Download - osteoporotic Fragility fractures treatment
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HOPE SELLING
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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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