Osteoporosis, Osteomalacia and Paget's Disease

Question 1

What is the main function of cortical bone?

Answer 1

Mechanical and protective function

Always on outside and surrounds trabecular bone

Question 2

What is the main function of trabecular bone?

Answer 2

Metabolic function

~20% of bone

Question 3

What type of bone is more actively remodeled?

Answer 3

Trabecular bone

Question 4

What is the temporal different in bone resorption versus bone formation?

Answer 4

Bone resorption is relatively rapid (requires about 2 weeks)

Bone formation is slow, requiring 4-6 months

Question 5

What kind of bone has a higher turnover rate?

Answer 5

Trabecular or cancellous – higher surface to volume ratio

Cortical or compact bone has a lower turnover rate, less vascularity

Question 6

What gives bone its compressive strength? What about its tensile strength?

Answer 6

Compressive - mineral

Tensile-protein

Question 7

What is the primary protein of bone’s extracellular matrix?

Answer 7

Type 1 collagen

Question 8

What types of cracks are less able to propagate?

Answer 8

Transverse cracks to cement lines

Question 9

What is the dual physiology of bone?

Answer 9

Mechanical physiology - loading and unloading

Mineral physiology - Ca balance, phosphate balance

Question 10

What is thought to play a role in decreased bone density in older adults?

Answer 10

Decreased sensitivity to mechanical loading

Question 11

How should we look at osteoporosis?

Answer 11

Instead of thinking of it as patients suffering from low bone mineral density (BMD), consider osteoporosis as a risk factor for fractures

Question 12

How does WHO define osteoporosis?

Answer 12

Skeletal disorder categorized by compromised bone strength predisposing to an increased risk of fracture

Question 13

What two main features reflect the integration of bone strength?

Answer 13

Bone density (easily measured) 
Bone quality (not as easily measured)

Question 14

How is osteoporosis established on a DEXA scan?

Answer 14

T-score >-2.5 in a postmenopausal women or man over 50

*but not all >-2.5 should be diagnosed with osteoporosis

Question 15

How are long bones loaded?

Answer 15

By bending - tension on one side and compression on the other

Question 16

How are vertebrae loaded?

Answer 16

Primarily in compression and torsion

Question 17

What does BMD correlated with?

Answer 17

Compressive strength but doesn’t give any information about tensile strength

Question 18

What is the single most powerful predictor of future fractures?

Answer 18

Past fractures

Question 19

How does sex contribute to risk?

Answer 19

Lifetime fracture risk for women is 50%

For men it is 25-30%

Question 20

What is responsible for this differences in the sexes of fracture percentage?

Answer 20

Male bones grow larger
Female bones go through rapid bone loss peirimenopausally
Female loss in trabecular bone tens to be patchier than in males – impact on strength

Question 21

What are some other risk factors for increased hip fractures?

Answer 21

Age

Use of glucocorticoids at doses >7.5 mg

Question 22

What are the two best fracture risk calculators?

Answer 22

FRAX

Garvan

Question 23

What is another differential when thinking about osteoporosis?

Answer 23

Osteomalacia

Question 24

What leads to osteomalacia?

Answer 24

If the mineral components of bone matrix are not present in sufficient quantity then the matrix will be under mineralized and weak.

Question 25

What test shows if osteomalacia is present?

Answer 25

Dynamic histomorphometry Use tetracycline Normal bone -- have 2 sharp lines that mark the mineralization front Osteomalacia -- have a smudge and increased ostend volume

Question 26

What are some common lab findings in osteomalacia?

Answer 26

Elevated PTH (secondary) Elevated Alk phos Elevated P1NP

Question 27

Is it possible for a person to have both osteomalacia and osteoporosis?

Answer 27

Yes

Question 28

Drugs that work by limiting the initiation of new bone remodeling units

Answer 28

Antiresorptives - bone formation takes longer than bone resorption, inhibiting the process of remodeling allows the remodeling space to be filled --> reduction in fracture risk and increase in BMD

Question 29

What percent of CaCO3 is elemental calcium?

Answer 29

40%

Question 30

What percent of Ca citrate is elemental calcium?

Answer 30

21%

Question 31

Estrogens and selective estrogen receptor modulators

Answer 31

Tamoxifen Raloxifene Prevent increased remodeling that occurs after menopause

Question 32

Bisphosphonates

Answer 32

Oral - Alendronate, Risedronate | IV - Pamidronate, Zoledronic acid

Question 33

Mechanism of bisphosphonates

Answer 33

Resemble pyrophosphate but oxygen replaced by carbon | Inhibit conversion of mevalonate to farnesyl, interfere with protein modification in osteoclasts, leading to apoptosis

Question 34

Injected decoy for RANKL Binds to RANKL, making it unable to bind endogenous receptor RANK and interrupts RANKL-RANK signaling preventing osteoclast differentiation

Answer 34

Denosumab

Question 35

Synthetic produced fragment of PTH | When given episodically exerts an anabolic effect and increases bone mass

Answer 35

Teriparatide

Question 36

What is the storage form of vitamin D?

Answer 36

25-OH vitamin D - 25-hydroxylated in the liver

Question 37

What is the active form of vitamin D?

Answer 37

1, 25-OH vitamin D 1-hydroxylated in the kidney Has direct effects on the intestinal epithelium to increase Ca and phosphate absorption and on bone to increase remodeling

Question 38

What are some things that may cause secondary hyperparathyroidism?

Answer 38

Nutritional deficiency Renal disease leading to impaired vitamin D activation GI disease leading to malabsorption Use of medications that accelerate vitamin D clearance (anti-epileptic drugs)

Question 39

What is the role of FGF23?

Answer 39

Key regulator of phosphate homeostasis, acting as a phosphaturic hormone Inhibits the expression of 1-hydroxylase, reducing vitamin D activation

Question 40

What are some examples of hypophosphatemic disorders?

Answer 40

Tumor induced osteomalacia Autosomal dominant hypophosphatemic rickets Autosomal recessive hypophosphatemic rickets X-linked hypophosphatemic rickets All include elevated levels of FGF23, hypophosphatemia and osteomalacia

Question 41

How does osteomalacia present during growth?

Answer 41

Rickets

Question 42

What is Paget's Disease?

Answer 42

Foci of exerverant, unregulated bone turnover 1. Woven bone 2. Increased vascularity 3. Bone deformity - bowing, osteitis deforming