The Leiden Fracture Liaison Service

1. The Leiden Fracture Liaison Service
Dr. F. Malgo
Center for Bone Quality
Leiden University Medical Center
The Netherlands
Leiden Center for Bone Quality
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2. Disclosures
Leiden Center for Bone Quality 19-Dec-182
(potentiële) belangenverstrengeling Geen
Voor bijeenkomst mogelijk relevante
relaties met bedrijven
Bedrijfsnamen
• Sponsoring of onderzoeksgeld
• Honorarium of andere (financiële)
vergoeding
• Aandeelhouder
• Andere relatie, namelijk …
•
•
•
•
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3. Introduction
• Fragility fractures are associated with increased morbidity and mortality and
growing personal, societal and economic burdens
• An estimated 3.5 million fractures occur in Europe each year
• One in three women and one in five men aged 50 years or older will sustain
a fracture in their lifetime
• The number of patients who do not receive adequate attention after a
recently sustained fracture remains alarming
19-Dec-183 Leiden Center for Bone Quality
1. Hernlund et al. Arch Ost 2013
2. Svedbom et al. Arch Ost 2013
3. Bliuc et al. JAMA 2009
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4. Introduction
• An FLS is a multidisciplinary care trajectory offering
• Screening for osteoporosis using DXA
• Screening for underlying factors for increased fracture risk
• FLSs lead to a reduction in mortality and in the incidence of new fractures
• FLSs have been shown to be cost-effective
19-Dec-184 Leiden Center for Bone Quality
1. Akesson et al. Osteoporos Int 2013
2. McLellan et al. Osteoporos Int 2003
3. Huntjens et al. Osteoporos Int 2010
4. McLellan et al. Osteoporos Int 2011
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5. Leiden Fracture Liaison Service
19-Dec-185 Leiden Center for Bone Quality
Primary fracture care;
Cast application/surgery
Follow-up visit at
outpatient clinic
Traumatology
Visit FLS coordinator
Patient consent
to FLS?
Visit FLS coordinator
(if not done previously) • Clinical risk factors
• Laboratory investigations
• BMD measurement and VFA
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6. Prevalence of underlying factors
Study design
• Prospective cohort study
• Patients ≥ 50 years with a recent fracture
• 2 year inclusion period
Exclusion criteria
• Fracture of the skull, hands or feet
• Pathological fractures
• Failure of prosthesis
• Poor general condition
19-Dec-186 Leiden Center for Bone Quality
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7. Prevalence of underlying factors
19-Dec-187 Leiden Center for Bone Quality
1562 patients presented
to the ER with a fracture
856 patients referred to
FLS and invited to take
part in the study
709 patients included in
the study
686 patients included in
final analysis
706 patients not
referred to FLS
147 patients refused
23 patients missed data
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8. Prevalence of underlying factors
19-Dec-188 Leiden Center for Bone Quality
Normal BMD
(n=102)
Osteopenia
(n=385)
Osteoporosis
(n=199)
P-value
Age (years) 64.7 ± 9.9 66.0 ± 9.8 70.5 ± 10.2 < 0.001
Male/female (%) 35/67
(34%/66%)
113/272
(29%/71%)
34/165
(17%/83%)
0.001
Previous Fracture
(%)
41 (40%) 163 (42%) 83 (42%) 0.918
Calcium (mmol/L) 2.40 ± 0.12 2.41 ± 0.12 2.41 ± 0.11 0.648
Creatinine (μmol/L) 74.4 ± 15.3 74.7 ± 19.1 72.3 ± 26.4 0.422
LS BMD (g/cm2) 1.11 ± 0.12 0.95 ± 0.12 0.80 ± 0.14 < 0.001
FN BMD (g/cm2) 0.86 ± 0.10 0.70 ± 0.07 0.58 ± 0.08 < 0.001
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9. Prevalence of underlying factors
19-Dec-189 Leiden Center for Bone Quality
Smoking Alcohol Steroids RA EM
0%
5%
10%
15%
20%
25%
Prevalence of secondary factors for bone fragility
using FRAX clinical risk factors Normal BMD
Osteopenia
Osteoporosis
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10. Prevalence of underlying factors
19-Dec-1810 Leiden Center for Bone Quality
CKD MGUS 1∞HPT 2∞HPT HG HT
0%
5%
10%
15%
20%
Prevalence of secondary factors for bone fragility
using laboratory investigations
* Normal BMD
Osteopenia
Osteoporosis
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11. Prevalence of underlying factors
Summary
• 57% of patients with a recent fracture had ≥ 1 underlying factor for
increased bone fragility
• Comparable number of underlying factors in patients with normal BMD,
osteopenia and osteoporosis (47% vs. 57% vs. 62%; p = 0.05)
• 41% of all underlying factors for increased bone fragility were reversible
19-Dec-1811 Leiden Center for Bone Quality
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12. Prevalence of underlying factors
Conclusion
• High prevalence of underlying factors for increased bone fragility
in patients with a recent fracture, independently of BMD status
• High number of underlying factors for increased bone fragility were reversible
• Screening for underlying factors for bone fragility should be considered in the
setting of Fracture Liaison Services, not only in patients with osteoporosis but
also in those with osteopenia or normal BMD
19-Dec-1812 Leiden Center for Bone Quality
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13. VFA versus spine radiography
• Vertebral fractures are associated with increased mortality and morbidity,
and decreased quality of life
• Vertebral fractures have been shown to be predictive for the risk of new
vertebral and non-vertebral fractures
• Vertebral Fracture Assessment (VFA) is performed by bone densitometers in
the same session as BMD measurements
• Conventional spine radiography is considered as the “gold standard” for
