1. Dr. K K Sawlani Department of Medicine KGMU, Lucknow 30.07.14
OSTEOPOROSIS
Dr. K K Sawlani
Department of Medicine
KGMU, Lucknow

2. OSTEOPOROSIS A disease characterized by low bone mass
(reduced bone density) and micro-architectural deterioration of bone tissue, leading to enhanced bone fragility and a consequent increase in fracture risk.
Most common bone disease
Affects million of people worldwide

3. Development of osteoporotic bone
This slide shows how the imbalance in turnover leads to a deterioration in bone micro architecture.
A comparison of normal (left) and osteoporotic (right) trabecular structures is shown in these two scanning electron micrographs.
In osteoporosis the trabecular continuity is disrupted by trabecular perforation, and thin rods replace the normal plate-like trabeculae.
Rizzoli R, ed. In: Atlas of Postmenopausal Osteoporosis (First Edition). Science Press, 2004.
Rizzoli R ed In Atlas of Postmenopausal Osteoporosis (1st edition) Science Press, 2004

4. OSTEOPOROSIS
Fractures related to osteoporosis affect around 30 % of women and 12 % of men in developed countries.
Major public health problem
Osteoporotic fractures can affect any bone
The most common sites are
Spine (vertebral fracture)
Forearm (Colles fracture)
Hip

5. Vertebral Fracture

6. Hip Fracture

7. Wrist Fracture (Colles fracture)

8. OSTEOPOROSIS Hip fractures are the most serious
Immediate mortality is about 12 %
Continued increase in mortality of about 20 % when compared with age matched controls.
Account for the majority of health care cost associated with osteoporosis.

9. OSTEOPOROSIS
The prevalence increases with age reflecting that bone density decreases with age especially in women
Accompanied by increased risk of fractures
Fall in bone density
Increased risk of falling

10. Pathopysiology
Occurs because of defect in attaining peak bone mass and/or because of accelerated bone loss.
In normal individuals bone mass increases to reach a peak between the age of 20 and 40 years but falls thereafter.

11. Age-related changes in bone mass
Attainment of peak bone mass
Consolidation
Age-related bone loss
Menopause
Bone mass
Men
Fracture threshold
This figure illustrates the changes in bone mass throughout life and highlighted the two main causes of low bone mass mentioned in the definition
The two main causes of osteoporosis are the menopause and ageing
Bone mass in both men and women increases until a peak is attained at around age 30
In women, there is a phase of accelerated bone loss following the menopause. Rates of bone loss in postmenopausal women can be as great as 6% per year
In women, oestrogen deficiency is the major determinant of bone loss after the menopause
Compston JE. Clin Endocrinol 1990; 33: 653–682.
Women
Age (years)
Compston JE. Clin Endocrinol 1990; 33: 653–682.

12. Pathopysiology
Peak bone mass and bone loss are regulated by both genetic and environmental factors.
Polymorphisms have been identified in several genes that contribute to pathogenesis.
Many of these are in the RANK and Wnt signaling pathways which play critical role in regulating bone turnover.

13. Major risk factors Non modifiable Modifiable Age Race Female gender
Early menopause
Slender build
Positive family history
Modifiable
Low calcium intake
Low vitamin D intake
Estrogen deficiency
Sedentary lifestyle
Cigarette smoking
Alcohol excess (> 2 drinks/day)
Caffeine excess (> 2 servings / day)

14. Post menopausal osteoporosis
Most common cause
Accelerated phase of bone loss after menopause due to estrogen deficiency.
Causes uncoupling of bone resorption and bone formation
Amount of bone reduced by osteoclasts exceeds the rate of new bone formation by osteoblasts
Early menopause ( before the age of 45 years ) is important risk factor

15. Male osteoporosis Less common in men
Secondary cause can be identified in 50% of cases
The most common causes are
Hypogonadism
Corticosteroid use
Alcoholism
Testosterone deficiency results in increase in bone turnover and uncoupling of bone resorption and bone formation.
Genetic factors important in the cases with no identifiable cause.

16. Corticosteroid induced osteoporosis
Risk increases with prednisolone use mg daily for more than 3 months.
Reduced bone formation due to
Inhibitory effect on osteoblast function
Osteoblast and osteocyte apoptosis
Also reduce serum calcium
Inhibit intestinal calcium absorption
Renal leak of calcium
Secondary hyperparathyroidism with increased bone resorption
Hypogonadism may also occur with high doses.

