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HOPE SELLING

22

EVALUATION AND MEDICAL

MANAGEMENT OF FRAGILITY

FRACTURES

Thomas jeffersonian hospital and Rothman institute article in orthopedic

clinical of North America April 2014

Presented By: Harjot Singh Gurudatta

Moderator: DR. RAJAN SHARMA

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Definition of fragility fracture: (WHO)

Fracture during activity that would not normally injure

young healthy bone (i.e., fall from standing height or

less)

• Fragility fractures are a large and growing health issue

– 1 in 2 women and 1 in 4 men over 50 yrs of age will suffer a fracture in their remaining lifetime

• A prior fracture increases the risk of a new fracture 2- to 5-fold

• Yet few fracture patients receive evaluation and treatment of osteoporosis, the underlying

cause of most fragility fractures

– Calls for action to improve the evaluation and treatment of fracture patients have been published

around the World

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Fragility fractures are common

• 1 in 2 women and 1 in 5 men over age 50 will suffer a fracture in their remaining life time

• 55% of persons over age 50 are at increased risk of fracture due to low bone mass

• At age 50, a woman’s lifetime risk of fracture exceeds combined risk of breast, ovarian & uterine cancer

• At age 50, a man’s lifetime risk of fracture exceeds risk of prostate cancer

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Osteoporotic fractures:

Comparison with other diseases

1996 new cases,all ages184 300

750 000 vertebral

250 000 other sites

250 000forearm

250 000hip

0

500

1000

1500

2000

Osteoporotic fractures

Heartattack

Stroke Breastcancer

An

nu

al in

cid

en

ce

x 1

00

0

1 500 000

annual incidenceall ages

513 000

annual estimatewomen 29+

228 000

annual estimatewomen 30+

American Heart Association, 1996American Cancer Society, 1996Riggs & Melton, Bone, 1995; 17(5 suppl):505S-511S

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Consequences of hip fracture

Cooper. Am J Med 1997; 103(2A):12s-19s.

40%

Unable to walk

independently

30%

Permanentdisability

20%

Death within one year

80%

Unable to carry out at least one independent activity of daily living

One year after hip fracture

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Consequences of vertebral fractures

• Acute and chronic pain

– Narcotic use, decrease mobility

• Loss of height & deformity

– Reduced pulmonary function

– Kyphosis, protuberant abdomen

• Diminished quality of life:

– Loss of self-esteem, distorted body image, sleep disorders,

depression, loss of independence

• Increased fracture risk

• Increased mortality

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O'Neill et al. Osteoporos Int. 2001; 12:555-558

Consequences of distal radius fractures

• The most common fracture in women at middle age

– Incidence increases just after menopause

• The most common fracture in men below 70 years

• Only 50% report good functional outcome at 6 months

• Up to 30% of individuals suffer long-term complications

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Fragility fractures are common and have

severe consequences

Fragility fractures lead to major morbidity, decreased quality of life and increased mortality

– 10-25% excess mortality

– 50% unable to walk independently after hip fracture

– 50% show substantial decline from prior level of function (many lose

ability to live independently)

– Increased depression, chronic pain, disability

– Increased risk of subsequent fracture

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“…a systemic skeletal disease

characterized by low bone mass and

micro-architectural deterioration of

bone tissue, leading to enhanced

bone fragility and a consequent

increase in fracture risk.”

Definition of osteoporosis

World Health Organization (WHO), 1994

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Major risk factors for fractures

• Prior fragility fracture

• Increased age

• Low bone mineral density

• Low body weight

• Family history of osteoporotic fracture

• Glucocorticoid use

• Smoking

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Assessing bone density

• X-ray observation

– “Osteopaenic on x-ray” implies significant

bone loss already – decreased opacity,

thin cortices, wide canals, current fracture,

healing fractures

– A “late finding” in the course of the

disease, but may be the “first finding” for a

patient

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Assessment of bone mineral density by DXA

Current gold standard for diagnosis of osteoporosis

BMD (g/cm2) = Bone mineral content (g) / area (cm2)

Diagnosis based on comparing patient’s BMD to that of young, healthy individuals of same sex

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WHO criteria for diagnosis of osteoporosis

Kanis et al. J Bone Miner Res 1994; 9:1137-41

T-score: Difference expressed as standard deviation compared

to young (20’s) reference population

T-score

Normal - 1.0 and above

Osteopaenia - 1.0 to - 2.5

Osteoporosis - 2.5 and below

Severe (established) osteoporosis

- 2.5 and below, plus one or more osteoporotic

fracture(s)

15Bone strength is more than BMD

Images from L. Mosekilde, Technology and

Health Care. 1998

young

elderly

Image courtesy of David Dempster

BMD is surrogate criteria for OP as BP for Stroke

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Determinants of whole bone strength• Geometry

– Gross morphology (size & shape)

