Osteoporosis Flashcards
What is osteoporosis
low bone density (weak bones) leading to increased fracture risk
Why do men and women start losing bone density in 3-4 decade
Women: Menopause= estrogen deficiency= increased osteoclast activity= bone resorption>formation
Men: aging and secondary causes; occurs later 2/2 larger bone size and mass
What can all individuals do to reduce risk of osteoporosis
Incorporate healthy bone lifestyle from birth
Regular exercise, nutritious diet, avoid tobacco, minimize alcohol consumption
Fall prevention
RF of osteoporosis are
age, Hx of fracture, glucocorticoids, parent Hx of hip Fx, low body weight, cigarette smoking, excess alcohol, RA
Secondary osteoporosis RF are
hypogonadism premature menopause malabsorption chronic liver disease IBD
Age related osteoporosis results from
hormone, calcium, and vitamin D deficiency
leads to accelerated bone turnover and reduced osteoblast formation
Drug induced osteoporosis results from
systemis corticosteroids, thyroid hormone replacement, AED (phenytoin, phenobarbitol), depot medroxyprogesterone acetate
What is the FRAX tool
WHO created tool to assess probability of Fx in the next 10 years
-age, race, sex, Hx of fragile fx, BMI, glucocorticoids, current smoking, alcohol (3+/day), RA, femoral neck or total hip bone mineral density
What is the Garvan calculator
Uses 4 RF (age sex low trauma Fx and falls) +/- BMD to calculate 5 and 10 year risk estimates
Better than FRAX bc it includes falls and # of previous Fx instead of a bunch of other random RF
What is the standard diagnostic test fro BMD
DXA (dual energy x-ray absorptiometry)
Diagnosis of osteoporosis is based on
low trauma Fx OR
central hip/spine DXA using WHO T-score threshold
*For kids, pre-menopause women, and men <50, Dx based on Z score
What are T scores indicative of
Osteopenia (low bone mass): -1 to -2.5
Osteoporosis: Less than -2.5
(T scores applied to perimenopausal women, men 50+, and other races)
Absorptive therapies (keep it in the bone) include
*Calcium
*Vitamin D
**Bisphosphanates
calcitonin
Estrogen agonists
Estrogen
Testosterone
Teriparatide
Denosumab
What age group needs the most calcium and vitamin D
9-18 years old
What are the tow forms of calcium
- Calcium carbonate (can cause bloating, gas, constipation, hypercalcemia, hypophosphatemia; rarely, stones)
- Calcium citrate (hypercalcemia, hypophosphatemia)
What are the forms of vitamin D
D3: Cholecalciferol (not active, natural form)
D2: Ergocalciferol (plant derived)
D: Calcitriol, AKA 1,25 OH vitamin D (active)
When would you need to increase the dose of D3 (cholecalciferol)
In malabsorption
If taking anticonvulsants (carbamazepine, phenobarb, phenytoin)
What are the ADE of D3 (cholecalciferol)
Hypercalcemia (HA, weakness, cardiac disturbance)
Hypercalcuria
When would you Rx Ergocalciferol (D2)
if Vitamin D deficient
How is Calcitriol formed
D3 is hydroxylated in the liver and other tissues to make calcifediol (25 OH-D)
That is then metabolized in the kidneys to make calcitriol
Indications for using exogenous Calcitrol
renal osteodystrophy
hypoparathyroid
refractory rickets
What are the bisphosphanates (first line for osteoporosis)
Alendronate
Risedronate
IV Zoledronic acid (Reclast) (IV infusion q2 years)
(first line for post-menopause women, man and glucocorticoid induced osteoporosis)
-IV and oral Ibandronate only for post-menopausal women
What is the MOA of bisphosphonates
Mimic pyrophosphate (endogenous bone resorption inhibitor)= decrease osteoclast maturation, #, recruitment, and life span Half life is up to 10 years (becomes incorporated into bone)
Important notes for each bisphosphonate
Alendronate: Take in AM on empty stomach w/ 6=8 oz water. Dont eat and Stay upright for 30 min. Dont take w/ any other supplements
Ibandronate: same as Alendronate, but stay upright for 60 min
Risendronate: Same as Alendronate, but ER tab (Atelvia) is taken right AFTER breakfast
Zoledronic acid: DO NOT take if CrCl <35
How do you monitor bisphosphonates
Generally 1-2 years s/p initiation (determine efficacy)
Then q2 years with bone turnover markers
What are ADE of bisphosphonates
oral: Nausea, Dyspepsia
