1. Osteoporosis PHCL 442
Hadeel Al-Kofide MS.c

2. Topics to be covered Definition & epidemiology Pathophysiology
Classification
Risk factors
Diagnosis
Management:
Non-Pharmacological & Pharmacological

3. Definition
Osteoporosis is a systemic skeletal disorder characterized by: low BMD & microarchitectural deterioration of bone tissue, leading to enhanced bone fragility & a consequent increase in fracture risk
The condition is usually painless until a fracture occurs
It affects 1:2 women & 1:8 men

4. Pathophysiology
Normally there is a balance between osteoblast & osteoclast activity
In osteoporosis either one of 2 or both will happen:
Space where some bone has been resorbed (due to osteoclast) but not yet replaced during the remodeling process (with osteoblas), this happens by advanced age
Remodeling space is increased (due to osteoclast) in postmenopausal osteoporosis

5. Classification Primary:
Type I: Postmenopausal osteoporosis, it occurs in women 3-6 years after menopause (due to increase osteoclast resorption activity)
Type II: In both men & women after age 75, female to male ratio 2:1
Secondary:
Due to drugs, medical problems & other causes it is equal in men & women

6. Risk Factors for Osteoporosis
Age – especially after 60 yr
Female gender
Small stature
Caucasian, Asian, Latin American
Slight body build
Estrogen depletion (menopause or amenorrhea)
Family history of osteoporosis
Lack of exercise

7. Risk Factors for Osteoporosis
Cigarette smoking
Underweight
Excessive use of alcohol
Excessive fiber consumption
Excessive caffeine consumption
Inadequate lifetime calcium intake
Poor vitamin D status

8. Risk Factors for Osteoporosis
Use of certain medications
Phenytoin, Phenobarbital
Thyroid hormone
Corticosteroids
Methotrexate
Aluminum-containing antacids
Heparin

9. Risk Factors for Osteoporosis
Certain diseases or conditions
Hyperthyroidism
Diabetes
Chronic renal failure
Chronic diarrhea/malabsorption
Hyperparathyroidism
Chronic obstructive lung disease

10. Diagnosis Radiographic measurement of bone density
Laboratory biochemical markers
Bone resorption markers (eg., collagen cross-linked N- telopeptides)
Bone formation markers (eg., bone-specific alkaline phosphatase)
Bone biopsy with pathologic assessment: only used under research setting or with difficult to diagnosis cases

11. Bone Mineral Density Indications: In women with strong risk factors
In those with osteoporosis-related fractures (wrist, spine, proximal femur, or humerus after mild or moderate trauma)
For monitoring treatment

12. Bone Mineral Density
Techniques:

13. WHO Diagnostic Categories for BMD
Bone Mineral Density
WHO Diagnostic Categories for BMD
Normal
BMD not more than 1 SD below the peak bone mass or young adult mean (T-score above -1)
Osteopenia
BMD between 1 & 2.5 SD below the young adult mean (T-score between -1 and -2.5)
Osteoporosis
BMD 2.5 SD or more below the young adult mean (T-score at or below -2.5)
Severe osteoporosis (established osteoporosis)
BMD 2.5 SD or more below the young adult mean (T-score at or below -2.5) & the presence of one or more fragility fractures

14. Management

15. Management & Prevention
Keep in mind you have two prevent osteoporosis in 2 settings:
Premenopausal women
Postmenopausal women

16. Non-Pharmacological
Appropriate levels of exercise should be recommended
Smoking & alcohol abuse should be discouraged
Physiotherapy & pain relief are important in managing fractures

17. Pharmacological Calcium & vitamin D Hormone replacement therapy
Raloxifene
Bisphosphonates
Calcitonin
Parathyroid hormone peptides
Strontium ranelate

18. Calcium & Vitamin D
All patients at risk for osteoporosis (for prevention) & patients with osteoporosis (for treatment) should be on adequate Ca & vitamin D supplements
Calcium dose: 1200 mg elemental Ca
Vitamin D dose: 400 IU/day if age more than 70 years IU/day

19. Calcium & Vitamin D
Calcium carbonate: highest amount of calcium per tablet, but may cause intestinal gas &/or constipation
Calcium citrate: less calcium per tablet, but better absorbed than carbonate; no known side effects
Calcium phosphate: most diets already high in phosphorous; better to avoid this form
Calcium gluconate: requires many tablets to obtain sufficient calcium

20. Vitamin D inadequacy worldwide90
N=1285
81% 80
63% 70
59%
59% 60
51%
52% 50
Prevalence (%) 40 30 20 10
All
Australia
Latin America
Asia
Middle
East
Europe
Regions
Vitamin D inadequacy defined as serum 25(OH)D <30 ng/ml
1285 community-dwelling women with osteoporosis from 18 countries to evaluate serum 25(OH)D distribution.
Lim S-K et al, 2005

