V ED Internal medicine, endocrinology

1. Osteoporosis – causes, diagnostics and therapyprof. Marek Bolanowski, MD, PhDDepartment of Endocrinology, Diabetes and IsotopeTherapy V ED Internal medicine, endocrinology

2. Osteoporosis • A systemic disease of the skeleton characterized by low bone mass and microarchitecture deterioration of bone tissue leading to bone fragility and susceptibility to fractures. • WHO 1994 • normal bone osteoporotic bone

3. Osteoporosis • A disease of the skeleton characterized by an increased risk of fractures resulting from reduced mechanical bone strength. • Reduced bone strength depends on bone mineral density (BMD) and the quality of bone tissue. NIH 2001

4. Causes of osteoporosis • genetic 75-85% • peak bone mass • hormonal • estrogen deficiency • environmental • feeding, movement

5. Osteoporosis • Primary (involution) • Postmenopausal type 1 • Senile type 2 • Secondary

6. Osteoporotic bones

7. Typical change of body profile 55 65 75

8. Body profile in osteoporosis

9. Bone mass and density • Peak bone mass childhood • Bone mass and density loss adulthood

10. Bone structure and turnover • Trabecular (cancellous) bone 20% of skeletal mass 80% of bone turnover • Cortical (compact) bone 80% of skeletal mass 20% of bone turnover

11. Osteoporotic fracture • A fracture that is disproportionate to the causative forces which occurs following a fall from the patient’s own height, after all other causes have been ruled out. • Low-trauma (pathological) fractures may occur for reasons other than osteoporosis (cancer, bone cyst, osteomalacia...)

12. Osteoporotic fractures • Spine • Ribs

13. Forearm Humerus Proximal femur Osteoporotic fractures

14. Most common fractures type of fracture forearm spine femur • age > 55 > 65 > 75 • F:M 4:1 3:1 2:1 • bone trabecular trabecular cortical

15. Fractures • familial predisposition, low bone mass and density, previous fractures, low body mass, high height, medication, tendency to falling • women – at home, men – outside home • 20% of women and 30% of men die within 1 yr after femur fracture • 40% remain immobilized forever

16. Risk factors for fractures • Falls • Low BMD

17. Risk factors for falls • Related to the patient’s condition • External (environmental)

18. Risk factors for falls related to the patient’s condition • A history of falls, fear of falling • Muscle weakness, arthralgia and arthritis • Gait/balance disorders • Visual impairment • Impairment of cogitive functions, depression, memory disorders • Urinary incontinence • Age > 65 yrs, low body mass • Use of more than 4 drugs, use of psychotropic and hypertensive drugs

19. Enivironmental risk factors for falls • Poor lighting conditions (at home) • Poor vision (no spectacles/glasses) • Obstacles on the patient’s way (at home) • Slippery, uneven surfaces (ice, snow, rain...) • Lack of position changes facilities (barriers in toilet or bathroom) • Transportation and public traffic

20. Reduced bone strength • BMD • Bone quality

21. Bone quality • Direct assessment • Histomorphometry • Microstructure in μCT/μMR • Mechanical forces (bending, twisting…) • Indirect assessment • Bone markers • QUS • BMD

22. Bone mineral density • BMD – objective measurement by DXA • BMD – best single predictor of fracture risk • BMD decrease = increase of fracture risk

23. Indications for densitometry • Estrogen deficiency • Changes on vertebral X-ray • Steroid therapy • Hyperparathyroidism or other diseases associated with osteoporosis • Male hypogonadism, alcohol abuse • Therapy monitoring

24. Sites of measurements • distal and ultradistal forearm • lumbar spine (antero-posterior or lateral projection) • proximal femur – femoral neck, trochanter major, Ward’s triangle, total femur • heel, patella, tibia • fingers (phalangi) • total body

25. SPA DPA SPX, SXA DXA, DEXA, DPX (dual energy X-ray absorptiometry) QCT QMR USG, QUS Methods of measurements

26. Densitometry using DXA

27. Densitometry • BMD • bone mineral density • (g/cm2) “areal thickness” • integration of density and thickness • (g/cm3) in computed tomography • BMC • bone mineral content • (g)

28. BMD - best predictor of fracture risk • positive correlation with skeletal strength • decreases with age • negative correlation with bone fractures occurence

29. Bone mineral density • BMD

30. decrease of BMD by 1 SD 2 - 4 fold increase of fractures occurrence

31. T-score • difference between measured BMD value and theoretical mean peak bone mass • expressed in standard deviation (SD) • age independent

32. Z-score • difference between measured BMD value and mean age-matched theoretical normal BMD • expressed in SD • both BMD dispersion in the normal population and age-related bone loss are regarded

33. A reflects T-score = -3.0 SD, and Z-score = -2.0 SD in 50 y.o. subject. B reflects T-score = -2.0 SD, ans Z-score = +1.5 SD in 80 y.o. subject.

34. Densitometric criteria of osteoporosis T-score • Normal between -1.0 and +1.0 SD • Osteopenia between -2.5 and -1.0 SD • Osteoporosis lower than -2.5 SD • Established lower than -2.5 SD osteoporosis + fracture(s)

35. calcifications deformities fractures fat in bones (medulla) position analysis wrong data infiltrations osteolytic metastases osteomalacia position analysis wrong data False results

36. An example of lumbar spine DXA

37. An example of femoral neck DXA

38. An example of femoral neck DXA

39. An example of „total body” scan

40. Osteoporosis on X-ray • No more for diagnostics • When BMD loss more than 30% • Fractures • Deformities

41. Assessment of fracture risk • DXA and quantitative ultrasound • Clinical risk factors • Markers of bone turnover • Bone formation • Bone resorption

42. Clinical risk factors - CRF • Age • Sex • Body mass • Height • Previous fractures • Parental hip fracture • Current smoking • Steroids • Rheumatoid arthritis • Secondary osteoporosis • Alcohol > 3 units daily • Femoral neck BMD

43. http://www.shef.ac.uk/FRAX/tool.jsp?lang=po

47. Endocrine disorders Gastrointestinal disorders Malnutrition states Renal failure Cancer Transplantations Genetic disorders Locomotor system dysfunction Immobilization steroids immunosuppressants cytotoxic anticonvulsants heparin aluminium lithium GnRH agonists Conditions that increase risk of osteoporosisSecondary osteoporosis

48. Secondary osteoporosis • Bone loss, microarchitecture alterations and fragility fractures due to an underlying disease or medication. • Premenopausal women, younger men, not typical target population for routine osteoporosis screening. • Limited response to anti-osteoporosis therapy. • Secondary causes – 30% of osteoporosis in women. • Secondary causes – 70% of osteoporosis in men.

49. Conditions that increase risk of osteoporosis Endocrine disorders • Menstrual abnormalities/amenorrhoea • Hyperprolactinemia • Male hypogonadism • Primary hyperparathyroidism • Hyperthyroidism • Hypercortisolism – Cushing syndrome

50. Biochemistry calcium, phosphate urea, creatinine, GFR blood count, sedimentation glucose, HbA1c urine analysis monoclonal protein Hormonal PTH TSH, fT4, fT3 cortisol, ACTH PRL sex steroids 1,25-dihydroxycholecalciferol 25-OH-vit. D Laboratory tests