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Hot Topics on the

NOS Helpline
Rose Toson
Osteoporosis Specialist Nurse
(Information and Support)

12 October 2017
AIMS

1. Explore current clinical issues –


implications for ‘patients’-helpline
“Hot Topics”
2. Sharing our dilemmas & solutions
3. Look at the evidence & current
guidance

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The Helpline Nurses

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What do we do ?o?

• Give information & support on all aspects of


osteoporosis & bone health

• Speak with public, carers, AHPs and respond to


email & letter enquiries

• Give talks to support groups, AHPs & others e.g.


Nursing in Practice conference

• Research the evidence & write osteoporosis


literature

• Work hard at professional updating!

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What do we get
asked?
Risks
Drug treatments
benefits
Complementary therapies
Problems with
daily living Problems Side effects
Exercise with taking
Fracture
physiotherapy management
Alcohol
Pain smoking food
Helpline

Preventing osteoporosis
understanding and fractures
Risk factors
osteoporosis
Diagnosis and fracture Fall
risk assessment prevention
exercise
Types of
Scan results
scanning access
Respond to media stories

‘Drinking too
much cola can
cause weak bones
and even
paralysis, experts
warn’
Helpline

Explain new diagnosis / understand


osteoporosis
Fracture risk assessment

Drug treatments & adverse effects

Living with fractures

Carers / advocates
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Explain osteoporosis-
what worries our
callers

• Receptionist phoned me to tell me to collect a


prescription-it wasn’t explained to me-we can
explain the diagnosis

• I don’t understand my test results – explain these

• I’m fit and health conscious-why has this happened


to me? Explain risk factors

• I don’t like taking drugs- can I manage with diet


and exercise? Fracture risk assessment

• I’m sensitive to drugs –give the facts about Tx


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Explaining
osteoporosis

The Living Skeleton - Stage 1

Osteoblast
filling the cavity
Osteocytes with new bone -
Cells inside bones detect process takes
mechanical loading & 3 to 4 months
need for bone
renewal & repair

All the cells


‘communicate’ with each
other to regulate the
bone renewal processes

Osteoclast
dissolving bone &
creating a cavity –
process takes
3 to 4 weeks
Explaining
osteoporosis

The Living Skeleton


But it’s a lot more complicated
than that… !

CELL SCIENCE AT A GLANCE


Bone remodelling at a glance
Julie C. Crockett, Michael J. Rogers, Fraser P. Coxon, Lynne J. Hocking, Miep H. Helfrich 11
J Cell Sci 2011 124: 991-998;
Explaining
osteoporosis

Osteoblast
(on an artificial surface in a lab)

© Bone Research Society 2015-2016

Osteoclast dissolving bone

© 2011 AMMRF, University of Sydney

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Explaining
osteoporosis

© Bone Research Society 2015-2016


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Explaining osteoporosis &
fracture risk
Fracture pathogenesis

Fracture
Bone
strength Trauma

Bone Bone Risk of Type


architecture mass fall of fall

Bone Bone Bone Intrinsic Extrinsic


size density loss
Assessing
fracture risk

Risk factors
Modifiable Non modifiable
• BMD • Age

• Alcohol • Gender

• Weight <20kg m2 • Ethnicity

• Smoking • Previous fragility fracture

• Physical inactivity • Family history osteoporosis /


parental hip fracture
• Co-existing disease: eg
Diabetes, RA, Epilepsy, • Early menopause
Gastrointestinal /Endocrine
disease • BMD

• Pharmacological
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Preventing, treating &
managing osteoporosis

New Guidance to be aware of

NOGG Clinical guideline for the prevention and


treatment of osteoporosis
Updated March 2017

SDCEP Oral Health Management of Patients at


Risk of Medication-related Osteonecrosis of the Jaw
Updated May 2017

NICE Bisphosphonates for treating osteoporosis


Updated August 2017
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Fracture risk
assessment

Issues with guidance-what to do?