17. Secondary causes of osteoporosis
Endocrine disease
Hypogonadism
Hyperthyroidism
Hyperparathyroidism
Cushing,s disease
Inflammatory disease
Inflammotory bowel disease
Ankylosing spondylitis RA
Gastrointestinal
Malabsorption
Chronic liver disease
Lung disease
COPD
Cystic fibrosis
Drugs
Miscellaneous

18. Secondary causes of osteoporosis
Drugs
Corticosteroids
Thyroxine over-replacement
Anticonvulsants
GnRH agonists
Thiazolidinediones- pioglitazone
Alcohol intake
Heparin

19. Secondary causes of osteoporosis
Miscellaneous
Myeloma
HIV infection
Systemic masotcytosis
Renal failure
BMI < 18
Anorexia nervosa
Heavy smokers

20. Clinical Features Asymptomatic until a fracture occurs
Incidental osteopenia on X-ray performed for other reasons.
Spine fracture
Acute back pain ( 1/3 cases)
gradual loss of height , kyphosis and chronic pain
Peripheral fracture
Local pain, tenderness and deformity
Often with an episode of minimal trauma

21. Investigations
Measurement of bone mineral density (BMD) by dual energy X-ray absorptiometry (DEXA).
BMD can also be measured by computed tomography (CT) and ultrasound.
Central (spine and hip) are best predictors of fracture risk.
Peripheral( radius, heel and hands) are less expensive and widely available.

23. Investigations
T-Score: The number of SDs the patient value is below or above the mean value for young normal subjects.
Good predictor of fracture risk
Z-score: The number of SDs the patient value is below or above the mean value for age matched normal controls.
Whether or not the BMD is appropriate for age.
Absolute BMD: expressed in g/cm2
Used to calculate changes in BMD during follow up.

24. Diagnosis Any patient who sustains a fragility fracture.
On the basis of BMD T-score
≥ -1 = normal
Between -1 and -2.5 = Osteopenia
≤ -2.5 = Osteoporisis

25. Changes in BMD with age (T-score values)
Souce- Davidsons textbook of Medicine 22nd edition

26. Diagnosis
History: early menopause, smoking, excessive alcohol intake, corticosteroid therapy
Examination: Signs of endocrine disease, neoplasia, and inflammatory diseases
A history of fall should be taken
Unstable gait and unsteadiness

27. Diagnosis - Investigations
Renal function
Alkaline phosphatase
Serum calcium, Vit D 25 (OH)
Parathyroid (PTH)
Thyroid function tests
Immunoglobulins and ESR
Celiac disease antibody testing
Testosterone (men)
24 hour urine calcium, sodium and creatinine.

28. Management The aim of treatment is to reduce the risk of fractures
Non-pharmacological
Pharmacological

29. Non Pharmacological Treatment
Smoking cessation
Moderation of alcohol intake
Adequate dietary calcium intake
Exercise
Vitamin D
Fall prevention
Good nutrition

30. Pharmacological Treatment
Several drugs have been shown to reduce the risk of osteoporotic fractures.
Effect on vertebral and non-vertebral fracture is variable.
Considered with
BMD T-score < 2.5
BMD T-score < 1.5 in corticosteroid induced
Vertebral Fractures ,unless resulted from significant trauma

31. DXA Results T Score Classification Action > minus 1.0
Normal
Lifestyle measures.
< minus 1.0 > minus 2.5
Osteopenia
Consider specific treatment where there is ongoing risk, e.g. steroids, and in those who have had a minimal trauma fracture.
< minus 2.5
Osteoporosis
Prevent falls.
Treatment may be indicated.
Look mainly at T-score of total hip and mean of lumber spine. Other area of the hip and individual vertebrae may help especially where results are borderline.
Low BMD is an important predictor for fracture.
A borderline result may be significant for someone with other risk factors or who is likely to fall, but is of less significance in an otherwise fit person in their fifties.
All males with osteoporosis, except the very elderly or frail, should be investigated as 50% will have an underlying cause which may need treatment.

