Osteoporosis Presentation intended for community outreach

1. FRAGILITY FRACTURES &
OSTEOPOROSIS:A HEALTH
CARE CRISIS
KENNETH J EDWARDS,M.D,F.A.C.S

3. OSTEOPOROSIS
 MAJOR HEALTH CRISIS
 DECREASED BONE MASS
 MICROARCHITECTURAL DETERIORATION
 ALTERED QUALITY

4. OSTEOPOROSIS
 AFFECTS 50% OF WOMEN OVER 50
 LIFETIME RISK OF FRACTURE OF HIP,WRIST, AND SPINE
IS 40%

5. Osteoporosis - Types
 Postmenopausal osteoporosis (type I)
 Caused by lack of estrogen
 Causes PTH to overstimulate osteoclasts
 Excessive loss of trabecular bone
 Age-associated osteoporosis (type II)
 Bone loss due to increased bone turnover
 Malabsorption
 Mineral and vitamin deficiency

6. FRAGILITY FRACTURE
 FRACTURE OCCURING IN FALL FROM STANDING HEIGHT
OR LESS
 LOW TRAUMA RESULTING IN BIG FRACTURES

7. Fragility fractures are common
 1 in 2 women and 1 in 5 men over age 50 will suffer a
fracture in their remaining life time1
 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
1. Johnell et al. Osteoporos Int. 2005; 16: S3-7

8. Fractures will be more common
 Fracture incidence projected to increase 2- to 4-fold
in the next decades due to aging of the population
 In Europe
 12% to 17% of population >65 in 2002
 20% to 25% of population >65 in 2025
Aged 70+
Men Women
1990
2030
Men Wome
n

9. Bone mass
Bone
structure
Bone quality
Fall Risk
Impact of
fall
Skeletal
strength
Fracture risk
Type of fall
Energy
reduction
External
protection
Neuromuscular
function
Environmental
risks
Age
Pathogenesis of fragility fractures

10. NORMAL VS OSTEOPOROTIC BONE

13. Costs of Osteoporosis
 Affects 1 in 2 women and 1 in 8 men > 50 years old
 Causes 1.5 million fractures/year - 700,000 spine, 300,000
hip and 300,000 wrist, 25,000 deaths from complications
 Menopause is the biggest risk factor for disease
 Disease often not diagnosed until after 1 or more fractures
have occurred
 Prevalence could rise to 41 million by 2015 from 28 million
today
 Cost to health care estimated at $14 billion ($38M/day)
 Psychological and social effects of disease are immense

14. Projected to
reach 3.250
million in
Asia by 2050
Adapted from Cooper et al, Osteoporos Int. 1992; 2:285-9
Estimated number of hip fractures:
(1000s)
1950 2050
600
3250
1950 2050
668
400
1950 2050
742
378
1950 2050
100
629
Total number of
hip fractures:
1950 = 1.66
million
2050 = 6.26
million
Projected number of osteoporotic
hip fractures worldwide

15. All fractures are associated with morbidity
Cooper. Am J Med. 1997; 103(2A):12s-19s
40%
Unable to
walk
independentl
y
30%
Permanent
disability
20%
Death within
one year
80%
Unable to carry out at
least one independent
activity of daily living

16. Vertebral fractures restrict daily activities
2.8
7.8
21.7
2.1
4.2
8.6
3.6
12.6
44.7
2.2
4.6
9.9
0
5
10
15
20
25
30
35
40
45
Oddsratio
Back pain Difficulty with
>3 daily
activities
>3 activities
affected due
to back pain
Medical
consultation
1 #
2 #
3 #
Adapted from Ross PD et al.
No vertebral
fractures over the
last four years
People with vertebral fractures have greater pain, disability and
healthcare utilisation, on average, than those without fracture

17. 1.91.81.92.0Minor fracture
2.43.31.71.9Forearm
1.81.44.42.3Spine
1.91.42.52.3Hip
Minor fractureForear
m
SpineHipSite of prior
fracture
Risk of subsequent fracture
Prior fracture increases the risk
of subsequent fracture
Klotzbuecher et al. J Bone Miner Res 2000; 15:721-727
A prior fracture increases the risk of new fracture 2-
to 5-fold

18. Cost of osteoporosis in the United States
Ray et al. J Bone Miner Res 1997; 12:24-35
Total annual
cost
$13.8
Billion
$3.9
(28%)
$1.3
(10%)
$8.6
(62%)
Hospitalization
Outpatient
Nursing Home

