“Management of osteoporosis in
primary care – can anything be
learned from the UK experience?”
Dr. Mark S Cooper
Consultant Senior Lecturer in Endocrinology
University of Birmingham
Royal Orthopaedic Hospital and UHB Foundation
NHS Trusts
Overview
Importance of osteoporosis
Changing approach to how risk of osteoporotic
fracture is estimated
Evolution (and implosion) of guidelines for detecting
and treating osteoporosis in the UK
Implications for primary care when guidelines change
e.g. if ways of assessing fracture risk change
Osteoporosis disease continuum
Kyphotic
spine
Healthy
spine
Menopausal
Osteopaenic/
osteoporotic
Postmenopausal
woman without
fracture
Established
osteoporosis
Severe
osteoporosis
Postmenopausal woman Postmenopausal woman
with 2 or more fractures
with fracture
Fractured Neck of Femur
High morbidity and
mortality, reduced
independence,
expensive to society
Impact of osteoporosis - individual
Approximately one in five patients die within a year as
a result of their hip fracture
Half who fracture a hip cannot live independently
subsequently and 64% will need a walking aid
40% of patients with clinical vertebral fracture have
constant pain, most have difficulty with daily living
The reduction in quality of life from a vertebral
fracture is half of that following hip fracture
Impact of osteoporosis – health service
More than 2 million hospital bed days are lost to
fracture per year in England
Mean length of stay 25 days, 1 in 5 orthopaedic beds
occupied by patients with hip fracture
Admission rate for fractured NOF has increased in
England by over 2%/year since 1990
A conservative estimate for social/hospital cost of hip
fracture is <£1.8 billion/year in the UK
This is expected to rise to £2.1 billion by 2020
Definition of osteoporosis
World Health Organisation:
“A progressive systemic skeletal disease
characterised by low bone mass and microarchitectural deterioration of bone tissue, with a
consequent increase in bone fragility and
susceptibility to fracture”
Distinct from osteomalacia where there is normal
amount of bone but inadequate mineralisation
Consequence is an increased risk of fracture
Normal versus osteoporotic bone
Microarchitechture
deterioration
Low bone mass
Normal
Osteoporosis
Operational definition of osteoporosis
Risk factors for fracture
•
•
•
•
•
•
•
•
•
•
Age
Gender
Prior Fracture
Low BMD
Parental history of fracture*
Low BMI
Current Smoking*
Alcohol intake*
Ever Corticosteroid use
Secondary causes (e.g. RA, early menopause, coeliac disease)
* Largely independent of BMD
Previous emphasis almost entirely on BMD assessment. Can the factors
that are independent of BMD be incorporated into guidelines?
Incidence of Fracture per
100,000 Person-Years
Relationship between osteoporosis
and fracture
Bone density
Bone turnover
Bone structure
etc
Fragility
(falls “independent” fracture risk)
FRACTURE
Falls risk
Evolution of UK
guidelines
RCP guidelines
2001
NICE – National Institute
for Health and Clinical
Excellence
NICE
Established in 1999 to address ‘post-code’ lottery
Large disparities were present in access to medical
services between regions in England (and rest of UK)
Until then, general lack of health economic evaluation for
medications
NICE set up to evaluate whether treatments were cost
effective relative to each other
Funding for NICE approved (cost effective) medications
should then be made available everywhere in England
NICE
In 2005 NICE produced guidance for secondary
prevention of osteoporotic fracture
Only applied to post-menopausal women, didn’t cover
patients taking steroids
Covered bisphosphonates, raloxifene, and teriparatide
Extensive economic modelling to determine when drugs
would be cost effective judged against NICE standards
Calcium and vitamin D use recommended along with all
treatments if possibility of deficiency of either
Summary algorithm
Teriparatide recommended:
in women >65 years who have had an unsatisfactory
response to, or are intolerant of, bisphosphonates
and:
• have an extremely low BMD (with a T-score of –4
SD or below),
or
• have a very low BMD (with a T-score of –3 SD or
below)
+ multiple fractures (more than two)
+ 1 or more additional age independent risk factor
Consequences of NICE guidelines 2005
General acceptance
Debate about role of DXA scanning – needed or not?
Requirement not to scan removed ‘post-code’ issue
Teriparatide guidance resulted in access to this medication
to those most at need. Primary Care Trusts were obliged
to fund this if NICE conditions met
However, access to treatment for other groups potentially
reduced e.g. women at high risk of fracture that had not
yet fractured (primary prevention)
Review of NICE guidelines 2008
It was intended that NICE review secondary prevention
guidelines in 2008
Also were to produce primary prevention guidance
Since first guidelines were produced very little new
effectiveness data published but cost of alendronate had
fallen dramatically
Stakeholders expected a corresponding improvement in
cost-effectiveness of treatment BUT…..