21. Hormone Replacement Therapy
In the past was considered as 1st line treatment
It is an appropriate option in younger postmenopausal women at high risk of fracture, particularly those with vasomotor symptoms
Generally a second line treatment option because risk-benefit balance is unfavorable in older women

22. Raloxifene Mechanism of action:
Selective estrogen receptor modulator (SERM)
Mixed estrogen receptor agonist/antagonist
Acts as an agonist in the bone, reducing turnover by inhibiting osteoclast recruitment & activity
Acts as an antagonist in the breast & uterus

23. Raloxifene Role in Therapy:
Second line agent for the treatment of postmenopausal osteoporosis
Advantage:
Favorable changes in lipid profile
Decreases the risk for CV events and breast cancer

24. Raloxifene Dose: 60 mg/day Adverse effects: Hot flushes, & leg cramps
Increase in the relative risk of venous thromboembolism

25. Bisphosphonates Mechanism of action:
Deposited in bone at the site of mineralization; apparently causing the death of osteoclasts which results in decreased bone resorption
They have very long half life 1-2 years
Less than 10% absorbed

26. Bisphosphonates
Alendronate & risedronate have been shown to reduce vertebral & non-vertebral fractures, including hip fractures
They are considered first line options for treating postmenopausal osteoporosis

27. Bisphosphonates Dose: Alendronate Oral 70 mg 1/w, or 5 mg or 10 mg OD
Most common regimen used
Alendronate Oral
70 mg 1/w, or
5 mg or 10 mg OD
Etidronate Oral
400 mg OD for 2 w every 3 mo
Ibandronate Oral IV
150 mg 1/mo
3 mg 1/3 mo
Risedronate Oral
35 mg 1/w, or
5 mg OD
The only one with IV form

28. Bisphosphonates Adverse effects:
Acid regurgitation, dyspepsia, abdominal distention, gastritis, nausea & dysphagia
Esophageal ulceration & strictures
Musculoskeletal pain, headache & rash

29. Bisphosphonates Contraindications:
Not given if CrCl less than 35 ml/min
If hypocalcaemia exists it should be corrected before starting therapy
Caution in patients with upper GI problem (esophagus)

30. Bisphosphonates Precautions:
Oral bisphosphonates must be taken fasting, with a full glass of water
The individual must be upright & stay sitting or standing without taking food or drink for the next minutes
This is done to prevent esophageal ulceration

31. Calcitonin Mechanism of action:
Inhibits osteoclast formation & attachment
Analgesic effect?
Dose:
200 IU/day by nasal spray
100 IU/day IM

32. Calcitonin Adverse effects: Rhinitis & epistaxis (from nasal form)
Arthralgia, headache & back pain
Flushing, nausea, vomiting & local irritation (IM)

33. Calcitonin Precautions:
Nasal form should be refrigerated until it is open for use
After opening it is only stable for 30 days at room temperature
Role in Therapy:
Not used as first line treatment
Mainly used in patients with back pain & acute vertebral fracture

34. Parathyroid Hormone Mechanism of action:
Produced normally by PT gland, helps control calcium exchange between the bones & the blood stream
Low dose synthetic human PTH causes anabolic response, increasing the number and action of osteoblasts

35. Parathyroid Hormone Side effects: Asymptomatic mild hypercalcemia
Increase risk of osteosarcoma
Dose:
Teriparatide (rPTH): 20 mcg/d SC for upto 24 months

36. Parathyroid Hormone Contraindications:
Children, adolescents & patients with paget’s disease because of increased risk of osteosarcoma
Hypercalcemia
Role in Therapy:
Postmenopausal women & men with osteoporosis who are at high risk for fracture, such as individuals with prior osteoporotic fractures (mainly as second line agent)

37. Strontium Ranelate Mechanism of action:
It has a dual mode of action, both increasing bone formation & decreasing bone resorption
It has been shown to enhance osteoblastic cell replication & increase collagen synthesis while it decreases bone-resorbing activity of mature osteoclasts

38. Strontium Ranelate Adverse effects:
Diarrhoea, nausea, headache, dermatitis & eczema
Rare: DVT
Contraindications:
Not recommended in patients with a CrCl below 30 ml/min
Dose:
2 g sachet once daily 2 hours after food, must taken as suspension in water & drink immediately

39. Strontium Ranelate Role in Therapy:
Postmenopausal women & men with osteoporosis who are at high risk for fracture, such as individuals with prior osteoporotic fractures (mainly as second line agent)

40. Which Dug for Which Patient??

41. Which drug for which patient? LOOK AT THE ATTACHED GUIDELINE
Agent
Rx PM OP to reduce risk of
Steroid induced OP
OP in men
Vertebral fractures
Hip fractures
Alendronate a
Risedronate r
Etidronate
Raloxifene
Strontium ranelate
Teriparatide
LOOK AT THE ATTACHED GUIDELINE

42. Thank you