Dr K K Sawlani Department of Medicine KGMU Lucknow 300714 OSTEOPOROSIS A disease characterized by low bone mass reduced bone density and microarchitectural deterioration of ID: 356110
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Slide1
OSTEOPOROSIS
Dr. K
K
Sawlani
Department of Medicine
KGMU,
Lucknow
30.07.14Slide2
OSTEOPOROSIS
A disease characterized
by low
bone
mass
(reduced bone density) and micro-architectural deterioration of
bone
tissue, leading
to enhanced bone fragility
and a consequent increase in fracture risk.
Most common bone disease
Affects million of people worldwideSlide3
Development of osteoporotic bone
Rizzoli R ed In Atlas of Postmenopausal Osteoporosis (1
st
edition) Science Press, 2004Slide4
OSTEOPOROSIS
Fractures related to osteoporosis affect around 30 % of women and 12 % of men in developed countries.
Major public health problem
Osteoporotic fractures can affect any bone
The most common sites are
Spine (vertebral fracture)
Forearm (
Colles fracture)Hip Slide5
Vertebral FractureSlide6
Hip FractureSlide7
Wrist Fracture (Colles
fracture)Slide8
OSTEOPOROSIS
Hip fractures are the most serious
Immediate mortality is about 12 %
Continued increase in mortality of about 20 % when compared with age matched controls.
Account for the majority of health care cost associated with osteoporosis.Slide9
OSTEOPOROSIS
The prevalence increases with age reflecting that bone density decreases with age especially in women
Accompanied by increased risk of fractures
Fall in bone density
Increased risk of fallingSlide10
Pathopysiology
Occurs because of defect in attaining peak bone mass and/or because of accelerated bone loss.
In normal individuals bone mass increases to reach a peak between the age of 20 and 40 years but falls thereafter.Slide11
0 10 20 30 40 50 60
Bone mass
Age (years)
Attainment of peak bone mass
Consolidation
Age-related bone loss
Men
Women
Menopause
Fracture threshold
Age-related changes in bone mass
Compston JE. Clin Endocrinol 1990;
33
: 653–682.Slide12
Pathopysiology
Peak bone mass and bone loss are regulated by both genetic and environmental factors.
Polymorphisms have been identified in several genes that contribute to pathogenesis.
Many of these are in the RANK and
Wnt
signaling pathways which play critical role in regulating bone turnover.Slide13
Major risk factors
Non modifiable
Age
Race
Female gender
Early menopause
Slender build
Positive family historyModifiableLow calcium intakeLow vitamin D intake
Estrogen deficiency
Sedentary lifestyle
Cigarette smoking
Alcohol excess (> 2 drinks/day)
Caffeine excess (> 2 servings / day)Slide14
Post menopausal osteoporosis
Most common cause
Accelerated phase of bone loss after menopause due to estrogen deficiency.
Causes uncoupling of bone resorption and bone formation
Amount of bone reduced by
osteoclasts
exceeds the rate of new bone formation by
osteoblastsEarly menopause ( before the age of 45 years ) is important risk factorSlide15
Male osteoporosis
Less common in men
Secondary cause can be identified in 50% of cases
The most common causes are
Hypogonadism
Corticosteroid use
Alcoholism
Testosterone deficiency results in increase in bone turnover and uncoupling of bone resorption and bone formation.Genetic factors important in the cases with no identifiable cause.
Slide16
Corticosteroid induced osteoporosis
Risk increases with
prednisolone
use 5-7.5 mg daily for more than 3 months.
Reduced bone formation due to
Inhibitory effect on
osteoblast function
Osteoblast and osteocyte apoptosisAlso reduce serum calcium
Inhibit intestinal calcium absorption
Renal leak of calcium
Secondary hyperparathyroidism with increased bone resorption
Hypogonadism
may also occur with high doses.Slide17
Secondary causes of osteoporosis
Endocrine disease
Hypogonadism
Hyperthyroidism
Hyperparathyroidism
Cushing,s
disease
Inflammatory diseaseInflammotory bowel diseaseAnkylosing spondylitis
RA
Gastrointestinal
Malabsorption
Chronic liver disease
Lung disease
COPD
Cystic fibrosis
Drugs
MiscellaneousSlide18
Secondary causes of osteoporosis
Drugs
Corticosteroids
Thyroxine
over-replacement
Anticonvulsants
GnRH agonistsThiazolidinediones
- pioglitazoneAlcohol intake HeparinSlide19
Secondary causes of osteoporosis
Miscellaneous
Myeloma
HIV infection
Systemic
masotcytosis
Renal failureBMI < 18Anorexia nervosa
Heavy smokersSlide20
Clinical Features
Asymptomatic until a fracture occurs
Incidental
osteopenia
on X-ray performed for other reasons.