Secondary Prevention
Guidance
2008
First Line Option – Secondary Prevention
Alendronate is recommended as a treatment option for
the
secondary
prevention
of
osteoporotic
fragility
fractures in postmenopausal women who have a T-score
of −2.5 SD or below. In women aged 75 years or older, a
DXA scan may not be required if the responsible
clinician considers it to be clinically inappropriate or
unfeasible.
Alternative Treatment Options – Secondary Prevention
In the secondary prevention of osteoporotic fragility fractures
Risedronate and etidronate are recommended as first alternative treatment
options in postmenopausal women:
– Who are unable to comply with the instructions for the administration of alendronate
– Who have a contraindication to or are intolerant of alendronate
and
– who also have a T-score, age and number of ‘independent clinical risk factors’ as
indicated in the following table
Age (years)
No Clinical Risk
Factor
1 Clinical Risk
Factor
2 Clinical Risk
Factors
50-54
Not recommended
-3.0
-2.5
55-59
-3.0
-3.0
-2.5
60-64
-3.0
-3.0
-2.5
65-69
-3.0
-2.5
-2.5
70 or older*
-2.5
-2.5
-2.5
* : For woman aged 75 years or older, a DXA scan may not be required if the responsible clinician considers
it to be clinically inappropriate or unfeasible.
Independent clinical risk factors = parental history of hip fracture, alcohol intake of 4 or more units per day,
rheumatoid arthritis.
Other Treatment Options – Secondary Prevention
In the secondary prevention of osteoporotic fragility fractures
Raloxifene and Strontium Ranelate are recommended as alternative treatment option
in postmenopausal women:
–
–
–
Who are unable to comply with the instructions for the administration of alendronate and
risedronate or etidronate
Who have a contraindication to or are intolerant of alendronate and risedronate or etidronate
Who also have a T-score, age and number of ‘risk factors’ as indicated in the following table
Age (years)
No Clinical Risk
Factor
1 Clinical Risk
Factor
2 Clinical Risk
Factors
50-54
Not recommended
-3.5
-3.5
55-59
-4.0
-3.5
-3.5
60-64
-4.0
-3.5
-3.5
65-69
-4.0
-3.5
-3.0
70-74
-3.0
-3.0
-2.5
75 or older*
-3.0
-2.5
-2.5*
* : For woman aged 75 years or older, with 1 or more independent clinical risk factor or indicators of low
BMD has not previously had her BMD measured, a DXA scan may not be required if the responsible
clinician considers it to be clinically inappropriate or unfeasible.
Other Treatment Options – Secondary Prevention
In the secondary prevention of osteoporotic fragility fractures
Teriparatide is recommended as alternative treatment
option in postmenopausal women:
– Who have a contraindication to or are intolerant of alendronate,
risedronate and strontium ranelate or who have an unsatisfactory
response (another fragility fracture despite adherence for 1 yr and a
BMD decline below pre-treatment baseline).
and
– Who are 55-64 years and have a T-score < -4.0 SD plus more than 2
fractures
– Who are 65 years or older and have a T-score < -4.0 SD or a T-score
< -3.5 SD and more than 2 fractures
Secondary prevention 2008 overview
Much more complicated guidance
Use of risedronate, raloxifene and strontium more
restricted in an age and risk factor dependent manner
Teriparatide use now allowed for women age 55-65 if very
high risk of fracture
Primary Prevention Guidance
2008
Initial guidance was restricted only
to generic alendronate
In initial proposals it was indicated that only generic
alendronate and etidronate would be evaluated
If generic alendronate or etidronate not tolerated then no
treatment should be offered
After considerable protests, and an upheld appeal that
other treatments should be evaluated revised guidance
produced
Revised guidance is not easy to summarise!
First Line Option – Primary Prevention
Alendronate is recommended as a treatment option for the primary prevention of
osteoporotic fragility fractures in the following groups:
Age (years)
Minimum requirements of clinical risk factors
and/or indicators of low BMD
Dexa T-score
Age 65 or younger
One risk factor and an indicator of Low BMD
T-score of −2.5 SD or
below
Age 65-69
One risk factor
T-score of −2.5 SD or
below
Age 70-74
One risk factor or an indicator of Low BMD
T-score of −2.5 SD or
below
Age 75 or older
Two risk factors or indicators of Low BMD
Not required if the
clinician considers it
inappropriate or
unfeasible.