NOGG 2017 SIGN 2015 (SIGN 2015) NICE (NICE CG146 2017)

FRAX to indicate when Use Q fracture to Use either FRAX or Q


DXA is needed Accurately assess risk fracture to assess risk
33-99 All women >65
Use of glucocorticoids Includes more All men >75
>7.5mg-no account of variables, including
recurrent doses ethnicity
/cumulative effects of
alcohol/smoking/
fragility fractures
Can incorporate BMD Can’t incorporate
to calculate absolute BMD. Provides
10 year risk 40-90 threshold for BMD
years (incorporates assessment
mortality risk) Considers cumulative
fracture risk 18
Fracture risk
assessment

Issues with guidance-what to do?


NOGG 2017 SIGN 2015 NICE
www.shef.ac.uk/NOGG www.sign.ac.uk/sign142 (NICE CG146 2017)

Drug Tx initiated Drug Tx initiated NICE (TA 2017)


based on risk based on BMD says BP are cost
assessment (T score <-2.5) effective at a low
fracture risk –
expert guidance
provides advice on
when drugs are
clinically
appropriate. (SIGN
2015; NOGG 2016)

Ensure exclusion of diseases that mimic osteoporosis, elucidation of


the cause of the osteoporosis and the management of any
associated morbidity (NOGG 2017) 19
Fracture risk
assessment

Issues with guidance-what to do?


• Use of clinical judgement in assessing fracture risk

• BMD is a measure of ‘quantity’ of bone rather than ‘quality’

• Low bone density associated with increased fracture


risk in post menopausal women (and older men)

• Less emphasis on assessing BMD before starting treatment

• NICE 2017 Treatment choice should be made on an individual


basis, where possible starting treatment with the least
expensive formulation.

• Helpline is hearing of people being offered treatment who


may be at low risk e.g. relatively young (50’s/60’s) and
perhaps naturally lean and slim.
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Fracture risk
assessment

Case Study

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Fracture risk
assessment

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What worries callers-
understanding risk
What worries callers-
understanding risk

Wong C, Girt M Vertebral compressions fractures: a review of current management and multimodal therapy
Multidiscip Health 2013; 6:205-21

Risk of VF strongly associated with BMD

Risk x 2 for each SD < average vertebral BMD

Risk x 5 times greater following previous FF

20% of those with VF have a further VF within 1 year

Over 1/3 all postmenopausal VF occur in those not


categorised as having osteoporosis (T score >-2.5-<-1.4)

All those with VF are high risk of other FF


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Issues for Callers

• My jaw will rot if I take the treatment -risks & benefits


of Tx

• Adverse effects of drug treatments –provide the facts

• I’ve had 3 years on Prolia -can I have a drug holiday?

• What shall I do now that strontium ranelate


(Protelos)is no longer available? – risk assessment

• Living with /caring for someone with fractures –


symptom management & signposting

• What I’ve heard on the news…talk to us!


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Issues for callers-which
drug treatment should
I have?
Aim to strengthen bone and reduce fracture risk
Anti-resorptives:
• Bisphosphonates- alendronic acid (Fosamax)
risedronate (Actonel)
ibandronate (Bonviva)
zoledronic acid (Aclasta)
• RANKL inhibitors -denosumab (Prolia)
• SERM -raloxifene (Evista)
• Hormone therapy (HRT)

Anabolic agents:
• Synthetic PTH -teriparatide (Forsteo)
Antiresorptive
drugs
Bisphosphonates – how they work
Osteoclast on bone surface

Bisphosphonate

• Bisphosphonate drug is deposited on bone


• Osteoclast attaches tightly to bone surface & produces an acid solution to dissolve minerals in
bone then enzymes to dissolve collagen & protein matrix
• As the osteoclast dissolves the bone it absorbs the bisphosphonate drug
• What happens next is not completely understood, but…
• The drug causes the osteoclast to self destruct / die early & their activity and bone break-
down is reduced
• As osteoclast is ‘killed’, messages to osteoblasts are reduced causing slight reduction in
osteoblastic activity
NICE Bisphosphonates for
treating osteoporosis
Technology appraisal guidance
[TA464]

Recommendations (Cost effectiveness only)


Change to previous guidance

1.1 Oral bisphosphonates are recommended as


options for treating osteoporosis in adults only if:

• the person is eligible for risk assessment as defined


in NICE's guideline on osteoporosis and

• the 10-year probability of osteoporotic fragility


fracture is at least 1%.

