“management of osteoporosis in primary care – can anything be learned from the uk experience?”...
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“Management of osteoporosis in primary care – can anything
be learned from the UK experience?”
Dr. Mark S CooperConsultant Senior Lecturer in Endocrinology
University of BirminghamRoyal Orthopaedic Hospital and UHB Foundation
NHS Trusts
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
Overview
Osteoporosis disease continuumOsteoporosis disease continuum
Severe osteoporosis
Postmenopausal woman with 2 or more fractures
Osteopaenic/osteoporotic
Postmenopausal woman without
fracture
Healthy spine
Kyphotic spine
Menopausal Established osteoporosis
Postmenopausal woman with fracture
Fractured Neck of Femur
High morbidity and mortality, reduced
independence, expensive to society
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 - individual
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
Impact of osteoporosis – health service
World Health Organisation:
“A progressive systemic skeletal disease characterised by low bone mass and micro-architectural 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
Definition of osteoporosis
Normal versus osteoporotic bone
Normal Osteoporosis
Micro-architechture deterioration
Low bone mass
Operational definition of osteoporosis
Risk factors for fractureRisk 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
Fragility(falls “independent” fracture risk)
Bone densityBone turnoverBone structureetc
Falls risk
FRACTURE
Evolution of UK guidelines
RCP guidelines RCP guidelines 20012001
NICE – National Institute for Health and Clinical
Excellence
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
NICE
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
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)
Consequences of NICE guidelines 2005
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…..
Review of NICE guidelines 2008
Secondary Prevention Secondary Prevention GuidanceGuidance
20082008
First Line Option – Secondary PreventionFirst 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 –Alternative Treatment Options – Secondary PreventionSecondary Prevention
RisedronateRisedronate and and etidronateetidronate are recommended as are recommended as first alternativefirst alternative treatment treatment options in postmenopausal women:options in postmenopausal women:– Who are unable to comply with the instructions for the administration of alendronateWho are unable to comply with the instructions for the administration of alendronate– Who have a contraindication to or are intolerant of alendronateWho have a contraindication to or are intolerant of alendronate
andand– who also have a T-score, age and number of ‘independent clinical risk factors’ as who also have a T-score, age and number of ‘independent clinical risk factors’ as
indicated in the following tableindicated in the following table
Age (years)Age (years) No Clinical Risk No Clinical Risk FactorFactor
1 Clinical Risk 1 Clinical Risk FactorFactor
2 Clinical Risk 2 Clinical Risk FactorsFactors
50-5450-54 Not recommendedNot recommended -3.0-3.0 -2.5-2.5
55-5955-59 -3.0-3.0 -3.0-3.0 -2.5-2.5
60-6460-64 -3.0-3.0 -3.0-3.0 -2.5-2.5
65-6965-69 -3.0-3.0 -2.5-2.5 -2.5-2.5
70 or older*70 or older* -2.5-2.5 -2.5-2.5 -2.5-2.5
In the secondary prevention of osteoporotic fragility fractures
* : 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 PreventionOther Treatment Options – Secondary Prevention
Raloxifene Raloxifene and and Strontium RanelateStrontium Ranelate are recommended as alternative treatment option are recommended as alternative treatment option in postmenopausal women:in postmenopausal women:
– Who are unable to comply with the instructions for the administration of alendronate Who are unable to comply with the instructions for the administration of alendronate andand risedronate or etidronaterisedronate or etidronate
– Who have a contraindication to or are intolerant of alendronate Who have a contraindication to or are intolerant of alendronate andand risedronate or etidronate risedronate or etidronate
– Who also have a T-score, age and number of ‘risk factors’ as indicated in the following tableWho also have a T-score, age and number of ‘risk factors’ as indicated in the following table
Age (years)Age (years) No No Clinical Clinical Risk Risk FactorFactor
1 1 Clinical Clinical Risk Risk FactorFactor
2 2 Clinical Clinical Risk Risk FactorsFactors
50-5450-54 Not recommendedNot recommended -3.5-3.5 -3.5-3.5
55-5955-59 -4.0-4.0 -3.5-3.5 -3.5-3.5
60-6460-64 -4.0-4.0 -3.5-3.5 -3.5-3.5
65-6965-69 -4.0-4.0 -3.5-3.5 -3.0-3.0
70-7470-74 -3.0-3.0 -3.0-3.0 -2.5-2.5
75 or older*75 or older* -3.0-3.0 -2.5-2.5 -2.5*-2.5*
In the secondary prevention of osteoporotic fragility fractures
* : 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 PreventionOther Treatment Options – Secondary Prevention
TeriparatideTeriparatide is recommended as alternative treatment is recommended as alternative treatment option in postmenopausal women:option in postmenopausal women:– Who have a contraindication to or are intolerant of alendronate, Who have a contraindication to or are intolerant of alendronate,
risedronate and strontium ranelate or who have an unsatisfactory risedronate and strontium ranelate or who have an unsatisfactory response (another fragility fracture despite adherence for 1 yr and a response (another fragility fracture despite adherence for 1 yr and a BMD decline below pre-treatment baseline).BMD decline below pre-treatment baseline).