– Microarchitecture

• Properties of bone material / bone matrix

– Mineralization

– Collagen characteristics

– Microdamage

Applied load

Bone strength> 1 fracture

Factor of

risk

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Bone remodelling balance influences bone

strength

SIZE & SHAPE macroarchitecture

microarchitecture

MATERIAL tissue composition

matrix properties

BONE REMODELLINGformation / resorption

AGEING, DISEASE and THERAPIES

Bone strength

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High Bone Turnover

Resorption > Formation

Decreased Bone Strength

Disrupts Trabecular Architecture

Decreases Bone Mass

Increases Cortical Porosity

Decreases Cortical Thickness

STOCHASTIC REMODELLING

Alters Bone Matrix Composition

L. Mosekilde

Tech and Health Care, 1998

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Bone size (mass)

Bone shape

Architecture

Matrix properties

Fall

incidence

Fall

impactBone

strength

Fracture risk

Fall characteristics

Energy absorption

External protection

Neuromuscular function

Environmental risks

Age

But bone quality is not the only factor…

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Optimal care of the fragility fracture patient

• Diagnosis of “fragility” fracture

– Identify “fragility” fracture & underlying disease, incorporate into

existing workup

– Influences treatment plan from the onset

• General fracture management

– Stabilize patient, pain relief, fracture care

• Rehabilitation

– Minimize dependence, maximize mobility

• Secondary prevention

– Treat and monitor underlying disease, prevent future fractures

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Optimal care of the fragility fracture patient

• Diagnosis of “fragility” fracture

– Identify “fragility” fracture & underlying disease, incorporate into

existing workup

– Influences treatment plan from the onset

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High risk for secondary osteoporosis

• Severe chronic liver or kidney diseases

• Steroid medication (>7.5mg for more than 6 months)

• Malabsorption (eg. Crohn´s disease)

• Rheumatoid arthritis

• Systemic inflammatory disorders

• Hyperthyroidism

• Primary hyperparathyroidism

• Antiepileptic medication

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Fragility fracture patient assessment * In addition to routine pre-op or fracture evaluation

• Family history of OP

• Menarche / Menopause

• Nutrition

• Medications

– (past and present)

• Level of activity

• Fracture history

• Fall history & risk factors for falls

• Smoking, alcohol intake

• Risk factors for secondary OP

• Prior level of function

History

should include:

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• Height

• Weight

• Limb exam

– ROM, strength, deformity, pain, neurovascular status

• Spine exam

– pain, deformity, mobility

• Functional status

Physical exam

should include:

Fragility fracture patient assessment In addition to routine pre-op or fracture evaluation

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• SR / CRP

• Blood count

• Calcium

• Phosphate

• Alkaline Phosphatase (AP)

• GGT

• Renal function studies

• Basal TSH

• Intact PTH

• Protein-immunoelectrophoresis

• Vit D (25 and 1.25)

Laboratory tests*

NOTES:

- * These are in addition to

routine pre-op labs such as

coagulation studies

- These are screening labs,

more may be indicated based

on these results

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Bone mineral density and spine radiograph for

vertebral fracture assessment

• Bone mineral density assessment by DXA

– Establish severity of osteoporosis

– Baseline for monitoring treatment efficacy

• Consider spine radiographs (thoracic and lumbar, AP and ML views) for patients with:

– Back pain

– Loss of height > 4 cm

– Progressive kyphosis

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DEXA– Flaws?

• DEXA overestimate the bone mineral density of taller subjects and underestimate the bone mineral density of smaller subjects.

• In DEXA, bone mineral content is divided by the area of the site being scanned.

• DEXA calculates BMD using area (aBMD: areal Bone Mineral Density), it is not an accurate measurement of true bone mineral density, which is mass divided by a volume.

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DEXA– Flaws?

• The confounding effect of differences in bone size is due to the missing depth value in the calculation of bone mineral density.

• The radiation dose is approximately 1/10th that of a standard chest X-ray

• BMD testing with DXA is very susceptible to operator error.

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DEXA– Flaws?

• A repeat BMD measurements should be done on the same machine each time, or at least a machine from the same manufacturer.

• Error between machines, or trying to convert measurements from one manufacturer's standard to another can introduce errors large enough to wipe out the sensitivity of the measurements.

• DEXA results need to be adjusted if the patient is taking strontium, and calcium supplements.

• Metallic artifacts in cloths or pockets cause errors.

• Osteomalacia, Osteoarthritis of spine, old Fractures of spine and hip, aortic calcification affect BMD readings.

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Who should be screened?

• Problem of over-interpretation of results, & healthy average people think they are at a much higher risk.

• In 2000 an NIH consensus conference concluded: "Until there is good evidence to support the cost-effectiveness of routine screening, or the efficacy of early initiation of preventive drugs, an individualized approach is recommended.