19. Economic impact of osteoporosis
Annual direct cost
Disease Prevalence including hospitalization
(millions) (US$ billion)
Cardiovascular 4.6 20.3
disease
Asthma 15 7.5
Osteoporosis 10 13.8
Information supplied by National Heart, Lung & Blood Institute,
National Osteoporosis Foundation, American Heart Association
Annual economic cost of treating fractures in the USA is similar to that of
treating cardiovascular disease and asthma

20. Osteoporotic fractures:
comparison with other diseases
1996 new
cases,
all ages
184 300
750 000
vertebra
l
250 000
other
sites
250
000
forear
m
250
000
hip
0
500
1000
1500
2000
Osteoporotic
fractures
Heart
attack
Stroke Breast
cancer
Annualincidencex1000
1 500 000
annual
incidence
all ages
513 000
annual estimate
women 29+
228 000
annual estimate
women 30+
American Heart Association, 1996
American Cancer Society, 1996
Riggs & Melton Bone, 1995; 17:505S-511S

21. ETHNIC DIFFERENCES

22. OSTEOPOROTIC FRACTURES
POSE A LIFETIME RISK OF
DEATH COMPARABLE TO BREAST
CANCER

23. BIOLOGY OF BONE

24. Two Components of the Bone
 Cortical Bone
 Dense and compact
 Runs the length of the long bones, forming a hollow cylinder
 Trabecular bone
 Has a light, honeycomb structure
 Trabeculae are arranged in the directions of tension and
compression
 Occurs in the heads of the long bones
 Also makes up most of the bone in the vertebrae

25. Cancellous or Trabecular Bone

26. Bone Cells
 Osteocytes - derived from
osteoprogenitor cells
 Osteoblasts
 Osteoclasts

27. Osteocytes
 Trapped osteoblasts
 In lacunae
 Keep bone matrix in good condition and can release calcium
ions from bone matrix when calcium demands increase
 Osteocytic osteolysis

28. Osteoclasts
 Resorb bone matrix from sites where it is deteriorating
or not needed
 Digest bone matrix components
 Focal decalcification and extracellular digestion by acid
hydrolases and uptake of digested material
 Disappear after resorption
 Assist with mineral homeostasis

29. Osteoblasts
 Make collagen
 Activate nucleation of hydroxyapatite crystallization onto the
collagen matrix, forming new bone
 As they become enveloped by the collagenous matrix they
produce, they transform into osteocytes
 Stimulate osteoclast resorptive activity

30. Bone Remodeling Process

31. Bone Remodeling Process
 Proceeds in cycles – first
resorption than bone
formation
 The calcium content of bone
turns over with a half-life of
1-5 years

32. Why Remodel Bone ????
 Allows bone to respond to loads (stresses)
 Maintain materials properties
 Allows repair of microdamage
 Participates in serum Ca2+ regulation

33. Hormonal Influence
 Vitamin D
 Parathyroid Hormone
 Calcitonin
 Estrogen
 Androgen

34. Vitamin D
 Osteoblast have receptors for (1,25-(OH)2-D)
 Increases activity of both osteoblasts and osteoclasts
 Increases osteocytic osteolysis (remodeling)
 Increases mineralization through increased intestinal
calcium absorption
 Possibly linked to CLL,Heart Disease

36. VITAMIN D
 35-50% AMERICANS DEFICIENT
 INSTITUTE OF MEDICINE: 600 IU/DAY < 70
800 IU/DAY >70
 5-10 MIN/SUN 3000 IU VIT D
 NEED 3-4 DAYS/WEEK

37. PARATHYROID HORMONE
 Accelerates removal of calcium from bone to increase Ca
levels in blood
 PTH receptors present on both osteoblasts and osteoclasts
 Osteoblasts respond to PTH by
 Change of shape and cytoskeletal arrangement
 Inhibition of collagen synthesis
 Stimulation of IL-6, macrophage colony-stimulating factor
secretion
 Chronic stimulation of the PTH causes hypocalcemia and leads
to resorptive effects of PTH on bone

38. Calcitonin
 C cells of thyroid gland secrete calcitonin
 Straight chain peptide - 32 aa
 Synthesized from a large preprohormone
 Rise in plasma calcium is major stimulus of calcitonin
secretion
 Plasma concentration is 10-20 pg/ml and half life is 5
min

39. Actions of Calcitonin
 Osteoclasts are target cells for calcitonin
 Major effect of clacitonin is rapid fall of plasma calcium
concentration caused by inhibition of bone resorption
 Magnitude of decrease is proportional to the baseline
rate of bone turnover