andand
– Who are 55-64 years and have a T-score < -4.0 SD plus more than 2 Who are 55-64 years and have a T-score < -4.0 SD plus more than 2 fracturesfractures
– Who are 65 years or older and have a T-score < -4.0 SD or a T-score 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< -3.5 SD and more than 2 fractures
In the secondary prevention of osteoporotic fragility fractures
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
Secondary prevention 2008 overview
Primary Prevention GuidancePrimary Prevention Guidance
20082008
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!
Initial guidance was restricted only to generic alendronate
First Line Option – Primary PreventionFirst Line Option – Primary Prevention
Age (years)Age (years) Minimum requirements of clinical risk factors Minimum requirements of clinical risk factors and/or indicators of low BMDand/or indicators of low BMD
Dexa T-scoreDexa T-score
Age 65 or youngerAge 65 or younger One risk factor One risk factor and an indicator of Low BMD an indicator of Low BMD T-score of −2.5 SD or T-score of −2.5 SD or belowbelow
Age 65-69Age 65-69 One risk factorOne risk factor T-score of −2.5 SD or T-score of −2.5 SD or belowbelow
Age 70-74Age 70-74 One risk factor One risk factor oror an indicator of Low BMD an indicator of Low BMD T-score of −2.5 SD or T-score of −2.5 SD or belowbelow
Age 75 or olderAge 75 or older Two risk factors Two risk factors oror indicators of Low BMD indicators of Low BMD Not required if the Not required if the clinician considers it clinician considers it inappropriate or inappropriate or unfeasible.unfeasible.
Alendronate is recommended as a treatment option for the primary prevention of osteoporotic fragility fractures in the following groups:
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 PreventionAlternative Treatment Options – Primary Prevention
RisedronateRisedronate and and etidronateetidronate are recommended as are recommended as first alternativefirst alternative treatment options in:treatment options in:– women unable to comply with the instructions for the administration of women unable to comply with the instructions for the administration of
alendronatealendronate
– women who have a contraindication to or are intolerant of alendronatewomen who have a contraindication to or are intolerant of alendronate
andand
– who also have a T-score, age and number of ‘independent clinical risk factors’ who also have a T-score, age and number of ‘independent clinical risk factors’ as indicated in the following tableas indicated in the following table
Age (years)Age (years) No Risk FactorNo Risk Factor 1 Risk Factor1 Risk Factor 2 Risk Factors2 Risk Factors
65-6965-69 Not recommendedNot recommended -3.5-3.5 -3.0-3.0
70-7470-74 -3.5-3.5 -3.0-3.0 -2.5-2.5
75 or older75 or older -3.0-3.0 -3.0-3.0 -2.5*-2.5*
In the primary prevention of osteoporotic fragility fractures
Clinical risk factors = parental history of hip fracture, alcohol intake of 4 or more units per day, rheumatoid arthritis.
Other Treatment Options – Primary PreventionOther Treatment Options – Primary Prevention
Strontium RanelateStrontium Ranelate is recommended as an alternative treatment option in: is recommended as an alternative treatment option in:– women unable to comply with the instructions for the administration of alendronate women unable to comply with the instructions for the administration of alendronate
andand risedronate or etidronate risedronate or etidronate– women who have a contraindication to or are intolerant of alendronate women who have a contraindication to or are intolerant of alendronate andand
risedronate or etidronaterisedronate or etidronate
andand– who also have a T-score, age and number of risk factors as indicated in the following who also have a T-score, age and number of risk factors as indicated in the following
tabletable
Age (years)Age (years) No Risk FactorNo Risk Factor 1 Risk Factor1 Risk Factor 2 Risk Factors2 Risk Factors
65-6965-69 Not recommendedNot recommended -4.5-4.5 -4.0-4.0
70-7470-74 -4.5-4.5 -4.0-4.0 -3.5-3.5
75 or older75 or older -4.0-4.0 -4.0-4.0 -3.0-3.0
RaloxifeneRaloxifene is not recommended as a treatment option for the primary prevention of is not recommended as a treatment option for the primary prevention of osteoporotic fragility fractures in PMO.osteoporotic fragility fractures in PMO.