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Who to screen • Women > 65 years.

• Men > 70 years.

• Postmenopausal women /men >50 years with clinical risk factors.

• H/o fracture at age > 50 years.

• Chronic steroid use.

• Risk factor for secondary OP

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Bone density at various sites for prediction of hip fractures Cummings SR, Black DM, Nevitt MC, Browner W, Cauley J, Ensrud K, et

al. The Study of Osteoporotic Fractures Research Group. Lancet 1993; 34: 72-75.

• BMD poor predictor of fractures.

• When different scanners are used on the same patients, the proportion of patients diagnosed with osteoporosis varies from 6% up to 15%.

• Over 80% of low trauma fractures occur in people who do not have osteoporosis (T score –2.5).

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NOF recommendations

• National Osteoporosis Foundation US and the American Association of Clinical Endocrinologists recommend routine monitoring of bone mineral density within two years of starting treatment.

• The UK National Osteoporosis Guidelines Group,

US National Institutes of Health, and the

Osteoporosis Society of Canada do not make a

recommendation either way on monitoring.

NHS no recommendation

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FRAX

Do you know what is your T – Score?

Take one minute test!

Do you know what are your chances of

getting fractures in next 10 years?

Go online FRAX site!

For Treatment consult your physician

or your “Osteoporosis Society”

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Dr. Judith Brenner New York University

power of the FRAX tool

• Add daily consumption of two or more alcoholic drinks, and the risk becomes 9 percent.

• Instead of 60, say the woman is 80 years old, slender and with no family or personal history of fractures, smoking or steroid use. Dr. Brenner calculated her risk of fracturing a hip in 10 years as 10 percent and of having any major osteoporotic fracture at 35 percent.

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Rehabilitation in the fragility fracture patient

Goal is to improve strength,

balance, position sense, reactions to:

– Improve level of function /

independence

– Decrease risk of falls

– Decrease risk of fractures

Balance (position sense, reaction)

Mechanical vibration plate

Limb and core strength

Mobility in activities of daily living

Safety in gait and transfers

Sensory and visual limitations

Home safety evaluation and adaptation

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Interventions to reduce future fracture risk

• Basics

– Nutrition, exercise, fall prevention strategies

– Modify risk factors as able (smoking, excess alcohol)

– Treat co-morbidities (i.e., endocrine disorder?)

• Pharmacological agents

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Interventions: General recommendations

• Regular physical activity

– Maintaining safe ambulatory status, indep ADLs

– Daily limb and core home exercise routine

• Sufficient intake of calcium and vitamin D

– daily 1000-1500 mg calcium, 400-800 IU vitamin D

– by foods or foods and supplements combined

• Adequate nutrition

• Avoid cigarettes, excess alcohol

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Who to treat ?

Prior h/o hip/vertebral #

or

T Score < -2.5

or

T Score -1 to -2.5 &

10 yr risk (FRAX) :

HIP # > 3 % or

major osteoporotic # > 20 %

Postmenopausal women

/men > 50 yrs

with

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Pharmacological agents for treatment of

osteoporosis

Effective therapies are widely available and

can reduce vertebral, hip and other fractures

by 30% to 65%,

even in patients who have already suffered a

fracture

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Bisphosphonates

• Alendronate (FOSAMAX®)

• Risedronate (ACTONEL®)

• Ibandronate (BONVIVA®)

• Zolendronate (ACLASTA®)

Pharmacological agents shown to reduce

fracture risk

SERMs

• Raloxifene (EVISTA®)

Stimulators of bone formation

• rh-PTH (FORTEO®)

Mixed mode of action

• Strontium ranelate (PROTELOS®)

Hormone therapy

• Estrogen / progestin

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Bone marrow precursors

OsteoblastsOsteoclast

Lining cells

Stimulators of

Bone FormationFluoride

PTH analogs

Sr Ranelate (?)

Inhibitors of

Bone

Resorption

Estrogen, SERMs

Bisphosphonates

Calcitonin

Inhibitors ofRANKL

Cathepsin K

Therapeutic strategies

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Mainstay of treatment :

BisphosphonatesApproval in US for osteoporosis

• Alendronate week : 1995

• Risedronate : 2000

• Ibandronate mnth: 2005

• Zoledronate yearly.iv : 2007.

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Treatments & Efficacy

Vertebral Fx Non-vertebral Fx

Other Fx Hip Fx

Oral

HRT Yes Yes Yes

Etidronate* Yes

Alendronate* Yes Yes Yes

Risedronate* Yes Yes Yes

Ibandronate* Yes [Yes]

Raloxifene* Yes

Calcitriol* Yes

Strontium Ranelate* Yes Yes [Yes]

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Vertebral Fx Non-vertebral Fx

Other Fx Hip Fx

Subcutaneous

Teriparatide* Yes Yes

1-84 PTH* Yes

Denosumab* Yes Yes Yes

Intravenous

Pamidronate

Ibandronate*

Zoledronate* Yes Yes Yes

Intranasal or Subcutaneous

Calcitonin* Yes

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Vertebral Fx Nonvertebral Fx

Other Fx Hip Fx

Alendronate* Yes Yes Yes

Risedronate* Yes Yes Yes

Zoledronic acid* Yes Yes Yes

PTH* Yes Yes ???

