Management of osteoporosis, Paget's disease

Question 1

Initiating OP treatment

Answer 1

• previous wrist fractures in >65
• T-score <-2.5
• Spine T-score much less than femoral neck T-score
• rapid bone loss
• men on androgen deprivation therapy
• women on aromatase inhibitors for breast cancer
• long-term GC use
• recurrent falls

Question 2

Non-nitrogen bisphosphonate MOA

Answer 2

metabolized in cell to compounds that replace terminal pyrophosphate in ATP
forms non-functional molecules that compete with ATP in cellular metabolism –> apoptosis of osteoclasts

NOT considered effective anti-resorptive therapy

Question 3

Nitrogen bisphosphonate examples

Answer 3

pamidronate
neridronate
olpadronate
alendronate
ibandronate
risedronate
zoledronate

Question 4

Nitrogen bisphosphonate MOA

Answer 4

Bind and block famesyl disphosphate synthase in HMG-CoA reductase pathway
–> inhibits connecting of some small proteins to cell membrane, resulting in osteoclast apoptosis

Much higher potency than non-nitrogen bisphosphonates

Question 5

Nitrogen bisphosphonate indication

Answer 5

Alendronate, risedronate, zoledronic acid - vertebral, hip, non-vertebral fractures

Alendronate standard treatment for osteoporosis

Question 6

Bisphosphonate side effects

Answer 6

upset stomach
inflammation/erosion of esophagus - need to remain upright for 30-60 min
Osteonecrosis of the jaw - mostly seen in chemotherapy
Atypical femoral fractures - stress fracture of lateral femoral cortex, subtrochanteric femur fractures (but benefits of reducing fragility fracture > risk of AFF)
A-fib in women

Question 7

Estrogen indication

Answer 7

intractable hot flashes

do not use for preventing fractures due to extensive side effect profile (thrombotic event)

Question 8

Selective estrogen receptor modular example

Answer 8

raloxifene

Question 9

selective estrogen receptor modulator action

Answer 9

partial agonist of estrogen receptor
effective at preventing vertebral fractures only
increased risk of strokes
SE: hot flashes, leg cramps

Question 10

RANKL mab example

Answer 10

denosomab

Question 11

RANKL mab effects

Answer 11

prevents vertebral, hip, non-vertebral fractures

Question 12

RANKL mab SEs

Answer 12

urinary and respiratory infections
cataracts
constipation
rash
joint pain

Question 13

PTH hormone and analogues

Answer 13

Intermittent dosing stimulates osteoblasts more than osteoclasts
The only bone formation therapy
Effective at preventing vertebral and non-vertebral fractures
NOT effective at preventing hip fractures

Question 14

Indications for anabolic therapy

Answer 14

post-menopausal women - high risk of fracture, failed/intolerant to previous therapy
Male osteoporosis: failed/intolerant to previous therapy
Steroid-induced osteoporosis

Question 15

Contraindications to anatobolic therapy

Answer 15

Metabolic bone disease (e.g. Paget’s)
Renal impairment
Hypercalcemia
Skeletal malignancies/bone mets

Question 16

Adherence to OP therapy

Answer 16

Zoledronic acid - yearly injection

Oral biphosphonates - low compliance

Question 17

Drug holidays

Answer 17

Anti-resorptive therapy do not lose effectiveness over time
Useful in certain groups
- those who did not require treatment!
- low fracture risk
- discontinuing GCs/aromatase inhibitors

Question 18

Glucocorticoid effect on bones

Answer 18

increase osteoclast differentiation
decrease osteoblast proliferation, differentiation, osteocalcin production, osteoprotegerin production
increase osteoblast and osteocyte apoptosis

predominantly affects trabecular bone - spine/wrists
start therapy early

Question 19

Paget’s disease epidemiology

Answer 19

second most common bone disorder after osteoporosis
increasing prevalence with age
etiology unknown

Question 20

Paget’s disease pathogenesis

Answer 20

1) osteolytic - predominant osteoclast activity
2) mixed stage - osteoblast and osteoclast activity - then predominance of osteoblasts
3) osteosclerotic quiescent stage

overall - net gain in bone mass, disordered bone

Question 21

Dx Paget’s disease

Answer 21

often incidents on radiographs
Imaging: enlarged, thick, coarsened cortices + cancellous bone
Elevated serum AP
Increased urinary output of hydroxyproline

Question 22

Management Paget’s disease

Answer 22

Bisphosphonates - different dosing than OP, decreases turnover rate
Calcitonin
Often require joint replacement
Need to follow up to look for osteosarcoma

Question 23

Male osteoporosis etiologies

Answer 23

> 50% is primary
1/4 GC use
others: hypogonadism, excessive alcohol intake, anticonvulsants

Question 24

OP Treatment failure definition

Answer 24

decrease in BMD greater than least significant change while on treatment
fragility fracture while on treatment

Question 25

OP treatment failure management

Answer 25

assess medication compliance
seek causes
Assess type of fracture
assess overall fall risk
consider switching to anabolic or iv bisphosphonate

Question 26

Other comorbidities associated with increased fracture risk

Answer 26

inflammatory arthritis
celiac disease
T2DM
IBD
COPD

Question 27

Recombinant PTH

Answer 27

Teriparatide