2. What is Osteoporosis?
■ Term used for diseases of diverse etiology that cause a
reduction in the mass of bone per unit volume
3. 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
6. Classification of Osteoporosis
Harrison’s Principles of Internal Medicine
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
7. 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. ■ 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
16. 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
17. 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
18. 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
21. 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
22. 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
23. 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
24. 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
25. 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
26. 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
27. 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
28. Pathophysiology
■ Type 2
– >70 years (senile)
– Low turnover
– Osteoblastic deficiency
– Decreased alkaline phosphatase
– Low collagen crosslink products
– Tx with parathormone analog, Ca, vit D
29. Ethnicity & Osteoporosis
• 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
National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of
Health, Department of Health and Human Services
30. 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
31. 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
32. 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
34. 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
35. ■ WHO definition
– DXA
■ 1-2.5 sd below mean – osteopenia
■ > 2.5 sd below mean – osteoporosis
36.
37. 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
38. 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
39. 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
40. 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
41. 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
42. 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
43. 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.
44. 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
47. 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
54. Medication for Tx and
prevention of OCF
■ Bisphosphonates
– Alendronate (Fosamax)
■ 35-70 mg/wk
– Ibandronate (Boniva)
■ 150 mg/month
– Risedronate (Actonel)
■ 35 mg/wk
55.
56. 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
57. Bisphosphonates
■ Bound to mineral exposed by the osteoclast
■ Osteoclasts resorb bone and associated bisphosphonate
■ Remaining bisphosphonate subsequently covered until
future bone resorption
58. Bisphosphonates
■ Morphologic response of osteoclast to the nitrogen
containing bisphosphonate is disappearance of the ruffled
border
■ Sato, J Clin Inves 88, 2095-105, 1991
59. 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
60. 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
61. 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
62. Medication for Tx and
prevention of OCF
■ Selective estrogen receptor modulators
– raloxifene (Evista)
■ 60 mg/d
63. How do they get fractures?
■ Minor/ Low energy
– picking up grocery bag
– sneeze
– minor fall
64. Clinical Presentation
■ Back pain
■ Focal kyphosis
■ Loss of height
■ Localized tenderness
■ Fingertips to lower thigh or knee suggest OCF
■ Glaser, Spine ‘97
67. Plain Radiographs
■ Marker at max pain site
■ Cobb angle
■ Fracture pattern
■ Limitations: poor judge
of acuity
68. 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
72. 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
73. 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
78. 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
80. 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
81. Clinical Outcomes
Kyphoplasty vs Vertebroplasty
■ Deformity/Ht loss
■ Low pressure injection
■ Less cement extrusion?
■ Equivalent pain relief
82. 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
83. 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
84. 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
85. 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
86. 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
88. 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
89. 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
91. 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
92. 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
93. 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
94. 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
95. Conclusion
■ Avoidance is key
■ Low threshold to investigate bone density
■ Treatment as needed
■ Anticipate fixation problems
