Osteoporosis Flashcards
WHO definition of Osteoporosis:
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Definition:
- low bone density & weakening of bone tissue
- increased fragility & vulnerability of fracture
- low bone density & weakening of bone tissue
- Most common skeletal disorder
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Only 1/3 are diagnosed
- >70% of fractures occur in women
- spine, hip, & wrist
- >70% of fractures occur in women
Primary vs Secondary Osteoporosis
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Primary:
- no known cause
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Secondary:
- caused by drugs or other diseases
What are the impacts of osteoporosis?
- pain both acute & chronic
- loss of mobility
- → esp after a vertebral fracture → restrictive lung disease & altered abdominal anatomy
- depression
- nursing home placement
- height loss/ kyphosis
- death
Risk Factors of Osteoporosis
- low bone mineral density; low Ca2+ intake
- female
- advanced age
- ethnicity – caucasian, asian
- h/o of trauma
- 1st degree family hx
- low body wt
- premature menopause (<45 yo)
- secondary osteoporosis
- i.e. RA
- PO steroid tx
- current smoking or EtOH ≥ 3 drinks/day
- low physical activity
- low sun exposure
Bone Structure
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Cortical:
- dense & compact
- responsible for bone strength
- 80% of skeleton
- on surface of long
- dense & compact
-
Trabecular (aka cancellous bone)
-
sponge-like appearance
- inner surfaces of long bones, vertebrate, pelvis & ribs
-
sponge-like appearance
Bone Resorption occurs for two reasons:
- liberate calcium and other ions
- clear out worn skeleton and promote the deposition of newer, better material
Z-scores vs T-scores in Bone Mineral Density results
When to screen for osteoporosis?
- all post-menopausal women ≥ 50 yo
- Men > 70 yo
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FRAX: fracture risk assessment tool
- evaluate 10-yr chance of developing hip & major osteoporotic fracture
What is the suggested role of FRAX in the assessment of risk of fracture?
What labs do you order to r/o secondary causes of osteoporosis?
- 25-OH vitamin D level
- to assess for hyperparathyroidism
- TSH level
- to assess for hyperthyroidism
- Testosterone level
- to assess for hypogonadism
- SCr
- Ca2+
- Phosphorous
- CBC
What are the goals of tx for osteoporosis?
- prevent fractures & other complications
- maintaining or increasing BMD
- Prevent secondary bone loss
- reduce morbidity & mortality associated with osteoporosis
What are the bone turnover biomarkers and what do they demonstrate?
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S-CTX (C-terminal telopeptide) - aka beta-CTX
- levels are high during high bone resorption/turnover
- specific marker for degradation of mature type I collagen (90% of which is located in the bone)
-
Draw a fasting level before 10am
- a decrease ≥ 25% from baseline 3-6 months after therapy = adequate therapeutic response
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PINP (Procollagen I Intact N-Terminal) serum
- carboxy-terminal of propeptide type I collagen
- Most sensitive marker of bone FORMATION
- The Trimeric form is the predominant type in normal renal funx
- useful for monitoring BONE FORMATION & antiresorptive therapies
- Baseline level before starting therapy then repeat 3-6months later
Postmenopausal osteoporosis tx algorithm
What calcium intake level in mg/d increases risk of kidney stones or CVD?
> 1200 mg/day
Calcium Supplements & % of Elemental Calcium
Bisphosphonates
MOA: taken up by osteoclasts during bone resorption → inhibit the funx of the osteoclasts by disrupting the ATP metabolic pathway
“Bisphosphonates Always IRritate & cause generaliZed pain” Z = zoledronic acid, irritate = heartburn & stomach irritation (need to take it correctly), pain = premedicate zoledronic acid with acetaminophen
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Drugs:
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Alendronate (Fosamax)
- prevention and tx
- do not lie down for 30 min after admin, do not take with other meds or fluids and take after an overnight fast with plain water
- prevention and tx
-
Ibandronate (Boniva)
- only approved for Postmenopausal osteoporosis
- admin is same as alendronate but 1 hour before morning meal and do not lie down for 1 hour after taking
- only approved for Postmenopausal osteoporosis
-
Risedronate (Actonel)
- tx osteoporosis
-
Zoledronic Acid (Reclast)
- prevent PM osteoporosis & tx osteoporosis in men & women
*
- prevent PM osteoporosis & tx osteoporosis in men & women
-
Alendronate (Fosamax)
Denosumab (Prolia)
Monoclonal antibody used to tx postmenopausal osteoporosis
- injection: SQ q 6 months
- need to keep refrigerated
-
SEs
- hypocalcemia
- infx
- severe bone pain
- esp extremities/back
- sciatica
- myalgias
- angina
- osteonecrosis
- (esp of the jaw)
- pancreatitis
What are the function of the parathyroid glands?
- they monitor & regulate serum calcium levels
- When calcium levels are low → increase release of PTH
- promote bone resorption (i.e. remove calcium from bone) → increase calcium levels in the blood
- PTH stimulates osteoblasts to express RANKL
- RANKL bind to RANK on the osteoclasts → increases the osteoclastic activity
- promote bone resorption (i.e. remove calcium from bone) → increase calcium levels in the blood
- when calcium levels are too high → lower PTH
- T½ of PTH = 3-5min (short!)
Parathyroid Hormone Analogs
- “PTH Analogs Always Terminate in ”-paratide””
- Always = abaloparatide
- Terminate = teriparatide
- Do NOT use more than 2 years!
-
SEs:
- Osteosarcoma
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Teriparatide (Forteo)
- Recombinant N-terminal human PTH → increases cAMP release → increased bone formation
- SEs:
- hypersensitivity, calciphylaxis, hypotension, depression
- hypercalcemia, constipation, insomnia, hyperuricemia, leg cramps, syncope, dzz (dizziness)
- Abaloparatide (Tymlos)
- SEs:
- anaphylaxis, hypotension, hypercalcemia, hypercalciuria, tachycardia, HA, palpitations, dzz (dizziness?)
- SEs:
Function of Calcitonin
CalcitonIN → calcium INto the bone
- Hormone from C-cells of thyroid gland
- released in response to increased calcium levels
- → this is protective against hypercalcemia
- stimulate production of active form of vitamin D
- decrease osteoclast activity
Calcitonin-salmon (Miacalcin)
- nasal spray or injx
- used for osteoporosis
-
SEs:
- hypersensitivity, anaphylaxis, bronchospasm, severe hypocalcemia
- HA, sinusitis, epistaxis, rhinitis arthralgia, back pain
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DDI:
- drugs that induce hypocalcemia
- loop diuretics, bisphosphonates, tobramycin → causes increased hypocalcemia
- drugs that induce hypocalcemia
What converts T4 to T3?
Deiodinases in the peripheral tissues → this ensures that end organs are able to produce enough T3 locally for metabolic funx
this also catabolizes T3 & T4 to inactive metabolites
Half-life of T4 vs T3
- T4: 7-10 days
- 99.97% = protein bound
- T3: 24 hours
- 99.7% = protein bound
Diagnostic Tests for Thyroid disorders
- Labs:
- TSH, Free T4, Free T3
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RAIU:
-
radioactive iodine uptake
- hyperthyroidism = elevated levels of RAIU
-
radioactive iodine uptake
-
Autoimmune antibodies:
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Hypothyroidism:
- antithyroid peroxidase antibodies (anti-TPOAb)
- antithyroglobulin antibodies (anti-TGAb)
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Grave’s Disease
- TSH receptor-stimulating antibodies (TSHR-SAb)
- Antithyroid peroxidase antibodies (anti-TPOAb)
-
Hypothyroidism:
