Osteoporosis / Calcium Disorders (lectures 1-3) Flashcards
Name the 3 locations you should target in the DXA scan for osteoporosis
Spine, Hip, and femoral head.
T/F - you need a Bone density >2.5 standard deviations below normal in 2 locations to diagnose osteoporosis.
False. It just needs to be in one location.
What are the T scores and Z scores, that are calculated by a DXA scan? Who are they used for, respectively?
T score = compares bone mineral density (BMD) to a normal 30 year old level of the same sex/race.
-Used for older folks (postmenopausal women, as well as men over 50 years old)
Z score = compares BMD to that of an age matched control (Z = exZact same age)
- used for children, premenopausal women, and men under 50
What is a DXA scan?
Dual X ray absorptiometry.
It is similar to xray, checks for bone density.
what does BMD stand for
bone mineral density
What T (or Z) score qualifies for osteopenia? For osteoporosis?
below -1 = osteopenia
below -2.5 = osteoporosis
T or F: Elderly woman trips on her steps, falls down, and breaks her hip. You get labs, which say -2.0 T score for all locations. What is the diagnosis?
Osteoporosis! Although labs are in the range of osteopenia, she has a low trauma fracture, which equals a diagnosis of osteoporosis, no matter the lab values.
Who should be tested for osteoporosis? (give for healthy and those with risk factors)
all women over 65 all men over 70 --- WITH RISK FACTORS -postmenopausal women under 65 -men between 50 and 70
What are the major risk factors for osteoporosis? -6
- prior fragility fracture
- parental history of hip fracture
- glucocorticoid therapy
- excess alcohol intake (>3/day)
- smoking
- rheumatoid arthritis
What are the secondary causes of osteoporosis that you should test for, or gather a history about? hint: there are a shit-ton (13).
- glucocorticoids
- smoking
- alcohol
- hyperparathyroidism (high PTH)
- hypogonadism
- chronic inflammatory diseases (esp. RA)
- hyperthyroidism
- malnutrition
- multiple myeloma
- chronic renal disease
- nutritional deficiencies (calcium/ vitamin D)
- malabsorptive conditions (Celiac or IBD)
- increased kidney excretion of calcium (renal wasting of calcium)
What percentage of patients with hip fractures recover to walk without assistance?
Only 50%!! 25% of hip fracture patients will need a nursing home for the rest of their life.
How do you diagnose osteoporosis?
- DXA scan T/Z score below -2.5
- low trauma fracture.
What are the non-pharmacologic therapies for osteoporosis?
Calcium and Vitamin D.
How does calcium help osteoporosis?
It increases bone density by 1.5%
Vitamin D helps osteoporosis by?
- decreases the risk of falls by 20% (Vitamin D receptors in muscle - better mm contraction/ balance)
- decreases the risk of fractures by 20%
Who should be treated with pharmacologic therapy for osteoporosis?
Anyone with T/Z score below -2.5, or who has a low trauma fracture.
Also, anyone with osteopenia (T score -1 to -2.5) is they have major risk factors for a fracture.
How do you calculate the risk of fracture in someone with osteopenia who you’re not sure if they need meds? What probabilities for general fractures/ hip fractures should be treated?
FRAX calculator.
10 year probabilities
>20% risk of major osteoporotic fracture
>3 % risk of hip fracture
treat for anything above these probabilities!
Who should be given Ca and Vitamin D? (just osteopenics, just osteoporosis, or both.)
Both! these therapies are combined with pharmacologic therapies, but they can be given on their own in someone with osteopenia.
What is the goal level of Vitamin D in someone with osteoporosis? What about a normal person
25OH vitamin D should be above 30 in osteoporotics,
> 20 is fine for a normal person.
What 2 general classes of drugs are there for osteoporosis medications?
- antiresorptives (inhibit osteoclasts)
- anabolics (enhance osteoblast activity)
What are the 4 classes of antiresorptive medications for osteoporosis?
SERM - -selective estrogen
receptor modulators
Bisphosphonates
RANKL receptor / biologic (Denosumab)
Hormones - Calcitonin/Estrogen, these are not recommended though.
Name the 3 main effects of PTH (parathyroid hormone)
- increases calcium reabsorption in the kidney
- increases P04- excretion in the kidney
- increases hydroxylation (activation) of 25 OH vitamin D in the kidney.
What is the SERM - -selective estrogen
receptor modulator - for osteoporosis?
Raloxifene
It is an agonist in bone, but an antagonist in breast tissue (protects against breast cancer. ) Neutral everywhere else.