32. CURRENT THERAPIES Anti-resorptive Anabolic
Calcium, Vitamin D, lifestyle modification
Adjunct to other treatments
mg/day of calcium
U/day of vitamin D

33. Treatment Options in Osteoporosis
Antiresorptive drugs
Bisphosphonates
Etidronate
Alendronate
Risedronate
Ibandronate
Zoledronate
Denosumab (monoclonal antibody against RANK-L)
SERMs
Raloxifene
Calcitonin
HRT (estrogen)
Anabolic drugs
Teriparatide(PTH 1-34)
Dual Action Bone Agents (DABAs)
Strontium ranelate

35. Bisphosphonates
Inhibit bone resorption by binding to hydroxyapatite crystals on bone surface
Osteoclasts reabsorb bone-drug released within cell-inhibt key signaling pathways.
Increase in Spine BMD of 5-8% and Hip BMD 2-4%.
Should be taken on an empty stomach with plain water.
No food should be eaten minutes after administration

36. Adverse effects of biphosphonates
Common
Upper GI intolerance (oral)
Acute phase response(intravenous)
Less Common
Atrial fibrillation (IV zoledronic acid)
Renal impairment (IV zoledronic acid)
Atypical subtrochanteric fractures
Rare
Uveitis
Osteonecrosis of the jaw

37. INDICATIONS FOR ANABOLISM
Pre-existing osteoporotic fractures
Very low BMD
Very high fracture risk
Unsatisfactory response to antiresorptive therapy
Intolerant to anti-resorptive therapy

38. TERIPARATIDE Daily SC injection 20 mcg Maximum 18-24 months
May be followed by anti-resorptive therapy
PTH is expensive and is reserved for severe osteoporosis, who fail to response to other therapies.
No advantage of combined anabolic and
anti-resorptive therapy

39. Selective estrogen receptor modulator (SERM)
Raloxifene
60 mg daily orally
Partial agonist of estrogen receptor in bone & liver
Antagonist in breast & endometrium
SE: muscle cramps, hot flushes, increased risk of VTE.
Bazedoxifene is a related SREM

40. HRT Cyclical HRT wirh estrogen and progestogen
Prevents post menopausal bone loss and reduces risk of fractures in post menopausal women
Primarily indicated for prevention of osteoporosis in women with early menopause
Women in early fifties with troublesome menopausal symptoms.
Increased risk of breast cancer and cardiovascular disease

41. Duration of therapy Oral biphosphonates long term (5 YRS)
HRT, raloxifene continuously
Denosumab continuously
Strontium ranelate not established
Teriparatide 2 yrs fb antiresorptive Tt

42. Response to drug treatment
Repeat BMD measurements after 2-3 yrs.
Spine BMD best for monitoring
Biochemical markers ( N-telopeptide) respond more quickly; can be used to assess adherence.

43. Surgery Reduce and stabilize osteoporotic fractures
Painful vertebral compression fractures
Vertebroplasty ( Injection of MMA)
Kyphoplasty ( balloon inflation – MMA)

44. Response to Drugs Fracture risk reduction
30-40% # risk reduction with antiresorptives
60% # risk reduction with teriparatide
BMD
2-3% BMD increase with anti-resorptives
4-6% BMD increase with teriparatide

45. Osteoporosis MCQ 1. Most common cause of osteoporosis Hypogonadism
Malabsorption
Post menopausal
Hyperparathyroidism

46. Osteoporosis MCQ
2. Most common bone disease is a. Osteomalacia b. Osteoporosis c. Secondaries bone d. Osteopetrosis

47. Osteoporosis MCQ
3. Which of the following drug is most common cause of drug induced osteoporosis a. Thyroxine over-relacement b. Corticosteroids c. Pioglitazone d. Anticonvulsants

48. Osteoporosis MCQ
4. Osteopenia is defined as T- Score of a. < -1 b. < -1 to < -2.5 c. < -2.5 d. None of the above

49. Osteoporosis MCQ
5. Risk of fracture in osteoporosis is best predicted by a. T-score b. Z-score c. Absolute BMD d. Serum calcium levels

50. Osteoporosis MCQ
6. Risk factors for osteoporosis are all except a. BMI > 30 b. Smoking c. Low calcium intake d. Immobilization

51. Osteoporosis MCQ
7. Following are all anti-resroptive drugs except a. Biphophonates b. Raloxifene c. Estrogen d. Teriparatide (PTH analogue)

52. Osteoporosis MCQ
8. Which of the following is drug of choice for severe osteoporosis (T-score 0f < -3.5 )
Teriparatide
Biphosphonates
Calcitonin
Strontium

53. Osteoporosis MCQ 9. Osteonecrosis of the jaw is seen with the use of
Calcitonin
PTH analogues
Biphosphonates
Raloxifene

54. Osteoporosis MCQ
10. The response to drug therapy is assessed by repeating BMD measurements after
3 months
6months
1 year
2 year