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- 2. OSTEOPOROSIS
- 3. OSTEOPOROSIS • Osteo means “bone” and porosis means “porous” • A clinical disorder characterized by abnormally low bone mass and defects in bone structure, a combination which renders the bone unusually fragile and at greater than normal risk of fracture in a person of that age, sex and race
- 4. WHO definition WHO defines Osteoporosis as Bone Mineral Density (BMD) that lies 2.5 SD or more below the average value for young healthy adult of same sex (T score <2.5 )
- 5. T score Compares your results to young healthy adult of same sex Z score Compares your results to young healthy adult of same sex
- 6. Osteoporosis-related fractures • Defined as fractures that occurs in the setting of trauma less than or equal to a fall from standing height • Exceptions of fingers, toes, face, and skull
- 7. EPIDEMIOLOGY INCIDENCE • 12 million Americans and 200 million people worldwide have osteoporosis • 34 million Americans have osteopenia • 2 million osteoporotic fractures occur each year
- 8. Vertebral fractures > Hip Fractures > Wrist Fractures
- 9. DEMOGRAPHICS • Male : Female ratio is 1:4 Low Peak Bone Mass Hormonal changes after menopause • Men have a higher prevalence of secondary osteoporosis
- 10. 50 years women have 40 % chance of having osteoporotic fracture during her lifetime Equivalent to risk of Cardiovascular Disease Kanis , J.A., Lancet 2002
- 11. TYPES OF OSTEOPOROSIS PRIMARY SECONDARY Type I : (POST MENOPAUSAL ) • Estrogen Withdrawal Effect • Almost exclusively trabecular Type II : (SENILE ) • Age Related >70 years • Trabecular > Cortical bone SYSTEMIC DISEASES : Hyperthyroidism Skeletal Metastases Multiple Myeloma DRUGS : Corticosteroids Anticonvulsants LIFESTYLE : Alcohol Smoking
- 12. Systemic Diseases Causing Osteoporosis Endocrinal Disorders : Cushing’s Syndrome Hyperparathyroidism Thyrotoxicosis Diabetes (type I and II) Adrenal Insufficiency Hypogonadal States Turners Syndrome Kleinfelters Syndrome (delayed puberty low bone mass that persists into adulthood) Rheumatological Disorders : Rheumatoid Arthritis Ankylosing Spondylitis Hematological Disorders Multiple Myeloma Leukemia Lymphoma Inherited Disorders Osteogenesis Imperfecta Marfans Syndrome Nutritional/ GI disorders Malabsorption Syndromes Chronic Liver Disease Pernicious anemia
- 13. DRUGS THAT CAUSE OSTEOPOROSIS Glucocorticoids Cyclospoprine Anticonvulsant Drugs Aromatase Inhibitors SSRIs Proton Pump Inhibitors Lithium OHA (Thiazolidinediones) Excessive Thyroxine
- 14. Risk Factors Modifiable Risk Factors Non-modifiable Risk Factors Inadequate Nutritional Absorption Lack Of Physical Activity Underweight (BMI < 18.5 kg/m2 ) Cigarette Smoking Alcohol Consumption >14U/wk in women >21U/wk in men Vitamin D Deficiency Advancing Age Sex (postmenopausal women) Asian Race Previous Hip Fractures Family history of osteoporosis Rheumatoid Arthritis
- 15. PATHOPHYSIOLOGY Bone Formation Bone Resorption Imbalance between Bone Formation and Bone Resorption
- 16. BONE REMODELLING • Continuous Process Osteoclasts resorb bone Osteoblasts form new bone • Why Remodelling ? 1. repair microdamage within the skeleton (eg: heavy weight lifting) 2. to supply calcium when needed from the skeleton to maintain serum calcium
- 17. Microtrauma • Microtrauma Activation of Osteoclasts • RANK-L present on Osteoblasts dissociates and binds to RANK on Osteoclasts Resorption
- 18. OSTEOBLAST Microtrauma Activation of Osteoclasts forms
- 20. • In young adults, resorbed bone is replaced by an equal amount of new bone tissue • After age 30–45, resorption slowly exceeds formation (exaggerated in postmenopausal women)
- 21. • Loss of estrogen increases production of RANKL and reduces production of osteoprotegerin, increasing osteoclast formation and recruitment.
