Transcript Falls, Dizziness and Syncope in older people

Osteoporosis and Fracture prevention
in older adults
Frances Dockery
Dept. of Ageing and Health
St Thomas’ Hospital
London
Osteoporosis
• Osteoclasts come from myeloid progenitor cells
• RANK-ligand – a cytokine produced by osteoblasts – major
stimulant of osteoclast differentiation Osteoprogegerin inhibts
• Osteoclasts secrete H+ ions; need acid surround – ↑ size, and
function (x 10-20 bone-resorptive abilities)
• Osteoblasts – from mesenchymal stem cells
• Can’t mineralise in acid environment
• Acid in bony environment:
• Hypoxia
• chronic kidney disease
• Age – yellow fatty marrow, less vascular
• Diabetes
• HIV
• Respiratory disease
• Coca-cola (3.5mEq KCl equivalent)
Osteoporosis
Fragility fractures
• Definition: a fracture as a result of a fall from standing
height or less
• On average, approx 30% of all fragility fractures will
be osteoporotic, or severely osteopenic
• Half of all hip fracture patients have had at least one
previous fragility fracture:
– Missed opportunity to prevent a hip fracture – which
has the highest morbidity and mortality
Early secondary
prevention – prevent
hip fractures
• A vertebral fracture =
– 1/5 will have a 2nd vertebral fracture within a year
– Associated with a 3-fold increase in hip fracture risk
– A 2-fold increase in mortality
• 1/3 to 1/4 hip fractures have died after 1 year
– (Expected mortality for age-matched would be 1/10)
Alendronate vs.
placebo in
established
osteoporosis
Vertebral
Non-vertebral
NNT:
-90 for 3 y to prevent 1 Hip #
-35 for 3 y to prevent 1 Vert #
NO PATIENT OVER
THE AGE OF 80RS !
Black, D. M. et al.
J Clin Endocrinol Metab 2000;85:4118-4124
Wrist
All fractures
Hip
DEXA BONE DENSITY
SCANNING
• T score: no. of standard
deviations below healthy young
same sex person
• Z score: no. of SD’s below agematched same sex person
• WHO defined cut-off defining
disease “osteoporosis”
– T of -2.4: disease not present
FRACTURE PREVENTION, UK
National Institute of Clinical Excellence (NICE):
Secondary prevention of fragility fracture:
• TREAT all female fragility fractures >75 yrs. No DXA needed
• Females >50 yrs: DXA first
• Males any age: DXA first
National Clinical Audit on Falls and Bone Health ‘07 & ‘09
Royal College of Physicians UK
• Showed significant deficiencies in both primary and
secondary care in falls and fracture prevention
Mr Fred Walker
• 86 year old man
• Hip fracture
• COPD, previous MI.
• Hiatus hernia
• Walked with stick pre- fracture, now just transferring with
zimmer frame
• Lives in care home
• Dementia, doesn’t recognise family most days
Mrs. Mavis Brown
• 80 years old. Trips on street. 1st fall in several years.
• Colles fracture
• Medications: Aspirin, Omeprazole
• Bone health advice?
• Keen to be screened before treatment for osteoporosis
• DXA scan: T score -2.1 total hip, -2.0 spine
• Advice now?
80% of Fractures Occur in Women Who
Are Not Osteoporotic
450
Fracture rate
No. of women with fractures
45
400
40
350
35
300
30
250
25
200
20
150
15
10
100
5
50
0
>1.0
1.0 to 0.5
0.5 to 0.0 0.0 to –0.5 –0.5 to –1.0 –1.0 to –1.5 –1.5 to –2.0 –2.0 to –2.5 –2.5 to –3.0 –3.0 to –3.5
< –3.5
Number of women with fractures
Fracture rate per 1000 person-years
50
0
BMD
Majority of fractures occur in T-score between -0.5 and -2.5
Reprinted from Siris et al. Arch Intern Med. 2004;164:1108.
Bone mineral density and risk factors
Hip Fx Rate
(per 1000 woman-years)
30
Need to move away
from BMD
measurement,
defining a ‘disease’
and treatment
threshold
25
20
15
10
5
0
Lowest
Third
Heel BMD
>=5
Middle
Third
3-4
Highest
Third
0-2
# Risk Factors
Calculating Absolute Fracture Risk
http://www.shef.ac.uk/FRAX
Data source – FRAX
>60,000 pts
•
•
•
•
•
•
•
•
European Prospective Osteoporosis Study (EPOS)
Canadian Multicentre Osteoporosis Study (CaMos)
Rotterdam, Netherlands
Rochester, US
Sheffield, UK
Dubbo, Australia
Hiroshima, Japan
Gothenburg, Germany
• Taiwanese data recently added
– FRAX launched – July 2010
FRAX - Taiwan
National Osteoporosis Guideline
Group (NOGG) – UK only
60yr old lady, UK. Colles fracture. T score -2.1
60yr old lady, UK. Colles fracture. T score -2.1 NOGG guidance
80yr old lady, UK. Colles fracture. T score -2.1
80yr old lady, UK. Colles fracture. T score -2.1
Limitations of FRAX/NOGG
• Proposes wide under-treatment of older age groups ..