Side effects of Raloxifene
DVT, hot flashes.
What are the most effective osteoporosis medications?
Bisphosphonates and Denosumab
How do bisphosphonates act?
they decrease differentiation of osteoclasts and they increase apoptosis of osteoclasts.
What are the oral bisphosphonates for bisphosphonates? What are the side effects?
Alendronate, Risedronate, ibandronate
oral BPs can cause esophagitis (avoid in upper GI disease/ Barrets)
What are the IV bisphosphonates for osteoporosis?
Ibandronate, zoledronic acid
IV bisphosphonates can cause flu-like symptoms.
Which drugs are “drug holidays” needed for? Why?
bisphosphonates.
TLDR - atypical subtrochanteric fractures
You need your osteoclasts to repair everyday wear-and-tear on your bones! After 4-5 years on BP therapy, you lose the ability to repair these small damages, results in the accumulation of microcracks and increased risk of atypical subtrochanteric fractures..
T/F- most patients will have hip pain before they get an atypical subtrochanteric fracture from bisphosphonate therapy.
True - 70% of them! Send them for an x ray if they report hip pain.
T/F - Osteonecrosis of the jaw often occurs without any provocation and it is a difficult-to-prevent side effect of bisphosphonate and denosumab therapy.
FALSE.
- almost always caused by invasive dental procedures which create a cut in bone.
- optimizing dental health before treatment, and aggressive antiseptic mouth wash use before/after dental procedures has greatly reduced rates, almost to baseline levels.
What is the mechanism of denosumab?
it is a floating RANKL receptor - binds RANKL, which decreases osteoclast formation, activity, and survival.
How is denosumab administered?
One sub q injection every 4 weeks
Contraindications for bisphosphonates - 1
kidney disease (creatinine
contraindications for denosumab
high risk of neoplasia
immunocompromised
This is because RANKL plays a role in the immune system.
How does teriparatide work?
It treats osteoporosis by mimicking PTH, leading to increased osteoblast maturation, and increasing osteoblast function.
Remember - paratide = synthetic parathyroid hormone
How is teriparatide administered?
daily sub-q injection
When is teriparatide given?
it is generally given only in the most severe cases, or in the case of antiresorptive failure/ contraindication. This is due to the 2 year treatment limit/ risk of osteosarcoma.
Contraindications for teriparatide
- those at higher risk of osteosarcoma (Paget disease, kids, )
- cancer within 5 years
- elevated PTH
How should teriparatide be given, long term?
2 year treatment limit!
Follow-up treatment with an anti-resorptive this prevents loss of the gained bone density and actually adds even more bone density. .
68 year old woman comes in. She is given a DXA scan, diagnosed with osteoporosis. Looking for secondary causes. You come across a high calcium level. What is the most likely condition that could cause both the high calcium and the osteoporosis?
Primary hyperparathyroidism.
what are the two categories of hypercalcemia?
PTH - dependent and PTH - independent
Healthy woman, lab shows high calcium. What lab should you order next?
PTH. Always PTH, to categorize PTH independent vs dependent.
What are the main conditions that cause PTH dependent hypercalcemia?
There is one - primary hyperparathyroidism.
But FHH (familial hypocalciuric hypercalcemia) mimics primary hyperparathyroidism, so watch out.
What is Familial hypocalciuric hypercalcemia (FHH)??
It is a disease caused by an inactivating mutation in the CaSR (calcium sensing receptor gene).
How is FHH differentiated from primary hyperparathyroidism?
FHH has very low urinary calcium, primary hyperparathyroidism does not! This is the main difference.
What are causes of PTH independent hypercalcemia?
- Malignancy (#1 cause in hospitalized patients)
- granulomatous disease
- vitamin A or vitamin D toxicity
- immobilization for long periods of time
- milk alkali syndrome (too much Ca intake)
68 year old woman with calcium of 10.8 (normal 8.5-10.5).
Her PTH is 53 (normal 10-65).
PTH independent or dependent?
Which lab should be ordered next?
PTH dependent - PTH should be low trying to compensate for high calcium!! “Abnormal normal”
24 hr Urine calcium (to rule out FHH)
Explain the mechanism of familial hypocalciuric hypercalcemia.
sensors in the kidney don’t work, so the kidney thinks you’re hypocalcemic and absorbs all your calcium.
Sensors in the parathyroid gland don’t work, so it cannot change the PTH to react to the hypercalcemia. PTH may be normal or slightly high. .
T/F - FHH is a harmful disease with bad prognosis.
False, No bad sequelae are seen, “reset of normal” - no treatment.
