Pharmaco: Osteoporosis Flashcards
List the antiresorptive agents
- Bisphosphonates
- Denosumab
- Estrogens
- Calcitonin
[Bisphosphonates]
MOA
Slow bone loss by increasing osteoclast death
[Bisphosphonates]
Examples
Alendronate (oral)
Risedronate (oral)
Zoledronic acid (IV)
[Bisphosphonates]
Fracture reduction:
- Vertebra fracture reduction
- Non-vertebra fracture reduction
- Hip fracture reduction
[Bisphosphonates]
Administration of oral bisphosphonates
Alendronate and Risedronate can be taken once a week (e.g., Alendronate 70mg/week, or 10mg/day; Risedronate 35mg/week or 5mg/day)
Risedronate can also be taken once a month (150mg/month)
Take oral bisphosphonates on empty stomach with at least 240ml of plain water (NOT mineral water), best 30min before breakfast and no food/drink/medications/supplements for at least 30min after administration; remain upright for 30min after administration
Rationale:
- Wait at least 30min before food as food will decrease absorption and bioavailability of the drug (esp multivalent cations)
- Do not lie down after taking medication to reduce upper GI irritation and risk of acid reflux
[Bisphosphonates]
Administration of IV bisphosphonates
Once a year - 5mg per year as a 30min IV infusion via a cannula through a vein
[ACE]
- Ensure pt is adequately hydrated before use
- Use with caution in pt with significant Vit D deficiency (replete Vit D before infusion if pt has Vit D deficiency)
- Check serum Calcium and Phosphate levels at 9-14 days after infusion if pt shows symptoms of hypocalcemia or hypophosphatemia
[Bisphosphonates]
Adverse effects
- GI SEs (nausea, abdominal pain, heartburn-like symptoms, diarrhea, constipation, stomach ache, bloatedness)
- Upper GI mucosa irritation (erosive esophagitis, dysphagia, esophageal ulcer and perforation)
- Headache
- Hypocalcemia (twitching in hands, face, feet, numbness, tingling)
- Musculoskeletal aches (bone, muscle, joint aches), muscle cramp
- Atypical femoral (hip) fractures (with prolonged use) - rare
- Osteonecrosis of the jaw, external auditory canal - rare
(Additional for IV)
- Flu-like symptoms (fever, malaise, headache) - mitigate by infusion of at least 30min, treat with acetaminophen/ibuprofen
- Worsen renal function
- Severe bone, joint, or muscle pain, musculoskeletal aches (arthritis, arthralgia)
- Ocular effects (e.g., iritis, uveitis)
[Bisphosphonates]
ONJ signs and symptoms
(to monitor and inform doctor)
- Pain in the mouth and/or jaw
- Swelling or sores inside the mouth
- Gum pain and swelling
- Numbness or feeling of heaviness in the jaw
- Loose teeth or tooth pain
- Delayed healing of wounds in the mouth
Often occur following tooth extraction and prolonged use of the medication
[Bisphosphonates]
Mechanism and risk of osteonecrosis of the jaw (ONJ)
Reduced osteoclast activity, but osteoblast activity continues, hence causing bone growth and increasing risk of atypical fractures in jaw bone, femur of hip, small bone in the ear
Risk: Rare, higher likelihood with IV zoledronic acid and in cancer patients
[Bisphosphonates]
Risk factors of ONJ
- Tooth extraction or other invasive dental procedures
- History of cancer, radiotherapy
- Poor oral hygiene
- Smoking
- Concomitant therapy - ABCCD (e.g., angiogenesis inhibitors, bisphosphonates, chemotherapy, corticosteroids, denosumab)
- Comorbid disorders (e.g., anemia, coagulopathy, infection, preexisting dental or periodontal disease)
[Bisphosphonates]
Advise to patient on management of ONJ
- Smoking cessation
- Avoid invasive dental procedures during bisphosphonate treatment
- Maintain good oral hygiene
- Avoid high cariogenic foods
[Bisphosphonates]
Pt has invasive dental treatment, bisphosphonates not yet started:
Delay bisphosphonate treatment, start only after pt has fully healed from the dental procedure (may take a few months)
[Bisphosphonates]
Pt has invasive dental treatment, bisphosphonates already started:
Discuss with dentist whether to continue or discontinue:
- Continue: if dental procedure is low risk, pt close monitoring of S&S of ONJ, and flag up when S&S identified; American association suggests continuing if pt has been treated for less than 4y and no clinical risk factors
- Discontinue: if high risk dental procedure, restart a few months later; American association suggests discontinuing if pt has been treated for more than 4y or has taken concomitant glucocorticoid
*glucocorticoid-induced osteonecrosis
[Bisphosphonates]
If ONJ develops while on treatment,
Refer to oral surgeon/dentist to determine whether continue or discontinue
[Bisphosphonates]
Mechanism and risk of atypical femoral fracture
What to monitor?
Reduced osteoclast activity, but osteoblast activity continues, hence causing bone growth and increasing risk of atypical fractures in jaw bone, femur of hip, small bone in the ear
Risk: Rare, monitor for thigh/hip/groin pain while on treatment
[Bisphosphonates]
If pt develops atypical femoral fracture while on tx, what should be done?
Discontinue bisphosphonates treatment as there is a risk of delayed fracture healing may occur
[Bisphosphonates]
Precautions
- Active upper GI disease
- Risk factors for developing osteonecrosis of the jaw or external auditory canal
[Bisphosphonates]
Contraindications
PO: (use IV instead if any of these CIs)
- Esophageal or gastric abnormalities such as gastric ulcers, erosive esophagitis, Barrett’s esophagitis, uncontrolled GERD
- Aspiration risk and difficulty swallowing
- Inability to stand or sit upright for at least 30min
- After bariatric surgery in which surgical anastomoses are present in the GIT (inadequate oral absorption and potential surgical anastomotic ulceration)
*Abnormalities of the esophagus may delay emptying
*Reflux esophagitis may cause irritation to GI mucosa
*After bariatric surgery, surgical anastomoses may present
PO/IV:
- Preexisting hypocalcemia
- Severe renal impairment (bc kidney regulates calcium levels)
- Pregnancy and lactation
[Bisphosphonates]
Contraindicated with what CrCl
Contraindicated if:
PO Alendronate/Risedronate: CrCl <30ml/min
IV Zoledronic acid: CrCl <35ml/min
[Bisphosphonates]
Duration of treatment should typically not exceed ____
Explain.
5 years
- Within 5y, if BMD not normalized, then Bisphosphonates may not have anymore benefits
- Weigh risk vs benefit of using beyond 5y (risk of fracture vs harm of adverse effect such as atypical fractures)
- Individualized decision based on pt risk and benefit
- FRAX may be used to predict fracture risk even when pt alr on tx
- May be appropriate to continue if 10 year total risk of fracture exceeds 20% or If there is previous vertrabra fracture
[Denosumab]
MOA
Human monoclonal antibody against RANKL (RANK ligand inhibitor)
*RANKL is found on surface of stromal cells, osteoblasts, T cells
*RANKL initiates remodeling by acting on RANK on osteoclast, thereby stimulating osteoblast to break down bone
=> Denosumab binds to RANKL and prevents it from binding to RANK on osteoclast, thereby preventing bone resorption; it also prevents the development of osteoclasts