IV: Flu-like illness
rare: perforation, ulceration, GI bleeding, MSK pain, atypical Fx, sub-trochanteric femoral fracture
BBW: ONJ
What are the bone turnover markers of resorption
Type 1 collagen degradation (PYD, DPD, C and N nucleopeptides)
TRACP 5b, Cathepsin K, Matrix metalloproteinases
What are the bone turnover markers of formation
Procollagen type 1 propeptides (PICP, PINP, osteocalcin)
BALP
DO NOT USE bisphosphonates if
CrCl <30-35
Serious GI conditions (barrett’s esophagus, achalasia, esophageal varicies)
Pregnant
What is ONJ
osteonecrosis of jaw; more common in those w/ cancer, chemo, radiation, and glucocorticoid therapy on higher dose IV bisphosphonate
What is a “drug holiday”
Patients taken of bisphosphanates and followed w/ bone turnover markers and central DXA BMD
AKA, 5 years after being taken off Alendronate therapy, post-menopause women showed prolonged suppression of bone turnover and maintenance of BMD
Who meets criteria for a drug holiday
Women w/o evidence of low rtauma Fx who repsonded well to bisphosphanates who’s T score is in “osteopenic” range (> -2)
*Best results if women are low risk (T score > -2.5). NOT for high risk women w/ T score < -3.5
What is calcitonin
third line med; for women 5 years post-menopause
Tx for pain relief w/ acute vertebral Fx
refrigerate and prime nasal spray
What is endogenous calcitonin
hormone released from thyroid when calcium is high
promotes deposition of calcium into bone (inhibits osteoclasts, stimulates osteoblasts)
What are the second gen estrogen agonist/antagonist
Raloxifen, Bazedoxifene (selective estrogen receptor modulators)
decrease bone resorption= increased BMD and decreased fractures
*Bazedoxifen is for post-menopausal women w/ a uterus, no progesterone needed!!
What hormone therapy can you give for osteoporosis
Estrogen therapy (short term for women who need to manage menopause Sx) Testosterone (or methyltestosterone for women) increase BMD
What is Teriparatide (anabolic Tx)
Recombinant product that acts like first 34 AA in PTH
Good for post-meno women, men, and pt on glucocorticoids at high risk (T score < -3.5)
What is the MOA of teriparatide
increases bone formation, bone remodeling rate, and osteoblast number and activity
leads to improved bone mass and architecture
How do you take teriparatide
It is a pre-filled pen (subQ injection into thigh or abdomen w/ site rotation- 20mcg daily up to 2 years)
1st dose pt should sit or lie down (orthostatic hypo)
Refrigerate before and after use
Use new needle w/ each dose
Throw away after 28 days
What is Abaloparatide
Synthetic analog of human PTH that stimulates bone formation
FDA approved for high risk postmenopausal osteoporosis
-consider antiresorptive Tx to protect against bone loss after d/c abaloparatide
What is Denosumab
binds to and inhibits RANKL os surface of osteoclast precursor cells and mature osteoclasts
Inhibits osteoclastogenesis
Good for postmenopausal women and chemo induced osteoporosis
Dissipates when d/c
**Give 60 mcg subQ q6 months
ADE of Denosumab are
back, extremity, and MSK pain
increased cholesterol, cystitis, low serum calcium, skin problems
What should be used FIRST vs LAST when treating osteoporosis
First line: Alendronate, Risedronate, Zoledronic acid, and Denosumab (decrease vertebral, hip, and other Fx)- second are Ibandronate, raloxifen, and teriparatide
Last resort: Calcitonin
What is Vertebroplasty and Kyphoplasty
bone cement is injected into fractured vertebral space to alleviate debilitating pain 6-52 weeks s/p vertebral Fx
ADE: cement leakage= nerve damage, Fx around cement
What is osteomalacia
soft bones; undermineralized adult bones
(same as rickets in kids)
Caused by severe, prolonged VD deficiency (MC), d/o causing hypophosphatemia, and long term anticonvulsants
What do osteomalacia patients present with
pathologic Fx and/or deep bone pain, proximal muscle weakness; BMD and no other Sx
Extremely low 25 (OH) vitamin D (calcifediol)
How do you treat osteomalacia
high dose (50,000 units q1 wk for 8 wks) Ergocalciferol (D2) When you reach Calcifediol level >30, change to chronic VD maintenance therapy (D2 50,000 q 1-2x month OR OTC D3 1000-2000 units qd)
