endo: osteo Flashcards
fragility fractures
spine, hip, wrist, humerus, rib, pelvis
- occurs spontaneously or from minor trauma (fall from a standing height or less)
BMD =< 2.5 SD
osteoporosis, provided that other causes of low BMD have been ruled out (such as osteomalacia)
BMD: -1 to -2.5 SD
low bone mass (osteopenia)
BMD >= -1 SD
normal bone density
Z-score =< -2
expected range for age
Z-score > 2 SD
prompt careful scrutiny for coexisting problems eg. glucocorticoid therapy or alcoholism
site of BMD measurement with DXA
spine and hip
does measurement of spine/hip BMD detect responses to therapy earlier?
spine
decr bone mass can occur because
- peak bone mass is low
- bone resorption is excessive
- bone formation during remodelling is decr
most post-menopausal women with osteoporosis have
age- or estrogen deficiency-related bone loss due primarily to excessive bone resportion
adequate calcium intake
1200mg daily
adequate vitD intake
800IU
higher/lower dose of vitD required if patient is taking concomitant antiseizure medications
higher
1250mg of calcium carbonate
500mg of elemental Ca (40%)
calcium citrate
21% of elemental Ca
alendronate vs risedronate
limited studies comparing the two agents, but risedronate has fewer GI side effects
alendronate dosing
10mg once daily or 70mg once weekly
risedronate immediate release dosing
5mg once daily or 35mg once weekly or 150mg once monthly
risedronate, delayed release (enteric coated)
35mg once weekly
zoledronic acid dosign
5mg every 12 months, IV
ibandronate dosing
(oral) 150mg once monthly
(iv) 3mg every 3 months
- no evidence for hip fracture reduction
- no direct evidence for nonvertebral fracture reduction
discontinuation of therapy after
all except zoledronic acid: 5 yrs
z: 3 yrs
before initiation of oral biphosphonates, assess for:
- normal Ca
- vit D>= 20ng/mL
- eGFR >= 30ml/min
- comorbidities that may preclude use or alter adm of meds: abnormalities of esophagus (stricture, etc.) or inability to remain upright for at least 30-60mins
- plans for invasive dental procedures: discuss risk factors for developing osteonecrosis of the jaw
take biphosphonates before or after food?
before, poorly absorbed orally (<1% of the dose) hence taken before food for maximal absorption
biphosphonates should be taken
- alone, on an empty stomach
- first thing in the morning
- with 240ml of water
- aft adm, do not take any food, drinks, supplements, meds for at least half an hr
- remain upright (sitting or standing) for at least 30 minutes after adm to minimise the risk of reflux
why must we take biphosphonates with water?
minimise risk of tablet getting stuck in the esophagus
why must we take biphosphonates while fasting and waiting half an hour until eating or drinking?
bioavail may be srsly impaired by:
- ingestion with liquids other than plain water - such as mineral water, coffee, or juice
- retained gastric contents with insufficient fasting time
- gastroparesis
- eating or drinking too soon afterwards
when shud we take enteric-coated, delayed-release risdronate?
immediately after breakfast, with 120ml of water
adr of IV biphosphonates? and how to min?
flu-like sx: w/ longer infusion time eg. 45-60mins
hypoCa: correct vitD deficiency before infusion
clinically significant BMD decr - what should we evaluate for?
- poor adherance to therapy
- inadequate GI absorption
- inadequate intake of Ca and vitD
- development of a disease or disorder with adverse skeletal effects
- adequate Ca and vit D supplementation?
- secondary causes of bone loss
low risk for fracture in near future: definition and duration of therapy
- stable BMD
- no pervious verterbral or hip fractures
3yrs for zolendronic acid
5yrs for alendronate or risedronate
high risk for fracture in near future: definition and duration of therapy
- history of osteoporotic fracture before or during therapy
- Tscore =< -3 in the absence of fractures
A: 10yrs
R: 7yrs
Z: 6yrs
typical length of drug holiday`
3-5 yrs
typically restart biphosphonates within the first 5 yrs of the drug holiday when one of the following occurs:
-Reproducible bone loss (approximately 5 percent) on at least two dual-energy x-ray absorptiometry (DXA) measurements taken at least two years apart, using the same make and model DXA scanner.
-Evidence of bone loss on one DXA measurement at the spine and the hip.
