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Osteoporosis.ppt
1. What is Osteoporosis?
• Term used for diseases of diverse
etiology that cause a reduction in the
mass of bone per unit volume
2. What is Osteoporosis?
• Term used for diseases of diverse
etiology that cause a reduction in the
mass of bone per unit volume
• Osteomalacia – in which mineralization
of the organic matrix is defective
5. Classification of Osteoporosis
1. Common forms unassociated with other diseases
1. Idiopathic (juvenile and adult)
2. Type 1
3. Type 2
2. Conditions in which osteoporosis is a common feature
1. Hypogonadism
2. Hyperadrenocorticism
3. Thyrotoxicosis
4. Malabsorption
5. Scurvy
6. Calcium deficiency
7. Immobilization
8. Chronic heparin administration
9. Systemic mastocytosis
10. Adult hypophosphatasia
3. As a feature of heritable disorders of connective tissue
1. Osteogenesis imperfecta
2. Homocystinuria
3. Ehlers-Danlos syndrome
4. Marfan’s syndrome
4. Disorders in which osteoporosis is associated but pathogenesis not understood
1. Rheumatoid arthritis
2. Malnutrition
3. Alchoholism
4. Epilepsy
5. Diabetes mellitus
6. COPD
7. Menkes’ syndrome
Harrison’s Principles of Internal Medicine
6. The Problem
• Ten million Americans (80% women and 20% men)
have osteoporosis
• Estimated that 44 million more have low bone mass
and at risk for developing osteoporosis.
• ½ women and ¼ men over age 50 will have an
osteoporosis-related fracture in their lifetime.
» National Osteoporosis Foundation
9. The Problem
• 150,000 hospitalizations per year for the
medical management of spinal
fractures.
• Vertebral fractures accounted for over
400,000 total hospital days and
generated charges in excess of $500
million.
» Gehlbach, Osteoporosis Int ‘03
10. The Problem
• In 2002, U.S. economic cost to care for
osteoporotic fractures (hospital and nursing home
direct expenditures)
– more than $18 billion
– daily cost of $49 million
• The 2030 projected cost
– more than $60 billion
– $164 million daily
» National Osteoporosis Foundation
11. Physiology
• Osteoclasts
– Large (20-100μm), multinucleated
– Derived from pluripotential cells similar to
macrophages
– Differ from macrophages – production of
tartrate-resistant acid phosphatase
– Inactive or ‘resting’ until stimulated by
RANK ligand (RANKL)
12. Physiology
• The control of the osteoclast as well as
bone homeostasis is very complex
involving
– Mechanical factors
– Immunological factors
– Hormonal factors
– Neurological factors
– Metabolic factors
13.
14. • Activated cells bind to bone through cell attachment
proteins called integrins
• Cell becomes polarized, ‘ruffled border’ appears in
sealed zone
• pH lowered by production of H ions from the carbonic
anhydrase system which dissolves HA crystals and
removes organic matrix through proteolytic digestion
20. Pathophysiology
• Cancellous bone remodeled at 30%/yr
and cortical bone 3%/yr
– Surface area phenomena
• Women lose spinal bone at 2-4%/yr
immediately after menopause
21. Tobacco and osteoporosis
• Impaired osteoblast metabolism
– Breakdown products are toxic to O-blasts through
DNA, RNA, and protein synthesis and toxic free
radical injury
– Free radicals cause cellular membrane injury via
lipid peroxidation
» Fang, Bone ’91
» Galante, Clin Physiol Biochem ’93
» Ramp, Proc Soc Exp Biol Med ‘91
22. Tobacco and osteoporosis
• Protective effects of estrogen negated
– Hepatic metabolism and hydroxy
inactivation of estrogen accelerated
– In women, early menopause and
resistance to exogenous hormone
replacement is common
» Jensen, NEJM ’85
» Michnovicz, NEJM ’86
» Hopper, NEJM ‘94
25. Steroid induced
osteoporosis
• Most common cause of drug-induced
osteoporosis
• calcium absorption from gut
• urinary calcium excretion
• Abundant callus at endplates of
collapsed vertebrae is a strong indicator
of corticosteroid-induced osteoporosis
» Adachi, Am J Med Sci ’97
» Boulos, Ann of Long-Term Care ‘03
26. Steroid induced
osteoporosis
• Bone loss begins immediately and greatest in the first
year (average of 5% loss)
• Significant trabecular bone loss with doses of prednisone
