OSTEOPOROSISCurrent advances in management/treatment

Sharon Abdy BSc(Hon), RGNOsteoporosis Specialist Nurse

Musculo-skeletal UnitFreeman Hospital

Newcastle upon Tyne

QUALITATIVE DEFINITION OF OSTEOPOROSIS

“Osteoporosis is a skeletal disorder characterized by Osteoporosis is a skeletal disorder characterized by compromisedcompromised bone strengthbone strength predisposing a person to an predisposing a person to an increased risk of fractureincreased risk of fracture” Consensus Development Conference, 2001.

Normal Osteoporosis

OSTEOPOROSISBone – Cortical/Trabecular

Cells – Osteoblast (bone formation)Osteoclast (bone resorption)

Cell turnover is normally closely coupled

Bone resorption greater than formation = osteoporosis and fractures

RISK OF FRACTURE

Bone Density

Bone Turnover

Bone Architecture

Skeletal Geometry

Mineralisation

Postural Instability

Slow Responses

Frailty

Environment

Lack of Padding

Bone Q

uality

MAJOR OSTEOPOROTIC FRACTURES

EPIDEMIOLOGY

1:2 women and 1:5 men will have a fracture after the age of 50. In UK, approx 3 million have osteoporosis

Approximately 300,000 fragility fractures each year in the UK. Cost of treating these fractures is £1.8 billion annually (NOS 2010)

1,150 people are dying in the UK every month as a result of hip fracture

EPIDEMIOLOGY

Over 200 million people worldwide suffer from osteoporosis. (Cooper et al, Osteoporosis Int., 1992)

Markov model of the natural history of osteoporosis predicts for the UK population of age 50-59, by 2020 there will be 230,000 fractures costing approx £2.1 billion to treat.

Substantial impact on UK health services unless effective interventions in place.

BONE HEALTH/FRACTURES

Based on a PCT of 300,000 it is estimated there will be:

55,000 post menopausal women 17,400 with undiagnosed osteoporosis6,900 with a previous fracture (any kind)900 presenting each year with a new fracture

Department of Health (2009)

MORBIDITY AND MORTALITY

Hip fractures account for more than 20% of orthopaedic bed occupancy in the UK (average hospital stay 26 days) - 50% lose independence, 20% die within 4 months, 30% within 12 months (Dept

of Health 2009)

80% of older women would rather die than experience a hip fracture leading to poor quality of life/nursing home (NOS)

In patients over 60 years of age, fractures account for more than 2 million hospital bed days in England exceeding diabetes, heart disease, and chronic obstructive pulmonary disease.(NOGG – Executive Summary 2008)

VERTEBRAL FRACTURES

Common site of fracture in the elderlyCompression/collapse/wedgeOften undiagnosedHeight lossPain severe initially in most casesChange in body shape Lack of sleep/depressionProblems mobilising

FALLS AND FRACTURES

Each year over 35% of over 65’s experience one or more falls. In England, it is estimated that this age group will rise by 1/3 by 2025.

Age 80 and over will double.Age 100 and over will increase 4 fold.

A significant increase in falls is therefore expected

Department of Health has developed a systematic approach to falls and fractures prevention.

Announced £162 million investment in services for older people in England.

CLINICAL SUSPICION

Aim - Identify and target persons who are at high risk of osteoporosis/low trauma fractures.

Objective – Risk assessment

“Silent epidemic”

RISK FACTORSOpportunistic case finding based on risk factors independent of bone mineral density (BMD) and through association with low BMD

Untreated early menopause (<45 years)Conditions causing prolonged immobility inc RA,

ankylosing spondylosisMalabsorption syndrome ie CrohnsLow BMI (<22)

Parental hip fractureRheumatoid arthritisHigh alcohol consumption

DUAL XRAY ABSORPTIOMETRY

Most accurate and reliable means of measuring bone density

Measures the lumbar spine (L1-4) and total femur, values expressed as T and Z scores

Radiation dose similar to natural background radiation

Takes 10 mins maximumNon invasive

QUANTITATIVE DEFINITION OF OSTEOPOROSIS

Bone Mineral Density (BMD) 2.5 standard deviations or more below the mean value for young normal adults (T-score <-2.5).