Foolish? Ageist?
• NO account of falls risk is included
– 1SD BMD reduction increases hip fracture risk x2
– A sideways fall increases hip fracture risk x3 !
• Cannot estimate treatment benefit without global
assessment – what is the falls risk / what are the other
reversible falls and/or fracture risk factors?
• Far more may be gained by treated their urinary frequency
and arranging cataract surgery..
NOGG and NOF guidelines for management of osteoporosis,
with their application to a cohort of 1471 healthy older women
Bolland, M. J. et al. J Clin Endocrinol Metab 2010;95:1856-1860
21%
46%
US: better at identifying those who subsequently fractured,
but at far greater resource utilization – long term costs saved
80yr old lady, China. Colles fracture. T score -2.1
80yr old lady, Taiwan. Colles fracture. T score -2.1
80yr old lady Hong Kong. Colles fracture. T score -2.1
Drug therapies in osteoporosis
*=data in older age groups
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•
•
•
•
•
•
•
•
Alendronate – Men.
Hwang, J Bone Miner Metab. 2010
Risedronate*
Ibandronate – 3-monthly injection. ↓ vertebral # only.
Strontium* – ↓ risk most sites 1y in pts >80yrs
Teriparatide* – injection, expensive
Calcitonin – injection, nausea, short-term use
Raloxifene* – vertebral only. ↑ VTE and stroke risk.
Tibolone – ↑ stroke rise
Denosumab (RANK ligand inhibitor)
• Ethnic and racial differences in fracture incidence
• Ibandronate in Japanese vs. Caucasian women:
Similar pharmacokinetics (Phase I studies)
Pillai, Int J Clin Pharmacol Ther. 2006
• Alendronate for 2 yrs: similar skeletal benefits in
Asian and Caucasian (Hawaii)
Wasnich, Osteoporos Int. 1999
Noncompliance Increases Fracture Risk
•Compliance with oral bisphosphonates is poor
•Up to 50% of patients are noncompliant within 1 year
•Probability of fracture increases as compliance decreases
- Siris ES et al. Mayo Clin Proc.2006;81:1013-1022.
- Seeman E, Compston J, Adachi J et al. Osteoporos Int 2007 18:711–719
- Cramer J and Silverman S. Am J Med 2006 119 12S-17S
ZOLEDRONIC ACID
HORIZON-2 study (Recurrent Fracture Trial)
Lyles et al. N Engl J Med 2007
Double-blind, randomized, placebo-controlled trial
2127 men and women with recent hip fracture
5mg annual infusion Zoledronic Acid vs. placebo
Calcium/Vitamin D supplements throughout
Demographics
Sex, n (%)
Male
Female
Age group (year), n (%)
<65
65-74
75-84
≥85
Age (year)
Mean (SD)
Min, Max
Caucasian
ZOL 5 mg
(n = 1065)
Placebo
(n = 1062)
248 (23.3)
817 (76.7)
260 (24.5)
802 (75.5)
172 (16.2)
307 (28.8)
446 (41.9)
140 (13.1)
192 (18.1)
269 (25.3)
449 (42.3)
152 (14.3)
74.4 (9.48)
50.0, 95.0
91.4%
74.6 (9.86)
50.0, 98.0
90.9%
Cumulative Incidence (%)
Reduced Cumulative 3-Year Risk of Clinical
Fractures by 35%
20
18
Hazard Ratio, 0.65 (95% CI, 0.50–0.84)
P = 0.001
16
Absolute Risk Reduction, 5.3%
35%
14
12
10
8
6
ZOL 5mg (n=1065)
Placebo (n =1062)
4
2
0
0
4
8
12
16
20
24
28
32
36
Month
No. at Risk
ZOL 5 mg 1065 1013
950
895
762
628
473
316 212
129
Placebo
947
884
742
611
443
305
119
1062 1010
Adapted from Lyles et al 2007
190
Cumulative Incidence (%)
Non-significant reduction in Hip Fracture Risk
6
Hazard Ratio, 0.70 (95% CI, 0.41–1.19)
P = 0.18
5
30%NS
4
3
2
ZOL 5 mg (n = 1065)
Placebo (n = 1062)
1
0
0
4
8
12
16
20
Month
24
28
32
36
ZOL 5 mg 1065 1027
978
931
794
664
499
344
233
139
Placebo
981
927
787
664
492
347
223
139
No. at Risk
1062 1025
Adapted from Lyles et al 2007
Cumulative Incidence (%)
Reduced Risk of All-Cause Mortality
18
28%
Hazard Ratio, 0.72 (95% CI, 0.56–0.93)
P = 0.01
Absolute Risk Reduction, 3.7%
16
14
12
10
8
6
4
ZOL 5 mg (n = 1065)
Placebo (n = 1062)
2
0
0
4
8
12
16
20
24
28
32
36
Month
No. at Risk
ZOL 5 mg 1054 1029
987
943
806
674
507
348
237
144
Placebo
993
945
804
681
511
364
236
149
1057 1028
Adapted from Lyles et al 2007
Denosumab
