When we assumed that
all fractured patients were suffered
on the last day during the study period,
Wakasugi M, et al. J Bone Miner Metab 2013

16. How much higher is the incidence of hip fracture in the Japanese dialysis patients than that of the general population?
General population
HD patients ?
JRDR
SIR
Hip fracture incidence among Japanese general population
Hip fracture incidence among
Japanese HD patients
SIR can be interpreted as the relative increase in hip fracture incidence among the HD patients compared with that of the general population.

17. Patient selection process
Prevalent patients, JSDT2007
n = 275,119
HD patients
Hemodialysis, thrice per week
n = 200,529
Excluded:
1. History of hip fracture (n = 3,540)
2. Missing pertinent data (n = 68,848)
JRDR
Subjects for this study
n = 128,141
Hip fracture incidence among
Japanese HD patients

18. Characteristics of study participants and all dialysis patients as of December 31, 2007
Female, %
38.1
38.6
Mean age (SD), years
　male
63.6 (12.3)
64.2 (12.5)
　female
65.4 (12.5)
66.0 (12.9)
Dialysis vintage, %
　< 5 years
48.6
49.5
　5 - 9 years
26.2
25.0
　 years
12.7
12.2
　 years
6.3
6.2
　 years
3.4
3.6
　25 years ≤
2.7
3.5
Primary cause of end-stage kidney disease, %
Chronic glomerulonephritis
38.8
40.4
Diabetic nephropathy
33.8
33.4
History of cardiovascular diseases, %
myocardial infarction
5.9
6.6
cerebral infarction
10.5
11.7
cerebral bleeding
3.7
4.0

19. Patient selection process
Prevalent patients, JSDT2007
n = 275,119
HD patients
Hemodialysis, thrice per week
n = 200,529
Excluded:
1. History of hip fracture (n = 3,540)
2. Missing pertinent data (n = 68,848)
JRDR
Subjects for this study
n = 128,141
Hip fracture incidence among
Japanese HD patients
1-year follow up until the end of 2008
1,437 hip fractures occurred.

20. Observed number of hip fracture stratified by age and sex
Men
Women
Observed number of hip fracture
Age, years
7.57 per 1,000 person-years
17.43 per 1,000 person-years

21. The incidence rose with increasing age
Men
HD patients
General population
Women
Incidence, per 1,000 person-years
Age, years

22. The incidence rose with increasing age
Men
HD patients
General population
Women
Incidence, per 1,000 person-years
Age, years
SIR (95%CI ) (95%CI )

23. Standardized incidence ratios stratified by dialysis vintage and sex
Men
Women
Standardized incidence ratio
Error bars indicate
95% confidence intervals.
5.5
3.8
Vintage, years
Mean age 　　　
　　(SD) 　　 　(12.7)　 (12.6) (12.5) (12.3) (12.1) (10.1)　　 　　　 　(12.7) (13.2) (12.8) (12.7) (12.1) (10.1)

24. How much higher is the incidence of hip fracture in the Japanese dialysis patients than that of the general population?
General population
HD patients
5 times ?
JRDR
Hip fracture incidence among Japanese general population
Hip fracture incidence among
Japanese HD patients
Hip fracture risk among Asian dialysis patients is also significantly higher than in the general population.

25. Using data from JSDT registry (JRDR), we found and reported
Increased risk of hip fracture among Japanese hemodialysis patients.
Wakasugi M, et al. J Bone Miner Metab 2013
Regional variation in hip fracture incidence among Japanese hemodialysis patients.
Wakasugi M, et al. Ther Apher Dial 2014
Hip fracture

26. Universal health care system
Substantial regional variation in hip fracture incidence exists in the Japanese general population.
General population
Universal health care system
Lack of racial and ethnic variation
Hip fracture incidence among Japanese general population

27. Substantial regional variation in hip fracture incidence exists in the Japanese general population.
Created based upon data from Yaegashi Y et al. Eur J Epidemiol 2008; 23:219-25
Men
Women
eastern Japan
eastern Japan
Standardized incidence ratio (SIR)
1.20~
1.10~1.19
1.00~1.09
0.90~0.99
~0.89
western Japan
western Japan
Hip fracture incidence is higher in western Japan than in eastern Japan.

28. This trend has continued since 1987, when the first nationwide survey was carried out.
Yoshimura N, et al. J Bone Miner Metab 2005; 23[Suppl]:78-80
SIR
Men
Women
The etiology of the regional variation remains unclear.

29. Substantial regional variation in hip fracture incidence exists in the Japanese general population.
Created based upon data from Yaegashi Y et al. Eur J Epidemiol 2008; 23:219-25
Men
Women
eastern Japan
eastern Japan
Standardized incidence ratio (SIR)
1.20~
1.10~1.19
1.00~1.09
0.90~0.99
~0.89
western Japan
western Japan
Several administrative, climatic, and cultural differences are observed between eastern and western Japan.

30. Does regional variation in hip fracture incidence also exist among HD patients?
General population
HD patients ?
5 times
JRDR
Common risk factors
older age, female gender, etc.
Dialysis patient-specific factors
A beta-2M-amyloidosis and related osteopathy, secondary hyperparathyroidism, etc.

