Osteoporosis
TAREK NASRALLA, MD
RHEUMATOLOGY
DEPARTMENT, AL AZHAR
Osteoporosis
TAREK NASRALLA, MD
RHEUMATOLOGY
DEPARTMENT, AL AZHAR
Introduction
•
•

Most common bone disease
Major risk factor for fracture
Definition







A systemic skeletal disease characterized by 2
main elements
low bone mass
microarchitectural deteri...
MECHANISMS OF
OSTEOPOROSIS






‘High turnover’ – excessive bone resorption > excessive bone
formation
- estrogen defi...
PATHOGENESIS
ROLE OF SYSTEMIC HORMONES






Calcium-regulating hormones – Calcitonin,
parathyroid hormone, Vitamin D...
PATHOGENESIS
LOCAL CYTOKINES AND PROSTAGLANDINS
Cytokines - IL-I , IL-6 and TNF-a - potent stimulators of bone
resorption ...
RISK FACTORS FOR
OSTEOPOROSIS
AGE
 Bone mass decreases with age
 Age-related bone loss begins in the 4th or 5th decades
...
Risk Factors
•
•
•
•
•

SEX
More common in women
Overall fracture rate increased threefold in
women
Lower mean peak bone m...
Risk Factors
RACE
 Risk of hip fractures is lower in African-American women than
in Caucasians
- higher peak bone mass
- ...
Risk Factors
GENETICS
 Play a contributory role in bone density and
fracture risk
 Vitamin D receptor genotypes – may af...
Risk Factors








Sedentary life style (decreased bone mass and
physical functioning)
Slender habitus
Low peak bo...
Risk Factors






Medications – steroids, excess thyroid hormone,
methotrexate, heparin, anticonvulsants, cyclosporine...
RISK FACTORS - NUTRITION








Calcium deficiency
Vitamin D deficiency
Protein excess or deficiency
Phosphoric ac...
DISEASES ASSOCIATED
WITH OSTEOPENIA








PTH
Hyperthyroidism
Cushing’s
Myeloma
Mastocytosis
Liver disease
Renal ...
Protective factors







higher body mass index
black race
estrogen
diuretic therapy (thiazides)
exercise
Moderate ...
SYMPTOMS OF
OSTEOPOROSIS







Asymptomatic
Pain with fracture (or not)
Decreased height
“Dowager’s hump”- kyphosis...
LABORATORY EVALUATION
To exclude secondary causes of osteoporosis
 Calcium, phosphorus, BUN, Cr., TSH, CBC,
alkaline phos...
DIAGNOSIS OF OSTEOPOROSIS









PLAIN RADIOGRAPHS
Detectable changes with 30-50% bone loss
Trabecular thinning
...
WHO Diagnostic Criteria for Osteopenia





and Osteoporosis Based on Bone Mass
Measurements

Category
Normal

Osteopen...
Indications for bone densitometry







Estrogen-deficient women at clinical risk of
osteoporosis
Vertebral abnorma...
NOF TREATMENT
GUIDELINES





Postmenopausal women with vertebral or hip
fractures
T-score less than –2 with no risk fa...
TREATMENT OF
OSTEOPOROSIS
NON- PHARMACOLOGIC THERAPY
 Diet - Calcium and Vit D
 Exercise
 Smoking cessation
PHARMACOLOG...
CALCIUM AND VITAMIN D







For post menpausal women and older men: Daily
calcium intake – 1500mg/day
Shown to decr...
VITAMIN D






Important for calcium absorption, affects PTH
Elderly need more—less response to sunlight,
less effici...
Exercise and Smoking Cessation
EXERCISE
 Associated with lower risk of hip fractures
- increased muscular strength
 Asso...
ESTROGENS






Anti-resorptive, can stop bone loss and decrease
fractures
Was considered primary therapy in
postmenop...
Bisphosphonates










Alendronate (fosomax) – treatment dose: 10mg/day or
70mg weekly, prevention dose: 5mg/da...
Selective estrogen receptor modulators