• Monoclonal antibody to RANK ligand – the main activator
of osteoclasts
• 6-monthly injection
• Reduced fracture risk all sites in post-menopausal women
(FREEDOM, n=>7,000), androgen-deprived men (HALT,
n=1400), Phase 3 trial
• 30% of patients in FREEDOM were age >75yrs.
• 83% aged >70 yrs in HALT
• Almost all Caucasian ..
What about renal failure (CKD)
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•
•
•
Dialysis patients have a 4-fold increase in hip fracture risk
DXA a poor predictor of fracture in CKD (esp spinal readings)
PTH rises with eGFR <60 due to ↓ 1,25 OH activity
PTH commonly >200
• Bisphosphonates – none are licensed for eGFR <30
– Risk of precipitation adynamic bone disease – osteoblasts
& osteoclasts “switched off” ? over-suppression of PTH
• Keep PTH <70. Keep PO4 down. Calcitriol. Falls prevention
• Cinacalcet – Calcium-sensing receptor antagonist
• Switches PTH off – short-term ‘fix’ - Balance.. adynamic bone
– being trialled to reduce fracture rates in renal failure
Fracture Liaison Service
• How to keep the
hip fractures
from
happening…
• Address the first
fracture –
prevent the next
When to stop treatment for
osteoporosis
• Unclear..
• Bone turnover markers still suppressed 5 years
after stopping Alendronate No increased fracture
risk, but for high risk patients may benefit from
continuing beyond 5 years to reduce vertebral
fracture risk
FIT Trial – Black, JAMA 2006)
Secondary Fracture prevention at STH
• Audit in Orthopaedic fracture clinic 2007:
• <75yrs: 21% screened / treated for osteoporosis
• >75yrs: 40% screened / treated for osteoporosis
• >70 yrs: 20% referred for falls clinic
• Intervention: Referral forms (patient name only, needed)
for Falls /Osteoporosis clinics, left in fracture clinic
• Re-audit 2009:
• 75yrs: 43% screened / treated for osteoporosis
• >75yrs: 17% screened / treated for osteoporosis
• >70 yr olds: 25% referred for falls clinic
• Intervention: Fracture Liaison Nurse appointed 2009
FRACTURE, AGED OVER 50 YRS
HIGH IMPACT
FRACTURE, NIL
RISK FACTORS –
NO F/U
FLP ASSESSMENT (falls & osteoporosis risk factor checklist)
FRACTURE
LIAISON SERVICE
PATHWAY STH
LOW IMPACT FRACTURE
GP
LETTER,
CC TO
PATIENT
OUT OF AREA
WITHIN LOCAL CATCHMENT AREA
Checklist for falls
clinic referral
<70yrs
NO OSTEOPOROSIS
TREATMENT
ON ADEQUATE
TREATMENT FOR > 2YRS
•Dizziness
•Poor balance
DXA &
BLOODS
DXA &
BLOODS
AGE >70Y
OR
<70Y WITH FALLS
RISK FACTORS
(per checklist)
BLOODS +/- DXA
•Poor vision
•TGUG >15sec’s
NURSE-LED TELEPHONE
CLINIC – GP LETTER, CC
TO PATIENT (+ option for
all GP’s to refer to clinic)
OSTEOPOROSIS
CLINIC (failed Rx
and CKD)
FALLS CLINIC
(if not recently known
to falls service)
Screening tool / GP advise letter
Blood Results (Date): 02/06/2009
Creatinine
63
Hb
13.6
Corrected Calcium
2.26
Clinic Name: Fracture Liasion Service
Consultant: Dockery
Clinic Date: 26 June 2009
Dear Dr Mcadam-freud
Re: MRS ELAINE O'GORMAN
Hospital No: 1543574K
Address: 55 ROTHSAY STREET, LONDON, SE1 4UF
Date of Birth: 21-09-1952
NHS No: 4564033778
DXA Results (Date): 18/06/2009
Spine T score
-2.7
Osteoporosis Treatment History
Nil
Falls Risk Factors
No of falls in last 12 months
Poor vision
Urinary incontinence
Sedative medications
Lying BP
Timed-up-and-go
0
16
normal
FRAX & NOGG Guidance (National Osteoporosis Guideline Group)
Treatment recommended
Yes
Action Plan
Osteoporosis treatment
Falls clinic recommended
Yes
Yes
Osteoporosis clinic recommended
Lifestyle advise given
Conclusion
She has Osteoporosis according to DXA scan. I tried to contact Mrs O’Gorman by telephone but no
response. Treatment with an anti-resorptive, such as Alendronate or Risedronate is indicated in
conjunction with Ca/vitamin D supplements, if you could kindly arrange. She should also
have thyroid function checked as not done here unfortunately.
