The National Institute for Health Research School for Primary Care Research (NIHR SPCR) is a partnership between the Universities of Bristol, Cambridge, Keele, Manchester, Newcastle, Nottingham, Oxford, Southampton and University College London.

School for Primary Care Research

RISK OF FRAGILITY FRACTURE OVER 10 YEARS ACROSS EIGHT INFLAMMATORY CONDITIONS: A UK POPULATION STUDY

Zoe Paskins, Rebecca Whittle, Samantha Hider, Alyshah Abdul Sultan, Edward

Roddy, Christian Mallen

School for Primary Care ResearchThe National Institute for Health Research School for Primary Care Research (NIHR SPCR) is a partnership between the Universities of Birmingham, Bristol, Keele, Manchester, Nottingham, Oxford, Southampton and University College London.

Background 1• Rheumatoid Arthritis (RA) is associated with a 1.5

fold increased risk of fractureVan Staa et al A & R 2006

• Mechanisms explaining increased fracture risk:– Corticosteroids– Immobility, risk of falls– Pro-inflammatory cytokines (such as IL1, IL6, IL11, IL15,

IL17 and TNFα) act as primary mediators of accelerated bone loss

Mundy et al Nut Rev 2007

School for Primary Care ResearchThe National Institute for Health Research School for Primary Care Research (NIHR SPCR) is a partnership between the Universities of Birmingham, Bristol, Keele, Manchester, Nottingham, Oxford, Southampton and University College London.

Background 2• Other inflammatory conditions associated with increased risk of fracture:

– Ankylosing Spondylitis (AS)– Systemic Lupus Erythematous (SLE)– Inflammatory Bowel Disease (IBD)

Vosse et al ARD 2008; Bultink et al OI 2014; Van Staa et al Gastroenterology 2003

• Other common primary care inflammatory conditions for which an association with increased risk of fracture is not clear:– Psoriasis– Gout– Polymyalgia rheumatica (PMR) and Giant Cell arthritis (GCA)

Dreiher et al J Inv Derm 2009, Modalshi et al 2016 Br J Derm Dennison et al Arch Osteo 2015, Kim et al JBMR 2016, Paik et al Arth Rheum 2016, Tzeng et al 2016

School for Primary Care ResearchThe National Institute for Health Research School for Primary Care Research (NIHR SPCR) is a partnership between the Universities of Birmingham, Bristol, Keele, Manchester, Nottingham, Oxford, Southampton and University College London.

Aim

• To estimate and compare the population level absolute and relative risk of fragility fracture among patients with eight common inflammatory conditions

School for Primary Care ResearchThe National Institute for Health Research School for Primary Care Research (NIHR SPCR) is a partnership between the Universities of Birmingham, Bristol, Keele, Manchester, Nottingham, Oxford, Southampton and University College London.

Method 1• Retrospective cohort design using Clinical Practice Research

Datalink (CPRD)• Exposed individuals

– over the age of 40 years– with incident diagnoses of RA, AS, SLE, IBD, gout, GCA,

PMR and psoriasis were identified from 1990–2004 and followed up until 2015

• For each exposure group, four age-, gender- and practice-matched controls were randomly selected

School for Primary Care ResearchThe National Institute for Health Research School for Primary Care Research (NIHR SPCR) is a partnership between the Universities of Birmingham, Bristol, Keele, Manchester, Nottingham, Oxford, Southampton and University College London.

Method 2• Outcome: first major osteoporotic fracture (MOF) (WHO

definition) of wrist, vertebrae, hip, humerus• Incidence rates of MOF per 10,000 person-years, compared to

controls using Cox regression models• Covariates:

– Baseline - patient demographics (age and gender); lifestyle-related (body mass index, smoking status and alcohol consumption); COPD, diabetes, renal disease, use of HRT and thiazides

School for Primary Care ResearchThe National Institute for Health Research School for Primary Care Research (NIHR SPCR) is a partnership between the Universities of Birmingham, Bristol, Keele, Manchester, Nottingham, Oxford, Southampton and University College London.

Results

School for Primary Care ResearchThe National Institute for Health Research School for Primary Care Research (NIHR SPCR) is a partnership between the Universities of Birmingham, Bristol, Keele, Manchester, Nottingham, Oxford, Southampton and University College London.

RA AS IBD SLE

Exposed (n=9,187)

Unexposed (n=35,813)

AS Exposed (n=3083)

AS Unexposed (n=11947)

Exposed (n=6,423)

Unexposed (n=25,139)

Exposed (n=924)

Unexposed (n=3608)

Follow up time; median (IQR)

10.10 (6.35, 13.05)

11.01 (7.09, 13.76)

11.43 (7.70, 14.51)

11.43 (7.70, 14.48)

10.92 (6.99, 13.65)

11.15 (7.47, 13.85)

11.19 (7.25, 14.17)

11.44 (7.65, 14.31)

Male; n (%) 2869 (31.23)

11226 (31.35)

1136 (36.85)

4399 (36.82)

2930 (45.62)

11,496 (45.73)

136 (14.72) 545 (15.11)

Age; median (IQR)

62.17 (53.63, 71.89)

62.00 (53.49, 71.50)

55.16 (47.34, 65.24)

55.21 (47.46, 65.14)

58.16 (49.13, 68.84)

58.06 (49.28, 68.48)

54.83 (47.52, 64.88)

55.00 (47.90, 64.90)

School for Primary Care ResearchThe National Institute for Health Research School for Primary Care Research (NIHR SPCR) is a partnership between the Universities of Birmingham, Bristol, Keele, Manchester, Nottingham, Oxford, Southampton and University College London.