(including inhaled) greater than 7.5 mg per day
» Adachi, Am J Med Sci ’97
• Increased risk of vertebral and hip fractures even with
doses equivalent to 2.5-7.5 mg
» van Staa, J Bone Min Res‘00
27. Steroid induced
osteoporosis
• 30-50% of patients who undergo
corticosteroid therapy sustain fractures
• Fracture risk up to 15% in first year of
treatment
» Adachi, Am J Med Sci ’97
» Cohen, Proc AC Rheum ’02
» van Staa, J Bone Min Res ‘00
» Boulos, Ann of Long-Term Care ‘03
28. Steroid induced
osteoporosis
• Corticosteroids raise the fracture risk up
to six-fold across all ages, regardless of
bone mass prior to steroid treatment
• Calcium and vit D should be offered to
all patients receiving glucocorticoids
» Adachi, Am J Med Sci ’97
» Cohen, Proc AC Rheum ’02
» van Staa, J Bone Min Res ‘00
» Boulos, Ann of Long-Term Care ‘03
29. Bone Mineral Density
• Close correlation between low bone
mineral density and increased fracture
risk
» Hochberg, Arth Rheum, 42: 1246-54, 1999
» Nevitt, Bone 25: 613-619, 1999
• Close correlation between increased
bone turnover and increased fracture
risk
» Adachi, Calc Tissue Int59 Suppl 1: 16-19, 1996
30. Bone Mineral Density
• 1 standard deviation drop
(10%) in BMD is
associated with a doubling
of the fracture risk
» Cummings, Lancet 341: 72-
5, 1993
» Huang, J Bone Min Res 13:
107-13, 1998
31. Pathophysiology
• Type 1
– Post menopausal women
– Enhanced osteoclastic resorption
– High turnover
– C and N terminal collagen crosslink
degradation products
• N-telopeptide and pyridinoline
– Treat with antiresorptive agents
• Estrogen, raloxifene, calcitonin, bisphosphonates
32. Pathophysiology
• Type 2
– >70 years (senile)
– Low turnover
– Osteoblastic deficiency
– Decreased alkaline phosphatase
– Low collagen crosslink products
– Tx with parathormone analog, Ca, vit D
33. Ethnicity & Osteoporosis
National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of
Health, Department of Health and Human Services
• Hispanic women at highest
risk
• 10% of Hispanic women over
50 have osteoporosis now
• 49% are estimated to have
low bone mass, putting them
at risk for the disease
34. Ethnicity & Osteoporosis
National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of
Health, Department of Health and Human Services
• Hispanic women
get less calcium
than RDA
• Twice as likely to
develop diabetes
• Rate of hip fractures
on the rise
35. Ethnicity & Osteoporosis
Caucasian and Asian-American Women also
at high risk
National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes
of Health, Department of Health and Human Services
36. Ethnicity & Osteoporosis
• African-American
women get 50% of
RDA of calcium
• Lupus and sickle-
cell anemia can
raise osteoporosis risk
Source: National Institute of Arthritis and Musculoskeletal and Skin Diseases, National
Institutes of Health, Department of Health and Human Services
37. Ethnicity & Osteoporosis
• Osteoporosis undertreated
in African-American women
• Risk doubles every 7 years
• African-American women
more likely to die from hip
fractures
National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of
Health, Department of Health and Human Services
39. Men & Osteoporosis
• 2 million American men suffer from
Osteoporosis
• Millions more are at risk
• 80,00 hip fractures each year
• One-third die one year after
fracture
Source: National Institute of Arthritis and Musculoskeletal and Skin Diseases, National
Institutes of Health, Department of Health and Human Services
40. • WHO definition
– DXA
• 1-2.5 sd below mean – osteopenia
• > 2.5 sd below mean – osteoporosis
41.
42. • T-score compares bone density to
the optimal peak bone density for
same gender
– T-score of greater than -1 is considered
normal
– T-score of -1 to -2.5 is considered
osteopenia, and a risk for developing
osteoporosis
– T-score of less than -2.5 is diagnostic of
osteoporosis
• Z-score - compare results to others
of same age, weight, ethnicity, and
gender
– Z-score of less than -1.5 raises concern
of factors other than aging as
contributing to osteoporosis
• factors include thyroid abnormalities,
malnutrition, medication interactions,
tobacco use, and others.
