1. Osteoporosis in thalassemia patients
Mohammadreza bordbar, md
Pediatric hematologist
Hematology research center
Shiraz university of medical sciences

2. Osteoporosis overview

3. overview Prevalence: 10 million Americans with osteoporosis
Affects 18-28% of women and 6-22% of men over the age of 50 years old
Half of all postmenopausal women and a quarter of men over 50 years old will have an osteoporosis related fracture

4. Osteoporosis in thalassemia
High prevalence up to 50% of TDT
Multifactorial
Different pathogenesis from non-transfused patients

5. Contributing factors
Ineffective erythropoiesis and progressive marrow expansion
Nutritional deficiencies (vitamin D, C, zinc)
Smoking
Physical inactivity
Low sun exposure
Iron overload and toxicity to osteoblasts
Iron chelation (Deferoxamine and cartilage damage)
Liver disease
Endocrinopathies

6. Endocrine disorders Hypogonadism Diabetes Hypothyroidism
Hypoparathyroidism
GH and IGF-1 deficiency

7. Clinical findings Mostly asymptomatic (silent disease) Kyphosis
Cervical lordosis
Acute or chronic back pain
Vertebral compression fracture
Hip fracture
Atraumatic or low impact fracture

8. HIP FRACTURE

9. OSTEOPOROSIS nORMAL

10. VERTEBRAL FRACTURE

11. DIAGNOSIS Dual Energy X-ray Absorptiometry (DXA) , the standard method
Quantitative Computed tomography (QCT)
Single Energy Quantitative Computed Topography (SEQCT)

12. DXA scan

13. DXA image

14. Dxa interpretation

15. Z-score Pre-menopausal women Men under the age 50 Children
Z-score ≤ defined as “ below the expected range for age”
Z-score > defines as “within the expected age for age”
Osteopenia no longer used in this age group
T-score should not be used

16. Laboratory work up CBC BUN, Creatinine, LFT, FBS Ca, Ph, Mg 25(OH)-D3
24 hr urine calcium
Full endocrine work up

17. treatment Non-pharmacologic:
- increasing weight-bearing and muscle-strengthening exercise
- optimum calcium and vitamin D intake
-quit smoking

18. treatment Treat underlying cause if possible
Treatment of hypogonadism and induction of puberty
Calcitonin (IV or inhalation)
Bisphosphonates
Selective estrogen receptor modulators (raloxifene)
Parathyroid hormone(teriparatide)
Denosumab

20. bisphosphonates Generally 1st line of treatment
Alendronate, risendronate, zolendronic acid, ibandronate
Suppress resorption by preventing osteoclast attachment to bone matrix
Cannot be used with GFR < 30-35%
Decrease vertebral and non-vertebral fracture risk

21. Alendronate Decrease fracture risk at spine, hip and wrist by 50%
Dosage: 70 mg/wk, suggested for 3-5 years
Sitting upright with a large glass of water at least 30 min before breakfast
Not to be used with PPI
GI discomfort

22. Zoledronic acid The most potent bisphosphonate available
Dosage: 4 mg every 3-6 months for 3 years
Reduce spine, hip and non-vertebral fracture by 70%, 40% and 25% respectively
Adverse effects:
Flu-like syndrome (chills, fever, bone pain, myalgia) during the first 3
days of infusion
hypersensitivity reaction, bronchospasm

23. Selective estrogen receptor modulators
Raloxifene (Evista) :
-beneficial effects of estrogen
- prevention and treatment of osteoporosis in postmenopausal women
- 6o mg oral daily dose
- 35% reduction in the risk of vertebral fractures
- reduce the risk of breast cancer
- Adverse effects: hot flashes, stroke, DVT, leg cramp

24. denosumab

25. Denosumab (Prolia) 
humanized monoclonal antibody directed against the receptor activator of the nuclear factor-kappa B ligand (RANKL)
 decreases bone resorption by inhibiting osteoclast activity
Reduces vertebral fracture by 68%, and hip fracture by 40%
Can be used in renal impairment
Dosage: 60 mg SC every 6 months

26. Denosumab Adverse effects: Contraindications:
Atypical fragility fractures
AVN of Jaw
Possible increased risk of infections (cellulitis, endocarditis)
Suppression of bone turnover (delayed fracture healing)
Contraindications:
current hypocalcemia
Pregnancy
hypersensitivity

27. prevention Regular exercise Enough sun exposure
Adequate intake of calcium and vitamin D
Avoid smoking and alcohol consumption
Correction of anemia
Treatment of iron overload
Logical use of iron chelators especially deferoxamine
Treatment of hypogonadism and other endocrinopathies

28. Thank you for your attention

29. Any Question?