Osteroporosis - clinical features and management

1. OSTEOPOROSIS
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2. CONTENT
S
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3. DEFINITIONS
Osteoporosis is defined as low bone mass and
microarchitectral deterioration of bone tissue, leading to
enhanced bone fragility and a consequent increase in fracture
risk.
World Health organization (WHO) defines Osteoporosis as a
bone density that falls 2.5 standard deviations (SD) below the
mean for young healthy adults of the same race and gender—
also referred to as a T-score of–2.5.
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4. Normal bone x osteoporotic
bone 5

5. EPIDEMIOLOGY
US - 9 million adults have osteoporosis, additional 48 million
at risk
More frequently with increasing age - bone tissue is
progressively lost.
One in three women and one in 12 men over the age of 50
worldwide are estimated to have osteoporosis.
7% of postmenopausal women had osteoporosis.
Asians and white population – equal risk
Lower in African Americans
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6. Epidemiology of fractures: At least
1.5 million fractures occurs in each
year in the US as a consequence of
osteoporosis.
In US and Europe, osteoporosis
related fractures are more among
women than men.
3 lakh hip fracture,7 lakh vertebral
fracture and 250,000 wrist fracture
occur each year in the US.
Multiple fractures lead to height loss,
kyphosis, secondary pain
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7. ETIOLOGY AND RISK
FACTORS
The magnitude and significance of the risk factors varies by
gender, ethnicity, age, and the duration of risk factor presence.
4 major risk factors age, low BMD, gender, Family history.
The other factors that can contribute to osteoporosis are
Sedentary life style
Low body weight
Cigarette and excessive alcohol use
Low calcium intake & malnutrition
Estrogen deficiency
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8. Immobility
Low sun exposure
Medical problems like Rheumatoid arthritis,
hyperthyroidism, hyperparathyroidism, Cushing’s
syndrome,dementia, parkinsonism
Medications like immunosuppressants, diuretics, cancer
chemotherapy, aluminium (antacids), glucocorticoids
etc.
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12. PATHOPHYSIOLOGY
Bone loss due to normal age related changes in
bone remodelling as well as extrinsic and
intrinsic factors that exaggerate this process.
Bone remodelling has two primary functions:
To repair micro damage within the skeleton to
maintain skeletal strength.
To supply calcium supply from the skeleton to
maintain serum calcium.
After age 30 to 45,the resorption and formation
processes become imbalanced, and resorption
exceeds formation.
Excessive bone loss can be loss due to an
increase in osteoclastic activity and/or
osteoblastic activity. 10

13. Calcium and Vitamin
D deficiency - Peak
bone mass may be
impaired by inadequate calcium
intake, leading to increased risk
of osteoporosis.
It induces secondary
hyperparathyroidism and an
increase in the rate of
remodelling to maintain normal
serum calcium levels.
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14. Estrogen deficiency causes bone loss by
a) Activation of new bone remodelling sites
b) Exaggeration of the imbalance b/w bone formation and resorption
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15. DRUG
INDUCED
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Glucocorticoid are the most
common cause of medication
induced osteoporosis
Other medication include
anticonvulsants and
immunosuppressants

16. Vit D deficiency: Vit D deficiency leads to
compensatory secondary
hyperparathyroidism and is an important risk
factor for osteoporosis and fractures.
Physical inactivity: Prolonged bed rest and
paralysis, results in significant bone loss.
Chronic disease : Disease associated with
an increased risk of osteoporosis in adult are
turner syndrome, Cushing's syndrome, DM
1,thyrotoxicosis, malnutrition, pernicious
anaemia, pregnancy and lactation.
Cigarettes consumption : over a long
period has detrimental effect on bone mass.
These effects may be mediated directly, by
toxic effects on osteoblasts, or indirectly by
modifying estrogen metabolism.
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17. CLINICAL
MANIFESTATIONS
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General : fractures occur after bending,
lifting, or falling.
Symptoms : pain, immobility, bruising,
depression and lower self esteem.
Signs : Shortened stature, Kyphosis, or
Lordosis, Bone pain or fracture(commonly of
vertebra ,hip or forearm).