43. Fracture Risk Factors
• 75% for all caucasian women > 75 years
• One OCF = 5-fold risk for another
• Low body weight, recent weight loss,
family hx of fx, smoking, age
» Kaufmann, AAOS bulletin ‘99
44. Compression Fractures
• Osteoporotic compression fracture risk stratification
Risk factor
Amount increase
(fold)
Two or more osteoporotic
compression fractures
12
BMD 2 SD below normal 4-6
Family history of vertebral
fracture
2.7
Premature menopause 1.6
Smoking history 1.2
Melton ’97, Ross ’91
45. Why bother treating this?
Morbidity
• Acute and chronic debilitating pain
• Altered spinal configuration leads to
reduction of motion and strength
• Significant performance impairments in
physical, functional, and psychosocial
domains in older women
» Gold. The Downward Spiral of Vertebral Osteoporosis:
Consequences, June 2003.
» Nevitt, Annals Int Med ’98
» Lyles, Am J. Med ‘93
46. Why bother treating this?
Morbidity
• Decreased pulmonary function and
increased lung disorders
• Increased incidence of sleep disorders
• Decreased appetite and potential for
malnutrition due to stomach compression
» Silverman, Bone ‘92
» Gold, Bone ‘96
47. Why bother treating this?
Morbidity
• Clinical anxiety and/or depression
• Loss of self-esteem and compromised
social roles
• Increased dependence on family and
friends
» Silverman, Bone ‘92
» Gold, Bone ‘96
» Kado, Arch Intern Med ‘99
48. Why bother treating this?
Mortality
• 23% increased mortality rate compared
to women without spinal fractures
(women ≥ 65 and ≥ 1 spinal fracture)
• 2-3 times more likely to die of
pulmonary causes than those without
fractures
» Kado, Arch Intern Med ‘99
49. Even worse than hip fractures
• 9-fold increase in the relative risk of
dying following a spinal fracture
• 7-fold increase following a hip fracture
– compared to women without any fractures
» Cauley. Risk of Mortality Following Clinical
Fractures, Osteoporosis Int, 2000;11:556-61.
50. Mortality after vertebral
compression fracture in Medicare
population
• 1997-2004, 5% sample
• 97,142 patients
• 53.9%, 30.9%, and 10.5% survival rates
at 3, 5, and 7 years
• Significantly and consistently lower than
controls (age, gender, race matched)
» Lau, JBJS 90: 1479-86, 2008
53. Who should have
Bone Densitometry?
• Anyone with a fragility fracture
• All women age 65 and older
• Postmenopausal women younger than
65 with risk factors
• Men over 50 with risk factors
64. Prevention
Over 50
postmenopausal women may be lose bone mass at a rate of 1 to 6 percent per year
calcium-rich diet and a healthy lifestyle that includes exercise of at least 20 minutes at least 3 times per week
67. Medication for Tx and prevention
of OCF
• Bisphosphonates
– Alendronate (Fosamax)
• 35-70 mg/wk
– Ibandronate (Boniva)
• 150 mg/month
– Risedronate (Actonel)
• 35 mg/wk
68.
69. Bisphosphonates
• Most effective inhibitors of bone
resorption
• Most dramatic effect is reduction of risk
of multiple spinal fractures (up to 84%)
• Effects may be estimated by measuring
C-terminal and N-terminal collagen
degradation products
» Levis, J Am Ger Soc 50: 409-15, 2002
» Rodian, JBJS 85-A: 8-12, 2003
70. Bisphosphonates
• Bound to mineral exposed by the
osteoclast
• Osteoclasts resorb bone and associated
bisphosphonate
• Remaining bisphosphonate
subsequently covered until future bone
resorption
71. Bisphosphonates
• Morphologic response of osteoclast to
the nitrogen containing bisphosphonate
is disappearance of the ruffled border
» Sato, J Clin Inves 88, 2095-105, 1991
72.
73. N containing bisphosphonates
alendronate and risedronate
• Directly inhibit farnesyl diphosphate
synthase
– Disrupting geranylgeranyl diphosphate
production
• GGPP tethers proteins to cell membranes integral
to cellular shape and ruffled border formation
» Bergstrom, Arch Biochem Biophy 373: 231-4, 1999
» Van Beek, Biochem Biophys Res Com 264: 108-11, 1999
74.
75.
