Osteoporosis in thalassemia patients

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Presentation transcript:

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

Osteoporosis overview

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

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

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

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

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

HIP FRACTURE

OSTEOPOROSIS nORMAL

VERTEBRAL FRACTURE

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

DXA scan

DXA image

Dxa interpretation

Z-score Pre-menopausal women Men under the age 50 Children Z-score ≤ - 2.0 defined as “ below the expected range for age” Z-score > - 2.0 defines as “within the expected age for age” Osteopenia no longer used in this age group T-score should not be used

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

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

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

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

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

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

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

denosumab

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

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

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

Thank you for your attention

Any Question?