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 ★

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

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.

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.

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.

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.

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 (1978 - 79) Stockholm (1972 - 81) Rochester (1965 - 74) Okinawa (1987) Japanese Tottori (1986 - 88) ★ Niigata Niigata (1985) ★ Tottori Asians Singapore (1962 - 63) Okinawa Yamamoto K et al. Osteoporosis Int 1993;Suppl. 1:S48-50 ★

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.

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

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

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

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.

This assumption is considered reasonable Σ ＝ (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.

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.

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

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.

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

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 　10 - 14 years 12.7 12.2 　15 - 19 years 6.3 6.2 　20 - 24 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

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.

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

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

The incidence rose with increasing age Men HD patients General population Women Incidence, per 1,000 person-years Age, years SIR 6.2 (95%CI 5.7 - 6.8) 4.9 (95%CI 4.6 - 5.3)

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 64.8 64.9 64.8 64.3 62.1 59.5 　　　 67.6 67.2 67.4 66.0 63.5 61.5 　　(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)

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.

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

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

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.

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.

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.

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.

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

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

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

SIRs of hip fracture across the 12 districts for male HD patients Standardized incidence ratio (SIR) 1.3 ≤ 1.20 - 1.29 1.10 - 1.19 0.80 - 0.99 ≤ 0.69 1.00 - 1.09 0.70 - 0.79 SIRs for male general population eastern Japan SIR 1.20 ≤ 1.10 - 1.19 1.00 - 1.09 0.90 - 0.99 ≤ 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

SIRs of hip fracture across the 12 districts for female HD patients Standardized incidence ratio (SIR) 1.4 ≤ 1.20 - 1.39 1.00 - 1.19 0.70 - 0.89 ≤ 0.49 0.90 - 1.09 0.50 - 0.69 SIRs for female general population eastern Japan SIR 1.20 ≤ 1.10 - 1.19 1.00 - 1.09 0.90 - 0.99 ≤ 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

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.

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

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.” http://www.e-stat.go.jp/SG1/estat/List.do?lid=000001109855

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

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

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

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

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.

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.

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.

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.