- 22. VIT D AND BONE RESORPTION OSTEOBLAST osteoclast PTH PTHr Vit D Deficiency Hyperparathyroidism
- 24. CLINICAL FEATURES SYMPTOMS • Mostly asymptomatic • Fragility fractures: pathological fractures that are caused by : 1. everyday-activities (e.g., bending over, sneezing) 2. minor trauma (e.g. falling from standing height) • vertebral (most common) > femoral neck > distal radius (Colles fracture) > other long bones (e.g., humerus)
- 25. • Vertebral compression fractures : Commonly asymptomatic Acute back pain Possible point tenderness without neurological symptoms Multiple fractures thoracic kyphosis and Loss of height
- 26. XRAYS • Osteoporosis cannot be diagnosed from plain radiographs • Radiological osteopenia : Bone which appears to be less ‘dense’ than normal on X-ray
- 27. • Typical signs of radiological osteopenia : – Loss of trabecular definition – Thinning of the cortices – Compression fractures of the vertebral bodies (wedging or compression of the vertebral end plates) – Codfish vertebra
- 28. LAB INVESTIGATIONS DIAGNOSIS Investigate Secondary Causes Dual Energy Xray Absorptiometry (DEXA) SCAN (Gold Standard ) Others: (FDA Approved) Quantitative CT Quantitative Ultrasound Liver Function Tests Renal Function Tests Thyroid Function Tests Serum Vitamin D Serum / 24 Hr Urine Calcium Urine Bence jones Protein/Bone Biopsy
- 29. Biochemical markers of Bone Turnover BONE FORMATION BONE RESORPTION Serum Bone – Specific ALP Serum Osteocalcin Serum Propetide of Type I collagen Urine and Serum cross- linked N-Telopeptides Urine and Serum cross- linked C-Telopeptides Do not predict rates of bone loss well enough But provides assessment of treatment response
- 30. DEXA Dual Energy Xray Absorptiometry • GOLD Standard for measuring BMD • High Accuracy • 2 photons with different attenuation profiles produced • The more dense the bones (from greater mineral content), the more energy is absorbed, and the less energy detected
- 31. DEXA Advantages High Accuracy Low Radiation Dose to patient Very little Scatter Radiation to Technician Takes only about 20 min Limitations Cant differentiate Cortical or Trabecular Bone Bone spurs (OA) falsely increase bone density
- 32. Indications for BMD measurement (The International Society for Clinical Densitometry) • All women 65 years and older and All men 70 years and older • Adults > 50 years with Risk Factors • Adults with fragility fracture • Anyone being considered for pharmacological therapy for osteoporosis
- 33. Fracture Risk Assessment Tool FRAX
- 34. FRAX • Developed by WHO • Predicts 10 year probability of having major osteoporotic fractures • Hip, vertebrae, humerus, wrist
- 35. Management • Prevention > Treatment • Fracture Risk Assesment • Patient Education to reduce modifiable risk factors (Smoking, Alcohol ) • Review patients medications (Glucocorticoids, Thyroxine , Anticonvulsants )
- 36. Non Pharmacological Treatments : • Exercise – both resistance and balance training. – weight-bearing exercise helps prevent bone loss but does not appear to result in substantial gain of bone mass. – avoid twisting or bending the spine quickly while transitioning between different positions. • Diet Rich in Calcium and Vitamins (Dairy products, Ground Nut , Soyabeans and Sardines
- 37. Dietary Supplements • Calcium and Vitamin D – Several studies show that Calcium, mostly with accompanying vitamin D leads to ∼20–30% fracture risk reduction – A systematic review confirmed a greater BMD response to antiresorptive therapy when calcium intake was adequate.
- 38. Pharmacological Therapy : Prevention Treatment ESTROGEN CALCITONIN TERIPARATIDE DENOSUMAB BISPHOSPHONATES Alendronate Zolendronic Acid Ibandronate Risedronate
- 39. BISPHOSPHONATES • DOC for osteoporosis treatment • Alendronate • Risedronate • Ibandronate • Zoledronic acid • are approved for the prevention and treatment of postmenopausal osteoporosis
- 40. • Alendronate • Risedronate • Zoledronic acid • approved for the prevention and treatment of GLUCOCORTICOID INDUCED osteoporosis
- 41. MECHANISM OF ACTION • Inhibit Osteoclast • Alendronate : Inhibiting ATP in osteoclasts Apoptosis of Osteoclasts • Risedronate/ Zolendronate : Inhibit Mevalonate pathway (cholesterol synthesis ) enzyme farnesyl pyrophosphate synthase no maturation of osteclast Apoptosis of Osteoclasts
- 42. Precautions • Empty Stomach (inc reflux with food ) • Full glass of Water (Dilute) • Donot lie down till 30 min (gastric emptying )
- 43. Side Effects • Osteonecrosis of the jaw (usually follows a dental procedure in which bone is exposed ) • Atypical femoral fracture (Subtrochanteric Fracture ) (overall risk appears quite low, especially when compared to the number of hip fractures saved by these therapies)
- 44. Denosumab • Monoclonal Antibody • approved by the FDA in 2010 • Given Subcutaneously • Every 6 months
- 45. MECHANISM OF ACTION • Fully human monoclonal antibody to RANKL • binds to RANKL, inhibiting its ability to initiate formation of mature osteoclasts from osteoclast
- 46. Side effects • Hypersensitivity reactions • Hypocalcemia • Skin reactions including dermatitis • Rash, and eczema When denosumab is discontinued, there is a rebound increase in bone turnover and an apparent acceleration of bone loss.