WHO Report, 1994

OSTEOPOROSIS

LIFESTYLE

HEALTHY LIFESTYLE

SMOKINGFRAX include smoking as a risk factor

for osteoporosis Cut down or stopInduces early menopause - increases

osteoclast activityAffects bone formation - osteoblast activityFoundation Trust – No smoking policy

HEALTHY LIFESTYLEALCOHOL

Affects skeletal cell activity

Increased risk of falling

Increased risk of fracture >3 units daily is a risk factor

HEALTHY LIFESTYLEDIET

Well balanced

Calcium rich (700-1000mgs per day)

Supplements unnecessary if diet adequate

Booklet - Diet and Bone Health (NOS)

HEALTHY LIFESTYLEEXERCISE

Regular exercise

Load bearing

Not excessive (eating disorders)

Booklet - Exercise and Osteoporosis (NOS)

OSTEOPOROSIS MANAGEMENT

TREATMENTS

TREATMENTSDecision to treat is multi-factorial:

Guidelines FRAX Tool

DXA results X-rays

Patient history Patient choice

FRACTURE RISK ASSESSMENT

Prior fracture after age of 50

Parental hip fractureCurrent smokingOral steroidsAlcohol intake > 2

units/dayLow BMIChronic conditions (RA)

0

10

20

30

40

50

50 60 70 80

Age

% 10

Yea

r Risk

of fr

actur

e

-4 -3 -2 -1 0

Kanis et al, Osteoporos Int 2001; 12: 989-995.

Ten Year Absolute Risk of Fracture

FRACTURE RISK ASSESSMENT

www.shef.ac.uk/FRAX

USING FRAXCRFs

High

Treat

Intermediate Low

BMD

Reassessprobability

High Low

Treat

Kanis et al, WHO Report, 2008.

0

10

20

30

40

40 50 60 70 80 90

10 year fracture probability (%)

0

10

20

30

40

50

60

70

40 50 60 70 80 90

Age (years)

Consider treatment

No treatment

Consider treatment

No treatment

ASSESSMENT WITHOUT BMD ASSESSMENT WITH BMD

www.shef.ac.uk/NOGG

USING FRAX AND NOGG

NATIONAL OSTEOPOROSIS GUIDELINE GROUP (NOGG)

Endorsed by a number of large organisations.Launched Autumn 2008. Provides a guidance

update previously developed by Royal College of Physicians on prevention/treatment of osteoporosis, also diagnosis/management.

Aim of guideline is to provide a framework from which local protocols can be developed.

Can be used with the FRAX tool online.Hard copies also available for health professionals

and patients.

NICE TECHNOLOGY FINAL APPRAISAL DETERMINATION (FAD)

Primary prevention of fractures TAG160

First and second line treatment recommendations based on risk factors and DXA (unless age 75 and over with 2 or more risk factors = no DXA).

Does not take in to account men, young women, previous fracture history, osteopenia confirmed by DXA and use of long term corticosteroids.

NB: NICE is also developing a clinical guideline to be used alongside FAD (available in approx 12/12).

NICE TECHNOLOGY FINAL APPRAISAL DETERMINATION (FAD)

Secondary prevention of osteoporotic fractures TAG161

First and second line treatment options for:

Age 75 and over without the need for DXA

Age 65-74 if osteoporosis confirmed by DXA

Under 65 if low bone density confirmed by DXA + additional risk factors

STEROID GUIDELINESoral glucocorticoids for >3 months

Age >65 with a history of a prior fragility fracture should commence bisphosphonates without the need for DXA

<65 consider DXA. If T Score -1.5 or lower, treatment indicated

TREATMENT CHOICES (NICE)

Bisphosphonates - AlendronateRisedronateEtidronate

Strontium RanelateRaloxifeneDenosumabTeriparatideCalcium and vitamin D

ADDITIONAL TREATMENTS

● Ibandronate

● Zoledronate & Pamidronate

● Hormone Replacement Therapy

BISPHOSPHONATES

Treatment of choice for the management of osteoporosis.