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NICE Bisphosphonates for
treating osteoporosis
Technology appraisal
guidance [TA464]

Recommendations (Cost effectiveness only)


1.2 Intravenous bisphosphonates (ibandronic acid and
zoledronic acid)
• recommended as options for treating osteoporosis in adults
only if: the person is eligible for risk assessment as defined in
NICE's guideline on osteoporosis

• and the 10-year probability of osteoporotic fragility fracture is


at least 10%

• or the 10-year probability of osteoporotic ff is at least 1% and


the person has difficulty taking oral bisphosphonates
(alendronic acid, ibandronic acid or risedronate sodium)

• or these drugs are contraindicated or not tolerated.

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NICE Bisphosphonates for
treating osteoporosis
Technology appraisal guidance
[TA464]

Recommendations (Cost effectiveness only)


1.3 Estimate the 10-year probability of
osteoporotic fragility fracture using the FRAX or
QFracture risk tools, in line with NICE's guideline on
osteoporosis.

1.4 Choice of treatment should be made on an


individual basis after discussion between the
responsible clinician and the patient/carer.

Those already being treated with bisphosphonates


outside the new recommendations may continue..
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NICE Bisphosphonates for
treating osteoporosis
Technology appraisal
guidance [TA464]

Recommendations (Cost effectiveness only)

1.5 These recommendations are not intended to affect treatment


with alendronic acid, ibandronic acid, risedronate sodium and
zoledronic acid that was started in the NHS before this guidance
was published.

1.5 NICE guidance (TA160 and TA161) remains valid


except sections related to use of bisphosphonates, which is
superseded by the new guidance.

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Issues for callers: adverse
effects of bisphosphonates

MHRA 2015 Advice for healthcare professionals


Consider osteonecrosis of the external auditory canal in
patients receiving bisphosphonates with:

• ear symptoms, including chronic ear infections,


• suspected cholesteatoma

Possible risk factors


• steroid use and chemotherapy
( with or without local risk factors such as infection or
trauma)

Advise patients to report any ear pain, discharge, infection


whilst on bisphosphonate therapy

Report any cases on a Yellow Card


Issues for callers: adverse
effects Bisphosphonates
(& Denosumab)

Osteonecrosis of the Jaw (ONJ)

What is ONJ?
• Very delayed healing of a wound inside the mouth usually following a
dental extraction
• An area of jaw bone is left exposed
• May be prone to becoming infected

What ONJ is not


• Crumbling jaw bone
• Just jaw pain
• Just a dental infection

Why does ONJ happen? Osteoporosis Dorset

• It’s not clear why it happens


Comparing the risks of
fractures vs. ONJ

Risk of ONJ
with alendronic
acid is between
1 in 1000 &
1 in 10,000

Risk of a major
fracture
without
alendronic acid
is 1 in 4 (28%)

Which risk would you choose?


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Scottish Dental Clinical Effectiveness Program

Oral Health Management of Patients at Risk of Medication-


related Osteonecrosis of the Jaw (MRONJ) March 2017

Drugs Associated with MRONJ Prescribed in the United Kingdom

Drug Type Drug Name Trade names

Bisphosphonate alendronic acid Binosto,Fosamax, Fosavance


risedronate sodium Actonel, Actonel Combi
zoledronic acid Aclasta, Zometa
ibandronic acid Bondronat, Bonviva, Iasibon
Quodixor
pamidronate disodium Aredia
Sodium chlodronate Bonefos, Clasteon,Loron

RANKL Inhibitor denosumab Prolia, Xgeva

Anti-angiogenic bevacizumab Avastin® sunitinib Avastin


Sutent® aflibercept Sutent
Zaltrap
MRONJ
Anti-angiogenic drugs target the processes by which new blood
vessels are formed and are used in cancer treatment to restrict tumour
vascularisation