Spine fracture
Acute back pain ( 1/3 cases)
gradual loss of height , kyphosis and chronic pain
Peripheral fracture
Local pain, tenderness and deformity
Often with an episode of minimal traumaSlide21
Investigations
Measurement of bone mineral density (BMD) by dual energy X-ray
absorptiometry
(DEXA).
BMD can also be measured by computed tomography (CT) and ultrasound.
Central (spine and hip) are best predictors of fracture risk.
Peripheral( radius, heel and hands) are less expensive and widely available.Slide22Slide23
Investigations
T-Score: The number of SDs the patient value is below or above the mean value for
young normal subjects.
Good predictor of fracture risk
Z-score: The number of SDs the patient value is below or above the mean value for
age matched normal controls.
Whether or not the BMD is appropriate for age.
Absolute BMD: expressed in g/cm
2
Used to calculate changes in BMD during follow up.
Slide24
Diagnosis
Any patient who sustains a fragility fracture.
On the basis of BMD T-score
≥ -1 = normal
Between -1 and -2.5 =
Osteopenia
≤ -2.5 =
OsteoporisisSlide25
Changes in BMD with age (T-score values)
Souce
-
Davidsons
textbook of Medicine 22
nd
editionSlide26
Diagnosis
History: early menopause, smoking, excessive alcohol intake, corticosteroid therapy
Examination: Signs of endocrine disease, neoplasia, and inflammatory diseases
A history of fall should be taken
Unstable gait and unsteadinessSlide27
Diagnosis - Investigations
Renal function
Alkaline phosphatase
Serum calcium,
Vit
D 25 (OH)
Parathyroid (PTH)Thyroid function tests
Immunoglobulins and ESRCeliac disease antibody testingTestosterone (men)24 hour urine calcium, sodium and creatinine
.Slide28
Management
The aim of treatment is to
reduce the risk of fractures
Non-pharmacological
PharmacologicalSlide29
Non Pharmacological Treatment
Smoking cessation
Moderation of alcohol intake
Adequate dietary calcium intake
Exercise
Vitamin D
Fall prevention Good nutritionSlide30
Pharmacological Treatment
Several drugs have been shown to reduce the risk of osteoporotic fractures.
Effect on vertebral and non-vertebral fracture is variable.
Considered with
BMD T-score < 2.5
BMD T-score < 1.5 in corticosteroid induced
Vertebral Fractures ,unless resulted from significant traumaSlide31
DXA Results
T Score
Classification
Action
> minus 1.0
Normal
Lifestyle measures.
< minus 1.0 > minus 2.5
Osteopenia
Lifestyle measures.
Consider specific treatment where there is ongoing risk, e.g. steroids, and in those who have had a minimal trauma fracture.
< minus 2.5
Osteoporosis
Lifestyle measures.
Prevent falls.
Treatment may be indicated.Slide32
CURRENT THERAPIES
Anti-
resorptive
Anabolic
Calcium, Vitamin D, lifestyle modification
Adjunct to other treatments
1000-1200 mg/day of calcium
800-1200 U/day of vitamin DSlide33
Treatment Options in Osteoporosis
Antiresorptive
drugs
Bisphosphonates
Etidronate
Alendronate
Risedronate
Ibandronate
Zoledronate
Denosumab
(monoclonal antibody against RANK-L)
SERMs
Raloxifene
Calcitonin
HRT (
estrogen
)
Anabolic drugs
Teriparatide
(PTH 1-34)
Dual Action Bone Agents (DABAs)
Strontium
ranelateSlide34Slide35
Bisphosphonates
Inhibit bone resorption by binding to
hydroxyapatite
crystals on bone surface
Osteoclasts
reabsorb bone-drug released within cell-
inhibt
key signaling pathways.Increase in Spine BMD of 5-8% and Hip BMD 2-4%.
Should be taken on an empty stomach with plain water.