- 47. TERIPARATIDE • PTH ANALOGUE • PTH 1-34 • Full Molecule of PTH is 84 AA Osteoclastic • Pth 1-34 Osteoblastic • 20 mcg S/C daily
- 49. Osteoporosis Osteomalacia Definition Reduced bone mass, normal mineralization Bone mass variable, reduced mineralization Age Postmenopausal (Type I) or elderly (Type II) Any age Etiology Endocrine abnormality, age, idiopathic, inactivity, alcohol, calcium deficiency Vit D deficiency, hypophosphatemia, renal tubular acidosis Symptoms and signs Pain and tenderness at fracture site Generalized bone pain and tenderness Xray Axial fracture predominance Appendicular fracture predominance, Serum Ca Normal Low or normal Serum PO4 Normal Low or normal ALP Normal Elevated
- 51. Paget Disease • Localized Sites Of Increased Bone Turnover • Enlargement And Thickening Of The Bone • Internal Architecture Is Abnormal • Unusually Brittle Bone
- 52. Pathophysiology • Starts At Metaphysis To Involve Diaphysis • Marked Increase In Osteoblastic And Osteoclastic Activity • Accelerated Bone Turnover • Osteolytic Or Vascular Stage – Large Resorption Filled With Vascular Fibrous Tissues – Adjacent Area Osteoblastic Activity – Involves Both Periosteum And Endosteum – Increased Bone Thickness • Osteoblastic Stage – Thickened Bone Becomes Increasingly Sclerotic And Brittle.
- 53. Clinical Feature • M=F • >50yrs Of Age • Localised Or Generalized • Sites : Pelvis And Tibia – Femur, Skull, Clavicle And Spine • Mostly Asymptomatic • If Symptomatic Dull Aching Pain Or Features Of Complication
- 54. • Deformity – Anterior Tibial Bow – Anterolateral Femoral Bow • Osteitis Deformans – Bent Limb, Thick Bone, Warm Skin • Skull Base Thickening – Short Neck – Cranial Nerve Compression • Steal Syndrome • Spinal Claudication
- 55. Xray • Flame Shaped Osteolytic Areas • Osteoporosis Circumscripta • Thick Sclerotic Bone With Coarse Trabeculation • Radionucleotide Scan – Identifies Active Lesions
- 56. • Ivory vertebrae sign • Picture frame sign
- 57. Biochemistry • Serum Calcium And Phosphate Normal • ALP Reflects Osteoblastic Activity
- 58. Complication • Fracture • Osteoarthritis • Nerve compression and Spinal stenosis • Bone sarcoma • High Output Cardiac failure • Hypercalcemia • Intraop bleeding
- 59. Treatment • IV Zoledronate • Surgery – Fracture Fixation – Arthroplasty For Severe And Painful Osteoarthritis – Decompression For Nerve Entrapment And Canal Stenosis
- 60. Hyperparathyroidism • Excess secretion of parathyroid hormone • Cause – Primary : Adenoma/Hyperplasia – Secondary : Persistent Hypocalcemia – Tertiary:
- 61. Primary Hyperthyroidism • Solitary Adenoma • 40-60 yrs • Women: Men 2:1 • Asymptomatic • Unexpectedly high Ca in routine examination
- 62. Effect of High PTH • Tubular resorption • Interstitial absorption • Bone resorption
- 63. Clinical Feature • Calcinosis , Stone formation Recurrent UTI Calcification of soft tissue • Loss of bone substance • Subperiosteal erosion, endostoeal cavitation, • Osteitis Fibrosa cystica • Hemorrhage and giant cell reaction
- 64. Xray
- 65. • Rugger Jersey sign • Salt pepper sign • Brown Tumor
- 66. Biochemistry • Hypercalcaemia, • Hypophosphataemia • Serum PTH Concentration Raised • Serum Alkaline Phosphatase Is Raised
- 67. Treatment • Conservative • Adequate Hydration And Decreased Calcium Intake • Indications For Parathyroidectomy – Marked And Unremitting Hypercalcaemia, – Recurrent Renal Calculi, – Progressive Nephrocalcinosis – Severe Osteoporosis.
- 68. Reference • Apley & Solomon's System of Orthopaedics and Trauma – 10e • Harrison Principle of Internal medicine 21e • Review article : Diagnosis and Treatment of Osteoporosis: What Orthopaedic Surgeons Need to Know – Journal of the American Academy of Orthopaedic Surgeons 2019 • Review article : Diagnosis and Treatment of Osteoporosis – Institute for Clinical Systems Improvement / European Journal of Rheumatology 2017
Notes de l'éditeur
- classical – and almost pathognomonic – feature, which should always be sought, is subperiosteal cortical resorption of the middle phalanges