Osteoporosis Flashcards
Define the following:
Bone disorder of…
- low bone density
- impaired bone architecture
- compromised bone strength
- increased fracture risk
Osteoporosis
At what age do men and women begin to lose bone mass due to reduced bone formation?
30s-40s
____________ deficiency during menopause increases _________ activity, increasing bone _________ more than ___________.
Estrogen deficiency during menopause increases osteoclast activity, increasing bone resorption more than formation.
Why are men at a lower risk for developing osteoporosis and osteoporotic fractures?
They have
- larger bone size
- greater peak bone mass
- increase in bone width with aging
- fewer falls
- shorter life expectancy
What does male osteoporosis result from?
aging or secondary causes
- incorporate a bone-healthy lifestyle beginning at birth and continuing throughout life
- emphasize regular exercise, nutritious diet, tobacco avoidance, minimal alcohol use
- fall prevention to prevent and treat osteoporosis
The following are…
prevention techniques that should be used at all ages
What 3 deficiencies lead to accelerated bone turnover and reduced ostoblast formation that causes age related osteoporosis?
- VItamin D
- Calcium
- Hormones
What results from systemic corticosteroids, thyroid hormone replacement, antiepileptic drugs (phytoin, phenobarbital), depot medroxyprogesterone acetate?
Drug incuded osteoporosis
What are the two predictive tools?
FRAX tool & Garvan calculator
World Health Organization (WHO) created tool which uses risk factors to predict the percent probability of fracture in the next 10 years
Which predictive tool?
FRAX tool
Which predictive tool?
- uses four risk factors (age, sex, low-trauma fracture, and falls) with the option to also use BMD.
- Calculates 5- and 10-year risk estimates of any major osteoporotic and hip fracture.
Garvan Calculator
Which predictive tool?
- Tool corrects some disadvantages of FRAX
- includes falls and number of previous fractures
Garvan calculator
What is the diagnostic standard for osteoporosis/ bone mineral density?
dual-energy x-ray absorptiometry (DXA)
Diagnosis of osteoporosis is based on what 3 things?
low trauma fracture
OR
central hip
and/or
spine DXA using WHO-T score thresholds
What is the T-score range for Osteopenia?
-1 and -2.5
What is the T score range for Osteoporosis?
< or equal to -2.5
Dx of osteoporosis in children, premenopausal women and men < 50 y/o should be based on a Z score at or below what?
-2.0
What are the medications of choice for osteoporosis?
biphosphonates with calcium and Vit D
What are the 2 basic forms of Calcium?
calcium carbonate
calcium citrate
Which type of calcium is indicated on the label of calcium supplements?
elemental calcium
What are the adverse effects of carbonate?
gas, upset stomach, bloating, constipation
rare kidney stones
What are the 2 adverse effects for both types of calcium?
hypophosphotemia
hypercalciumia
Metabolism of which drug?
*Hepatic metabolism to 25 (OH) Vit D and then renal metabolism to 1,25 (OH) Vit D
- Which one is the active form?
Vitamin D3 (Cholecalciferol)
- 1, 25 (OH) Vit D
Adverse effects of Vitamin D3 (Cholecalciferol- natural form)
-
Hypercalcemia
- cardiac rhythm disturbance
- HA
- weakness
- Hypercalcuria
Which drug is indicated for VItamin D deficiency?
Vitamin D₂ (ergocalciferol) plant-derived form
What is the plant-derived form of Vitamin D?
Vitamin D2 (ergocalcifereol)
Where is Vitamin D first hydroxylated and what does it form?
Liver, forms 25(OH)D (calcifediol)
When should you use Vitamin D (calcitriol: 1, 25, (OH))?
3 instances
- Renal osteodystrophy
- Hypoparathyroidism
- Refractory rickets
Which biophosphonate is indicated only for postmenopausal osteoporosis?
ibandronate (IV and oral)
“you get stretch marks (bands) after menopause”
MOA of biphosphonates
Mimic pyrophosphate: an endogenous bone resorption inhibitor
Decreased osteoclast maturation, number, recruitment, bone adhesion and life span
What is the half-life of biphosphonates?
10 yrs: becomes incorporated into the bone
Administered in the morning on an empty stomach with 6–8 ounces of plain water. Do not eat and remain upright for at least 30 minutes following administration.
Do not coadminister with any other medication or supplements, including calcium and vitamin D.
Which drug?
Alendronate
Administration instructions same as for alendronate, except must delay eating and remain upright for at least 60 minutes.
Which drug?
Ibandronate
Administration instructions same as for alendronate, except delayed-release product is taken immediately following breakfast.
Which drug?
RIsedronate
Can premedicate with acetaminophen to decrease infusion reactions.
_Contraindicated if CrCl <35 mL/min**_
Which drug?
Zoledronic Acid
Monitoring for biphosphonates
bone turnover markers
3 ADEs of biphosphonates
PO: nausea, dyspepsia
IV: transient flu-like illness
Rare adverse effects of biphosphonates
perforation, ulceration, GI bleeding (PUG)
Musculoskeletal pain
atypical fx
ONJ
COntraindications of biphosphonates
CrCl 30-35mL/min
serious GI conditions:
esophagus abnormalities delaying emptying-stricture or achalasia
esophageal varices
barrett’s esophagus
Pregnancy
Black box warning of biphosphonates regarding ONJ
ONJ occurs more commonly in patients with cancer, chemotherapy, radiation, and or glucocorticoid therapy receiving higher-dose intravenous bisphosphonate therapy.
