Exam 2: Bone modifying Agents Flashcards
Epidemiology of Hypercalcemia of Malignancy (HCM)
increased bisphosphonate use
What does absorption =
elimination of calcium in the blood
Pathophysiology of HCM
- increased PTH
- increased calcitriol
- increased resorption
- decreased elimination
- bone mets
Humoral HCM
- caused by PTHrP
- stimulated osteoclasts in bone marrow and renal calcium retention
Local osteolytic hypercalcemia
caused by cytokines and PTHrP
Renal HCM etiology
- increased calcium reabsorption
- decreased phos reabsorption
symptoms of hypercalcemia
- lethargy
- confusion
- weakness
- shortened QT
- widened T wave
- heart block
- arrhythmias
- a systole
- seizures
- stupors
Corrected Calcium
Serum calcium + 0.8(4-serum albumin)
Mild HCM Asymptomatic or Mild Symptoms
- 10-12 mg/dL
- encourage hydration
- d/c medications that increase serum calcium or decrease renal flow
- repeat calcium in 4 weeks
Mild HCM Moderate Symptoms
- 10/12 mg/dL
- Hydration (normal saline)
Bisphosphonate
- zolendronic acid IV OR
- Pamidonate IV
- can be repeated after 7 days if needed
Moderate HCM
- 12-14 mg/dL
- hydration reduces calcium more quickly than bisphosphonate
- Zolendronic acid
- repeat 7 days if needed
Severe HCM
- > 14 mg/dL
- Hydration 200 mL/hr
- Zolendronic acid
- Calcitonin (tachyphylaxis after 48 hour, used for severe symptoms or very high calcium or after bisphosphonate)
Refractory HCM Treatment
- phosphates
- gallium nitrates
- denosumab
Chronic HCM Management
- Zolendronic acid
- pamidronate
0.9% NS in HCM
- dilutes calcium and improves renal elimination
Loop diuretics in HCM
- increases urinary calcium excretion
Bisphosphonates in HCM
- blocks bone resorption
Calcitonin in HCM
blocks bone resorption and increases calcium excretion
IV bisphosphonates MOA
- affinity for hydroxyapatite
- inhibit osteoclast activity by inducing direct osteoclast apoptosis and inhibiting differentiation and maturation
- decreases bone resorption
- increasing mineralization
- concentrate at active bone remodeling sites
Bone in cancer patients
- tumor cells secrete cytokines and growth factors
- increased production of receptor activate or nuclear factor kappa B ligand (RANK-L)
- increased osteoclasts leads to increased bone resorption
Cancers with bone affinity
- breast
- prostate
- myeloma
- lung
- kidney
Skeletal Related Events (SRE) Definition
- pathologic fracture
- need for bone radiation
- need for bone surgery
- spinal cord compression
- hypercalcemia
Diagnosis of SRE’s
- bon pain or tenderness
- radiograph
- CT can show bony destruction
- MRIs in patient with normal X-rays and positive bone scans
- PET
Risk Factors for Fractures in Women
- bone mineral densit <-2.5
- on AI
- age > 65
- corticosteroid use > 6 months
- BMI < 20 kg/m2
- family history of hip fractures
- history of fracture before age of 50
- smoking
Risk Factors for Fractures Men with Prostate Cancer
- androgen deprivation therapy
- smoking
Treatment of Bone Mets Overview
- goal is palliative
- radiation
- chemo
- IV bone modifying agents
- Radioisotopes
Radiation Therapy for bony mets
- pain relief within 1-2 weeks
- radioisotops
IV Bisphosphonate for SRE’s prevention
- pamidronate
- zoledronic acid (more expensive)
- renal adjustment dosing needed
- do not use <30 mL/min
- no adjustments are warrented if these are used for HCM
Other considerations for bisphosphonates
- supplement with calcium and vitamin D
Denosumab MOA
RANK-L
Denosumab considerations
- rapidly reduces bone turnover
- lack of affinity for hydroxyapatite and more evenly spreads throughout the bone
- may suppress residual osteoclast function in patients who poorly responds to bisphosphonates
Denosumab brand name
- Xgeva for bony mets
- Prolia for osteopenia
Dose adjust for denosumab?
- No renal
- supplement with calcium and vitamin D as it causes hypocalcemia
Adverse effects of bone modifying therapies
osteonecrosis of jaw
Renal dysfunction
Zoledronic acid > pamidronate > denosemab in terms increased renal dysfunction
Which medication is safe in renal dysfunction
denosumab
Which medication causes the most hypocalcemia
denosumab
