Inflammation of the Joint

(over 100 specific diseases)

Rheumatoid Arthritis
Gout
Degenerative Joint Diseases
Ankylosing spondylitis
JRA
Psoriatic Arthritis
Bacterial Arthritis
Systemic Lupus
Erythematosus
Scleroderma
ARTHRITIS: Inflammation of the Joint
Pain
Swelling
Redness
Warmth
IL-8
IL-6
GM-CSF
IL-1
TNF-
FGF
Fibroblast/ type
B synovial cells
Metalloproteinases
Prostaglandins
Complement
IL-6
IL-1
IL-6
IL-8
GM-CSF
M-CSF
Macrophage/ type A
synovial cells

IL-1
TNF-
Adhesion molecule
expression on
blood vessels
HLA-DR
Complement
metalloptoteinases
CYTOKINE NETWORKS IN SYNOVITIS
+ FEEDBACK
IL-8
IL-6
GM-CSF
IL-10
IL-1
TNF-
FGF
Fibroblast/ type
B synovial cells
Metalloproteinases
Prostaglandins
Complement
IL-6
TGF-
IL-4
IL-1
IL-6
IL-8
GM-CSF
M-CSF
Macrophage/ type A
synovial cells

IL-1
TNF-
Adhesion molecule
expression on
blood vessels
HLA-DR
Complement
metalloptoteinases
CYTOKINE NETWORKS IN SYNOVITIS
+ FEEDBACK
- FEEDBACK
Points to Remember
Cells involved in Inflammation:
- macrophage, fibroblast, T-cells
Pro inflammatory cytokines:
- IL-1, TNF alpha, IL-6
- IL-8, FGF, GM-CSF
Anti inflammatory cytokine:
- IL-10, TGF-B, IL-4
Degenerative Joint Disease / Osteoarthritis
A group of disorder in which the balance between
degeneration and synthesis within the cartilage and
subchondral bone is disturbed resulting to cartilage and
subchondral bone destruction

Dippe, Paul
Osteoarthritis

Most common form of arthritis
10% of the worlds population
50% of people over the age of 60 years
At age 75, more than 80% of people have symptoms
of the disease
More common in women than in men
Risk Factors for Osteoarthritis
Age
Female sex
Race
Genetic factors
Repetitive stress
Obesity
Congenital / Developmental defects
Prior inflammatory joint dse.
Metabolic / Endocrine disorders
Clinical Features
Deep ache, localized pain
Aggravated by activity, relieved by rest
Transient joint stiffness
Bony swelling, crepitus
Progressive cartilage loss
Biochemical markers in Osteoarthritis
Major tissue of
origin
Biochemical markers
Synovium Hyaluran, type 2 collagen
propeptide, proteases
Subchondral bone Type 1 collagen crosslinks,
osteocalcin, alk. phosphatase,
Cart. oligomeric protein (COMP)
Management of Degenerative Joint Disease
Non-pharmacologic
Pharmacologic
Surgery
Changes in lifestyle for patients with Osteoarthritis
General measures
- Maintain optimal weight
- Encourage activity and regular general exercise
- Maintain positive approach
Specific measures
- Strengthening of local muscles
- Use of appropriate footwear and walking aids
- Pay attention to specific problems caused by disability (such as
shopping, housework, and job)
Pharmacologic Agents

1. Analgesics

Simple Analgesics (acetaminophen)
Other Analgesics (opioids, tramadol)
or combination


Acetaminophen is the first line agent for OA
ACR recommendation

Pharmacologic Agents

1. Analgesics

2. NSAIDs

Anti inflammatory effects
Safety concern
- renal, GI, platelet function
- CV risk

Phospholipids
Phospholipase A
Arachidonic Acid
( PG, thromboxanes, prostacyclins)
Lipooxygenase Cyclooxygenase
(-) NSAIDs

(leukotrienes, bradykinin)

Mechanism of Action of NSAIDs New hypothesis
Arachidonic Acid
Prostaglandins
Prostaglandins

Protection of
gastric mucosa
Homeostasis
Mediates pain
Inflammation and fever
Conventional
NSAIDs
COX-1 COX-2
Coxibs
COX-1 COX-2
- produces PG from AA - produces PG from AA
- constitutively expressed - inducible

- governs PG production - governs PG production
that mediate hemostatic that mediate
inflammation
function

