Osteoporosis is a systemic bone disease characterized by low bone mass and deterioration of bone structure, leading to increased bone fragility and risk of fracture. It is most commonly seen in postmenopausal women and the elderly. Key risk factors include aging, female sex, family history, small body frame, cigarette smoking, excessive alcohol, low calcium/vitamin D intake, and certain medications. Diagnosis is made through bone mineral density testing and x-rays. Treatment focuses on lifestyle modifications like exercise and fall prevention as well as pharmacologic therapies like bisphosphonates, parathyroid hormone, and estrogen to preserve bone mass.

1. Osteoporosis
TAREK NASRALLA, MD
RHEUMATOLOGY
DEPARTMENT, AL AZHAR

2. Osteoporosis
TAREK NASRALLA, MD
RHEUMATOLOGY
DEPARTMENT, AL AZHAR

4. Introduction
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Most common bone disease
Major risk factor for fracture

5. Definition
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A systemic skeletal disease characterized by 2
main elements
low bone mass
microarchitectural deterioration of bone tissue
with a consequent increase in bone fragility and
susceptibility to fracture
bone present is normally mineralized

7. MECHANISMS OF
OSTEOPOROSIS
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‘High turnover’ – excessive bone resorption > excessive bone
formation
- estrogen deficiency (menopause)
- hypogonadism (testosterone deficiency)
- hyperparathyroidism
- hyperthyroidism
‘Low turnover’ – decreased bone formation >decreased bone
resorption
- liver disease (primarily primary biliary cirrhosis)
- heparin
- alcoholism
Increased bone resorption and decreased bone formation
- Glucocorticoids

8. PATHOGENESIS
ROLE OF SYSTEMIC HORMONES
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Calcium-regulating hormones – Calcitonin,
parathyroid hormone, Vitamin D
Estrogen - inhibits bone resorption
deficiency (menopause) - increased bone resorption
and rapid bone loss.
Androgens - deficiency results in bone loss with
increased bone turnover similar to estrogen deficiency
Growth hormone/insulin-like growth factor - major
determinant of skeletal growth

9. PATHOGENESIS
LOCAL CYTOKINES AND PROSTAGLANDINS
Cytokines - IL-I , IL-6 and TNF-a - potent stimulators of bone
resorption and can also inhibit bone formation.
- IL-4 and IL-13 inhibit bone resorption
 Prostaglandins – particularly E2, increase both bone resorption
and formation
- many of the local and systemic factors that regulate bone
metabolism also affect prostaglandin synthesis in bone
 Local Growth factors - IGFs - important in maintaining the
differentiation and function of osteoblasts
- Others: TGF-beta, PTHrP, Fibroblast growth factor
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11. RISK FACTORS FOR
OSTEOPOROSIS
AGE
 Bone mass decreases with age
 Age-related bone loss begins in the 4th or 5th decades
 slow loss of cortical and trabecular bone in both men
and women
 Fracture risk also increases with age
 Decreased calcium and vitamin D intake and reduced
sun exposure can lead to secondary
hyperparathyroidism, which may play a role in agerelated bone loss

13. Risk Factors
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SEX
More common in women
Overall fracture rate increased threefold in
women
Lower mean peak bone mass
Accelerated bone loss after menopause
About 75 percent of bone lost after menopause
may be related to estrogen deficiency rather than
age

14. Risk Factors
RACE
 Risk of hip fractures is lower in African-American women than
in Caucasians
- higher peak bone mass
- slower rate of bone loss after menopause
 Asian women have a lower risk of fracture than Caucasian
women.
 Though, bone mineral density is lower in Asian women - ? due
to their smaller body habitus
 Differences in fracture risk across different ethnic groups cannot
be explained on the basis of differences in bone mineral density
alone

15. Risk Factors
GENETICS
 Play a contributory role in bone density and
fracture risk
 Vitamin D receptor genotypes – may affect the
ability to bind vitamin D
 Variants in BMP2 gene – identified in families
with osteoporosis
 Variants of estrogen receptor alpha and beta
(ESR1 and ESR2) gene