18. DIAGNOSIS
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Conventional radiography
Dual-energy X-ray
absorptiometry (DXA)
Biomarkers
Quantitative computer
tomography
Ultrasound

20. WHEN TO TREAT?
• When BMD > 2.5 SD below the mean value for
young adults ( T score < -2.5 ) in either spine ,
total hip or femoral neck
• Consider treatment in postmenopausal women
with fracture risk factors even if BMD not in
osteoporosis range

21. NON PHARMACOLOGIC
TREATMENT
Diet changes : For all individuals, a well-
balanced diet with adequate calcium and
vitamin D is essential for healthy bones.
Calcium contributors - Dairy products like
milk, yogurt, cheese, ice cream, cottage cheese,
and fortified orange juice or soy products.
Most vitamin D comes from sun- induced
skin conversion
Vitamin D contributors - fatty fish, few
unfortified foods
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22. • Fruits and vegetables containing Mg - essential
for healthy bone.
• Patient education to avoid consuming excessive
amounts of VitA  increased risk of fracture in both
men and women.
• Vitamin C influences collagen production  increases
osteoblast formation and survival.
• Moderate protein intake is recommended.
• Caffeine and Hypophosphatemia - decreases
BMD
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23. Social habit changes:
Smoking causes bone loss and
increases hip fracture risk by
several mechanisms such as
early menopause
decreased body weight
enhanced estrogen metabolism
increased PTH concentrations
decreased vitamin
concentrations.
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24. Excessive alcohol use - associated with
low BMD and subsequent fracture in
some studies.
Malnutrition associated with alcoholism
could also play a role. Alcohol use also
may increase the risk of falls.
Exercise : Long-term exercise during
youth increases peak BMD.
Physical activity, especially aerobics,
weight bearing, and resistance exercise
and walking preserves BMD .
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25. Prevention of fall : Ambulation-assistive devices (canes and
walkers)
The living environment should be evaluated and modified.
Vision should be assessed.
Proper lighting
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26. PHARMACOTHERAP
Y
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Two FDA-approved indication for
osteoporosis medication- prevention and
treatment.
There are two main classes of drugs.
Anti- resorptive therapy - Prevents
remodeling.
Bone formation Therapy - Improves bone
formation.
Newer procedures – Vertebroplasty &
Kyphoplasty

27. ANTIRESORPTIVE THERAPY
Calcium
Vitamin D & its metabolites
Selective estrogen modulators
Bisphosphonates
Calcitonin
Estrogen & hormonal therapy
Tibolone
Phytoestrogen
Testosterone and AnabolicSteroids
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28. BONE FORMATION THERAPY
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Teriparatide (Parathyroid Hormone)
Strontium
HMG - CoA Reductase Inhibitors
(Statins)
Growth Hormones and Factors
Fluoride

29. ANTIRESORPTIVE
THERAPY
Calcium : adequate calcium intake is considered
standard for osteoporosis prevention and treatment
for all people.
Dose 200 – 1500 mg / day.
Adr include gas, upset stomach, rare kidney stones.
Drug interaction: absorption decreased with PPI,
decrease absorption of alendronate, etidrona
fluoride, tetracycline and phenytoin
te,
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30. 27
Calcium Preparation Elemental Calcium Content
Calcium citrate 60 mg/300 mg
Calcium lactate 80 mg/600 mg
Calcium gluconate 40 mg/500 mg
Calcium carbonate 400 mg/g
Calcium carbonate+ 5g vitamin
D2 (OsCal 250)
250 mg/tablet

31. Vitamin D and Its Metabolites
Vitamin D 400 units with calcium 500 mg
twice daily increased spine and hip BMD in
seniors with vitamin D deficiency.
Vitamin D maintain muscle function &
decreasing pain.
Orally administered vitamin D3, in a dosage of
100,000 units once every 4 months for 5 years,
reduced the risk of fracture by 22% to 33% in a
population of men and women.
Doxercalciferol (1α-hydroxyvitamin D2) is
under investigation for osteoporosis treatment.
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32. Bisphosphonates:
MOA: It binds to the hydroxyapatite in bone,
they decrease resorption by inhibiting osteoclast
adherence to bone surfaces.
Etidronate - inhibit bone mineralization that
could lead to osteomalacia.
Alendronate(5mg daily)
Risedronate(5mg daily)
Ibandronate (2.5mg/day)
Risedronate -glucocorticoid-induced
osteoporosis
Alendronate – 5mg/d x 2 yr , 10mg/d x
9 months thereafter
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33. • Zolendronate
• 5mg slow infusion annually
• Reduced risk of vertebral # by 70%, non
vertebral # by 25% , hip # by 40%