In the primary prevention of osteoporotic fragility fractures
Criticisms of NICE guidelinesCriticisms of NICE guidelinesClinically perverse – if alendronate not tolerated in a patient then second Clinically perverse – if alendronate not tolerated in a patient then second
line alternative almost certainly restricted unless patient waits until line alternative almost certainly restricted unless patient waits until
fractures or starts to consume excessive alcohol etcfractures or starts to consume excessive alcohol etc
Using original health economic evaluation all these treatments were cost Using original health economic evaluation all these treatments were cost
effective – model changed by NICE in multiple ways, all of which effective – model changed by NICE in multiple ways, all of which
reduced reduced the cost effectivenessreduced reduced the cost effectiveness
e.g. the evidence for hip fracture reduction with strontium accepted by e.g. the evidence for hip fracture reduction with strontium accepted by
the European Licensing Agency but rejected by NICE as a post-hoc the European Licensing Agency but rejected by NICE as a post-hoc
analysis (this has recently been ruled unlawful by the Court of Appeal)analysis (this has recently been ruled unlawful by the Court of Appeal)
Model assumes 100% compliance for side effects but 50% compliance Model assumes 100% compliance for side effects but 50% compliance
for effectiveness etc, etc, etcfor effectiveness etc, etc, etc
Consequences of NICE guidelinesConsequences of NICE guidelinesNo one uses primary prevention guideline because of their complexity No one uses primary prevention guideline because of their complexity
and clinical perversityand clinical perversity
Follow up guidelines for men, younger women and steroid users stalled Follow up guidelines for men, younger women and steroid users stalled
(abandoned?) as no ‘experts’ prepared to produce these in the context (abandoned?) as no ‘experts’ prepared to produce these in the context
of current guidanceof current guidance
As a result of ‘experts’ pointing out errors in analysis people who know As a result of ‘experts’ pointing out errors in analysis people who know
about osteoporosis now excluded from NICE meetings relating to its about osteoporosis now excluded from NICE meetings relating to its
evaluation or treatmentevaluation or treatment
Permanent lack of confidence in the role of NICE as an agency that Permanent lack of confidence in the role of NICE as an agency that
judges cost-effectiveness fairlyjudges cost-effectiveness fairly
Primary care use of medications for primary prevention remains limitedPrimary care use of medications for primary prevention remains limited
ACT4148
Comparison to Australian situationComparison to Australian situation
Health economic evaluation appears to be much more Health economic evaluation appears to be much more
embedded in Australian systemembedded in Australian system
Evaluation judged by panel that appears to have sufficient Evaluation judged by panel that appears to have sufficient
clinical expertise available to avoid ‘clinical perversity’ clinical expertise available to avoid ‘clinical perversity’
evident in some NICE decisionsevident in some NICE decisions
It appears that the Prescriptions Benefits Advisory It appears that the Prescriptions Benefits Advisory
Committee does not try to develop its own guidelines (in Committee does not try to develop its own guidelines (in
contrast to NICE)contrast to NICE)
Alternative approach to determining risk Alternative approach to determining risk and guiding treatmentand guiding treatment
WHO have introduced its own way of estimating fracture risk using WHO have introduced its own way of estimating fracture risk using
information from large numbers of patientsinformation from large numbers of patients
Most areas of the world are moving towards using this fracture risk Most areas of the world are moving towards using this fracture risk
algorithm (FRAX)algorithm (FRAX)
Web based and easy to useWeb based and easy to use
Incorporates all the information and gives individual items appropriate Incorporates all the information and gives individual items appropriate
weightingweighting
In UK output can be used to determine treatment (developed by National In UK output can be used to determine treatment (developed by National
Osteoporosis Guidelines Group – NOGG)Osteoporosis Guidelines Group – NOGG)
73 Treatment Discordant
7 Lifestyle/ NOGG Treat
42 Treated/ NOGG Lifestyle
37 Osteoporosis spine
6 No Information
24 referred to Metabolic clinic
5 Disagree NOGG(4 Treat/NOGG
lifestyle)
13 Agree NOGG(7 Treat/6 lifestyle)
Implications of FRAX – reduced emphasis on spine fracture risk n=288 patients
ConclusionsConclusions UK NICE guidelines for osteoporosis emphasise the use of UK NICE guidelines for osteoporosis emphasise the use of alendronate in patients at increased risk of fracturealendronate in patients at increased risk of fracture
Attempts by NICE to incorporate fracture risk estimates that go Attempts by NICE to incorporate fracture risk estimates that go beyond BMD problematic, difficult to use and hard to justify when beyond BMD problematic, difficult to use and hard to justify when accurate fracture risk estimation tools now availableaccurate fracture risk estimation tools now available
Other osteoporosis drugs can be used if alendronate intolerant but Other osteoporosis drugs can be used if alendronate intolerant but differing thresholds present difficulties in patient encountersdiffering thresholds present difficulties in patient encounters
Long term, use of FRAX and NOGG thresholds more likely to have Long term, use of FRAX and NOGG thresholds more likely to have more impactmore impact