Clinical risk factors = parental history of hip fracture, alcohol intake of 4 or more units per day, rheumatoid
arthritis.
Indicators of low BMD = low body mass index (defined as less than 22 kg/m2) and medical conditions
such as ankylosing spondylitis, Crohn’s disease, conditions that result in prolonged immobility, and
untreated premature menopause.
Alternative Treatment Options – Primary Prevention
In the primary prevention of osteoporotic fragility fractures
Risedronate and etidronate are recommended as first alternative
treatment options in:
– women unable to comply with the instructions for the administration of
alendronate
– women who have a contraindication to or are intolerant of alendronate
and
– who also have a T-score, age and number of ‘independent clinical risk
factors’ as indicated in the following table
Age (years)
No Risk Factor
1 Risk Factor
2 Risk Factors
65-69
Not recommended
-3.5
-3.0
70-74
-3.5
-3.0
-2.5
75 or older
-3.0
-3.0
-2.5*
Clinical risk factors = parental history of hip fracture, alcohol intake of 4 or more units per day, rheumatoid
arthritis.
Other Treatment Options – Primary Prevention
In the primary prevention of osteoporotic fragility fractures
Strontium Ranelate is recommended as an alternative treatment option in:
– women unable to comply with the instructions for the administration of alendronate
and risedronate or etidronate
– women who have a contraindication to or are intolerant of alendronate and
risedronate or etidronate
and
– who also have a T-score, age and number of risk factors as indicated in the following
table
Age (years)
No Risk Factor
1 Risk Factor
2 Risk Factors
65-69
Not recommended
-4.5
-4.0
70-74
-4.5
-4.0
-3.5
75 or older
-4.0
-4.0
-3.0
Raloxifene is not recommended as a treatment option for the primary prevention of
osteoporotic fragility fractures in PMO.
Criticisms of NICE guidelines
Clinically perverse – if alendronate not tolerated in a patient then second
line alternative almost certainly restricted unless patient waits until
fractures or starts to consume excessive alcohol etc
Using original health economic evaluation all these treatments were cost
effective – model changed by NICE in multiple ways, all of which
reduced reduced the cost effectiveness
e.g. the evidence for hip fracture reduction with strontium accepted by
the European Licensing Agency but rejected by NICE as a post-hoc
analysis (this has recently been ruled unlawful by the Court of Appeal)
Model assumes 100% compliance for side effects but 50% compliance
for effectiveness etc, etc, etc
Consequences of NICE guidelines
No one uses primary prevention guideline because of their complexity
and clinical perversity
Follow up guidelines for men, younger women and steroid users stalled
(abandoned?) as no ‘experts’ prepared to produce these in the context of
current guidance
As a result of ‘experts’ pointing out errors in analysis people who know
about osteoporosis now excluded from NICE meetings relating to its
evaluation or treatment
Permanent lack of confidence in the role of NICE as an agency that
judges cost-effectiveness fairly
Primary care use of medications for primary prevention remains limited
ACT4148
Comparison to Australian situation
Health economic evaluation appears to be much more
embedded in Australian system
Evaluation judged by panel that appears to have sufficient
clinical expertise available to avoid ‘clinical perversity’
evident in some NICE decisions
It appears that the Prescriptions Benefits Advisory
Committee does not try to develop its own guidelines (in
contrast to NICE)
Alternative approach to determining risk
and guiding treatment
WHO have introduced its own way of estimating fracture risk using
information from large numbers of patients
Most areas of the world are moving towards using this fracture risk
algorithm (FRAX)
Web based and easy to use
Incorporates all the information and gives individual items appropriate
weighting
In UK output can be used to determine treatment (developed by National
Osteoporosis Guidelines Group – NOGG)
Implications of FRAX – reduced emphasis
on spine fracture risk n=288 patients
73 Treatment
Discordant
7 Lifestyle/
NOGG Treat
42 Treated/
NOGG Lifestyle
37 Osteoporosis
spine
24 referred to
Metabolic clinic
5 Disagree NOGG
(4 Treat/NOGG
lifestyle)
6 No Information
13 Agree NOGG
(7 Treat/6 lifestyle)
Conclusions
UK NICE guidelines for osteoporosis emphasise the use of
alendronate in patients at increased risk of fracture
Attempts by NICE to incorporate fracture risk estimates that go
beyond BMD problematic, difficult to use and hard to justify when
accurate fracture risk estimation tools now available
Other osteoporosis drugs can be used if alendronate intolerant but
differing thresholds present difficulties in patient encounters
Long term, use of FRAX and NOGG thresholds more likely to have
more impact