- essentially important in:
gastric, bowel mucosa
kidney, platelets
Risks factors for UGI adverse events
Age >65 y.o.
Co-morbid clinical conditions
Oral glucocorticoids
History of PUD; UGIB
Anticoagulants
Pharmacologic Agents

Few joint involvement
NSAIDs, capsaicin


1. Analgesics
2. NSAIDs

3.Topical Agents
Pharmacologic Agents

(+) effusion
Relief lasts for a few weeks



1. Analgesics
2. NSAIDs
3.Topical Agents

4. Intraarticular
Steroid Injection
Pharmacologic Agents





1. Analgesics
2. NSAIDs
3.Topical Agents
4. Intraarticular Steroid
Injection

5. DMOADs

Modify morphologic changes in
the joints
- glucosamine / chondroitin
- viscosupplementation
- doxycycline


Pharmacologic Agents





1. Analgesics
2. NSAIDs
3.Topical Agents
4. Intraarticular Steroid
Injection
5. DMOADs

6. Other Agents

Antidepressants
Mild tranquilizers


Surgical Treatment for Osteoarthritis
History of joint locking
- arthroscopy for removal of loose body
Persistent synovitis
- arthroscopic washout or radioisotope
synovectomy
Joint replacement is highly effective for hip & knee
- consider early referral for opinion
Points to Remember - Osteoarthritis
Most common form of arthritis
Identify risk factors
- age is the most powerful risk factor
Deep ache localized pain related to activity
Hand lesions
- heberdens, bouchards nodes
Progressive cartilage loss
Paracetamol 1
st
line agent
Rheumatoid Arthritis
Chronic, inflammatory
Articular, extra-articular
Oligo, polyarticular
Young, female/male ratio (4:1)
Remission and relapse
Unknown etiology
- genetic predisposition (HLA-DR4)
Rheumatoid Arthritis
Etiology is unknown
- Genetics
- HLA DR4
- Infection
- mycoplasma, EBV, CMG, parvo,
rubella virus
- Superantigens
- staph, strep, M. arthritidis
- Environmental
- cigarette smoking
Extra-articular manifestation of RA
rheumatoid nodules
vasculitis
pulmonary
- pleural effusion, fibrosing alveolitis, nodules
cardiac
- pericarditis, mitral valve disease, conduction defects
skin
- palmar erythema, cutaneous vasculitis
Feltys syndrome
- sero (+) RA, splenomegaly, neutropenia


Extraarticular Manifestations of RA
Immune Abnormalities
Rheumatoid Factor
- anti - immunoglobulins
- anti IgG/IgM - immunologic hallmark
- Rose-Waaler assay
- (+) 80% of RA pts.
- high titer associated
- extra-articular sx
- progressive disease
- poor prognosis
ANA




Other causes of (+) RF test:
- other CTD - leishmaniasis
- viral infections - TB
- leprosy - liver diseases
- SBE - sarcoidosis


Revised criteria for RA diagnosis
- symmetrical joint involvement*
- joint stiffness of at least1 hour duration*
- Involvement of at least 3/14 joints of the body*
- Hand joint involvement*
- (+) subcutaneous nodules
- (+) RA test
- radiographic findings
- Juxtaarticular osteoporosis, cystic lesions, evosions

* At least 6 weeks duration
4/7 criteria


Treatment of RA
Experimental
agents
Cyclophosphamide,
MTX, Azathioprine
Gold salts, antimalarials,
Penicillamine
Salicylates, NSAIDS, analgesics
Education, rest, exercise, social service
Intraarticular
Steroid injection
Mechanical
devices
DMARDs
Non-analgesic
Slow onset of action 10-20 weeks
More toxic than NSAIDs
Mechanism of action:
Decrease leukotriene B4 synthesis in
neutrophils
Decreases IL-1 concentration in SF
Disease Modifying Drugs (DMARDs)

Gold salts
Antimalarials
Sulfasalazine
D- Penicillamine
Methotrexate
Cyclosporin-A
Biologic Agents
Anti TNF
- Etanercept
- Infliximab
- Adalimumab
T cell inhibitor
- Abatacept
B cell inhibitor
- Rituximab
Interleukin 1 receptor antagonist
- Anakinra
Adverse effects of Biologic Agents

Opportunistic infection
CHF
Demyelinating disease
Systemic lupus erythematosus
Injection site reaction
Neutropenia

