“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