Week 4: Osteoporosis/ Bone Metabolism

Question 1

What are 2 great markers for bone turnover?

Answer 1

deoxypyridinoline or N-telopeptide

hydroxyproline was the old marker…

Question 2

What are Looser’s zones?

Answer 2

radiographic finding in osteomalacia- pseudofractures

Question 3

What is the pathogenesis of osteomalacia (generally) and what are causes? What happens to cortical bone on xray? How is it diagnosed?

Answer 3

Impaired mineralization due to hypophophatemia +/- hypocalcemia +/- vit D deficiency

cortical bone gets thinner, trabeculations disappear

bone biospy is the definitive diagnosis. will have layer of unmineralized osteoid

Question 4

What height loss is associated with morphometric fracturs?

Answer 4

recaleld loss of >5 cm or a measured loss > 2cm

Question 5

Which diseases is bowing of the femur assoicated with?

Answer 5

Paget’s, osteomalacia

Question 6

What would alk phos levels be in someone with Paget’s? Is it symmetric or assymmetric? What bones does it usually involve?

Answer 6

v. high

usually assymmetric

long bones, skull, pelvis

Question 7

How to vertebral fractures differ between osteoporosis and osteomalacia? In which can you see proximal muscle weakness?

Answer 7

Osteoporosis: more likely anterior wedge

Osteomalacia: more likely mid-height- more likely to have muscle wekness from lack of vit D

Question 8

Would raloxifene make hot flushes better or worse in menopausal women?

Answer 8

Worse- it is a selective estrogen receptor modulator

Question 9

What do OB secrete to regulate bone resorption? How do estrogen, cortisone, calcitriol modify this? Progesterone?

Answer 9

osteoblasts secrete RANKL, this activates osteoclasts via the RANK receptor. OB also secrete osteoprotegrin (OPG) a decoy receptor..

estrogen upregulates OPG

PTH, cortisone, calcitriol upregulate RANKL secretion

progesterone “activates osteoblasts” according to week review

Question 10

What is the normal relationship between BMD and age in women?

Answer 10

peaks around 25, stable till perimenopause, then declines ~1% per year, a bit more during early menopause

Question 11

How is vitamin D activated? Effects od calcitriol

Answer 11

ingested , liver hydroxylates into 25-OH D3, then kidney hydroxylates into 1,25 D3 (1- alpha hydroxylase)

Causes gut absorbtion of calcium, bone resorption and kidney retention of Ca and P (unlike PTH which excretes P and retains Ca)

Question 12

Drugs available to treat OP?

Answer 12

Drug options:
• Antiresorptive
o 1st gen bisphosphonates (toxic ATP metabolite accumulation→ OC apoptosis)(proven for vertebral fractures only)
• etidronate
o Bisphosphonates (changes cell signaling in some other way→OC apoptosis)
• Alendronate
• Risedronate
• Zoledronic acid
o Denosumab
• Ab to RANKL
• 68% reduction of vertebral fractures
o Raloxifene (estrogen agonist- related to tamoxifen)
o Estrogen therapy (too many risks…stroke, cancer, )
• Bone formation
o Teriparatide (recombinant PTH)
• Use single daily injection rather than continous infusion- better mimics PTH physiology and activates OB more than OC…confusing because primary action of PTH is bone resorption.

Question 13

What risk factors do the CAROC and FRAX systems use?

Who do they apply to?

Answer 13

CAROC: Risk based on age, sex, T-score from femoral neck. Gives low (<10%), medium (10-20%) and high risk (>20%)

FRAX: risk based on sex, age, BMI, prior fracture, parental hip fracture, prolonged glucocorticoid use, RA, current smoking, EtOH intake and BMD of femoral neck

**apply to treatment naive men and women over fifty **

Question 14

What are the three phases of Paget’s?

Answer 14

1. Osteolytic: bone resorption
2. Sclerotic: decreased turnover, loss of vascularity
3. Mixed: both