Factors Associated with Poorer Prognosis
Insidious polyarticular onset
Male patients
Extraarticular manifestations
Functional disability at one year after start of disease
Substantially raised concentration of RF
Presence of HLA-DR4
X-ray evidence of erosion within three years of start of
disease
Points to Remember
Polyarticular, symmetrical
Joints stiffness more than 1 hour
Cartilage destruction, bone erosions
Asso. with deformities, extra articular features
ACR revised criteria for diagnosis
Disease modifying, biologic agents
Gouty Arthritis
King of diseases; disease of Kings
inflammatory arthritis due to urates
acute, episodic
monoarthritis polyarticular
Hyperuricemia
- biochemical hallmark

Classification of Hyperuricemia and Gout
Primary
- Enzymatic Defect
HGPRT deficiency
PRPP overactivity
Secondary
- Endogenous
Family history
Body build
Kidney function, HPN
Inc. cell breakdown
- Exogenous
diet, drugs
alcohol, stress
starvation
Renal
Handling
of Urates
Gouty Arthritis
Statements
- Hyperuricemia is not gout
- Gout is a result from hyperuricemia
- Extremely painful episodes of arthritis
- Tendency to abuse NSAIDS, steroids
- Treatable / Preventable




The most important differential diagnosis for
acute gouty attack is
infection


The most feared complication of Gouty
Arthritis is kidney involvement
Risk Factors for the Development of Gout Alcohol
Association of alcohol consumption and the risk of incident gout
- 12 year cohort study
- Biennial questionnaires
- 47,150 male health professionals with no gout at baseline
Alcohol intake strongly associated with an increased risk of gout
- Highest risk with beer consumption
- Moderate risk with liquor consumption
- Lower risk with wine consumption

Choi et al. Lancet, 2004;363:1277-1281
Risk Factors for the Development of Gout
Diet
High meat consumption

High seafood consumption

High dairy consumption

High consumption of
purine-rich vegetable


risk gout

risk gout

risk of gout

no association


Choi et al. NEJM, 2004;350(11):1093-1103



Risk Factors for the Development of Gout
Drugs
- low dose steroids
- aspirin
- anti TB drugs - pyrazinamide
- diuretics


Treatment
Acute Attack
- NSAIDS, Colchicine
- Analgesics
- IV/IM corticosteroids
- Non pharmacologic measures

Hyperuricemia
- Allopurinol
- Uricosuric drugs
PROPHYLACTIC COLCHICINE DOSES
CClr > 60
CClr 40-60
CClr 30-40
CClr < 30


0.6 mg BID
0.6 mg QD
0.6 mg Q2 Days
0.6 mg Q3 Days



- COLCHICINE NOT EXTRACTED BY DIALYSIS
- DO NOT USE IN DIALYSIS PATIENTS

- REDUCE COLCHICINE BY 50% FOR AGE >= 70
- CAUTION WITH DRUG INTERACTIONS:
e.g., CSA, Statins, Macrolides, Gemfibrozil
Points to Remember
Acute, episodic; mono/oligoArthritis
Hyperuricemia biochemical hallmark
(+) uric acid crystal on SF, tophi definitive Dx
Young male, post menopausal women
Provocative factors:
- inc. purine foods
- trauma, surgery
- alcohol ingestion
- ACTH, glucocorticoid withdrawal
- hypouricemic therapy
- medical illness stroke, MI
- drugs diuretics, PZA, low dose aspirin
Spondyloarthropathies
Ankylosing spondylitis
Psoriatic arthritis
Reiters disease / Reactive arthritis
Enteropathic arthritis (IBD)
General Features
Familial aggregation HLA-B27
( - ) rheumatoid factor test
Asymmetric peripheral oligoarthritis
Axial skeleton involvement
Sacroiliitis low back pain
Enthesopathic

Ankylosing Spondylitis
Marie Strumpell disease, Bechterews disease
2
nd
3
rd
decade of life
Male preponderance 3:1 ratio
Syndesmophyte formation ( bamboo spine )
Enthesitis, sacroiliitis
Clinical Features
Dull pain, insidious onset
Low back morning stiffness
- relieved by activity, aggravated by rest
Peripheral asymmetric oligoarthritis
Acute anterior uveitis
- most common extra articular Mx
Aortic insufficiency
( + ) Schobers test
Radiographic Findings
Syndesmophyte formation
- ossification of annulus fibrosus
Vertebral body disk margin erosion
Squaring of vertebral bodies
Sclerosis of SI joint, sacroiliitis
Diagnosis
Modified NY criteria (1984)
- Hx of inflammatory back pain
- LOM sagittal, frontal planes of LS
- limited chest expansion
- definite radiographic sacroiliitis