Various preparations – oral, IV bolus injections, IV infusions.

Well tolerated if taken correctly.Side effects mainly gastric with oral treatment, flu

symptoms with IV.Long term side effects unknown therefore not

recommended for young pre menopausal women particularly of child bearing age.

BISPHOSPHONATE TREATMENT IN OSTEOPOROSIS

Alendronate 1st line and Risedronate 2nd line (NICE)

BMD and hip fractures by 35-50%.

Complex instructions for administration. Side effects. Increased risk of oesophageal carcinoma??

BISPHOSPHONATESCyclical Etidronate (Didronel PMO)

Indication for treatment same as Risedronate. Licensed since January 1992.Increases bone density and may reduce vertebral

fractures.Disodium etidronate (days 1-14) in the middle of a

4 hour fast followed by a Cacit drink (days 15-76).Fewer gastric side effects, possible alteration in

bowel habit.Compliance issue!

STRONTIUM RANELATEProtelos

Third line treatment recommendation (NICE) if unable to tolerate 1st and 2nd line. T score lower.

Decreases bone resorption AND increases bone formation BUT can spuriously elevate bone density.

Significant increases in spine and hip bone density over 3 years with a positive vertebral fracture reduction in the over 80’s.

Side effects - DVT risk (slight), possible diarrhoea, stop if unexplained rash (hypersensitivity).

Daily 2g sachet (Granules). Timing issue!

RALOXIFENE (Evista)Fourth line treatment recommendation (NICE) for

secondary prevention only, when not able to take or tolerate other options.

Selective Estrogen Receptor Modulator. Mimics action of oestrogen on certain organs/tissues and blocks oestrogenic effects in others.

Licensed for prevention of low trauma vertebral fractures - post menopausal women. No hip data.

Side effects – hot flushes.Significantly reduces breast cancer risk.Daily 60mg tablet.

39

DENOSUMAB:PROLIA

1. Raisz LG. J Clin Invest 2005;115:3318–3325. 2. Eghbali-Fatourechi G et al. J Clin Invest 2003;111:1221–1230.3. Hofbauer LC et al. JAMA 2004;292:490–495. 4. Boyle WJ et al. Nature 2003;423:337–342.

39

Following the menopause, oestrogen levels decrease and lead to an excess in RANK Ligand.1,2 Increased RANK Ligand expression leads to bone resorption1,3,4

RANK Ligand

RANK

40

RANK Ligand

RANK

DENOSUMAB:PROLIA®

1. Prolia®, Summary of Product Characteristics, 2010.2. Boyle WJ et al. Nature 2003;423:337–342.

40

OPG

41

MODE OF ACTIONProlia inhibits osteoclast formation, function and survival.

Bisphosphonates bind to bone mineral at site of bone resorption.

DENOSUMAB:PROLIA® V BISPHOSPHONATES

1. Prolia®, Summary of Product Characteristics, 2010. 2. Boyle WJ et al. Nature 2003;423:337–342.3. Drake MT et al. Mayo Clin Proc 2008;83:1032–1045. 4. Russell RGG et al. Osteoporos Int 2008;19:733−759.

41

42

DENOSUMAB:PROLIA®

1. Cummings SR et al. N Engl J Med 2009;361:756–765.

*All non-vertebral fractures. However, fractures of the skull, face, mandible, metacarpals, fingers, or toes were excluded because they are not associated with decreased bone mineral density. Pathological fractures and those associated with severe trauma were also excluded.

Prolia® significantly reduced the risk of osteoporotic fracture at vertebral, hip and non-vertebral* sites1

2.3

7.2

0.71.2

8.0

6.5

43

DENOSUMAB:PROLIA®

1. Prolia®, Summary of Product Characteristics, 2010. 2. Cummings SR et al. N Engl J Med 2009;361:756–765.

Prolia®: continuous reductions in relative risk of new vertebral fracture, year after year1,2

TERIPARATIDE

The first anabolic treatment for osteoporosis. Costly.

Larger increases in BMD than with bisphosphonates.

Also increases periosteal new bone formation and skeletal size.

