**4. Palliative care for metastatic bone cancer patients**

The skeletal system is the third most known site for cancer metastases, particularly in end stages of the disease. The presence of bone metastases leads to poorer diagnosis, decrease of survival and is usually associated with several complications, including spinal cord compression, severe bone pain, pathological fracture, and hypercalcemia, etc. [62–65]. Nearly 60–84% of patients with late cancer experiences varying level of bone pain. Bon pain affects millions of patients worldwide, and approximately 450,000 patients in the USA alone annually [66, 67]. Generally, pain varies in severity depending on the stage of the disease. Most patients at the beginning of the disease experience infrequent dull aches, but as the disease advanced, pain becomes constant and increase in severity [68, 69].

Analgesic medications involve pain management with analgesics (non-opioid and opioid), adjuvants (corticosteroids, anticonvulsants), and bone-targeted therapies (NGF inhibitors; osteoclast inhibitors, such as denosumab and bisphosphonates). Radiotherapy (RT) is also used to reduce analgesic need, enhance the quality of life (QoL), also keep or improve skeletal function by minimizing the risk of metastatic spinal cord compression (mSCC) or pathological fractures [70].

Bone-seeking radiopharmaceuticals emitting-particles such as [223Ra] radium-dichloride at the top have been prescribed for bone-pain palliation. Beside [223Ra] a number of long-established and novel bone-seeking radiopharmaceuticals are prescribed for bone-pain palliation, including [89Sr] strontiumdichloride, [153Sm] samarium, [186Re] rhenium, [188Re] rhenium, [177Lu] lutetium, and [166Ho] holmium labeled [71–76]. the control of painful bone metastases is still a challenging problem. Bone-pain palliation with radiopharmaceuticals emitting-particles been utilized for decades, demonstrate an acceptable result. [223Ra] Radium shows higher advantages impact on survival over other radiopharmaceuticals; at the same time, still the expensive [223Ra] radium is not generally available [77].