Anti-resorptive drugs inhibit osteoclast differentiation and function,


leading to decreased bone resorption and remodelling

Estimated incidence of MRONJ in cancer patients treated with


anti-resorptive or anti angiogenic drugs = 1% (1 per 100 cases)

Estimated incidence of MRONJ in osteoporosis patients treated with


anti-resorptive drugs = 0.01-0.1% (1-10 cases per 10,000)

Scottish Dental Clinical Effectiveness Programme Oral Health Management of Patients at Risk of Medication-related Osteonecrosis of the
Jaw March 2017

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Classification of
Patient Risk
Consider:
• Anti-resorptive or anti-angiogenic drugs ?
• Medical condition
• Type and duration of drug therapy /other
complicating factors
• Low or high risk of MRONJ?
• DO NOT discourage taking their
medication or from undergoing dental
treatment. Record that this advice has
been given.

• Incidence 1:1000-1:10,000
• Most people can have extractions in their
dental surgery

• Accredited by NICE (from 2016)

Scottish Dental Clinical Effectiveness Programme Oral Health Management of Patients at Risk of Medication-related Osteonecrosis of
the Jaw March 2017
Issues for callers: adverse
effects Bisphosphonates
(& Denosumab)

Osteonecrosis of the jaw &


bisphosphonates & denosumab
What can you do to further reduce the risk of
ONJ?
• Oral bisphosphonates – dental check-up & treatment before
starting but only if: poor dental health
had a check-up a long time ago
due to have major dental treatment

• IV bisphosphonate & denosumab - dental check-up & treatment


before starting
Issues for callers:
the drugs cause
your bones to break

Bisphosphonates & denosumab risk of atypical thigh


bone fractures
What is an atypical thigh bone fracture?
• Incidence 5: 10,000

• An incomplete fracture (a crack) or complete fracture of the thigh bone (femur)

• Usually a distinctive appearance – looks different to normal fractures

• May occur after minor or no trauma

• Both legs may be affected – therefore check both femurs

• May have thigh pain weeks or months beforehand

• May take longer than usual to heal

What it is not
• Any & every thigh bone or hip fracture

• A increased risk of all bones breaking


Issues for callers:
the drugs cause
your bones to break

MHRA (2011)Atypical femoral fracture


• Drs & patients be aware of risk (rare)

• Regular Tx reviews, especially >5years

• Patient report pain, weakness or discomfort in the


thigh or groin area

• Often bilateral occurrence -examine both legs

MHRA Vol 4 Issue 11 (June 2011)


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Monoclonal human
antibody

Denosumab – how it works


PTH
RANK
receptor

RANKL

Osteoprotegerin

Osteoclast Matured
Osteoblast precursor osteoclast
Summary Product
Characteristics

Denosumab
• Treatment of osteoporosis in postmenopausal
women and in men at increased risk of fractures.

• In postmenopausal women Prolia significantly


reduces the risk of vertebral, non-vertebral and hip
fractures.

• Treatment of bone loss associated with hormone


ablation in men with prostate cancer at increased
risk of fractures (see section 5.1).

• In men with prostate cancer receiving hormone


ablation, Prolia significantly reduces the risk of
vertebral fractures
Osteoporosis drug
treatments

Monoconal human antibody:


denosumab (Prolia)
• Does not incorporate into bone matrix and bone turnover is
not suppressed after its cessation

• Stopping Tx can lead to high risk of multiple vertebral


fractures

• Patients at high fracture risk should either continue


denosumab therapy or be switched to an alternative
treatment

• Should not be stopped without considering need for anti-


resorptive treatment

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Osteoporosis drug
treatments

Monoclonal human antibody: denosumab (Prolia)

• MHRA drug safety update & changes to SPC June 2017 –


added osteonecrosis of the external auditory canal

• Risk factors: steroid use and chemotherapy and/or local


risk factors such as infection or trauma

• Consider in cases of chronic ear infections in people


receiving denosumab-could be signs of bone damage to
the ear

• Incidence not possible to calculate due to minimal data


available

• Use of Yellow card


Osteoporosis drug
treatments

Strontium ranelate (Protelos)

• Production stopped August 2017

• Treatment reviews needed

• DXA problematic due to replacement of calcium ions


in bone by SR
Issues for callers: I
Issues
don’tforwant
callers: I
this drug!
don’t like this drug!