Reeve et al, Br Med J 1980 1340-1344.

CALCIUM AND VITAMIN DNICE recommends as adjunct therapy unless known

adequate dietary calcium intake and are vitamin D replete

Numerous preparations Efficacy? MRC calcium and vitamin D study

(RECORD) – poor outcomes.Elderly, housebound, eating disordersSide effects – nausea, bloating, constipation,

occasional diarrhoea, hypercalcaemiaCalcium supplements found to increase risk of heart

disease

IBANDRONATE (Bonviva)

Not recommended by NICEOral and IVTablet – 150mg per month IV 3mg push over 15-30 secs every 3/12Increases bone density, decreases vertebral

fractures Convenient to take (for some)Side effects – possible transient flu like

symptoms

ZOLEDRONATE (Aclasta)

Not recommended by NICE5mg infusion annuallyDay caseBiochemical tests, renal failureAtrial fibrillation??Transient flu like symptoms, fever etc

HORMONE REPLACEMENT THERAPY

Patches

Tablets

Implants

Gels

VERTEBROPLASTY

Vertebral collapseGeneral or local anaestheticCement inserted in to vertebral bodyHardens within 20 minutesPain relief can be instantSingle or multiple sitesBest time for procedure- 6 weeks

to 3 months following fracture

KYPHOPLASTY

Osteoporotic collapse/malignancyGeneral or local anaestheticBalloon inserted in to vertebral bodyInflated creating cavity - removedCement inserted under low pressurePain relief can be instantSingle or multiple sitesUp to 75% regain lost mobility

PHYSIOTHERAPY

Specialist physiotherapist – Jane CookBone clinic patients – new and ?old vertebral

fracturesSession with Jane- balance, posture, exercise

tailored to individual capabilities.Provided with home exercise and pain

management plan.Reviewed six months later

TREATMENT ISSUES/CONCERNSProton Pump Inhibitors

Osteonecrosis of the Jaw

Delayed fracture healing

Atypical stress fractures

Aromatase Inhibitors

PROTON PUMP INHIBITORSA retrospective analysis from University of

Pennsylvania, Journal of American Medical Association. (2007)

Patients over 50 taking PPI’s over 12/12 have a 44% increased risk of hip fracture, increasing to 245% with long term, higher doses.

? Acid suppression decreasing calcium absorption.Failed to demonstrate direct causal relationship,

more a “potential association”. Not mirrored in profound acid suppression

conditions ie vagotomy.

OSTEONECROSIS OF THE JAWExposed bone in the maxillofacial region that

fails to heal.May have pain, swelling, soft tissue ulceration,

sinus formation, tooth looseningRarely seen in clinical practice, usually high dose

IV bisphosphonates.Existing dental problems should be treat prior to

commencing treatment.Fracture prevention needs to be discussed in

context with very small risk of ONJ

DELAYED FRACTURE HEALINGA suggestion that bisphosphonates

can delay fracture healing due to

suppression of bone turnover.Studies in rats/mice have found no

correlation.Treatment occasionally delayed

as a precaution in patient’s who

present with a poor healing fracture.

ATYPICAL FRACTURES OF FEMUR Patients presenting with atypical fractures of the

femoral shaft. Long term use of Alendronate. Bisphosphonates altering bone strength? Bone biopsies-severely suppressed

bone turnover and delayed/absentfracture healing.

Further studies to establish a clearassociation.

AROMATASE INHIBITORSBone loss can be more profound in patients

taking AI’s for breast cancer.Increases bone turnover and induces bone loss at

sites rich in trabecular bone, rate of 1–3% per year.

Rate to 7–8% per year in young women with treatment induced ovarian suppression.

Algorithms produced taking into account additional risk factors.

Bisphosphonates are treatment of choice.

CONCLUSIONOsteoporosis is a significant physical, mental and social burden to patients.

Enormous financial impact on the NHS

HOWEVER

ResearchNew treatments available Guidelines and guidance galore!Better access to DXA servicesFracture Liaison ServicesFalls management

OSTEOPOROSIS

ANY QUESTIONS?

+ =