Psoriasis Gout PMR GCAExposed (n=24,262)

Unexposed (n=95,290)

Exposed (n=36,789)

Unexposed (n=139,685)

Exposed (n=12,178)

Unexposed (n=46,567)

Exposed (n=2693)

Unexposed (n=10528)

Follow up time; median (IQR)

11.29 (7.32, 14.17)

11.36 (7.49, 14.32)

10.67 (6.62, 13.34)

10.86 (6.87, 13.51)

9.27 (5.74, 12.37)

9.64 (5.99, 12.64)

9.13 (5.87, 12.39)

9.96 (6.25, 13.04)

Male; n (%) 11,919 (49.13)

46,697 (49.01)

27,169 (73.85)

102,949 (73.70)

3736 (30.68)

14137 (30.36)

778 (28.89)

2991 (28.41)

Age; median (IQR)

57.80 (49.27, 67.70)

57.75 (49.32, 67.49)

63.77 (53.52, 73.45)

63.22 (53.23, 72.84)

73.27 (66.19, 78.97)

72.82 (65.79, 78.38)

72.31 (65.11, 78.32)

71.99 (64.60, 77.85)

School for Primary Care ResearchThe National Institute for Health Research School for Primary Care Research (NIHR SPCR) is a partnership between the Universities of Birmingham, Bristol, Keele, Manchester, Nottingham, Oxford, Southampton and University College London.

Condition

Number of exposed with MOF Rate of MOF per 10,000 py

Adjusted Hazard Ratio (95% Confidence Interval)

RA 944 101.61 (95.33, 108.30) 1.46 (1.36, 1.57)GCA 373 146.78 (132.61, 162.46) 1.35 (1.21, 1.52)PMR 1696 148.12 (141.24, 155.34) 1.30 (1.23, 1.37)IBD 464 67.35 (61.49, 73.77) 1.20 (1.09, 1.33)Psoriasis 1588 58.34 (55.54, 61.28) 1.11 (1.05, 1.17)AS 218 61.34 (53.72, 70.05) 1.14 (0.97, 1.34)SLE 80 78.83 (63.36, 98.21) 1.19 (0.93, 1.51)Gout 2047 53.19 (50.94, 55.55) 0.99 (0.94, 1.04)

School for Primary Care ResearchThe National Institute for Health Research School for Primary Care Research (NIHR SPCR) is a partnership between the Universities of Birmingham, Bristol, Keele, Manchester, Nottingham, Oxford, Southampton and University College London.

Condition

Number of exposed with MOF Rate of MOF per 10,000 py

Adjusted Hazard Ratio (95% Confidence Interval)

RA male female

148796

51.03 (43.44, 59.95)124.56 (116.20, 133.52)

1.60 (1.33, 1.94) 1.45 (1.34, 1.57)

GCA male female

49324

66.27 (50.08, 87.68)179.82 (161.27, 200.50)

1.41 (1.03, 1.93)1.35 (1.20, 1.53)

PMR male female

2441452

68.69 (60.59, 77.87)183.86 (174.64, 193.56)

1.37 (1.18, 1.59)1.30 (1.22, 1.38)

IBD male female

103361

32.16 (26.51, 39.01)97.94 (88.34, 108.58)

1.12 (0.90, 1.39)1.25 (1.11, 1.40)

Psoriasis male female

4181170

31.05 (28.21, 34.17)85.03 (80.30, 90.05)

1.20 (1.07, 1.33)1.08 (1.01, 1.15)

AS male female

41177

31.57 (23.25, 42.88)78.49 (67.74, 90.94)

1.08 (0.73, 1.58)1.16 (0.97, 1.38)

SLE male female

476

27.61 (10.36, 73.56)87.43 (69.83, 109.47)

0.93 (0.29, 2.90)1.20 (0.93, 1.54)

Gout male female

9551092

32.63 (30.62, 64.77)118.50 (11.67, 125.74)

1.06 (0.98, 1.14)1.01 (0.94, 1.08)

School for Primary Care ResearchThe National Institute for Health Research School for Primary Care Research (NIHR SPCR) is a partnership between the Universities of Birmingham, Bristol, Keele, Manchester, Nottingham, Oxford, Southampton and University College London.

Conclusions• Of the eight inflammatory conditions studied, RA is

associated with the highest risk of fracture (HR 1.46)• This study reports for the first time, an increase in fracture

risk in patients with psoriasis and no increase in fracture risk in gout

• Patients with PMR and GCA have a 1.4 fold increased risk of fracture

• Further planned analyses include investigation of the effect of drugs on fracture risk

This study was funded by the National Institute for Health Research School for Primary Care Research (NIHR SPCR). CDM is funded by the National Institute for Health Research (NIHR) Collaborations for Leadership in Applied Health Research and Care West Midlands, the NIHR School for Primary Care Research and a NIHR Research Professorship in General Practice (NIHR-RP-2014-04-026). The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health.

Acknowledgements

School for Primary Care Research

Milica BucknallGeorge PeatKelvin Jordan

Frances Rees