Raloxifene (Evista)
Approved for prevention and treatment
Increases B...
CALCITONIN
 Intranasal daily
 Can decrease pain of acute vertebral

fracture
 Well-tolerated
 Not much effect on BMD o...
TERIPARATIDE (FORTEO)








Parathyroid hormone
Intermittent administration stimulates bone formation
more than r...
Others
Isoflavones – phytoestrogen
- Commonly found in soy products
-Conflicting results in studies
 Thiazides diuretics ...
Potential therapies
Androgen – does not appear to be superior to
estrogen, virilizing effects
 Growth factors – stimulate...
Other therapies
Strontium ranelate - increases bone formation,
inhibits bone resorption
in clinical trials, increased BMD ...
OSTEOPOROSIS IN MEN







Occurs at later age
Incidence of hip fractures increases exponentially with
age
Mortality...
It’s Up To You Now!


What are you going to do to have strong bones
that last a lifetime?
Dr tarek osteopro2
Dr tarek osteopro2
Dr tarek osteopro2
Dr tarek osteopro2
Dr tarek osteopro2
Dr tarek osteopro2
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Dr tarek osteopro2
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Dr tarek osteopro2
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Dr tarek osteopro2

  1. 1. Osteoporosis TAREK NASRALLA, MD RHEUMATOLOGY DEPARTMENT, AL AZHAR
  2. 2. Osteoporosis TAREK NASRALLA, MD RHEUMATOLOGY DEPARTMENT, AL AZHAR
  3. 3. Introduction • • Most common bone disease Major risk factor for fracture
  4. 4. Definition     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
  5. 5. MECHANISMS OF OSTEOPOROSIS    ‘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
  6. 6. PATHOGENESIS ROLE OF SYSTEMIC HORMONES      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
  7. 7. 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 
  8. 8. 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
  9. 9. Risk Factors • • • • • 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
  10. 10. 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
  11. 11. 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
  12. 12. Risk Factors       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
  13. 13. Risk Factors    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.
  14. 14. RISK FACTORS - NUTRITION        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
  15. 15. DISEASES ASSOCIATED WITH OSTEOPENIA        PTH Hyperthyroidism Cushing’s Myeloma Mastocytosis Liver disease Renal disease       Celiac disease R.A. Osteogenesis imperfecta AIDS IBS Others
  16. 16. Protective factors       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
  17. 17. SYMPTOMS OF OSTEOPOROSIS       Asymptomatic Pain with fracture (or not) Decreased height “Dowager’s hump”- kyphosis Look for risk factors symptoms and signs of associated conditions
  18. 18. 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 
  19. 19. DIAGNOSIS OF OSTEOPOROSIS         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
  20. 20. WHO Diagnostic Criteria for Osteopenia    and Osteoporosis Based on Bone Mass Measurements Category Normal Osteopenia      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
  21. 21. Indications for bone densitometry       Estrogen-deficient women at clinical risk of osteoporosis Vertebral abnormalities Long-term steroid use Primary hyperparathyroidism Monitoring response to therapy Every 2 years (controversial)
  22. 22. NOF TREATMENT GUIDELINES    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
  23. 23. 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
  24. 24. CALCIUM AND VITAMIN D       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
  25. 25. VITAMIN D     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
  26. 26. 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
  27. 27. ESTROGENS     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
  28. 28. Bisphosphonates         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
  29. 29. Selective estrogen receptor modulators       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
  30. 30. CALCITONIN  Intranasal daily  Can decrease pain of acute vertebral fracture  Well-tolerated  Not much effect on BMD or fracture risk
  31. 31. TERIPARATIDE (FORTEO)        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
  32. 32. 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 
  33. 33. 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 
  34. 34. 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 
  35. 35. OSTEOPOROSIS IN MEN       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
  36. 36. It’s Up To You Now!  What are you going to do to have strong bones that last a lifetime?
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