-Evidence of bone loss on one DXA measurement at either site and accompanied by a fasting C-terminal telopeptide of type I collagen (CTX) >600 pg/mL (ie, above the upper limit of the premenopausal reference range).
biphosphonates moa
inhibit bone resorption by suppressing osteoclast activity
we typically initiate biphosphonates ___ weeks postfracture
2 weeks
- fracture healing req callus remodeling and the coupled activity of osteoclasts and osteoblasts: biphosphonates may imapir fracture healing
denosumab moa
fully human monoclonal antibody
- specifically binds RANKL, blocks binding of RANKL to RANK
- thereby reducing the formation, function, and survival of osteoclasts
- decr boen resorption and incr bone density
when is denosumab used as initial therapy
- certain patients at high risk of fracture eg, older patients who have difficulty with the dosing req of oral biphosphonates
- intolerant or unresponsive to other therapies, incl iv biphosphonates
- markedly impaired kidney function
duration of denosumab therapy
indefinite
- incr risk of veterbral fracture with discontinuation
- transitioning to other drug is complicated
denosumab dosing
60mg every 6 months, SC
- upper arm, thigh or abdomen
- 27gauge needle w syringe to withdraw and inject 1ml dose
- stored in refrigerator and brought to room temp by removing from refrigerator 15-30mins before adm
renal dose adj for denosumab
not req! not renally excreted
effects of desonumab on bone density and bone remodelling are
reversible with discontinuation of therapy
- results in bone loss within a relatively short time
discontinuation or delayed denosumab treatment beyond 2-3 months
administer a biphosphonate to prevent rapid bone loss and an incr in veterbral fracture as early as 7 months after the prior dose
- incr risk as delays in adm grow longer
how long after last dose of denosumab, should alendronate or zoledronic acid be administered?
6 months
should anabolic therapy be sequentiated after denosumab?
no, usually precedes
adr of denosumab
flatulence, hypercholesterolemia, back/extremity/musculoskeletal pain, severe bone or joint pain, infections (cystitis, cellulitis), skin reactions
denosumab: rates of oversuppression complications
did not seem to rise after 10 years of treatmetn
denosumab on fracture healing
few data
other indications for denosumab
- prevent osteoporosis and veterbral fracture in men with nonmetastatic prostate cancer receiving androgen deprivation therapy
- incr bone density in postmenopausal osteopenic women receiving adjuvant aromatase inhibitor therapy
- bone metastases
- treatment of hyperCa
when are anabolic agents used as initial therapy?
postmenopausal women with severe osteoporosis (T=<-3.0 even in the absence of fractures, or T=<-2.5 plus a fragility fracture)
- or in patients who were treated initially with biphosphonates but unable to tolerate them
rank anabolic agents according to preference of sue
based on efficacy and LT safety data:
teriparatide>abaloparatide>romosozumab (but has better BMD response)
dosing regimen of anabolic agents
teriparatide, abaloparatide: SC daily
romosuzumab: SC, monthly by HCP
following anabolic agent therapy
T,A: limited to 18-24months
R: limited to 12 monthly doses
-> to preserve BMD gains: use anti-resorptive agents
when decline in BMD >= 5%
switch from oral biphosphonate to an IV biphosphonate
- if lack of response is related to poor absorption
for postmenopausal women with severe osteoporosis who continue to frature after 1 yr of biphosponate therapy
discontinue the biphosphonate and switch to teriparatide
- effective in incr BMD in women previously treated with biphosphonates
bone turnover markers
NTX: N-teolpeptide
CTX: serum carboxy-terminal collagen crosslinks
monitoring of bone turnover markers
in pt who have conditions that might interfere with drug absorption or efficacy - small bowel resections, other types of malabsorption, or pt reluctant to take anti-resportive meds refularly
- measure fasting NTX and CTX: before and 3-6months after initiation
decr of >50% NTX or 30% CTX
compliance and drug efficac
approach with bone resorption markers only useful with
anti-resorptive therapy, not with recombinant PTD or romosozumab
BMD that is stable or improving is evidence for
treatment response
raloxifene moa
selective estrogen receptor modulator - inhibit bone resoprtion
when is raloxifene considered for osteoporosis?
when there is an independent need for breast cancer prophylaxis - has beneficial breast cancer risk reduction
moa of anabolic agents
stimulate bone formation and activate bone remodelling
why is estrogen-progestin therapy no longer a first-line approach for treatment of osteoporosis in postmenopausal women
incr risk of breast cancer, stroke, vte, cad
- possible indiations include women with persistent menopausal sx and cannot tolerate other drugs
romosozumab moa
monoclonal anti-sclerostin antibody
- sclerostin produced by osteocytes and inhibit bone formation
is combi therapy reco?
no
calcitriol
effective in perventing glucocorticoid-induced and post-transplant-related bone loss
- must be given w low calcium diet
- monitor for hyperCa, hypercalciuria, renal insufficiency
folic acid or vit b12
not reco
