Dr Zoe Paskins's presentation from Osteoporosis 2016: Risk of fragility fracture over 10 years across eight inflammatory conditions: A UK population study. Find out more at: https://nos.org.uk/conference

1. 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

2. School for Primary Care Research
The 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 fracture
Van 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

3. School for Primary Care Research
The 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

4. School for Primary Care Research
The 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

5. School for Primary Care Research
The 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

6. School for Primary Care Research
The 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

7. School for Primary Care Research
The 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

8. School for Primary Care Research
The 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)

9. School for Primary Care Research
The 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 GCA
Exposed
(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)

10. School for Primary Care Research
The 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)

11. School for Primary Care Research
The 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
148
796
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
49
324
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
244
1452
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
103
361
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
418
1170
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
41
177
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
4
76
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
955
1092
32.63 (30.62, 64.77)
118.50 (11.67, 125.74)
1.06 (0.98, 1.14)
1.01 (0.94, 1.08)

12. School for Primary Care Research
The 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

13. 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 Bucknall
George Peat
Kelvin Jordan
Frances Rees