Bone

Question 1

Important markers of bone formation

Answer 1

Procollagen peptide, osteocalcin, total and bone alkaline phophatase

Question 2

Important urine and serum markers of bone resorption

Answer 2

• Urine: (test second morning void; poorly correlate with BMD, but changes indicate response to Tx)
  •Calcium
  •Hydroxyproline
  •Pyridinoline
  •Deoxypyridinoline cross links of collagen
  •N-telopeptides
• Serum (and urine): C-telopeptides

Question 3

Regulators of osteoblast activity

Answer 3

Estrogen, Vit D

Question 4

Estrogen effect on bone density

Answer 4

Improves bone density by regulating osteoclastic/osteoblastic activity

Question 5

Vitamin D effect on bone density

Answer 5

Increased intake mediated by calcium in kidneys -> increased vitamin D receptors in osteoblasts

Question 6

Exogenous factors that directly stimulate osteoblast activity

Answer 6

Forteo (rPTH), Fluoride

Question 7

Osteoporosis risk factors

Answer 7

Age, personal hx of fracture, Caucasian, smoker, estrogen def, alcoholism, steroids, low BMI, RA

Question 8

Osteoporosis fracture risk reduction

Answer 8

o Weight bearing exercise/fall prevention
o Calc (1000-1300 mg/d), Vit D (600-800 IU/d)
o Reduce alcohol/stop smoking

Question 9

Osteoporosis screening

Answer 9

65, meno w/ RF, or FRAX >9.3% for major fx
o DEXA q15 for normal BMD or mild bone loss (T > -1.5)
o DEXA q5 for T-score between -1.5 and -1.99
o DEXA q1 for T-score between -2.0 and -2.49

Question 10

Who to treat for osteoporosis

Answer 10

Z-score = reference pop same age, sex, race
T-score = SD from mean peak BMD normal 30-year-old adult
- T-score ≤ -2.5 (osteoporosis)
- T -1 to -2.5 (osteopenia) w/ FRAX >20% or hip >3%
History of low trauma fracture (i.e. vertebrae/hip)

Question 11

Labs to obtain prior to osteoporosis treatment

Answer 11

CBC, BMP, Vit D, 24hr urine calc, TSH/FT4, PTH

Question 12

Treatments for osteoporosis (5)

Answer 12

Bisphophonates, raloxifene, Denosumab, Calcitonin, recombinant PTH

Question 13

Bisphosphonate MOA, instructions, contraindications

Answer 13

Inhibit osteoclasts; correct hypo-Ca
• PO: empty stomach/upright x 30min, also IV qYear;
• Contraindicated GERD, CKD; rare osteonecrosis of jaw

Question 14

Raloxifene MOA, target population

Answer 14

(SERM): Anti-resorptive
• Reduce vertebral fracture
• Risk VTE better suited for young post-menopausal b/c also decreases breast cancer

Question 15

Denosumab MOA, admin, contraindication

Answer 15

Anti-resorptive
• SQ inj q6mo
• Contraindication: hypocalcemia

human monoclonal antibody to RANKL, preventing activation of RANK. (prevents bone resorption by osteoclasts)

Question 16

Calcitonin MOA, admin, target population

Answer 16

Anti-resorptive;
• Nasal spray or SQ;
• Less robust reduction in fx; not for women w/i 5yr meno

Question 17

Recombinant PTH MOA, admin

Answer 17

Anabolic (stimulates osteoblasts)
• Teriparatide (Forteo) - SQ inj qDay; restricted to 2yr - risk of osteosarcoma;
• BMD lost quickly after d/c -> add anti-resorp after d/c

Question 18

Osteoporosis tx surveillance

Answer 18

Repeat DEXA 2 years after starting treatment
• DEXA not helpful at less than 1 year intervals.
• Telopeptides are helpful at assessing compliance with therapy.
• At 3 months, a decrease of at least 50% in either N-telo-peptide (urinary) or C-telo-peptide (serum) are signs of response to bisphosphanate therapy.
If BMD improved/stable, rpt DEXA w/ new risk factors

Question 19

Tamoxifen vs Raloxifene

Answer 19

o Both: Lower cholesterol, increase VTE risk, vasomotor sx, reduce breast cancer (T-50%, R-60%)
o Tamoxifen: Endometrial thickening/cancer risk (2.5x), vag estrogenization, decrease BMD; 10yr max
o Raloxifene: Increase BMD, no duration limit

Question 20

Other causes of low BMD

Answer 20

Hyperparathyroidism, multiple myeloma, hyperthyroidism, renal failure

Question 21

Hyperparathyroidism mechanism of decreased BMD

Answer 21

PTH increased in response to low serum calcium concentrations in an attempt to mobilize calcium from kidney and bone and to increase 1,25 dihydroxy vit D production
PTH release raises calcium concentration toward normal by:
• Decreased urinary calcium excretion due to stimulation of calcium reabsorption in the distal tubule
• Increased intestinal calcium absorption mediated by increased renal production of calcitriol
• Increased bone resorption

Question 22

What is RANKL

Answer 22

nuclear factor kB ligand

binds to receptor, RANK, stimulating the osteoclasts to resorb bone

not the same mechanism as bisphosphonates/estrogens that bind to surface of bone and interfere with osteoclast activity