Strontium ranelate* Yes Yes ???

Denosumab* Yes Yes Yes

Appropriate use of appropriate treatments can

halve the incidence of fractures

* plus calcium + vitaminD

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Taking Bisphosphonates

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Contraindications

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Hot topics

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Vitamin D levels

• 25-OHD Vit D status Manifestation Management

• <25 nmol/l Deficient Rickets/ Osteomalacia High-dose

calciferol

• 25-50 nmol/l Disease risk Vit D supps

• 50-75 nmol/l Adequate Healthy Lifestyle advice

• >75 nmol/l Optimal Healthy None

– Divide by 2.5 for ug/L

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Patients who did not need treatment in the first placeDiscontinue Treatment

Lower risk patients, if DXA is stable/increasingConsider a drug holiday after 3-5 years of treatment

Higher risk patients (fractures, corticosteroid Rx, very low BMD)Consider a drug holiday after 10 years of therapy

May use teriparatide or raloxifene (but not another potent antiresorptive agent – ie. denosumab) during the holiday from

bisphosphonates

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Treatment of vitamin D deficiency

Deficiency (25-OHD <25 nmol/l)

10 000 IU calciferol daily or 60 000 IU calciferol weekly for 8-12 weeks*

or

Calciferol 300 000 or 600 000 IU orally or by intramuscular injection once or twice

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Treatment of vitamin D insufficiencyInsufficiency (25-OHD 25-50 nmol/l) or

maintenance therapy following deficiency

1000-2000 IU calciferol daily

or

10 000 IU calciferol weekly

–

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Hormone replacement therapy

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HRT: A CONSENSUS

• Prime role of HRT is relief of menopausal Sx

• Risks/benefits need to be explained to each woman (breast Ca extra 2-6 cases per 1000 women treated with HRT for 5 years)

• Use lowest effective estrogen dose, assess CV risk

• Review need annually (esp aged>60)

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HRT: A CONSENSUS

• Can give up to age 50 if prem menopause

• Do not use as primary or secondary prev. of CAD/CVA, or Alzheimers

• Transdermal estrogen has lower DVT risk

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RALOXIFENE

• SERM licensed for OP

• Reduces vertebral (not non-vertebral) fracture risk, just as does calictonin

• Reduces development of new breast Ca.

• No increased risk of CVD (reduces CV events!)

• Increased risk of thromboembolism

• May worsen flushes

• Well tolerated, easy dosing

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NICE 2005:

(secondary prevention)

• Teriparatide – use in women >65 years unresponsive to / intolerance of bisphosphonates, and:

–with extremely low BMD (<-4)

–with very low BMD (<-3), multiple fractures PLUS an additional risk factor

National Institute for Clinical Excellence, Technology Appraisal 87, Jan 2005

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Emerging Rx’s in osteoporosis

Prof Compston

2010• Denosumab

– Monoclonal Ab to RANKL which drives osteoclasts

– Subcut every 6m/12m! 60mg

– Dramatic and quick effect

– Fracture reduction similar to Zoledronate

– Cost similar to risedronate (in 2010)!

– NICE appraised

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Denosumab Binds RANK Ligand and Inhibits

Osteoclast Formation, Function, and Survival

RANKL

RANK

OPG

Denosumab

Bone Formation Bone Resorption

Inhibited

Osteoclast Formation, Function,

and Survival Inhibited

CFU-GM Prefusion

Osteoclast

Osteoblasts

Hormones

Growth Factors

Cytokines

Adapted from: Boyle WJ, et al. Nature. 2003;423:337-342.

62Few Simple ways

• If you are or consider your self Obese,

• If you are exposed to Sun during your shopping in open markets at least twice a week,

• If you take Milk and you are a vegetarian,

• If you are taking regular Morning walk,

• If you are regular about exercises (YOGA).

• Your Relatives’ Death is not due to Fractures but due to age and co morbidity.

You need not know about your T-score

63Summary

– Globalization of Diagnosis of Osteoporosis & Osteopenia,

– BMD screening,

– Redefining Risk factors & role of fall and BMD in fractures,

– Cost effectiveness of drug treatment,

– Hype about Hip fractures,

– Role of Big Pharma in propaganda of diagnosis, management, corruption in scientific literature, misuse political system and creation a state of

“Fear psychosis & Hope selling”.

There is an acute need for reconsidering

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