Osteoporosis treatment issues


Persistence: Compliance
Time to treatment Adherence to dosing,
discontinuation timing and conditions of
Or administration of the
Ongoing refill of scripts drug
without a gap
70% of all treatments
not continued/not
taken as prescribed
within 1 year*

Fighting the media!


E.g. micro cracks in bone
Issues for callers:
can I have a drug
holiday?

Duration of treatment
• How long should I take my treatment?
• My friend is having a drug holiday
• My doctor said I can stop my Prolia

To see if you need to continue taking an osteoporosis drug treatment:

• Your doctor should review your fracture risk after 3 to 5 years


(depending on which drug treatment is taken)

• A ‘drug holiday‘ might be appropriate if your fracture risk isn’t high

• Some can stop treatment for between 1 to 3 years then re-start

• BUT……
Denosumab discontinuation: rebound
resorption, fragility fractures and
possible prevention.
F. Sanders and K. Poole

Osteoporosis Review Summer 2017, Vol 25, Number 1


• Denosumab =highly effective treatment during the period of
therapy

• Cessation of denosumab therapy has been associated with


increased bone resorption

• Vertebral fractures, often multiple have been reported


from various groups on withdrawal of denosumab
(cancel the denosumab holiday!)

• Little is known about the effectiveness of bisphosphonate or


other therapy initiation on denosumab discontinuation

• Although altering dosing interval and dose quantity might


reduce rebound bone turnover and associated fracture rate on
therapy cessation, this approach has not been formally tested
in clinical practice 48
Issues for callers:
can I have a drug
holiday?

Duration of treatment
• Bisphosphonates: ZA after 3 years /others 5
years
• Treatment withdrawal for 1-3 years:
Alendronic acid - 2-3 years

Risedronate & ibandronate - 1-2 years

Zoledronic acid - 3 years


• Denosumab-no fixed recommendation.
Freedom extension trial supports use to 10 years
Regular review is needed
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Issues for callers:
can I have a drug
holiday?

Duration of treatment
High risk groups staying on Tx
• Aged 75 years or more
• Previous hip or vertebral fracture
• Total hip or femoral neck BMD T-score is -2.5 SD or
higher
• Continuous prednisolone dose of 7.5 mg/day or
higher
• If one or more low trauma fractures during
treatment
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Issues for callers:
are there any new
drugs I can have

New drug treatments in development


Romosozumab: ‘Bone-forming’ human sclerostin monoclonal antibody - inhibits sclerostin
• Sclerostin is produced by osteocytes & stops bone formation
• Romosozumab binds onto sclerostin & reduces its action

So by inhibiting sclerostin:
• bone formation
increases

• bone breakdown
decreases
Sclerostin produced by
osteocytes
to stop bone formation51
New drug treatments in
development

Romosozumab (Evenity): sclerostin monoclonal


antibody (Amgen)
• Inhibits sclerostin (protein produced by osteocyte
that regulates/decreases bone formation) thus
allowing increased bone formation without
increased bone resorption
• Shown to have significant improvements in hip BMD
in 12 month period, compared to teriparatide.
• Licence declined by US Food and Drug
Administration (FDA) due to serious adverse
cardiovascular events (ARCH study May 17)
• FRAME study showed 73% reduction in VF (only)
• Bridge study-use in men. Outcomes awaited
Issues for callers:
are there any new
drugs I can have

New drug treatments in development

Abaloparatide : Parathyroid hormone-related protein


– Parathyroid hormone – regulator of calcium homeostasis
– PTH stimulates release of calcium from bone, but
– Given intermittently by injection it stimulates osteoblasts & bone formation
Osteoblasts