76. Medication for Tx and prevention
of OCF
• Calcitonin (Miacalcin, Calcimar, Fortical)
– Injection 50-100 IU/d
– Nasal spray 200 IU/d
• Acute fracture pain treatment also
– Efficacy diminishes after 12-18 months
77. Medication for Tx and prevention
of OCF
• Parathyroid hormone
– teriparatide (Forteo)
• Daily injection for up to 24 months
– Anabolic effect initially with subsequent
osteoclastic recruitment
• Effects may improved with intermittant dosing
with bisphosphonates
78. Medication for Tx and prevention
of OCF
• Selective estrogen receptor modulators
– raloxifene (Evista)
• 60 mg/d
79. How do they get
fractures?
• Minor/ Low energy
–picking up grocery bag
–sneeze
–minor fall
80. Clinical Presentation
• Back pain
• Focal kyphosis
• Loss of height
• Localized tenderness
• Fingertips to lower thigh or knee
suggest OCF
» Glaser, Spine ‘97
83. Plain Radiographs
• Marker at max pain site
• Cobb angle
• Fracture pattern
• Limitations: poor judge of
acuity
84. Bone Scan
• Excellent predictive value
for response to vertebral
augmentation
• DRAWBACKS: poor
detail, det. Level
• Best in conjunction with
CT in pts MRI not feasible
91. Clinical Management
Non operative
• Relatively benign course
• Predictable pain improvement over 6-8 wks
• 1500 mg calcium
• 400 IU vit D
• Serum testosterone for men
• Elevated alk phos - suspect osteomalacia
» Lane CORR ‘00
92. Clinical Management
Non operative
• Bracing poorly tolerated and its efficacy
has not been established
• 30% don’t respond to nonoperative
therapy
» Wasnich, Bone ’96
» Melton, Am J Epidemiology ‘89
105. 1) Normal Vertebra
Normal Vertebra
2) Fractured Vertebra
Spinal Fracture, also known as Vertebral
Compression Fracture (VCF)
3) IBT Insert
Through two small incisions, the doctor
creates narrow pathways into the
fractured bone and inserts two KyphX®
balloons.
4) IBT Inflated
The balloons are carefully inflated in an
attempt to raise the collapsed vertebra
and return it to its normal position. The
balloons are then deflated and removed,
leaving a cavity within the bone.
5) Filling the Cavity
The cavity is filled with a bone cement to
support the surrounding bone and prevent
further collapse.
6) Internal Cast
The cement forms an internal cast
that holds the vertebra in
place.
110. Vertebroplasty/Kyphoplasty
Biomechanics
• Amount of PMMA weakly correlates with
strength and stiffness
» Molloy, Spine ’03
» Kim, The Spine J ‘06
• Location of cement does not effect
loading behavior of bone
» Higgins, Spine ’03
• Stiffness equal with CaPO4 and PMMA
» Tomita, J Ortho Sci ’03
112. Clinical Outcomes
Kypho/vertebroplasty vs nonop
• Vertebral augmentation (kyphoplasty or
vertebroplasty) vs non operative care
– Significant pain level and functionality
improvement
» Grados, Rheumatology ’00
» Taylor, Spine ’06
» Kaufmann, Am J Neuroradil ’01
» Zoarski, J Vasc Inter Rad ’02
» Garfin, Spine ’01
» Lieberman, Spine 01
113. Clinical Outcomes
Kyphoplasty vs Vertebroplasty
• Deformity/Ht loss
• Low pressure injection
• Less cement extrusion?
• Equivalent pain relief
114. Clinical Outcomes
Kyphoplasty vs Vertebroplasty
• Biomechanical and Clinical studies
• Equal restoration of height,
strength, stiffness in cadaveric
model between kyphoplasty,
vertebroplasty, cavity creation
system, osteoplasty
» McCann, Spine ‘06
115. Clinical Outcomes
Kyphoplasty vs Vertebroplasty
• Immediate pain relief equal
• Slightly higher risk of extrusion with
vertebroplasty due to lower viscosity
• Slight advantage with improving height
in kyphoplasty
• Insignificant clinical difference
» Phillips, Spine ’02
» Grohs, J Spin Dis Tech ‘05
116. Clinical Outcomes
Kyphoplasty vs Vertebroplasty
• Immediate pain relief equal
• Slightly higher risk of extrusion with
vertebroplasty due to lower viscosity
• Slight advantage with improving height
in kyphoplasty
• Insignificant clinical difference
» Phillips, Spine ’02
» Grohs, J Spin Dis Tech ‘05
117. Fracture Age and Ability to Reduce
• Kushwaha and Lalibert, NASS 2002
– Looked at fracture reduction ability
• acute (<1 mo.)
