osteoporosis Flashcards
routine screening for osteoporosis
> =65 y.o
earlier for above average risk (other than menopause)
USPTF and AFP recommend age 60 in higher risk women
osteoporosis def
T-score<=-2.5 at lumbar spine, total hip or femoral neck on bone mineral density scan
or hx of fragility fracture
osteopenia
-1.0 <-2.5
who to consider w/u for secondary osteoporosis
all premenopausal women with oeteoporosis
men
postmenopausal women with low z-scores ,-2.0 or less
women who do not respond adequately to initial therapy
Meds that cause secondary osteoporosis
glucocorticoids aromatase inhibitors depo-medroxyprogesterone acetate unfractionated heparin GnRH agonist anticonvulsants - phenobarbital, phenytoin,carbamezapin (accel vit D metabolism) phenothiazine methotrexate (not with low RA doses, 20 mg OK) excessive vit A intake cyclosporine-severe trabecular bone loss tacrolimus
secondary causes of osteoporosis (food/disease)
malnutrition/malabsorption IBD (vit D largely absorbed in jejunum celiac disease gastric and bowel resection - ca absorbed in duodenum eton - inhibits osteoblasts vitamin D def/insuf
Role of Vitamin D
inc calcicum absorption in the gut
suppress PTH release
Dec renal ca and phosp excretion$)
generation of bioactive Vit D
exposure to UV light cholecalicferol (D3)
cholecalciferol and ergocalciferol (D2) obtained from diet
D2 and D3 converted in liver to 25-OH vit D (calcidiol- use in liver disease)
1,25-OHD (calcitrol) formed in kidneys through renal conversion (use in kidney disease, $$
25-OHD levels
normal > 30
deficiency < 20
insufficiency 20-30
high prevalence esp in elderly, northern latitudes, pregnancy, IBD, celiac disease
average daily cholecalciferol need
3000-5000/day
choleocalciferol
vitamin D3
preferred therapy
800-1000IU per day for insufficiency
VIt D deficiency therapy
50,000 IU Q week for 8 weeks, then 500-1000 IU if deficient
monitor Vit D metabolites levels 3 months after starting therapy - 25-OHD
Vit D supplement if kidney disease
Vitamin D metabolites - calcitrol (1-25 OHD)
endocrine causes of secondary osteoporosis
hyperthyroidism
hyperparathyroidism - surgical resection improves BMD
Cushings
Hyperprolactinemia
misc osteoporosis causes
immobilization smoker post organ transplant (esp first 3-6 months chronic disease - multiple myeloma (inc osteoclast activity) RA Chronic renal disease chronic liver disease systemic mastocytosis
Prevention/tx options for osteoporosis
Ca and Vit D
Weight bearing exercise
Meds: Bisphosphenates, SERM, PTH analogue, Calcitonin, Denosumab
calcium recommended intake
1000-1200mg WD for pre-meno and post-meno on anti-resorptive therapy
1500 mg QD for post-meno not on anti-resorptive
Vit D recommended intake
800 IU at least
Bisphosphonate
analogue of naturally occurring pyrophosphate
accelerates osteoclast turnover
inc BMD and reduces vertebral and non-vert fracture rates
inexpensive, lont-term needs a holiday, usually 12-18 month holiday, no guidelines, base on BMD
alendronate (fosamax)
10 mg QD, 70 mg po Q week
44% dec in vert frax
56% dec in hip fx over 4 years
risedronate (Actonel)
5 mg po q day 41% dec vert fx in 3 years, 39% dec nonvert fx 35 mg po q week, 75 mg po 2x/mo as effective as daily dosing well tolerated
ibandronate (boniva)
oral 2.5 mg/day or 20 mg QOD
50% dec in vert gx, no dec in nonvert fx
150 mg PO once monthly
IV 3 mg q 3 mo
zoledronic acid
5 mg IV once yearly
70% dec in ver fx, 41% dec hip fx
IV bisphosphonate SE
flu like syndrome after infusion hypocalcemia after infusion inc r/f afib no inc r/f jaw necrosis safety over 3 years not established
GI SE of oral bisphosphinates
poorly absorbed, must take on empty stomach 30 before eating, 60 min for ibandronate
ESOPHAGITIS - remain upright for one H afteringestion
CI in those with achalasia and esophageal stricture
GERD is a relative CI
duration of tx
consider trial of stopping after 5 years, unless very high risk
osteonecrosis of the jaw
most with IV bisphosphenate, associated with dental procedures
stop oral therapy 3 months before procedures, on patients taking oral therapy > 3 years, then restarting after healing is complete
dental exam before starting IV therapy
A fib and bisphos
higher a fib, pathogenesis not clear
bisphosphonate in renal disease
not recommended with cr cl < 35, lots of secondary osteo, more appropriately managed by endo
these drugs stay in your body for a long time at baseline, greater r/f dynamic bone disease
SERM
raloxifene: for prevention and tx of osteoporosis
binds estrogen receptors - antagonist/agonist
2.4 % inc of lumbar spine and hip
30-50 % reduction in vertebral fxs
NO reduction in NON-VERTEBRAL fx
SERM SE
inc thrombosis risk, vasomotor sx
dec r/f invasive breast CA
2nd line agent behind bisphos, less potent anti resorptive agent, doesn’t help with hip fx
calcitonin
potent antiresorptive agent rapid action on osteoclast intranasal dose, dec vert fx risk by 33% not as effective as bisphos or PTH unclear long-term efficacy analgesic effect for acute or chronic pain from fx
parathyroid hormone (Teriparatide)
recombinant PTH intermittent dosing stimulates osteoblasts inc GI Ca absorption inc renal tubular resorption of Ca leading to bone formation no more than 1-2 yr tx dec vert and non-vert fx dec fx risk after tx discontinued very expensive, last resort 20 mcg/day SQ
PTH SE
N/V, dizziness, hypercalcemia (CI kidney stones), leg cramps
PTH monitoring
BMD one year after starting
Ca levels 1,6 and 12 mos
renal function
uric acid
PTH and bisphos?
not recommended
coexistent therapy blunts response of PTH
3 month washout period of bisphos
sequential therapy may be beneficial
candidates for PTH therapy
T score <-2.5 with fragility fx
those who fail other tx options or are not able to tolerate other tx modalities
Denosumab
human IgG antibody to RANKL
controls osteoclast differentiation, activation and survival
monitoring osteoporosis therapy
recheck BMD in 1 year, then q2 years
can also check levels of bone turnover after 6 mos
urinary NTX excretion - dec > 50%
serum carboxy-terminal collagen crosslings
if BMD stable or imp - successful
if BMD decreases - confirm compliance, look for further causes, can recheck in one year or change therapy
monitoring therapy, pt on corticosteroid
baseline BMD
monitor q6mo, then q 6-12 months if not on therapy
annual follow-up measurements once on therapy
oosteoporosis in Men
incidence of fx inc with age, though 10 yrs later than women
mortality from hip and vert fx higher in men
2nd causeID in 40-60% of fx
osteo screening in men
screen >70, radiographis osteopenia, loss of height, fragility fx, long term steroids, intestinal disorders
therapies for osteoporosis approved for men
bisphos and PTH analogue