31. JRDR Data sources HD patients Prevalent patients, JSDT2007 n = 275,119
Hemodialysis, thrice per week
n = 200,529
Excluded:
1. History of hip fracture (n = 3,540)
2. Missing pertinent data (n = 68,848)
JRDR
Subjects for this study
n = 128,141
Hip fracture incidence among
Japanese HD patients
1-year follow up until the end of 2008
Wakasugi M, et al. Ther Apher Dial 2014

32. Japan was divided into 12 districts according to the classification set forth in a previous report
Prevalent patients, JSDT2007
n = 275,119
Hokkaido
Hemodialysis, thrice per week
n = 200,529
Tohoku
Hokuriku
Chugoku
Kinki I
Excluded:
1. History of hip fracture (n = 3,540)
2. Missing pertinent data (n = 68,848)
Kanto II
Kanto I
Tokai
Kitakyusyu
Subjects for this study
n = 128,141
Shikoku
Kinki II
Minamikyusyu
The standardized incidence ratio (SIR) was calculated for each district.
1-year follow up until the end of 2008
Wakasugi M, et al. Ther Apher Dial 2014

33. Mean age of HD patients did not differ across the 12 districts
Mean age, years
Hokkaido
Kanto I
Tohoku
Kanto II
Tokai
Hokuriku
Kinki II
Kinki I
Shikoku
Chugoku
Kitakyusyu
Minamikyusyu
Men
Tokai
Hokkaido
Kanto I
Kanto II
Kinki II
Tohoku
Kinki I
Shikoku
Hokuriku
Chugoku
Kitakyusyu
Minamikyusyu
Women
Error bars indicate 1 SD (standard deviation).
Wakasugi M, et al. Ther Apher Dial 2014

34. SIRs of hip fracture across the 12 districts for male HD patients
Standardized incidence ratio (SIR)
1.3 ≤
≤ 0.69
SIRs for male general population
eastern Japan
SIR
1.20 ≤
≤ 0.89
western Japan
(Created based upon data from Yaegashi Y et al. Eur J Epidemiol 2008; 23:219-25)
Wakasugi M, et al. Ther Apher Dial 2014

35. SIRs of hip fracture across the 12 districts for female HD patients
Standardized incidence ratio (SIR)
1.4 ≤
≤ 0.49
SIRs for female general population
eastern Japan
SIR
1.20 ≤
≤ 0.89
western Japan
(Created based upon data from Yaegashi Y et al. Eur J Epidemiol 2008; 23:219-25)
Wakasugi M, et al. Ther Apher Dial 2014

36. Regional variation in hip fracture incidence also exists among HD patients.
General population
HD patients ?
5 times
Common risk factors
older age, female gender, etc.
Dialysis patient-specific factors
A beta-2M-amyloidosis and related osteopathy, secondary hyperparathyroidism, etc.

37. Using data from JSDT registry (JRDR), we found and reported
Increased risk of hip fracture among Japanese hemodialysis patients.
Wakasugi M, et al. J Bone Miner Metab 2013
Regional variation in hip fracture incidence among Japanese hemodialysis patients.
Wakasugi M, et al. Ther Apher Dial 2014
Hip fracture

38. Japan is the most rapidly aging country in the world today.
Age Pyramid, Japan, 2012
Age group
12%
24%
Men
Women
Population
(in thousands)
Created based upon data from “Population Estimates by Age (5 Year Age Group) and Sex - October 1, 2012.”

39. Dialysis population is aging in Japan.
Age Pyramid of Dialysis Patients, 1980
Age group
Mean age
45 years old
Men
Women
Created based upon data from the JRDR as of December 31, 1980

40. Dialysis population is aging in Japan.
Age Pyramid of Dialysis Patients, 1990
Age group
Mean age
55 years old
Men
Women
Created based upon data from the JRDR as of December 31, 1990

41. Dialysis population is aging in Japan.
Age Pyramid of Dialysis Patients, 2000
Age group
Mean age
61 years old
Men
Women
Created based upon data from the JRDR as of December 31, 2000

42. Dialysis population is aging in Japan.
Age Pyramid of Dialysis Patients, 2012
Age group
30%
60%
Mean age
67 years old
Men
Women
Created based upon data from the JRDR as of December 31, 2012

43. The incidence rises with increasing age
Men
HD patients
General population
Women
Incidence, per 1,000 person-years
Age, years
Hip fracture is a major health issue due to an increasingly elderly population.

44. an important role in resolving the problems facing dialysis pts
The strategies for decreasing incidence of hip fracture are urgently required.
HD patients
Hip fracture
continue to play
an important role in resolving the problems facing dialysis pts
JRDR
Hip fracture is a major health issue due to an increasingly elderly population.

45. Using data from JSDT registry (JRDR), we found and reported
Increased risk of hip fracture among Japanese hemodialysis patients.
Wakasugi M, et al. J Bone Miner Metab 2013
Regional variation in hip fracture incidence among Japanese hemodialysis patients.
Wakasugi M, et al. Ther Apher Dial 2014
General population
HD patients
Hip fracture
5 times
Wakasugi M, et al.
J Bone Miner Metab 2013
JRDR
Wakasugi M, et al. Ther Apher Dial 2014
Common risk factors
older age, female gender, etc.
Dialysis patient-specific factors
A beta-2M-amyloidosis and related osteopathy, secondary hyperparathyroidism, etc.

46. Using data from JSDT registry (JRDR), we found and reported
Increased risk of hip fracture among Japanese hemodialysis patients.
Wakasugi M, et al. J Bone Miner Metab 2013
Regional variation in hip fracture incidence among Japanese hemodialysis patients.
Wakasugi M, et al. Ther Apher Dial 2014
General population
HD patients
5 times
Wakasugi M, et al. Ther Apher Dial 2013
Acknowledgments
We thank the participants in the JRDR, members of the committee of the JRDR, and all personnel at participating institutions involved in this survey.
Wakasugi M, et al. J Bone Miner Metab 2013
Common risk factors
aging, female gender,
fall, and so on.
HD patient-specific factors
Abeta-2M-amyloidosis and related osteopathy, secondary hyperparathyroidism, and so on.