• sub-acute (1-3 mo.)
• established (3-6 mo.)
• chronic (>6 mo.)
• Time since initial fracture alone does not
predict ability of balloon to reduce
• MRI reveals local edema and acute
component of fracture
118. Fracture Age and Ability to
Reduce
• 75% of chronic fractures can be
expanded
» Crandall, The Spine J ’04
• 50% >8 weeks expandable but earlier
better
» Chin, Neurosurgery ’06
123. Complications
• Rare
• Leakage
–More common in vertebroplasty
–Cement extrudes into disc space,
canal, basivertebral vein or
embolizes
» Taylor, Spine ‘06
124. Adjacent Fracture
• 5-25 x increased risk of fracture
after 1st fracture
» Trumees, Spine J ’04
• 10% risk of fracture within 90 days
after kypho/vertebroplasty
» Grados, Rheum ’00
» Lavelle, Spine J ‘06
125. Cancer and spinal fractures
• Insufficiency fractures
• Bone metastasis
• Multiple myeloma
126. Insufficiency Fractures
metastasis
• 17-50% of patients with breast carcinoma and
bone metastasis will experience new spinal
fractures each year
» Body, Cancer ‘03
• Up to two-thirds of patients with bone
metastasis experience severe pain and
disability
» Janjan, Sem Onc ‘01
• Up to 41% of patients receiving radiation to
treat bone metastasis experience bone
fractures
» Patel, Orthopedics ‘01
127. Insufficiency Fractures
multiple myeloma
• 15-30% of patients with multiple myeloma sustain
new spinal fractures annually
• Approximately 75% of patients with multiple myeloma
have bone pain at the time of diagnosis
• 50% of myeloma patients with bone pain in the back
have vertebral fractures
» Body, Cancer ‘03
128. Outcomes
augmentaion with vertebral
tumors
• Outcome and complication profile
similar to non tumor patients
» Alvarez, Eur Spine J ’03
» Fourney, J Neurosurgery ’03
» Martin, Radiology ‘03
132. Indications for reconstruction in
osteoporosis
• Neurological deficit
– Very rare
» Lee, CORR 323: 91-7, 1996
• Painful fractures not amenable to
kypho/vertebroplasty
• Progressive deformity with intractable
pain
133. Indications for reconstruction in
osteoporosis
• When surgery indicated the plan must be
individualized
• Understand co-morbidities
• Spine surgery principles apply with some
exceptions
– Anterior approach with diaphragmatic
manipulation is poorly tolerated in geriatric
patients
– Fixation is problematic
134. Osteoporotic fixation
• Pedicle screws most sound
• Wires and hooks can be used in
conjunction with screws
• Insertional torque directly correlates
with pullout strength
» Multiple authors
• Minimal bone mineral density unknown
135.
136. Osteoporotic fixation
• Although insertional torque important,
oversizing the screws too much places
the pedicle at risk for fracture
• 40% fracture rate when screw diameter
greater than 70% of outer pedicle
diameter
» Hirano, J Spin Dis 11: 493-7, 1998
137. Osteoporotic fixation
• Pullout resistance
– Proportional to insertional torque and BMD
Ryken ’95, Peiffer ’96, ’97, Hitchon ‘03
– Proportional to volume of bone between threads
Chapman ‘96
– Thread depth and outer diameter most important
– Conical screws with constant major diameter
Abshire ’01, Choi ‘02
– Triangulation
Ruland ’91, Suzuki ’01, Huang ‘03
141. Osteoporotic fixation adjuncts
Expandable screws
– Up to 50% increase in pullout strength
» Cook, J Spin Dis 13: 230-236, 2000
• PMMA
– Up to 500% increase with 2 cc
» Kostuik, unpublished data
• CaSO4
– 68% improvement
» Lotz, Spine 22: 2716-2723, 1997
142.
143.
144.
145. Osteoporosis poses other
problems
• Often coincides with spondylosis
– Combination of a stiff weak spine can be
disastrous
• Odontoid fractures very difficult to
manage
• HALO fixation challenging
• Anterior cervical fixation challenging
146.
147. Conclusion
• Avoidance is key
• Low threshold to investigate bone
density
• Treatment as needed
• Anticipate fixation problems