No food should be eaten 30-45 minutes after administrationSlide36
Adverse effects of
biphosphonates
Common
Upper GI intolerance (oral)
Acute phase response(intravenous)
Less Common
Atrial
fibrillation (IV zoledronic
acid)
Renal impairment (IV
zoledronic
acid)
Atypical
subtrochanteric
fractures
Rare
Uveitis
Osteonecrosis
of the jawSlide37
INDICATIONS FOR ANABOLISM
Pre-existing osteoporotic fractures
Very low BMD
Very high fracture risk
Unsatisfactory response to
antiresorptive
therapy Intolerant to anti-resorptive therapySlide38
TERIPARATIDE
Daily SC injection 20 mcg
Maximum 18-24 months
May be followed by anti-
resorptive
therapy
PTH is expensive and is reserved for severe osteoporosis, who fail to response to other therapies.
No advantage of combined anabolic and anti-resorptive
therapySlide39
Selective estrogen receptor modulator (SERM)
Raloxifene
60 mg daily orally
Partial agonist of estrogen receptor in bone & liver
Antagonist in breast &
endometrium
SE: muscle cramps, hot flushes, increased risk of VTE.
Bazedoxifene
is a related SREMSlide40
HRT
Cyclical HRT
wirh
estrogen and
progestogen
Prevents post menopausal bone loss and reduces risk of fractures in post menopausal womenPrimarily indicated for prevention of osteoporosis in women with early menopause
Women in early fifties with troublesome menopausal symptoms.Increased risk of breast cancer and cardiovascular diseaseSlide41
Duration of therapy
Oral
biphosphonates
long term (5 YRS)
HRT,
raloxifene
continuouslyDenosumab continuously
Strontium ranelate not establishedTeriparatide 2 yrs
fb
antiresorptive
Tt
Slide42
Response to drug treatment
Repeat BMD measurements after 2-3 yrs.
Spine BMD best for monitoring
Biochemical markers ( N-
telopeptide
) respond more quickly; can be used to assess adherence.Slide43
Surgery
Reduce and stabilize osteoporotic fractures
Painful vertebral compression fractures
Vertebroplasty
( Injection of MMA)
Kyphoplasty
( balloon inflation – MMA)Slide44
Response to Drugs
Fracture risk reduction
30-40% # risk reduction with
antiresorptives
60% # risk reduction with
teriparatide
BMD
2-3% BMD increase with anti-resorptives4-6% BMD increase with teriparatideSlide45
Osteoporosis MCQ
1. Most common cause of osteoporosis
Hypogonadism
Malabsorption
Post menopausal
Hyperparathyroidism
Slide46
Osteoporosis MCQ
2. Most common bone disease is
a.
Osteomalacia
b. Osteoporosis
c.
Secondaries
bone d. Osteopetrosis
Slide47
Osteoporosis MCQ
3. Which of the following drug is most common cause of drug induced osteoporosis
a.
Thyroxine
over-
relacement
b. Corticosteroids
c. Pioglitazone d. AnticonvulsantsSlide48
Osteoporosis MCQ
4.
Osteopenia
is defined as T- Score of
a. < -1
b. < -1 to < -2.5
c. < -2.5 d. None of the aboveSlide49
Osteoporosis MCQ
5. Risk of fracture in osteoporosis is best predicted by
a. T-score
b. Z-score
c. Absolute BMD
d. Serum calcium levelsSlide50
Osteoporosis MCQ
6. Risk factors for osteoporosis are all except
a. BMI > 30
b. Smoking
c. Low calcium intake
d. ImmobilizationSlide51
Osteoporosis MCQ
7. Following are all anti-
resroptive
drugs except
a.
Biphophonates
b. Raloxifene
c. Estrogen d. Teriparatide (PTH analogue)Slide52
Osteoporosis MCQ
8. Which of the following is drug of choice for severe osteoporosis (T-score 0f < -3.5 )
Teriparatide
Biphosphonates
Calcitonin
StrontiumSlide53
Osteoporosis MCQ
9.
Osteonecrosis
of the jaw is seen with the use of
Calcitonin
PTH analogues
Biphosphonates
RaloxifeneSlide54
Osteoporosis MCQ
10. The response to drug therapy is assessed by repeating BMD measurements after
3 months
6months
1 year
2 year