detection of vertebral fractures
19-Dec-1813 Leiden Center for Bone Quality
1. Center et al. Lancet 1999
2. Romagnoli et al. Osteoporos Int 2004
3. Johnell et al. Osteoporos Int 2006
4. Black et al. J Bone Miner Res 1999
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14. VFA versus spine radiography
• VFA has been incorporated in a number of clinical guidelines replacing
conventional radiography
• Advantages VFA:
• Patient-friendly
• Lower costs
• Lower radiation doses
• Lower radiation doses could lead to poor visualization
of the contours of vertebrae
19-Dec-1814 Leiden Center for Bone Quality
1. CBO Richtlijn Osteoporose en Fractuurpreventie 2011
2. Kanis et al. Osteoporos Int 2013
3. Van der Velde et al.Osteoporos Int 2017
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15. VFA versus spine radiography
Study design
• Patients ≥ 50 years with a recent fracture
• 2 year inclusion period
• Only patients with available data on both VFA and conventional radiography
were included in the study
Assessment of vertebral fractures
• VFA:
• Hologic QDR Physician Viewer software
• Quantitative evaluation followed by classification using Genant method
• Radiography:
• Radiology report and classification of investigator
• Semiquantitative classification of Genant
19-Dec-1815 Leiden Center for Bone Quality
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16. VFA versus spine radiography
• Sensitivity 0.77 (95% CI, 0.70-0.84)
• Specificity 0.80 (95% CI, 0.76-0.84)
19-Dec-1816 Leiden Center for Bone Quality
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17. VFA versus spine radiography
• 297 (55%) patients had ≥ 1 vertebrae that could not be evaluated by VFA
• 135 (25%) patients had ≥ 3 unevaluable vertebrae
19-Dec-1817 Leiden Center for Bone Quality
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18. VFA versus spine radiography
Summary
• VFA correctly detected 77% of all patients with a vertebral fracture
• VFA missed a vertebral fracture in 30 of 132 (23%) patients
• VFA correctly detected 80% as having no vertebral fracture
• VFA was false positive in 82 of 410 (20%) patients
• More than half of patients had ≥ 1 vertebrae that could not be evaluated by
VFA, the majority of which were at the upper thoracic spine region (level Th4
and Th5)
19-Dec-1818 Leiden Center for Bone Quality
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19. VFA versus spine radiography
Conclusion
• Underperformance of VFA in our center
• Interpretation of VFA data should be with caution
• Check the performance of VFA device against conventional radiography
19-Dec-1819 Leiden Center for Bone Quality
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20. Bone turnover markers
• Bone turnover markers can be easily measured in serum
• Bone formation marker: serum procollagen 1 N-terminal extension peptide
(P1NP)
• Bone resorption marker serum C-terminal crosslinked telopeptide of type I
collagen (CTX)
• BTMs decrease within weeks during treatment; BMD changes slowly
19-Dec-1820 Leiden Center for Bone Quality
1. Vasikaran et al. Osteoporos Int 2011
2. Van den Berg et al. Osteoporosis Int 2018
3. Garnero et al. J Bone Miner Res 1996
4. Seibel et al. Clin Biochem Rev 2006
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21. Bone turnover markers
Study design
• Patients ≥ 50 years with a recent fracture
• 2 year inclusion period
• Patients who started osteoporosis treatment with oral bisphosphonates,
intravenous bisphosphonates or denosumab
• Osteoporosis treatment started within 3 months of baseline
• Available data on BTMs and BMD at baseline and 12-15 months after start of
treatment
19-Dec-1821 Leiden Center for Bone Quality
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22. Bone turnover markers
19-Dec-1822 Leiden Center for Bone Quality
Total (n=127)
Age (years) 67.0 ± 9.3
Male/female (%) 32/95 (25%/75%)
Previous Fracture (%) 52 (41%)
P1NP (ng/mL) 75.8 ± 37.1
CTX (ng/mL) 0.388 ± 0.176
LS BMD (g/cm2) 0.84 ± 0.13
FN BMD (g/cm2) 0.63 ± 0.09
Treatment (oral BP / iv BO / Dmab) 88 / 20 / 19
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23. Bone turnover markers
19-Dec-1823 Leiden Center for Bone Quality
T =0 T = 3 T = 12
0
50
100
150
Follow-up visits
P1NP(ng/ml)
• After 12 months
• P1NP decreased by 64%
• Lumbar spine BMD increased 4.4%
• After 3 months
• P1NP decreased by 51%
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24. Bone turnover markers
19-Dec-1824 Leiden Center for Bone Quality
• After adjustment for time after fracture, (∆T0-T3) P1NP was not
predictive for (∆T0-T12) LS BMD
-50 50 100 150 200
-0.10
-0.05
0.05
0.10
0.15
Δ T0-T12 P1NP
ΔT0-T12 LS BMD
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25. Bone turnover markers
Summary
• Changes in P1NP after 12 months of treatment were predictive changes in
lumbar spine BMD after 12 months of treatment, also after adjustment for
time after fracture
• After adjustment for time after fracture, changes in P1NP after 3 months of
treatment were not predictive for changes in lumbar spine BMD after 12
months of treatment
19-Dec-1825 Leiden Center for Bone Quality
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26. Bone turnover markers
Conclusion
• Changes in bone turnover markers could be used to predict the effect of
treatment with antiresorptive drugs
19-Dec-1826 Leiden Center for Bone Quality
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27. Leiden Fracture Liaison Service
19-Dec-1827 Leiden Center for Bone Quality
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