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
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
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
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
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
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
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
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
35.
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
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
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
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
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:
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)
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?
65.
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