40. Other Systemic Hormones
 Estrogens
 Increase bone remodeling
 Androgens
 Increase bone formation

41. BIOLOGY OF OSTEOPOROSIS

42. ESTROGEN LOSS
 Estrogen loss triggers increases in IL-1, IL-6, and TNF
due to:
 Reduced suppression of gene transcription of IL-6 and TNF
 Increased number of monocytes
 Increased cytokines lead to increased osteoclast
development and lifespan

43. BONE DENSITY & FRACTURE RISK

44. Whole bone strength declines
dramatically with age
0
2000
4000
6000
8000
10000 Femoral neck
(sideways fall)
young
old
Courtney et al. J Bone Joint Surg Am. 1995; 77:387-95
Mosekilde. Technology and Health Care 1998; 6:287-97
Lumbar vertebrae
(compression)
Wholebonestrength
(Newtons)
0
2000
4000
6000
8000
10000
young
old

45. Cortical porosity increases with age
(41 iliac biopsies, age 19-90)
Age (years)
0
3
6
9
12
15
0 20 40 60 80
r = 0.78
P < 0.001
(%)
Brockstedt et al. Bone 1993; 14:681-91
4-fold increase in
cortical porosity from age
20 to 80
Increased heterogeneity
with age

46. 20-year-old80-year-old
Age-related changes in femoral neck cortex and
association with hip fracture
Those with hip fractures have:
• Preferential thinning of the inferior anterior cortex
• Increased cortical porosity
Bell et al. Osteoporos Int 1999; 10:248-57
Jordan et al. Bone, 2000; 6:305-13
Mayhew et al,
Lancet 2005

47. High Bone Turnover
Resorption > Formation
Decreased Bone
Strength
Disrupts Trabecular Architecture
Decreases Bone Mass
Increases Cortical Porosity
Decreases Cortical Thickness
Alters Bone Matrix Composition
L. Mosekilde
Tech and Health Care, 1998
Bouxsein. Best Practice in Clin Rheum. 2005; 19:897-911
Seeman & Delmas, New England J Med, 2006; 354:2250-61

48. Common Osteoporotic Fractures
Hip Shoulder Knee Elbow

49. POST-
OP
2
MONTHS
6
MONTHS
F 83yrs
Standard Screw: Complications

50. Vertebroplasty and kyphoplasty
 Filling void in crushed vertebral body with PMMA
 Patient prone – transpedicular injection of cement
 Vertebroplasty – high pressure injection – good pain relief
 Kyphoplasty – pre-insertion of balloon to create a void for low
pressure injection – aiming for height restoration

51. Balloon kyphoplasty : Can you uncrush a
bone?

52. APPROACH TO OSTEOPOROTIC
PATIENT
 PHYSICAL EXAM
 LABS/STUDIES
 TREATMENT

53. 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:

54. DRUGS THAT DECREASE CALCIUM
RETENTION
 CORTICOSTEROIDS
 HEPARIN
 LASIX
 NICOTINE
 CAFFEINE
 ANTACIDS

55. • SR / CRP
• Blood count
• Calcium
• Phosphate
• Alkaline Phosphatase (AP)
• 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

56. 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

57. WHO GUIDELINES FOR
OSTEOPOROSIS
 Normal: Not less than 1 SD below the avg. for young
adults
 Osteopenia: -1 to -2.5 SD below the mean
 Osteoporosis: More than 2.5 SD below the young adult
average
 70% of women over 80 with no estrogen replacement
therapy qualify
 Severe osteoporosis
 More than 2.5 SD below with fractures

58. When to Measure BMD in Postmenopausal
Women
 All women 65 years and older
 Postmenopausal women <65 years of age:
 If result might influence decisions about intervention
 One or more risk factors
 History of fracture

59. When Measurement of BMD Is Not
Appropriate
 Healthy premenopausal women
 Healthy children and adolescents
 Women initiating ET/HT for menopausal symptom relief
(other osteoporosis therapies should not be initiated
without BMD measurement)

60. DAILY CALCIUM REQUIREMENTS
 CHILD 700 MG
 TEEN/YOUNG ADULT 1300 MG
 ADULT 800 MG
 PREGNANCY 1500 MG
 LACTATION 2000 MG
 POST MENOPAUSAL 1500 MG
 MAJOR FRACTURE 1500 MG

