osteoporosis, fragility fracture

1. 1
HOPE SELLING

2. 2
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

3. 3
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

4. 4
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

5. 5
Osteoporotic fractures:
Comparison with other diseases
1996 new cases,
annual estimate
women 30+
184 300 all ages
annual incidence
all ages
250 000
hip
250 000
forearm
250 000
other sites
750 000
vertebral
2000
1500
1000
500
0
Osteoporotic
fractures
annual estimate
women 29+
Heart
attack
Stroke Breast
cancer
Annual incidence x 1000
1 500 000
513 000
228 000
American Heart Association, 1996
American Cancer Society, 1996
Riggs & Melton, Bone, 1995; 17(5 suppl):505S-511S

6. 6
Consequences of hip fracture
Permanent
disability
Death within
one year
Cooper. Am J Med 1997; 103(2A):12s-19s.
Unable to carry out at
least one independent
activity of daily living
Unable to
walk
independently
40%
30%
20%
80%
One year after hip fracture

7. 7
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

8. 8
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
O'Neill et al. Osteoporos Int. 2001; 12:555-558

9. 9
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

10. 10
Definition of osteoporosis
“…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.”
World Health Organization (WHO), 1994

11. 11
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

12. 12
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

13. 13
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

14. 14
WHO criteria for diagnosis of osteoporosis
T-score: Difference expressed as standard deviation compared
to young (20’s) reference population
Kanis et al. J Bone Miner Res 1994; 9:1137-41
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)

15. 15 Bone strength is more than BMD
BMD is surrogate criteria for OP as BP for Stroke
young
elderly
Images from L. Mosekilde, Technology and
Health Care. 1998
Image courtesy of David Dempster

16. 16
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

17. 17
Bone remodelling balance influences bone
strength
Bone strength
SIZE & SHAPE
macroarchitecture
microarchitecture
MATERIAL
tissue composition
matrix properties
BONE REMODELLING
formation / resorption
AGEING, DISEASE and THERAPIES

18. 18
High Bone Turnover
Resorption > Formation
Decreased Bone
Strength
Decreases Bone Mass
Disrupts Trabecular Architecture
Increases Cortical Porosity
Decreases Cortical Thickness
STOCHASTIC REMODELLING
Alters Bone Matrix Composition
L. Mosekilde
Tech and Health Care, 1998

19. 19
But bone quality is not the only factor…
Bone size (mass)
Bone shape
Architecture
Matrix properties
Fall
incidence
Fall characteristics
Energy absorption
External protection
Fall
impact
Bone
strength
Fracture risk
Neuromuscular function
Environmental risks
Age

20. 20
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

21. 21
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

22. 22
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

23. 23
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:

24. 24
Fragility fracture patient assessment
In addition to routine pre-op or fracture evaluation
• Height
• Weight
• Limb exam
– ROM, strength, deformity, pain,
neurovascular status
• Spine exam
– pain, deformity, mobility
• Functional status
Physical exam
should include:

25. 25
Laboratory tests*
• 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)
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

26. 26
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

27. 27
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.

28. 28
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.

29. 29
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.

30. 30
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.

31. 31
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

32. 32
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).

33. 33
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.
NHS no recommendation
• 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.

34. 34
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”

35. 35

36. 36
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.

37. 37
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

38. 38
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

39. 39
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

40. 40
Who to treat ?
Postmenopausal women
/men > 50 yrs
with
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 %

41. 41
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

42. 42
Pharmacological agents shown to reduce
fracture risk
Bisphosphonates
• Alendronate (FOSAMAX®)
• Risedronate (ACTONEL®)
• Ibandronate (BONVIVA®)
• Zolendronate (ACLASTA®)
SERMs
• Raloxifene (EVISTA®)
Stimulators of bone formation
• rh-PTH (FORTEO®)
Mixed mode of action
• Strontium ranelate (PROTELOS®)
Hormone therapy
• Estrogen / progestin

43. 43
Bone marrow precursors
Osteoblasts
Osteoclast
Lining cells
Stimulators of
Bone Formation
Fluoride
PTH analogs
Sr Ranelate (?)
Inhibitors of
Bone
Resorption
Estrogen, SERMs
Bisphosphonates
Calcitonin
Inhibitors of
RANKL
Cathepsin K
Therapeutic strategies

44. 44
Mainstay of treatment :
Bisphosphonates
Approval in US for osteoporosis
• Alendronate week : 1995
• Risedronate : 2000
• Ibandronate mnth: 2005
• Zoledronate yearly.iv : 2007.

45. 45
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]

46. 46
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

47. 47
Appropriate use of appropriate treatments can
halve the incidence of fractures
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
plus calcium + vitaminD

48. 48
Taking Bisphosphonates

49. 49
Contraindications

50. 50
Hot topics

51. 51
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

52. 52
Patients who did not need treatment in the first place
Discontinue Treatment
Lower risk patients, if DXA is stable/increasing
Consider 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

53. 53
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

54. 54
Treatment of vitamin D insufficiency
Insufficiency (25-OHD 25-50 nmol/l) or
maintenance therapy following deficiency
1000-2000 IU calciferol daily
or
10 000 IU calciferol weekly
–

55. 55
Hormone replacement therapy

56. 56
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)

57. 57
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

58. 58
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

59. 59
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

60. 60
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

61. 61
Denosumab Binds RANK Ligand and Inhibits
Osteoclast Formation, Function, and Survival
RANKL
RANK
OPG
Denosumab
Osteoclast Formation, Function,
and Survival Inhibited
Bone Formation Bone Resorption
Inhibited
CFU-GM Prefusion
Osteoclast
Osteoblasts
Hormones
Growth Factors
Cytokines
Adapted from: Boyle WJ, et al. Nature. 2003;423:337-342.

62. 62 Few Simple ways
You need not know about your T-score
• 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.

63. 63 Summary
There is an acute need for reconsidering
– 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”.

64. 64