16. Risk Factors
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Sedentary life style (decreased bone mass and
physical functioning)
Slender habitus
Low peak bone density
Hypogonadism
Pregnancy and Lactation (transient loss)
Pernicious anemia - suppression of osteoblast
activity

18. Risk Factors
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Medications – steroids, excess thyroid hormone,
methotrexate, heparin, anticonvulsants, cyclosporine
Homocystinuria and high homocysteine levels in
adults
VitB12 and folate supplementation in older adults
with high homocysteine level after a stroke has been
shown to decrease hip fractures (absolute risk
reduction 7% at 2 years)
Sato Y et al. JAMA 2005 Mar 2;293(9):1082-8.

19. RISK FACTORS - NUTRITION
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Calcium deficiency
Vitamin D deficiency
Protein excess or deficiency
Phosphoric acid excess
Cigarette Smoking (increases bone loss and
decreases intestinal calcium absorption)
Excessive caffeine intake
Vitamin A excess

20. DISEASES ASSOCIATED
WITH OSTEOPENIA
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PTH
Hyperthyroidism
Cushing’s
Myeloma
Mastocytosis
Liver disease
Renal disease
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Celiac disease
R.A.
Osteogenesis imperfecta
AIDS
IBS
Others

21. Protective factors
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higher body mass index
black race
estrogen
diuretic therapy (thiazides)
exercise
Moderate alcohol ingestion (associated with
increased bone mineral density), data relating to
fracture risk - mixed

23. SYMPTOMS OF
OSTEOPOROSIS
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Asymptomatic
Pain with fracture (or not)
Decreased height
“Dowager’s hump”- kyphosis
Look for risk factors
symptoms and signs of associated conditions

27. LABORATORY EVALUATION
To exclude secondary causes of osteoporosis
 Calcium, phosphorus, BUN, Cr., TSH, CBC,
alkaline phosphatase
Consider:
 PTH, serum 25-hydroxyvitamin D levels secondary hyperparathyroidism
 SPEP, UPEP – multiple myeloma
 In men, serum free testosterone
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28. DIAGNOSIS OF OSTEOPOROSIS
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PLAIN RADIOGRAPHS
Detectable changes with 30-50% bone loss
Trabecular thinning
Compression fractures
BONE DENSITOMETRY
Single-photon absorptiometry – screening, used at
peripheral sites (radius, calcaneus)
Dual x-ray absorptiometry (DEXA) -GOLD
STANDARD, precise measurements at hip and spine
OTHER METHODS – Quantitative computed
tomography, Ultrasound

29. WHO Diagnostic Criteria for Osteopenia
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and Osteoporosis Based on Bone Mass
Measurements
Category
Normal
Osteopenia
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Osteporosis
Bone mass
BMD within one standard
deviation of the young adult
reference mean (T-score)
BMD between 1- 2.5
standard deviations below the
young adult reference mean
BMD >2.5 standard
deviations below the young
adult reference mean or
presence of > one fragility
fractures

30. Indications for bone densitometry
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Estrogen-deficient women at clinical risk of
osteoporosis
Vertebral abnormalities
Long-term steroid use
Primary hyperparathyroidism
Monitoring response to therapy
Every 2 years (controversial)

32. NOF TREATMENT
GUIDELINES
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Postmenopausal women with vertebral or hip
fractures
T-score less than –2 with no risk factors
T-score –1.5 or below with risk factors

33. TREATMENT OF
OSTEOPOROSIS
NON- PHARMACOLOGIC THERAPY
 Diet - Calcium and Vit D
 Exercise
 Smoking cessation
PHARMACOLOGIC THERAPY (postmenopausal with
osteopenia or osteoporosis)
 “Estrogens”
 Bisphosphonates
 Selective estrogen receptor modulators
 Calcitonin
 Parathyroid hormone
 Others – Isoflavones, thiazide, tibolone

34. CALCIUM AND VITAMIN D
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For post menpausal women and older men: Daily
calcium intake – 1500mg/day
Shown to decrease fracture rate in institutionalized and
community elderly
Safe except in those with other causes of hypercalcemia
Probably does not increase risk of kidney stones.
Take calcium carbonate with food for absorption
Ca supplementation may favorably affect serum lipids