I have recently assessed this patient following a recent fragility fracture:
Osteoporosis Risk Factors
nd
Fracture site: Stress fracture 2 Metatarsal bone and toe
Height: 174
Weight: 84
BMI: 27.7
Previous fragility fracture
N
Parental history of hip #
Current smoker
Yes
Parental history of
osteoporosis
Rheumatoid arthritis
N
Steroid use 5mg x 3/12
Inflammatory bowel disease
N
Alcohol  3 units /day
Chronic liver disease
N
Type 1 Diabetes
Untreated overactive thyroid
N
Cushing’s
Premature menopause
N
Coeliac disease
(<45y)
Hypogonadism (male)
N/A
Anorexia / malnutrition
TSH
ESR
LFT’s
Yes
N
N
N
N
N
N
N
Alternatively if you wish to refer her to the osteoporosis clinic at this hospital please sign and stamp
the referral slip below and return to the above address/fax.
Yours sincerely
Electronically checked
Tempie Mambiravana
Fracture Liaison Nurse
CC Elaine Gorman
Total hip T score
From/ To (Approx)
Poor balance / gait
Dizziness
Anti-hypertensives
Cognitive impairment
1 minute standing BP
Rises from chair without using
arms
-0.7
PLEASE ARRANGE OSTEOPOROSIS CLINIC FOR THIS PATIENT AT GUY’S AND ST
THOMAS’ HOSPITAL
SURGERY STAMP
Signed __________________________
General Practitioner
STH FRACTURE LIAISION SERVICE
May 2009 – May 2010 (n=938 attendees)
AGE CATEGORIES
GENDER
M
29%
F
71%
500
450
400
350
300
250
200
150
100
50
0
459
274
182
23
<50Y
50-64Y
65-74Y
>75Y
692 pts assessed by Fracture Liaison Nurse
- Fracture and falls risk factors
- Bloods
- DXA scan
- Advise to GP
A previous fragility fracture was reported in 26%
of whOM only a third were ever screened with
DXA or treated for osteoporosis
STH experience with FRAX/NOGG:
n=610 fragility fractures
FRAX/NOGG ADVICE
Age
Men
<60y (n=90)
60-74y (n=60)
75y (n=28)
Women
<60y (n=186)
60-74y(n=146)
75y (n=100)
No
treatment
Refer DXA
Treat, no DXA
46%
52%
2%
52%
100%
47%
0%
2%
0%
4%
1%
4%
69%
70%
72%
27%
29%
24%
•Younger patients more likely to report risk factors - Alcohol, parental hip #, RA
•Age discrepancies still exist on excluding those with risks
DXA RESULTS in n =329 pts
Normal, 118,
36%
Osteoporosis,
71, 22%
Osteopenia,
140, 42%
• 21% (n = 30) of Osteopenic patients warranted antiresorptive treatment according to FRAX/NOGG
• Treatment recommended in 31% of all fragility fractures
OSTEOPOROSIS SCREENING &
TREATMENT AUDIT – 2nd cycle
FRAGILITY
FRACTURES
AGE > 75 YEARS EITHER
SCREENED / TREATED
AGE 50 – 74 YEARS
SCREENED / TREATED
2007:
40%
21%
2009:
43%
17%
2010:
87%
74%