61. CALCIUM SUPPLEMENTS
 CALCIUM CARBONATE
NEEDS ACIDITY(NO PPI’S)
 CALCIUM CITRATE
BETTER DISSOLUTION
MORE BIOAVAILABILITY

62. 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

63. BIPHOSPHONATES
 ALENDRONATE(FOSAMAX)
 IBANDRONATE(BONIVA)
 RESIDRONATE(ACTONEL)
 ZOLENDRONIC ACID(RECLAST)

64. BIPHOSPHONATES
 INHIBITS OSTEOCLASTIC ACTIVITY
 DECREASE BONE TURNOVER
 REDUCE HIP FRACTURE INCIDENCE
 REDUCE VERTEBRAL FRACTURE INCIDENCE
 GI SYMPTOMS
 NEED FOR PULSE DOSING DUE TO FRACTURES
 DOES IT CREATE BRITTLE BONE?

66. CALCITONIN
 MIACALCIN/FORTICAL
 DAILY NASAL SPRAY
 REDUCES SPINAL FX 37%
 REDUCES OSTEOPOROTIC BONE PAIN
 INHIBITS OSTEOCLASTIC ACTIVITY
 NO DATA ON HIP FRACTURES

67. ESTROGEN HORMONE THERAPY
 INCREASES BONE MASS
 REDUCES HIP FRACTURES
 REDUCES SPINE FRACTURES
 BREAST CANCER UP 40% AFTER 10 YRS
 UTERINE CANCER INCREASE
 INCREASED DVT

68. ESTROGEN AGONIST/ANTAGONIST
 RALOXIFINE(EVISTA)
 SELECTIVE ESTROGEN RECEPTOR MODULATOR(SERM)
 INDICATED FOR REDUCTION IN BREAST CA IN
OSTEOPOROTIC WOMEN
 REDUCES VERTEBRAL FRACTURES
 LITTLE EFFECT ON HIP FRACTURES
 INCREASED DVT

69. PARATHYROID HORMONE(FORTEO)
 PTS WITH PROLONGED STEROID USE
 DAILY INJECTION
 2 YEAR MAXIMUM USE
 MEANT FOR SEVERE OSTEOPOROSIS
 GOOD FOR BIPHOSPHONATE FRACTURES
 T SCORE<3.5
 STIMULATES OSTEOBLAST>OSTEOCLASTS

70. Effects of Exercise on Bone
 Two types of studies conducted
 Compare trained athletes with sedentary people
 Athletes and chronic exercisers have higher BMD
 Competitive runners in 60s have ~40% greater BMD than controls
 Weight lifters have 10-35% greater spine BMD
 Tennis players have 30% greater thickness of dominant humerus
 Early life experience is important (Peak BMD)
 Women who get hip fractures have lower levels of occupational
or leisure activity from 15-45 years old
 Significant associations between hip BMD and early-life exercise
both men and women

71. Interaction of Age with Exercise
 Increasing age causes deficits in response (I.e., gain of system
goes down)
 Probably caused by multiple factors
 Women from 60-80 show BMD increase of only 5-8% with exercise
 Increases in BMD with exercise reverts to normal within a few
months of terminating training
 Exercise clearly helps maintain bone as system gain or setpoint is
reduced

72. Tai Qi reduces fall risk
Quin et al. Arch Phys Med Rehabil. 2002; 83:1355-9
Wolff et al. J Am Geriatr Soc. 1996; 44:489-97

73. LAKELAND GERIATRIC FRACTURE
PROGRAM
 DESIGNED TO IMPROVE CARE OF GERIATRIC FRACTURE
PATIENT
 MULTIDISCIPLINARY APPROACH
 PARTNERSHIP WITH SYNTHES
 EVIDENCE BASED

74. LAKELAND GERIATRIC FRACTURE
PROGRAM
 EXPEDITE TIME TO SURGERY AND MOBILIZATION
 PAIN MANAGEMENT STANDARDIZATION
 DELERIUM PREVENTION
 POST –OP DISPOSITION
 HIP FRACTURE NAVIGATOR

75. LAKELAND GERIATRIC FRACTURE
PROGRAM
 BETTER IDEA OF OUTCOMES
 CONTINUOUS PROCESS IMPROVEMENT AS GOAL
 UNIQUE PROGRAM IN MICHIGAN

76. BOTTOM LINE
 TAKE CALCIUM AND VITAMIN D
 EXERCISE FOR IMPROVED BALANCE AND STRENGTH

77. Thank You