Osteoporosis Flashcards
What are the bisphosphonate drugs and what are their routes of administration?
risendronate, alendronate - PO
zolendronic acid - IV
What are bisphosphonates MOA
slow bone loss by increasing osteoclast cell death
What is an important counselling point for taking oral bisphosphonates?
take on an empty stomach with at least 240ml of plain water and wait at least 30 minutes before taking food (F impaired with food or drink)
How long does bisphosphonate therapy usually last
typically does not exceed 5 years
What are side effects of bisphosphonates?
(significant, oral, IV)
- Significant: atypical femoral fractures (w prolonged use), severe bone, joint or muscle pain, upper GI mucosa irritation, ocular effects (eg iritis, uveitis), hypocalcemia, ONJ/EAC
- Oral: nausea, abdominal pain, heartburn-like symptoms
- IV: flu-like symptoms
What are CI to bisphosphonates? (4)
pre-existing hypocalcemia
abnormalities of the esophagus (may delay emptying)
severe renal impairment (CrCl < 30)
pregnancy and lactation
What type of drug is denosumab and what is its MOA?
human monoclonal antibody against RANKL that prevents the development of osteoclasts
What is denosumab’s route and frequency of administration?
administered as SC injections every 6 months
What should be given together with denosumab
co-administer 1000mg Ca + ≥ 400 IU vitamin D daily
What are side effects of denosumab
muscle, back, bone or joint pain,
nausea and vomiting
constipation or diarrhea
slight tiredness
increased cholesterol levels
rare: atypical femur #, ONJ/EAC
Why should denosumab not be discontinued?
may cause increased risk of spinal column fractures when discontinued
What are CI to denosumab? (2)
hypocalcemia, pregnancy
In which populations is estrogen usually indicated
for bone health in younger women or in women whose menopausal symptoms also require treatment (has beneficial effects on both)
What type of drug is raloxifene and what is its MOA?
selective estrogen receptor modulator (SERM) with mixed estrogen receptor agonism and antagonism
Mimics the effects of estrogen on bone density in postmenopausal women and reduces rather than increases the risk of some types of breast cancer
What is calcitonin’s MOA
It reduces serum Ca, hence opposing the effects of PTH and therefore inhibits osteoclastic bone resorption
What is calcitonin’s routes of administration?
IV, SC, IM or nasal spray
What are side effects of calcitonin
red streaks on skin
injection site reaction
feeling of warmth,
redness of the face, neck and arms and occasionally upper chest
What are contraindications for calcitonin
hypersensitivity, hypocalcemia
What is romosozumab’s MOA?
It removes sclerostin inhibition of the canonical Wnt signialling pathway that regulates bone growth therefore increasing bone formation while decreasing bone resorption
In which population is romosozumab indicated in?
women at high risk of fractures or those who have failed or are intolerant to other osteoporosis therapies
What are side effects of romosozumab?
- Significant: MI, increased risk of CV death, stroke, transient hypocalcemia, hypersensitivity reactions (eg. angioedema, erythema multiforme, urticaria, dermatitis, rash)
- Rare: atypical femur fractures, ONJ
What are CI to romosozumab?
hypersensitivity
uncorrected hypocalcemia
history of MI or stroke (within the preceding year)
What is teriparatide’s MOA
Teriparatide stimulates new bone formation and increases bone strength
How should teriparatide be administered and how long should treatment be given?
OD SC injection with a maximum treatment duration of 24 months in a lifetime
What are side effects of teriparatide
serious calciphylaxis and worsening of previous stable cutaneous calcification
transient orthostatic hypotension
transient and minimal elevations of serum Ca or hypercalcemia
What are CI to teriparatide?
hypersensitivity
pre-existing hypercalcemia
skeletal malignancies or bone metasteses
other metabolic bone diseases (eg. Paget’s disease, hyperparathyroidism)
unexplained elevations of alkaline phosphatase
previous implant or external beam radiation therapy to the skeleton
hereditary disorders predisposing to osteosarcoma
severe renal impairment
pregnancy
What are causes for decrease in bone mass
Age, menopause, low serum Ca, alcohol abusers, smoking, physical inactivity, medication use (eg. use of PPI or long-term systemic glucocorticoid), secondary to other diseases
Which drugs are possible secondary causes for osteoporosis
glucocorticoids, immunosuppressants (ciclospirin), ASM (phenobarbital and phenytoin), aromatase inhibitors, GnRH agonists and antagonists, heparin and cancer chemotherapy
How does osteoporosis usually present
usually asymptomatic and often undiagnosed until the patient resents with a fragility fracture (low-trauma)
Which 2 populations should be assessed for osteoporosis and fracture risk
(1) Post-menopausal women
(2) Men ≥ 65 yo
What are risk factors for osteoporosis? (FLASHME)
- Family history of osteoporosis or fragility fractures; history of falls, fracture risk
- Low calcium intake (< 500mg/day), low body weight
- Ageing, early menopause (45 years or younger)
- Smoking and alcohol consumption
- Height loss (>2cm within three years)
- Medication use
Which assessment can be used for post-menopausal women?
Osteoporosis Self-Assessment Tool for Asians (OSTA)
What are the OSTA score stratifications and what do they indicate?
High risk (> 20) → consider DXA scan as the risk of finding osteoporosis (low BMD) is high in this group
Medium risk (0-20) → consider DXA scan if there are other risk factors
Low risk (< 0) → consider deferring DXA
What diagnosis does each T-score refer to?
- T-score ≤ -2.5 SD → osteoporosis
- T-score -1 to -2.5 SD → osteopenia
- T-score ≥ -1 SD → normal bone density
Compare between T and Z score and what they tell us
T-score compares BMD against a young adult reference population (aids in the diagnosis)
Z-score compares BMD against the expected BMD for the patient’s age and sex (predicts treatment response)
What are DXA scans for
DXA scans at the spine and hip can be predictive for fractures and it is therefore good to assess the treatment benefit there
When should osteoporosis treatment be initiated? (3)
(1) patients present with fragility fracture
(2) patients without fragility fracture byt DXA BMD T-score ≤ -2.5
(3) osteopenic (T-score -2.5 to -1) without fragility fracture but high fracture risk (eg. FRAX > 3% hip or > 20% major OP)
What are risk factors for ONJ
tooth extraction or other invasive dental procedures
history of cancer or radiotherapy
poor oral hygiene
concomitant therapy (angiogenesis inhibitors, bisphosphonates, chemotherapy, corticosteroids, denosumab)
comorbid disorders (anemia, coagulopathy, infection, pre-existing dental or periodental disease)
How should patients be counselled for ONJ
smoking cessation, avoiding invasive dental procedures during bisphosphonate treatment and maintaining good oral hygiene
What should be done to bisphosphonate therapy if patient suffers atypical femur #?
discontinue bisphosphonate therapy and consider continuing after 2-4 weeks or when the wound has healed (patient can sit up for 30 mins)
Investigate as to why the bisphosphonate therapy isn’t preventing fragility fractures, and condsider switching to a newer agent with more evidence
What should serum 25(OH) vitamin D levels be prior to starting pharmacologic treatment
≥ 20-30 ng/mL
