Osteoporosis Flashcards
What is osteoporosis?
A chronic skeletal disorder of compromised bone strength associated with low bone density (quantity) and deterioration of bone microarchitecture (quality) which often results in fragility fractures
What does bone strength depend on?
Bone mass and bone microacrchitecture
What do osteoclasts and osteoblasts do?
Osteoclasts excavate areas of damaged or weakened bone.
Osteoblasts then fill in the areas to form bone
What causes bone reabsorption to become greater than formation?
Menopause (accelerates bone loss), aging (begins after mid 30s), disease and drugs
Why is osteoporosis known as the silent thief?
Because it slowly steals bone density over many years without signs or symptoms until a bone breaks or fractures
Extreme curvature can form over time (kyphosis)
What is a compression fracture?
A loss of >25% of vertebral height with end plate disruption
Can cause 6-9 inches loss in height.
How do fragility fractures occur?
Spontaneously or from minor traumas like falling from sitting or standing height, at walking speed or climbing 3 stairs or coughing, hugging, sneezing.
What are some common sites for a fragility fracture?
Hip, spine and wrist
Not feet, ankle, hands, craniofacial
How is bone mineral density (BMD) assessed?
Using a Dual X-ray Absorptiometry (DXA) at the hip and spine
OP classification is a T-score less than -2.5
What else is used to determine risk of fragility fractures?
BMD, age, height, weight, risk factors
Who is eligible for BMD testing?
Fragility fracture, prolonged glucocorticoid use, >65 years use of high risk medications
Those >50 with RA, current smoking, high alcohol intake or low body weight
Those
What are some disorders strongly associated with osteoporosis?
Primary hyperparathyroidism, diabetes, hypogadism, chronic liver disease, Cushing disease, COPD, chronic inflammatory conditions
What will automatically increase a patient to the next fracture risk assessment category?
Fragility fracture after age 40, prolonged corticosteroid therapy (7.5 mg prednisone daily in previous year is equivalent to 3 months of it)
What confers high risk in the 10-year fracture risk assessment tool?
Hip/vertebral fracture, >1 non-vertebral non-hip fragility fracture
Who is a candidate for osteoporosis therapy?
Based on 10-year fracture risk calculation and fracture history
High risk should receive treatment, moderate may, low does not need
What are some high risk fracture history scenarios?
Fragility fracture of the hip or spine, 2 or more non-hip, non-spine fragility fractures or 1 non-spine, non-hip fragility fracture after age 40 and prolonged glucocorticoid use in the previous year
How should all patients maintain basic bone health?
Strength training twice a week, balance training or tai chi daily, 30 minutes aerobic physical activity daily, home safety and med assessment, calcium, vitamin D, smoking cessation, limit alcohol (2 per day), good nutrition (adequate protein, low sodium)
All very important adjunct to OP meds
Which medications put patients at risk for falls?
Medications taken for sleep, mood, anxiety, depression, hypertension, allergies, pain and muscle spasms. They may impair balance, coordination, vision, dizziness, drowsiness, confusion
How much calcium is needed daily?
1200 mg for those 50 years and older
1000 mg for those 19-50
Cannot get all from supplements (usually get ~300 mg from diet)
How much vitamin D is needed daily?
400-1000 IU daily for adults 50
What are some supplements of calcium available?
Calcium carbonate-Tums (must be taken with meals, GI complaints) Calcium citrate (can be taken with or without food, good for patients who can't tolerate CaCO3 or are on PPI or H2 blocker)
What are some side effects of over supplementation of calcium?
Kidney stones, increased risk of MI (without vitamin D)
What does vitamin D do?
Helps the body absorb and use calcium/phosphorous to build/maintain strong bones and teeth
Low levels results in increased bone reabsorption
Excess levels results in hypercalcemia and calcification of organs
What are the different types of vitamin D?
Vitamin D3 is synthesized in skin on exposure UV and fortified food and milk
Vitamin D2 is found in wild mushrooms, fungi, yeasts
Both must be converted to active form in liver
What are the optimal vitamin D serum levels?
> 75 nmol/L
2000 IU daily should be followed by serum monitoring
Check levels only after 3-4 months of supplementation/dose changes
What are some examples of anti-resorptive agents (inhibits bone loss)?
Biphosphates (alendronate, risendronate, zoledronic acid-IV) Monoclonal antibody (denosumab), SERM (raloxifene) and estrogen
What is an example of an anabolic agent?
PTH analogue (teriparatide)
How does denosumab work?
It is a RANK ligand inhibitor to stop it from binding to the RANK receptors on osteoclasts in circulation so they can’t work
Which drugs reduce the RANK ligand?
Estrogen and raloxifene
How does terparatide (rPTH) work?
A recombinant formulation of endogenous parathyroid hormone that stimulates osteoblast activity to form bone, increase GI and renal Ca reabsorption
Anabolic action
How do 1st generation biphosphates work?
Bind directly to bone hydroxyapatite crystals, are taken up by osteoclasts during remodeling and are incorporated into their ATP, accumulate and induce osteoclast cell death
Etidronate
Where does raloxifene work?
Spine
Agonist on bone, antagonist on breast and endometrium (no hyperplasia)
Where does teriparatide work?
Spine and non-vertebral bones
What is the first line therapy for patients with menopausal symptoms?
Estrogen
What are the first line treatments in men?
Alendronate, risedronate and zoledronic acid
How do 2nd and 3rd generation (nitrogen-containing biphosphonates) work?
Bind directly to hydroxyapatite crystals, taken up by osteoclasts during remodeling and act by inhibiting enzymes in the mevalonate pathway (needed for proteins required for osteoclast function), leading to death.
1st line therapy in males and females
More effective than 1st gen
How must biphosphonates be taken?
Take first thing in the morning with a full glass of water only on an empty stomach (food decrease absorption) and remain upright and avoid ingesting anything other than water for at least 30 minutes
Dairy, antacids, calcium and other divalent cations should be taken 2-3 hours after
What is the half-life elimination of biphosphonates?
Varies from months to years and is slowly released with the process of bone turnover
What are the adverse effects of biphosphonates?
GI related problems (acid reflux, nausea, ulcers), bone, joint and/or muscle pain, ocular disorders, acute phase reaction (IV-flu-like symptoms)
Rare: Osteonecrosis of jaw, atypical femur fractures
When should drug holidays be considered in patients taking biphosphonates?
Should be considered after 5 years in moderate risk patients
High risk patients are not candidates for drug holidays
What are the adverse effect of denosumab?
Increased risk of infection (activated T and B cells also express RANKL), dermatitis, eczema, rashes, musculoskeletal pain, hypersensitivity, rare incidence of ONJ
When is teriparatide indicated?
For severe osteoporosis (BMD
What are some adverse effects of teriparatide?
Transient hypocalcemia 4-6 hours post dose, orthostatic hypotension, dizziness, headache, nausea, arthralgia
Very costly
What must estrogen be prescribed with? When?
Progestin when the uterus is intact
What are the adverse effects of estrogen?
Increased risk of breast cancer, stroke, DVT with long term therapy
What are the adverse effects of raloxifene (SERM)?
Breast cancer risk reduction, increased risk of DVT or PE
Hot flashes, leg cramps/muscle spasms
Which medications negatively affect bone metabolism?
Glucocorticoids (increase osteoclast proliferation, decrease calcium absorption), aromatase inhibitors (blocks estrogen synthesis) and androgen deprivation therapy (males-increases bone turnover)
