1. V ED Internal medicine, endocrinology
Osteoporosis – causes, diagnostics and therapy prof. Marek Bolanowski, MD, PhD Department of Endocrinology, Diabetes and Isotope Therapy

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) Secondary Postmenopausal type 1
Senile type 2
Secondary

6. Osteoporotic bones

7. Typical change of body profile

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. Osteoporotic fractures
Forearm
Humerus
Proximal femur

14. type of fracture Most common fractures forearm spine femur
age > > > 75
F:M : : :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 Indirect 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. Methods of measurements
SPA
DPA
SPX, SXA
DXA, DEXA, DPX
(dual energy X-ray absorptiometry)
QCT
QMR
USG, QUS

26. Densitometry using DXA

27. Densitometry BMD BMC 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 and SD
Osteopenia between and SD
Osteoporosis lower than SD
Established lower than SD
osteoporosis + fracture(s)

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

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

47. Conditions that increase risk of osteoporosis Secondary osteoporosis
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

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. Laboratory tests Biochemistry Hormonal 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

51. Conditions that increase risk of osteoporosis
Gastrointestinal disorders
Malabsorption syndromes
Postresection syndromes, inflammatory bowel disease
Pancreatic exocrine insufficiency
Coeliac disease
Severe liver failure
Primary liver cirrhosis
Bariatric surgery

52. Conditions that increase risk of osteoporosis
Resulting in locomotor system dysfunction
Inflammatory systemic rheumatic diseases
Osteoarthritis
Injuries of the locomotor system
Congenital anomalies of the locomotor system
Multiple sclerosis
Parkinson’s disease
Alzheimer’s disease

53. Drugs that affect bone metabolism
Steroids (5 mg/d for more than 3 mo)
Thyroid hormones at suppression doses
Anticonvulsants
GnRH agonists
Aromatase inhibitors
Anticoagulants
Antimetabolites
Immunosuppressants

54. Densitometric criteria of osteoporosis
T-score
Normal SD SD
Osteopenia SD SD
Osteoporosis below SD
Advanced (severe) below SD
osteoporosis fracture
Z-score
Osteoporosis below SD

55. Physical activity Natural among children and adolescents
Depending on individual decision in adults
Important modifiable factor important for attaining optimal PBM
Ensure skeletal stabilization, balance between resorption and formation, general efficiency sprawność
Excessive could be harmful

56. Role of exercise
Exercising regularly in childhood and adolescence can ensure attainment of a proper peak bone mass and density.
Need to participate in weight bearing exercise: walking, dancing, jogging, stair climbing, racquet sports and hiking. 17

57. Prevention
Building strong bones in childhood and adolescence is the best defense.
A balanced diet rich in calcium and Vitamin D
Weight bearing exercise
A healthy lifestyle with no smoking or excessive alcohol intake.
Bone density testing and medication when appropriate.
Prevention is very important while there are treatments for osteoporosis there is currently no cure. A healthy lifestyle can be critically important in keeping bones strong. Building strong bones in childhood and adolescence is the best defense. A balanced diet rich in calcium and Vitamin D, weight bearing exercise, a healthy lifestyle with no smoking or excessive alcohol intake, a bone density testing and medication when appropriate. 12

58. Preventive recommendations
Maintain a calcium rich diet
Get plenty of vitamin D
Start or maintain a weight-bearing exercise
Don’t smoke and limit alcohol intake
Hormone replacement ? 19

59. Non-pharmacological actions to lower the risk of osteoporotic fractures
Life style changes
Normal body mass maintenance
Sufficient calcium intake
No smoking
No alcohol in excess
Exercises, physical activity
Every day independence
Minimalize falls risk
Therapy of neurological and rheumatological conditions
Avoiding of the medication influencing balance
Glasses, lighting, shoes...

60. ?

61. Management in osteoporosis
Identification of the population with high fracture risk
Elimination or limitation of fracture risk, when possible
Therapy

62. Prevention and therapy of osteoporosis
Decrease of bone resorption
Stimulation of bone formation
Sufficient Calcium + vit. D intake
Physical activity
Elimination of risk factors

63. Anti-osteoporosis therapy
Antiresorptive therapy
bisphosphonates, denosumab, HRT, SERM, calcitonin...
Anabolic therapy
PTH, strontium ranelate, fluor...
Additional therapy
calcium, vitamin D
physical activity, diet ...

64. Management in secondary osteoporosis
Identification of secondary causes of osteoporosis
Elimination of risk factors
Radical treatment
Hormonal therapy/replacement
Harmful medication withdrawal
Medical therapy
Antiresorptive
Anabolic

65. ?

66. News in therapy Bisphosphonate weekly (2000)
Bisphosphonate monthly (2005)
Bisphosphonate every 3 months (2005)
Bisphosphonate yearly (2008)
Strontium (2004)
PTH (2005)
Denosumab (2010)

67. Postmenopausal osteoporosis
treatment when fractures
or fracture risk
prevention T-score >–2.5
treatment regardless fractures
PTH
SERM
Bisphosphonate
Denosumab
Strontium ranelate
HRT
Therapeutic Management of Postmenopausal Osteoporosis
Age (yrs)

68. Bone formation markers
Osteocalcin (OC, BGP)
Extent of OC synthesis by osteoblasts
Alkaline phosphatase (BAP)
Cellular activity of osteoblasts
Type 1 procollagen propeptides (PICP, PINP)
Synthesis of new collagen by osteoblasts in bone and by fibroblasts in other tissues

69. Bone resorption markers
Type 1 collagen telopeptides
CTX, NTX, ICTP
Crosslinks
Serum free pyridinoline (PD), free deoxypyridinoline (DPD)
Urinary PD, DPD
Calciuria/creatinine
Hydroxyproline (HYP)/creatinine

70. Monitoring of therapy by markers
Markers useful in prognosing of individual response to the therapy.
Reduction in resorption markers after mo.
Reduction in formation markers after mo.
Dramatic increase of bone turnover after therapy discontunuation, first resorption, next formation.
Assessment after mo.
Optimal reduction by 40% to the baseline

71. Practical use of markers
Identfication of subjects with increased bone resorption
Assessment of effect of therapy
Decrease of resorption activity
Increase of formation activity
Patients’ compliance assessment

72. Target of therapy
Fractures prevention