35. VITAMIN D
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Important for calcium absorption, affects PTH
Elderly need more—less response to sunlight,
less efficient hydroxylation
Total Vit D 800 IU/day
higher doses may be required with
malabsorption or certain meds - anticonvulsants

37. Exercise and Smoking Cessation
EXERCISE
 Associated with lower risk of hip fractures
- increased muscular strength
 Associated with improvements in bone density:
2 – 6%
 Recommended exercise – 30mins, 3 days/week
SMOKING CESSATION
 Accelerates bone loss
 One pack/day in adult life associated in 5- 10%
reduction in bone density

39. ESTROGENS
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Anti-resorptive, can stop bone loss and decrease
fractures
Was considered primary therapy in
postmenopausal women
WHI study of estrogen and progesterone
stopped early due to adverse effects - breast
cancer, CAD, stroke and venous
thromboembolic events
No more effective than bisphosphonates

40. Bisphosphonates
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Alendronate (fosomax) – treatment dose: 10mg/day or
70mg weekly, prevention dose: 5mg/day or 35mg
weekly
Risedronate (actonel) – treatment and prevention dose:
5mg/day or 35mg weekly
New - Ibandronate (Boniva)– 150mg monthly dose
Increases bone density
Decreases vertebral and nonvertebral fractures
Beneficial effects for at least ten years
Bone loss after treatment is stopped
Side effects – pill-induced esophagitis, hypocalcemia

42. Selective estrogen receptor modulators
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Raloxifene (Evista)
Approved for prevention and treatment
Increases BMD
Less effective than estrogen and
bisphosphonates (though no direct
comparisons)
No increase in breast or endometrial cancer
Side effects: venous thromboembolism

44. CALCITONIN
 Intranasal daily
 Can decrease pain of acute vertebral
fracture
 Well-tolerated
 Not much effect on BMD or fracture
risk

45. TERIPARATIDE (FORTEO)
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Parathyroid hormone
Intermittent administration stimulates bone formation
more than resorption
Daily injection
Increases bone mass and decreases fractures (65-70 %
in vertebral fractures)
Compared to alendronate – greater increase in spine
bone density and decreased vertebral risk
Side effects: nausea, headaches, hypercalcemia
Reserved for high risk patients: daily injection, high
cost, risk of osteosarcoma

46. Others
Isoflavones – phytoestrogen
- Commonly found in soy products
-Conflicting results in studies
 Thiazides diuretics – useful in postmenopausal women with
hypertension
- modest decrease in bone loss
 Tibolone – synthetic steroid with estrogenic, androgenic,
progestagenic properties
-increases bone density, has not been shown to decrease fracture
risk
- may increase risk of endometrial hyperplasia, breast cancer
-widely used in Europe, not FDA approved
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47. Potential therapies
Androgen – does not appear to be superior to
estrogen, virilizing effects
 Growth factors – stimulate bone growth, useful
in growth hormone deficiency, conflicting trial
results with normal levels
 Statins – conflicting data, observational studies
report no effects on bone density
- small clinical trial showed modest increase in
forearm BMD
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48. Other therapies
Strontium ranelate - increases bone formation,
inhibits bone resorption
in clinical trials, increased BMD in spine and
femur and decreased fracture.
side effect – diarrhea
Folate and Vit B12 – may lower fracture risk in
elderly patients (with elevated homocysteine
level) after a stroke
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49. OSTEOPOROSIS IN MEN
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Occurs at later age
Incidence of hip fractures increases exponentially with
age
Mortality associated with hip fractures and other major
fractures is higher in men
Men are less likely to be evaluated or receive
antiresorptive therapy after a hip fracture
Consider serum free testosterone, SPEP, UPEP, PTH,
1,25(OH2)Vitamin D level or endocrine consult
Bisphosphonates proven effective in men

50. It’s Up To You Now!
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What are you going to do to have strong bones
that last a lifetime?