osteoporosis

Question 1

Define osteoporosis

Answer 1

disease characterised by low bone mass and microarchitectural deterioration of bone tissue, with a consequent increase in bone fragility and susceptibility in fracture risk’
Bone mineral density T score

Question 2

List risk factors for developing osteoporosis

Answer 2

postmenopausal women
caucasian/asian
hx of maternal hip fracture 
sex hormone deficiency
low body mass
lifelong low Ca intake 
sedentary lifestyle, immobility
excessive alcohol use & cigarette smoking
prior low trauma fracture

Question 3

List the secondary causes of diminished bone density?

Answer 3

these sec causes of bone loss should be excluded w a complete hx, physical exam and lab tests

Endocrine disorders
Cushing’s disease, hyperparathyroidism, hyperthyroidism, prolactinoma, hypogonadism

Celiac disease and other causes of malabsorption

Vitamin D deficiency

Hepatic or renal dysfunction

Genetic disorders, e.g., osteogenesis imperfecta

Systemic inflammatory disease, e.g., RA, IBD

Anorexia nervosa

Malignancies, e.g., multiple myeloma

Corticosteroids

Question 4

What factor plays a key role in bone loss?

Answer 4

age related bone loss in women and men begins around the age of 40. In women over this age, about 35% of compact bone and 50% of spongy bone in the skeleton is lost during their remaining lifetime. In contrast, men lose about two-thirds of this amount.
Women lose more bone because of menopause which is a/w decreased oestrogen levels. Additionally women have less bone to begin w so are generally at a greater risk for osteoporosis

Question 5

What factor plays a key role in fractures ?

Answer 5

AGE
incidence increases w age
2/3 women >80= osteoporotic fractures
1/3 60-70 = fractures

Question 6

What are the pathologic findings w osteopenia and osteoporosis

Answer 6

osteopenia - mineral density lower than normal- precursor to osteoporosis

The effects of postmenopausal bone loss are most apparent in trabecular/spongy/cancellous bone where the rate of bone loss increases 3 fold immediately following menopause

Gross features: Loss of cancellous bone, accentuation of vertical trabeculae in spine

microscopic
Thin trabeculae disconnected from each other
Increase in osteoclastic activity- bone resorption (may be uneven) or increased percentage of surface with resorptive pitting

vertebrae rich in trabecular bone- thus more prone to fractures

Question 7

Diagnosis of osteoporosis

Answer 7

BMD T score

radiographic measurement of bone density

Question 8

What is BMD T score

Answer 8

T score compare Bone mineral density to ideal peak mineral density and are measured in standard deviations above and below peak BMD.

BMD- measures degree of bone loss (g/cm2) . provides an estimate of a person’s fracture risk

Question 9

What is the normal,osteopenia,osteoporosis a/ T score

Answer 9

Normal: more than or equal to -1.0
Osteopenia : -1.0 to -2.5
Osteoporosis: less than or equal to -2.5
Severe osteoporosis: less than or equal to -2.5 w/ fragility fractures

Question 10

What are the factors that increase absolute fracture risk?

Answer 10

older age
prior fracture
lower T scores
multiple risk factor

Question 11

Pharm Treatment of osteoporosis

Answer 11

Calcium (1000mg/day) and vit D(800iu) supplement
bisphosphonates (apoptosis of osteoclasts) eg alendronate,residronate
hormone replacement
selective oestrogen receptor modulators
PTH
rank ligand inhibitor

Question 12

Other non pharm tx of osteoporosis

Answer 12

smoking,excess alcohol prevention
weight bearing exercises
good diet
correct sec causes where possible

Question 13

Describe examples of bisphosphonates

Answer 13

Alendronate
Primary nitrogen terminal bisphosphonate
70mg once weekly dose
5-7% gains in BMD & 40% reduction in fracture rate
Long t ½ of elimination ? years

Residronate
bisphosphonate w heterocyclic ring
35 mg po once weekly
 5% gain in BMD & 40% reduction in fracture risk
T ½ of excretion about 20 days

Ibandronate- 150mg orally once monthly
zoledronic acid iv 5mg once yearly

Question 14

Complications of BP

Answer 14

osteonecrosis of jaw

oesphagitis from oral bisphosphonates

Question 15

Example of anabolic agents

Answer 15

teriperatide (PTH) - 20mcg s/c daily
most potent anabolic agent
increases BMD seen often used for severe osteoporosis

strontium ranelate- anti resorbitive and anabolic ;; cardiac risk

Question 16

Example of hormones

Answer 16

HRT – consider for early post menopausal patients when indicated for symptom management – is effective note increased risk breast cancer after 5 yrs
Raloxifene – a SERM – 60 mg/d (HRT for bones not uterus or breast) - proven for vertebral fractures
Testosterone for deficient men

Question 17

How does oestrogen deficiency cause osteoporosis?

Pathophysiology in post menopausal woman?

Answer 17

accelerates bone resorption by
-increasing the activity of bone remodelling units and the number of osteoclasts recruited to resorption sites
-increasing osteoclast lifespan, as well as the formation of new osteoclasts. Thus, more bone is resorbed during resorption phase
-reducing osteoblast lifespan. Therefore, less bone is formed during the formation phase
-altering synthesis of both growth factors and degradative factors that act on bone
Together, these changes prolong the resorption phase of the remodelling cycle and shorten the formation phase

Question 18

Outline glucocorticoid induced osteoporosis

Answer 18

long term use of oral glucocorticoids in chronic disease (correlates to fracture risk)
-asthma,COPD, RA,IBD,lupus
regardless of age/gender
alot of bone loss in as little as 3 months
eg prednisone
spine fracture incidence higher–trabecular bone loss effect

Question 19

Pathophysiology of glucocorticoid induced osteoporosis

Answer 19

corticosteroids ultimately cause rapid bone loss

• decreased bone formation, inhibits osteoblasts and testoterone which leads to remodelling imbalance– rapid bone loss
• increased osteoclasts, inhibits oestrogen-> increased bone resorption–rapid bone loss
• increased Ca excretion -> sec hyperparathyroidism- >increased bone resorption – rapid bone loss
• reduced absorption of dietary calcium -> sec hyperparathyroidism->increased bone resorption–rapid bone loss