Definite AS:
- evidence of sacroiliitis + any of the other 3
criteria

AS vs other causes of LBP
Age of onset before 40
Insidious onset
Duration of sx > than 3 months before medical attention is sought
Prolonged morning stiffness
Improvement with exercise
Treatment
No definitive treatment
- appropriate exercise program
- NSAIDs
- sulfasalazine
- methotrexate
- intralesional cortisone injection
- biologic agents
Reactive Arthritis / Reiters Disease
Asymmetric oligoarthritis
Urethritis
Conjunctivitis
Mucocutaneous lesion
- balanitis
- keratoderma blenorrhagica
Clinical Forms
Post enteric infection
- shigella (flexneri), salmonella,
yersinia, campylobacter

Post genital infection
- chlamydia trachomatis
Psoriatic Arthritis
5 - 42 % of patients with psoriasis
Unknown cause
Indirect evidence:
- infection
- trauma
- inc. humoral / cellular immunity
- cytokine driven
- abn. fibroblast, dendritic cell, PMN function
Major Types of Psoriatic Arthritis
Asmmetric oligoA
- most common
Symmetric polyA
- RA like features
DIP involvement
- nail lesion
Arthritis mutilans
- deformities, young patients
Psoriatic spondylitis
Treatment
Patient education
Physical / occupational therapy
NSAIDs
Methotrexate + folic acid
Sulfasalazine
Gold salts
Antimalarials

Enteropathic Arthritis ( IBD )
Ulcerative colitis / Crohns disease
Intestinal bypass surgery
Whipples disease (intestinal lipodystrophy)
Features
oligoA, asymmetric
Spondylitis, sacroiliitis
Clubbing of fingers
Development of amyloid crohns
Osteoporosis inactivity malabsorption, steroids
Points to Remember
HLA - B27 association
(-) RA factor exam
Clinical features
- Musculoskeletal
- peripheral oligoA
- enthesitis
- sacroiliitis, spondylitis
- Systemic
- psoriasis
- IBD
- conjunctivitis, iritis
- genito urinary inflammation
- carditis
Systemic Lupus Erythematosus
chronic, inflammatory
multiorgan, multisystemic
unknown etiology
autoantibodies
immune complexes

Theories
Immunologic
autoantibodies, immune complexes
activity of polyclonal T;B cells
Genetics
concordance in monozygotic than dizygotic twins (24 58%: 0 6%)
complement deficiencies C1q, C2, C3, C4
Genetics
HLA-DR2 DR3 tissue types
Defective C4AQO allele
marker for ethnic groups
Environment
UV-B, UV-A rays
alfalfa, chemicals (hydrazine)
virus, type-C oncorna
Hormonal
woman, reproductive life
NZ mice
estrogen activates disease
androgens protective



Clinical Manifestations
Musculoskeletal
- arthritis
polyarticular, rheumatoid like
joint deformities
non-erosive
- myopathy
active disease
drug-induced (hypoK, steroids, antimalarials)
Clinical Manifestations
Malar rash
photosensitive, flat
or raised
non-scarring
Cutaneous
Clinical Manifestations
Discoid rash
20 %
circular, raised borders
central, atrophic,
hypopigmented area
scarring
photosensitive
Cutaneous
Clinical Manifestations
Oral ulcers
painless, shallow
buccal mucosa
disease activity
Lupus band test
- deposition of IgG at dermal-
epidermal junction
Renal
- pyuria, hematuria, proteinuria, casts (UA)
- subendothelial, subepithelial mesangial deposits (E/M)
- renal biopsy best guide to nephritis severity
- focal, mesangial, membranous, diffuse proliferative
Clinical Manifestations
Nervous system
- overdiagnosed
- CNS, PNS
- cognitive dysfunction most frequent
- seizures, psychosis
- neuropathy, autonomic dysfunction
- MRI (contrast) acute, chronic
- lumbar tap active disease, infection
Clinical Manifestations
Hematologic
- anemia NN, hemolytic
- leukopenia, lymphopenia
- thrombocytopenia
- arterial, venous thrombosis
- lupus anticoagulant, anticardiolipin
prolong PTT (APS)
Clinical Manifestations
Cardiopulmonary
carditis
pericarditis most common
myocarditis arrhythmias
endocarditis valvular insufficiency
transesophageal echocardiogram
Libmann-Sacks
Laboratories
ANA
- best screening test (WIL-2 or Hep-2 cells)
- (+) test nonspecific; supports diagnosis
- other conditions:
Elderly
chronic inflammatory conditions
other CTDs
viral infections
Laboratories
Autoantibodies in SLE
- anti-dsDNA
nephritis, activity
relatively disease specific
- anti-Sm
cutaneous, musculoskeletal
- anti-Ro (SS-A)
neonatal, elderly lupus
ANA negative lupus
may cause nephritis