34. Selective Estrogen Receptor Modulators (SERM)
Raloxifene - the first SERM approved for prevention and
treatment of postmenopausal osteoporosis, is an estrogen
agonist in bone tissue but an antagonist in the breast and
uterus. Dose - 60mg/day
Tamoxifen approved for breast cancer
prevention, also inhibits bone loss.
Investigational SERM - Arzoxifene,
bazedoxifene, lasofoxifene, and ospemifene
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35. Calcitonin
Calcitonin is released from the thyroid gland
when serum calcium is elevated.
Salmon calcitonin is used clinically because it is
more potent and longer lasting than the
mammalian form.
Calcitonin (200 IU daily, intranasal spray)is
indicated for osteoporosis treatment for post
menopausal women
Calcitonin may provide pain relief to some
patients with acute vertebral fractures, but this
effect is minimal. 35

36. Estrogen and Hormonal Therapy
Estrogens :
decrease osteoclast recruitment and activity.
inhibit PTH peripherally.
increase calcitriol conc. and intestinal Ca absorption.
decrease renal calcium excretion.
decrease cytokine concentrations .
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37. DOSE
• 0.3 mg/d esterified estrogen
• 5 mcg/d for ethinyl estradiol

38. BONE FORMATION
THERAPY
• Teriparatide (Parathyroid Hormone)
• Therapeutic doses improve BMD and reduce
fracture risk.
• Parathyroid hormone is currently the only
approved osteoporosis medication that works
by stimulating bone formation.
• Teriparatide works equally well in women and
men
• with osteoporosis.
• Teriparatide : decrease the risk of new
vertebral fractures by 65% with osteoporosis
and pre-existing fractures & non
vertebral fracture risk by 53% with
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39. Teriparatide is commercially available as a prefilled 3-mLpen
type delivery device that administers subcutaneous injections
in the thigh or abdominal area.
Strontium
Strontium stimulates bone formation and decreases bone
resorption.
strontium ranelate 1 g twice daily or 2 g once daily reduced
new vertebral fractures by 41%, and increased lumbar spine
BMD by 14% and femoral neck BMD by 8% compared with
placebo.
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40. HMG-CoA Reductase Inhibitors (Statins)
These were discovered to increase bone density in
animal models.
Although observational studies have linked statin
use with decreased fracture risk, a large case-
control study did not demonstrate reduction in
fracture risk for statin-treated patients
Fluoride
Although fluoride increases osteoblastic activity
and bone formation through intracellular signaling
pathways involving tyrosine phosphatases and
mitogen-activated protein kinases, it remains an
unapproved therapy despite 30 years of clinical
study.
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41. DONOSUMAB
• Fully human monoclonal ab to RANKL
• Inhibits ability to initiate mature osteoclast
formation
• Reduce osteoclast survival
• Twice yearly S/c administration
• Approved in 2010 by FDA for postmenopausal
women at high risk for #

42. Growth Hormones and Factors
Growth hormone (GH) and IGF-1
play important roles in bone turnover
and remodeling, with multiple effects
on other tissues.
The longer-term studies showed a
positive effect that continued to
increase for 1 to 2 years after
discontinuation of GH therapy.
Recombinant IGF-1 injections, with
or without IGF-3 binding protein,
increased both bone formation and
resorption.
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43. Vertebroplasty and kyphoplasty
The percutaneous injection of
polymethylmethacrylate (PMMA) bone cement
into a compressed vertebral fracture confers
significant pain relief for many patients.
Under local anesthetic, with computed tomography
scanning or fluoroscopic guidance, PMMA is
injected under slight pressure during vertebroplasty.
The procedure stabilizes the damaged vertebrae and
reduces pain in 70% to 92% of patients. Pain scores
usually improve by approximately 50% at 1 month
following the treatment.
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44. vertebroplas
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45. Kyphoplasty is a
newer procedure that
requires drilling into
the vertebral body
and inflating a
balloon to re-expand
the fracture. The
process is followed
by the injection of
about 7 mL of the
PMMAcement.
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