Management of osteoporosis, Paget's disease Flashcards
(27 cards)
Initiating OP treatment
- 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
Non-nitrogen bisphosphonate MOA
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
Nitrogen bisphosphonate examples
pamidronate neridronate olpadronate alendronate ibandronate risedronate zoledronate
Nitrogen bisphosphonate MOA
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
Nitrogen bisphosphonate indication
Alendronate, risedronate, zoledronic acid - vertebral, hip, non-vertebral fractures
Alendronate standard treatment for osteoporosis
Bisphosphonate side effects
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
Estrogen indication
intractable hot flashes
do not use for preventing fractures due to extensive side effect profile (thrombotic event)
Selective estrogen receptor modular example
raloxifene
selective estrogen receptor modulator action
partial agonist of estrogen receptor
effective at preventing vertebral fractures only
increased risk of strokes
SE: hot flashes, leg cramps
RANKL mab example
denosomab
RANKL mab effects
prevents vertebral, hip, non-vertebral fractures
RANKL mab SEs
urinary and respiratory infections cataracts constipation rash joint pain
PTH hormone and analogues
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
Indications for anabolic therapy
post-menopausal women - high risk of fracture, failed/intolerant to previous therapy
Male osteoporosis: failed/intolerant to previous therapy
Steroid-induced osteoporosis
Contraindications to anatobolic therapy
Metabolic bone disease (e.g. Paget’s)
Renal impairment
Hypercalcemia
Skeletal malignancies/bone mets
Adherence to OP therapy
Zoledronic acid - yearly injection
Oral biphosphonates - low compliance
Drug holidays
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
Glucocorticoid effect on bones
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
Paget’s disease epidemiology
second most common bone disorder after osteoporosis
increasing prevalence with age
etiology unknown
Paget’s disease pathogenesis
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
Dx Paget’s disease
often incidents on radiographs
Imaging: enlarged, thick, coarsened cortices + cancellous bone
Elevated serum AP
Increased urinary output of hydroxyproline
Management Paget’s disease
Bisphosphonates - different dosing than OP, decreases turnover rate
Calcitonin
Often require joint replacement
Need to follow up to look for osteosarcoma
Male osteoporosis etiologies
> 50% is primary
1/4 GC use
others: hypogonadism, excessive alcohol intake, anticonvulsants
OP Treatment failure definition
decrease in BMD greater than least significant change while on treatment
fragility fracture while on treatment
