bone modifying agents: hypercalcemia/ SREs

most common tumor type causing hypercalcemia of malignancy (HCM)

lung

most common cause of HCM

humoral- caused by parathyroid hormone related protein (PTHrP) and stimulates osteoclasts in the bone to increase calcium retention

what level of HCM do symptoms present and what are these symptoms

moderate and severe; dehydration, decreased GFR, lethargy, confusion, coma

cardiac symptoms of HCM

shortened QTc interval for moderate, heart block and arrhythmias for severe

corrected calcium equation

serum calcium + 0.8(4-serum albumin)

what corrected calcium levels indicate mild, moderate, and severe levels of hypercalcemia

mild= <12 mg/dL

mod= 12-14 mg/dL

severe= >14 mg/dL

treatment for asymptomatic HCM

hydration, discontinue possible contributing meds, repeat calcium in 3-4 weeks

treatment for moderate symptoms in mild HCM

hydration and bisphosphonate

hydration dosing for HCM

200-400 mL/hour of NS

bisphosphonate options + dosing for mild HCM

zoledronic acid: 4 mg IV over 15 minutes

pamidronate: 30-90 mg IV over 2 hours

does hydration or bisphosphonate lower calcium quicker and how much does this method lower calcium by

hydration, 1.6-2.4 mg/dL within 12-24 hours

who to give loop diuretics in with HCM

those with fluid overload

superior bisphosphonate for HCM

zoledronic acid

additional treatment option for severe HCM but what happens after 48 hours

calcitonin, tachyphylaxis

FDA medication for refractory HCM

denosumab

chronic HCM management

monthly bisphosphonate administration

MOA of IV bisphosphonates

inhibit osteoclast activity, decrease bone resorption, increase mineralization

why is bone resorption increased in cancer patients

tumor cells secrete cytokines and growth factors

classification for these events: pathologic fracture, need for bone radiation, need for bone surgery, spinal cord compression, hypercalcemia

skeletal related events (SREs)

symptoms of SRE

bony pain or tenderness

best way to diagnose SREs

radionucleotide bone scan

risk factors for fractures in cancer patients

age>65, on hormone inhibitor therapy for cancer treatment, corticosteroid use long term, underweight, smoking, family history

goal of treatment for bone metastases

palliation of symptoms

treatment options for bone metastases

radiation, chemo, IV bone modifying agents, radioisotopes

limitation of radiation therapy for SREs

can't re-irradiate the same areas multiple times

radioisotope used for treatment of bone metastases from thyroid cancer

131-iodine

radioisotope used for treatment in prostate cancer

radium-223

special feature of bisphosphonates when used for SREs but not HCM

renal adjustment dosing needed

CrCl cutoff for use of zoledronic acid

<30 mL/min

when must dose start being decreased for zoledronic acid

CrCl <60 mL/min

what to supplement with bisphosphonates for SREs

calcium and vitamin D to prevent hypocalcemia

suppresses residual osteoclast function in patients who poorly respond to bisphosphonates

denosumab

denosumab name and dosing for bone metastases

Xgeva 120 mg SQ q4weeks

denosumab name and dosing for osteopenia

Prolia 60 mg SQ q6months

benefits of denosumab therapy

no renal dose adjustments needed, can use in patients who cannot receive IV meds (SQ)

which meds have a higher chance of causing osteonecrosis of the jaw

zoledronic acid and denosumab> pamidronate

which bone modifying agent is most likely to cause hypocalcemia

denosumab

commonly used duration of treatment for SRE treatment

3 month dosing