- anti-La (SS-B)
always associated with Ro
Sjogrens syndrome, low risk for nephritis
- anti-histones
drug-induced
- anti-phospholipids
3 types LA, aCL, false VDRL test
LA, aCL clotting abnormalities, fetal loss, platelet
antibodies for B
2
glycoprotein

- antierythrocyte
hemolysis
- antineuronal
diffuse CNS lupus
- antiribosomal
CNS lupus
Psychosis
- antiRNP
MCTD
Revised Criteria for SLE
Malar rash
Discoid rash
Photosensitivity
Oral ulcers
Arthritis, non-erosive, polyarticular
Serositis carditis, pleuritis, effusion
Revised Criteria for SLE
Renal
+++ protein (U/A), >500mg/24hrs
Hematologic
blood -penias
Neurologic
seizures, psychosis
Immunologic
dsDNA, Sm, antiphospholipid
(+) ANA
Revised Criteria for SLE
4/11 criteria
97 % sensitivity; 98 % specificity
SOAP, BRAIN, MD
Treatment
no cure, rare complete sustained remission
non-pharmacologic
- doctor-patient relationship
- education
- support group
Pharmacologic Therapy
NSAIDs, analgesics
MS Sx
antimalarials
cutaneous vasculitis
opthalmologic consult
Steroids
major organ
monitor side effects
oral / pulse therapy
Immunosuppressives
azathioprine, cyclophosphamide, chlorambucil, MTX
oral / pulse therapy

Others
plasmapheresis
cyclosporins
immunoablation
high dose CYP
antibodies to CD
4

suppress T/B cell
IVIG
stem cell transplant
Prognosis
Factors assocd w/ poor prognosis
- creatinine levels
- hypertension
- nephrotic syndrome
- anemia, albumin, low C
3
/C
4
at diagnosis
- low socioeconomic status
Cause of Death
1
st
decade
- infection, active disease
2
nd
decade
- thromboembolic events
Osteoporosis
Silent disease
Systemic skeletal disease
1
Low bone mineral density (BMD)
BMD 2.5 standard deviations below the mean
BMD of young adults
Microarchitectural deterioration of bone
tissue
Bone fragility
Increased risk for fracture


1
Consensus Development Conference. Am J Med. 1991.
Wasnich RD: Primer on the Metabolic Bone Diseases
and Disorders of Mineral Metabolism. 4th edition,
1999, p 257
Incidence Rates for Vertebral, Wrist and Hip
Fractures in Women After Age 50
40
30
20
10
50 60 70 80
Vertebrae
Hip
Wrist
Age (Years)
A
n
n
u
a
l

i
n
c
i
d
e
n
c
e

p
e
r

1
0
0
0

w
o
m
e
n

Non-Modifiable
Age
Female sex
Maternal family history of
hip fracture
Low birth weight
Disease predisposing to
osteoporosis
Risk factors taken from Jordan & Cooper Best Practice and Res Clin Rheumatol, 2002
Categorized by Eli Lilly & Co.
Potentially Modifiable
History of falls
Body mass index
Drug therapy (e.g. corticosteroid
use, use of anti-convulsants)
Primary or secondary
amenorrhea
Early menopause
Smoking
Excessive alcohol consumption
Dietary calcium and vitamin D
deficiency