Another ADE of biphosphonates
Subtrochanteric femoral (atypical) fracture
Who can take a “drug holiday”?
women w/o evidence of a low-trauma fx
pts who have responded well to biphosphonate therapy
Those w/BMD increasing into the osteopenic range (T-score > -2)
What is a “drug holiday”?
Patients are taken off their bisphosphonate therapy and followed serially with bone turnover markers and central DXA BMD
Endogenous hormone released from the thyroid gland when serum calcium is elevated
Treatment for women who are at least 5 years past menopause
Third-line treatment
May provide pain relief with acute verterbral fracture
What is this describing?
Calcitonin
Refrigerate nasal spray until opened for daily use, then room temperature.
Prime with first use
Which drug?
Calcitonin
For postmenopausal women with an uterus; no progestogen needed
Which drug?
Bazedoxifene
decreases bone resorption, increasing bone mineral density and decreasing fracture incidence
Which drugs?
2nd gen mixed estrogen agonist/antagonist (EAA)
selective estrogen receptor modulators (SERMs)
Raloxifene, Bazedoxifene
Why is estrogen therapy used short-term to manage menopausal sx?
risks of estrogen therapy > bone benefits
Replacement of ___________ (male) or _________ (female) have demonstrated increases in BMD, but no data on fracture prevention exist
Replacement of testosterone (male) or methyltestosterone (female) have demonstrated increases in BMD, but no data on fracture prevention exist
Recombinant product representing the first 34 amino acids in human PTH
Increases bone formation, the bone remodeling rate, and osteoblast number and activity.
Both bone mass and architecture are improved
Indicated for postmenopausal women, men, and patients on glucocorticoids at high risk (Bone density T score < -3.5)
Which drug?
Teriparatide (Anabolic Therapy)
Commercially available as a prefilled “pen” delivery device
first dose should take place with the patient either sitting or lying down in case orthostatic hypotension occurs
Which drug?
Anabolic Therapies: Teriparatide
approved for treatment of high-risk postmenopausal osteoporosis
Synthetic analog of human parathyroid hormone (PTH) related peptide acting as an anabolic agent to stimulate bone formation
Which drug?
Abaloparatide (Tymlos)
What did the ACTIVE trial demonstrate about Abaloparatide (Tymlos)
reduced new vertebral and nonvertebral fractures and increased bone mineral density after 18 months
When___________ is discontinued, antiresorptive treatment should be considered as ______________to protect against bone loss.
When abaloparatide is discontinued, antiresorptive treatment should be considered as sequential therapy to protect against bone loss
MOA:
Binds to RANKL on the surface of osteoclast precursor cells and mature osteoclasts
Inhibits osteoclatogenesis and increases osteoclast apoptosis
Which drug?
RANKL inhibitor: Denosumab
Indications: Postmenopausal women and possibly chemotherapy induced osteoporosis
RANKL inhibitor: Denosumab
ADEs:
back, extremity, and musculoskeletal pain
increased cholesterol, cystitis, decreased serum calcium, skin problems
Which drug?
RANKL Inhibitor: Denosumab
What are the 4 1st line tx for osteoporosis?
Alendronate
Risedronate
Zoledronic acid
Denosumab
“AZRD”
Alt tx for osteoporosis
Ibandronate, raloxifene, and teriparatide
Agent of last resort
Calcitonin
When should you consider a Vertebroplasty and Kyphoplasty
Patients with debilitating pain between 6 and 52 weeks after a vertebral fracture might undergo vertebroplasty or kyphoplasty
bone cement is injected into the fractured vertebral space
Vertebroplasty and Kyphoplasty
ADEs:
cement leakage into the spinal column, which can result in complicating nerve damage, and vertebral fracturing around the cement
Vertebroplasty and Kyphoplasty
Define osteomalacia
“soft bones”
condition seen in adults in which the bone is significantly undermineralized
_________ is the childhood equivalent of osteomalacia.
Rickets
Cause of osteomalacia
MCC: severe, prolonged vitamin D deficiency
disorders that cause hypophosphatemia, medications like long-term antoconvulsant therapy
Clinical px of osteomalacia
pathologic fractures and/or deep bone pain, proximal muscle weakness, or no obvious symptoms but low BMD
Osteomalacia causes extremely low __________ concentration.
Osteomalacia causes extremely low 25(OH) vitamin D concentration (<10 ng/mL [<25 nmol/L]) concentration.
Tx for osteomalacia
Ergocalciferol once to twice weekly fofr at least 8 weeks
Once 25(OH) vitamin D concentrations are > 30 ng/mL (75 nmol/L), chronic maintenance vitamin D therapy can be instituted
Maintenance therapy:
oral ergocalciferol 1 or 2 times a mo
OR
nonprescription cholecalciferol once daily