‘Over-filled’ resorption cavity


with PTH therapy

Filled resorption cavity

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Issues for callers:
are there any new
drugs I can have

Drugs: New drug treatments in development


Abaloparatide : Parathyroid hormone related protein
– Daily self-administered subcutaneous injection
– (A skin patch version for short term wear also planned)
– Similar vertebral fracture reductions to teriparatide but greater
non-vertebral fracture reductions
– Similar safety profile to teriparatide
– Submitted to & approved by FDA for treatment of osteoporosis in
postmenopausal women

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Living with fragility fractures

What worries our callers


• Calcium causing heart attacks (any caller*)

• Acute & chronic pain

• Breathlessness, bloating, poor digestion, weight


loss, incontinence

• Disruption to lifestyle, low mood, loss of confidence

• Fear of falling / breaking more bones

• Adverse effects of drug Tx (any drugs)


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Management of acute
pain in vertebral
fractures

Short period of rest (or none1) whilst


pain-relieving medications are started

Early mobilisation with a rehabilitation, education and


exercise programme guided by a healthcare professional

Exercise and Bracing


physiotherapy
Education
Local heat or cold

Still in pain at 6-8 Vertebral


weeks augmentation
[1] Agulnek et al (2009) J Hosp Med 4(7):E20-E24.
Slide by Dr E Clark University of Bristol 2016
What worries
our callers

Calcium supplements & heart attack risk


What is the risk? (Reid 2010; Bolland 2011,)
• Not clear as not all studies agree there is an increased risk – recent
study was reassuring (Chung 2016). MHRA have said calcium
supplements still useful.
• If there is a risk, it may occur when calcium supplements are taken in
addition to a high calcium diet.

Why does it happen?


• It’s not clear- several theories proposed. Still under investigation.
• ? Laying down of excess calcium in blood vessels
• ? High calcium levels affect processes in blood and blood vessels
What worries
our callers

Calcium supplements & heart attack risk

How the potential risks be reduced?

• Use food as the main source of calcium


• Aim for 700mg (or 1000mg on treatments) of calcium daily
in food
• Use a calcium supplement to ‘top-up’ your diet if unable to get
this all from your food

• If a calcium supplement not needed, a vitamin D* supplement


might be.
Meeting the need
for exercise
information and
support
STRONG, STRAIGHT STEADY
STRONG SSS
- exercise and physical activity that will
strengthen bones safely
STRAIGHT
- moving, lifting and living safely with
osteoporosis
- help with pain and posture after spinal
fractures
STEADY
- balance and muscle strength to stop you
falling
Reminder!

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Reminder!r!

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Life with osteoporosis
-what did we learn?

This report is based on the experiences of


3,228 people who completed our detailed
questionnaire, and the 52 people who took
part in an in-depth interview or kept a
personal diary.

Of the people we surveyed, 57% had


fractured at least once, with 1 in 3 people
who have fractured reporting five or more.

It can be devastating!
NOS Life with osteoporosis Oct 2014 62
Life with osteoporosis
-what did we learn?

Participants had the courage to tell us


how the condition made them really
feel….
Frustrated Upset Self-conscious
Stupid Alone Scared Worried Old
Miserable Frightened Grotesque
Depressed Isolated Debilitated Afraid
Insecure Exhausted Agony Misery
Stress Nervous Annoyed Unattractive
Hate Ashamed Bitter Embarrassed
Sad Resentful Angry Unhappy Lonely
Tearful Invisible Uncomfortable
Useless Forgotten
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Bite sized updates

1. Eatwell guide: what’s changed?

2.Iodine in milk substitutes: <2% of that of cows milk*

3.Vitamin D3 more effective than D2:

4.20-40% young people cutting calcium from diet


(FSA 2000 & NOS 2017)

5. STRONG, STRAIGHT, STEADY project…

*Bath SC. (2018) 'Iodine supplementation in pregnant women from


mildly deficient regions'. The Lancet Diabetes and Endocrinology,
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Thank you
for listening

Questions?

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