Risk Factors for Osteoporosis and Fracture
Indirect
effects
Unitary model for postmenopausal
bone loss: role of oestrogen deficiency
Directly increases
osteoclast number
and longevity
Dietary
calcium
(decreased
absorption)
Secondary
hyperparathyroidism
Increased bone
resorption
Bone
loss
Decreased
bone
formation
Remodelling
imbalance
?
Adapted from: Riggs BL, et al. J Bone Miner Res 1998;13:76373
Oestrogen
deficiency
Glucocorticoid dose Dependent Effect on Fracture Risk
0.99
1.77
5.18
1.55
2.59
2.27
0
1
2
3
4
5
6
Hip Vertebral
Type of Fracture
Relative Risk
of Fracture
<2.5 mg
2.5 mg-7.5 mg
>7.5 mg
Dose*
Van Staa TP, et al. J Bone Miner Res. 2000.
*Prednisolone equivalent
N = 488 470
Most rapid bone loss occurs in the first 6-12 months of
Steroid therapy
WHO definition of osteoporosis
The T-score
the number of SDs from the mean (average) value of BMD at peak bone
mass
Patient category T-score
Normal Above 1
Osteopenia Between 1 and 2.5
Osteoporosis <2.5
Established osteoporosis <2.5 with non-traumatic fracture

WHO Study Group. WHO Technical Report Series 843, Geneva Switzerland:
WHO;1994:1129
How should patients be evaluated to determine if they have
osteoporosis?
AACE recommend that evaluation include
a comprehensive medical examination
X-rays in patients with suspected vertebral fractures
BMD measurements
assessment of risk factors for fractures
NOF guidelines are generally similar, but with greater emphasis on BMD
testing
Neither guidelines take into account bone markers for diagnosing
osteoporosis
AACE Osteoporosis Task Force. Endocr Pract 2003;9:54564
http://www.nof.org/professionals/clinical.htm
Diagnosis and assessment
X-rays
BMD
Ultrasound
Bone markers
Bone biopsy and histomorphometry
Indications for Bone Density Measurements

estrogen deficient women
- perimenopause
- early menopause
- premenopause
radiologic osteoporosis
previous low-trauma fracture
corticosteroid therapy
>7.5mg/day x 3 months
diseases causing secondary osteoporosis
monitor treatment response
Biochemical markers
of bone turnover in osteoporosis
Formation
(reflect osteoblast activity)
Resorption
(reflect osteoclast activity)
Serum osteocalcin
Serum total and bone
alkaline phosphatase
Serum type I collagen
propeptide
Urinary pyridinolines and deoxypyridinoline
Urinary and serum CTX*
Urinary and serum N-telopeptide of the
alpha chain of type I collagen (NTX)*

*CrossLaps
TM
Candidates for therapy: the AACE guidelines
The AACE guidelines indicate that the following women may benefit from
pharmacologic therapy
women with a prior vertebral or hip fracture
women with BMD T-score 2.5 without risk factors
women with borderline-low BMD if risk factors are present
women in whom nonpharmacologic preventive measures are
ineffective
AACE Osteoporosis Task Force. Endocr Pract 2003;9:54564
Therapeutic options for osteoporosis
Stimulators of bone formation
- Fluoride
- Parathyroid hormone


Mixed mechanism of action
- Vitamin D and metabolites
- Strontium ranelate

Recommended for all women
at risk for osteoporosis
- Calcium and vitamin D

Inhibitors of bone resorption

Bisphosphonates
- Alendronate
- Etidronate
- Risedronate

Calcitonin

Estrogen progestin

Selective estrogen receptor
modulators (SERMs)
- Raloxifene
Osteoporosis prevention
T-score >2.5
Osteopenia
treatment with or without
previous fracture
Osteoporosis treatment
with multiple fractures and at
risk for hip fracture
50 55 60 65 70 75 80 85
Raloxifine
Age (years)
HRT
Therapeutic Management of Postmenopausal Osteoporosis
Teriparatide
Bisphosphonates
Adapted from Seeman & Eisman, MJA Vol 180 15 March 2004, p298-303

Optimal Daily Calcium Requirements
1300 mg
1000 mg
1200 mg
Recommended Calcium
Intake (Daily)
Age
1997 Recommended Dietary Intakes
9-18 years
19-50 years
51 years or older
National Academy Press. Available at: http://books.nap.edu/catalog/5776.html. 1999.

Recommendations for Vitamin D Intake
Europe
The Scientific Committee for Food of the Commission of the European
Communities recommends
400 IU of vitamin D daily for the elderly (age 65)
United States
The Institute of Medicine has defined adequate daily intake of vitamin D
according to age
Adults up to age 50 200 IU
Adults 5170 400 IU
Adults >70 600 IU
No toxic effects reported in 61 healthy adults given 4000 IU/day in a clinical
study to assess the efficacy and tolerability profile of high vitamin D intake
Adapted from European Commission. Report on osteoporosis in the European community: Action on prevention. Luxembourg: Office for Official
Publications of the European Communities, 1998; Dietary Reference Intakes for Calcium, Phosphorus, Magnesium, Vitamin D,
and Fluoride. Washington, DC: Institute of Medicine, National Academy Press, 1997; Vieth R et al Am J Clin Nutr 2001;73:288294.
Widespread Prevalence of Vitamin D Inadequacy* Regardless of Geographic
Location
*Vitamin D inadequacy was defined as serum 25(OH)D <30 ng/ml; **Interim results of ongoing study
Study Design: Observational, cross-sectional study of 1285 community-dwelling women with osteoporosis from 18 countries to evaluate serum 25(OH)D distribution.
Adapted from Lim S-K et al. Poster presented at ISCD, February 1619, 2005, New Orleans, Louisiana,USA; Heaney RP Osteoporos Int 2000;11:553555.
P
r
e
v
a
l
e
n
c
e

(
%
)

0
10
30
40
60
80
90
Latin
America
51%
63%
Asia All
59%
Australia
59%
Europe
52%
Regions
N=1285
81%
Middle
East
50
70
20
In a cross-sectional observational international study in 1285 postmenopausal
women with osteoporosis**
Probable Reasons for High Prevalence of Vitamin D Inadequacy in Postmenopausal
Women
Lack of sunlight exposure
Vitamin D is not common in the diet
The ability to synthesize vitamin D in the skin
decreases with age
Lack of compliance taking daily supplements
Adapted from Marcus R Goodman & Gilmans The Pharmacological Basis of Therapeutics. 10th ed. New York: McGraw-Hill Medical Publishing
Division, 2001:17151743; Bringhurst FR Harrisons Principles of Internal Medicine. 16th ed. New York: McGraw-Hill Medical Publishing, 2005:2238
2249; Matsuoka LY J Clin Endocrinol Metab 1987;64:11651168; Parfitt AM Am J Clin Nutr 1982;36:10141031; Lawson RM Clin Nutr 2000;19:171
175.
Appropriate
neuromuscular
function
Vitamin D Inadequacy* Has Important Consequences
*Vitamin D inadequacy is defined as serum 25(OH)D <30 ng/ml.
Adapted from Parfitt AM et al Am J Clin Nutr 1982;36:10141031; Allain TJ, Dhesi J Gerontology 2003;49:273278; Holick MF Osteoporos Int
1998;8(suppl 2):S24S29; DeLuca HF Metabolism 1990;39(suppl 1):39; Pfeifer M et al Trends Endocrinol Metab 1999;10:417420;
Lips P. In: Draper HH, ed. Advances in Nutritional Research. New York, Plenum Press, 1994:151165.
Bone mineral
density
Parathyroid
hormone
Calcium
absorption
Risk of
fracture
Artistic rendition
Bisphosphonate mechanism
of action
Adapted from: Bone H, et al. Clin Ther 2000;22:1525
RESTING
RESORPTION
Osteoclast
FORMATION
Osteoblasts
BISPHOSPHONATES
INHIBIT OSTEOCLAST
-MEDIATED BONE
RESORPTION
PTH - Mechanism of Action
PTH binds to cell surface
G protein-coupled receptor
Stimulates differentiation
of bone lining cells and
preosteoblasts to osteoblasts
Decreases apoptosis
of osteoblasts
Net increase in number and
action of bone forming
osteoblasts
Osteoporosis has been thought of as a silent
epidemic.this is not true anymore. At present,
there is much noise in the field of research for
its prevention, diagnosis and treatment.

Ego Seeman
ARCOS meeting, Feb 2002
One of the Many Faces of Osteoporosis

You could have floored me when they told me. Its very frightening, very
frightening
I dont want to end up in a nursing home incapacitated.
Thank You !
Please visit:
http://crisbertcualteros.page.tl