Bone is one of the most frequent sites of malignant tumor metastasis. Bone metastasis is also one of the leading causes of death in lung cancer and other solid tumors. The diagnostic rate of bone metastasis in lung cancer is relatively low, and bone pain, pathologic fracture, local compression, and hypercalcemia also complicate the treatment.2.3% of patients with lung cancer have bone metastasis as the first symptom, and about 30%-40% of patients with progressive stage will develop bone metastasis. Many complex complications are also associated with bone metastases, including severe bone pain, pathologic fractures, epidural spinal cord compression secondary to vertebral metastases, hypercalcemia, and decreased behavioral ability. A retrospective study showed that 50% of patients with bone metastases from lung cancer experienced bone-related events. Although bone metastasis or not has no effect on patient survival, bone-related events can significantly shorten survival. Manifestations of bone metastases Bone metastases occur by hematogenous dissemination, and the high incidence sites include the pelvis, ribs, vertebrae and proximal long bones. Pain is the most common clinical manifestation. Inflammation and thickening of the periosteum are the source of pain, and therefore, bone pain should be managed to the greatest extent possible. Often bone metastases are present before bone pain occurs. A study found that 18.3% of patients with early stage non-small cell lung cancer developed bone metastasis by whole body bone scanning, but only 27.2% developed bone pain, and most of the patients had no pain symptoms. In patients with small cell lung cancer, 40% had positive bone images at diagnosis, while bone metastases were often diagnosed asymptomatically. Primary lung cancer bone metastases are usually osteolytic. Tumor cells disturb the balance between osteoclast-dependent resorption and osteoblast-dependent bone formation. Pathological fractures occur when bone strength is compromised, and collapse and expansion of the vertebral body can cause spinal cord compression. Both paraneoplastic syndrome without bone destruction and osteolytic bone metastases may cause hypercalcemia, leading to disease progression. Diagnosis of Bone MetastasesThere are several ways to examine bone metastases. X-rays are effective in diagnosing the extent of bone destruction, and the most commonly used bone imaging technique is radionuclide bone scanning. For patients with multiple bone metastases in weight-bearing bones, it is important to evaluate the risk of fracture and the degree of vertebral destruction, which can be severe enough to lead to spinal cord compression or even paraplegia. Both computed tomography (CT) and magnetic resonance imaging (MRI) can be used for radiotherapy planning and for further differential diagnosis of skeletal abnormalities. Positron emission tomography (PET) examination has recently been recommended for mediastinal staging in patients with primary lung cancer, and whole-body PET can also be applied for preoperative staging of patients with non-small cell lung cancer. Another study evaluated the diagnostic significance of PET and conventional bone scanning for bone metastases. The results showed that the accuracy of PET and bone scan was 96% and 66% respectively. Treatment of bone metastasis I. Surgery Stage IV lung cancer is mainly treated with palliative care, and surgical intervention can prevent certain special cases, repair pathological fractures and assist in treating spinal cord compression. Surgery for bone metastasis of lung cancer is aimed at palliative relief of pain and restoration of function. Prophylactic surgery is recommended in the following cases: to prevent fracture from long bone invasion; persistent or worsening localized bone pain despite completion of radiotherapy; isolated, well-demarcated peripheral osteolytic lesions involving more than 50% of the lesion in the cortex; and proximal femoral involvement with fracture of the lesser trochanter. In addition, the life expectancy of the patient should be considered before surgical treatment, e.g., patients with only 4 weeks are clearly not suitable to withstand orthopedic surgical treatment. Indications for surgical treatment of spinal cord compression due to vertebral bone metastases include vertebral instability, bone compression and/or compression damage to the nerves, intractable pain, and failure of conservative treatment.A trial at the 2003 ASCO meeting randomized patients with spinal cord compression to direct decompressive surgical resection + radiotherapy and immediate radiotherapy. The results showed that the surgical group gained the ability to maintain downward mobility more significantly than the radiotherapy alone group. Second, radiotherapy Radiotherapy has become the main treatment for bone metastasis pain and can be effective in controlling pain in patients with limited life expectancy. Radiotherapy is the most common treatment for the palliative care of painful bone metastases from lung cancer and can prevent the occurrence of acute pathologic fractures and spinal cord compression. One study compared single split treatment (8 Gy) with multiple split treatments (30 Gy/10 f). The results showed that patients in the single split group had a shorter maintenance of efficacy and often required re-treatment. The results of another trial confirmed this conclusion. However, for those patients with a shorter life expectancy, a single high-dose radiotherapy session provided short-term pain relief. Radiotherapy has an excellent role in the treatment of vertebral metastases secondary to spinal cord compression, with response rates of 40% to 60%. Ambulatory and non-paraplegic patients can receive radiotherapy combined with high-dose dexamethasone treatment, and it is recommended to apply prophylactic radiotherapy to asymptomatic patients with epidural spinal cord compression, and the symptoms of nerve compression can be used as the prognostic indicators of the patients before radiotherapy. Drugs Drugs also play an important role in the treatment of bone metastasis, which mainly include analgesic drugs, bisphosphonate compounds, biologically-targeted drugs and radiopharmaceuticals, etc. 1. Painkillers mainly include non-steroidal anti-inflammatory drugs (NSAIDs) and opioids NSAIDs can be used alone for severe pain or in combination with opioids, such as morphine, to treat more severe pain. The combination of long- and short-acting morphine analogues should be individualized, including a careful understanding of the patient’s pain and the frequency of constipation produced by its use.NSAIDs, tricyclic antidepressants, anticonvulsants, and sedatives can be used as a complement to morphine analgesic therapy. In some special cases, narcotics and neurosurgery are also involved. Patients may also seek the help of a pain management specialist for more difficult problems. 2. Bisphosphonate compounds are potent osteoclast inhibitors and are also effective against the growth of tumor cells. Bisphosphonate compounds specifically inhibit the activity of osteoclasts bound to hydroxyapatite, thereby inhibiting bone resorption. It confines the damaged bone surface and reduces osteoclast activity through a variety of mechanisms. Bisphosphonate compounds have been widely used in the treatment of a variety of diseases, including bone metastases, Paget’s disease, malignancy-associated hypercalcemia, and osteoporosis. Side effects include fever, nausea, and gastrointestinal disturbances (especially with oral administration). The drug should be used with caution in renal insufficiency. Treatment of Bone Metastases. Most bisphosphonate compounds can play an important role in the treatment of bone metastases in breast cancer and osteolytic disease in multiple myeloma, and their efficacy in bone metastases was evaluated in these patients. Bone-related events include pathologic fractures, hypercalcemia, spinal cord compression, and bone destruction after surgical treatment or radiotherapy. Two studies of progressive breast cancer established the basis for the treatment of bone metastases with pamidronate disodium. The results showed that the rate of bone-related events and the time to first occurrence were significantly lower in the pamidronate disodium group, and its effects continued for the next two years. Pain scores and analgesic use decreased, but patient survival time, quality of life, and behavioral abilities did not significantly improve. Zoledronic acid is a bisphosphonate compound with three covalent bonds. Results of a phase III clinical trial showed that pamidronate disodium and zoledronic acid had similar efficacy in patients with breast cancer and multiple myeloma. Bone metastases are also a major challenge in the treatment of other malignancies, so studies of zoledronic acid on bone metastases in lung cancer and other solid tumors have shown a delay of more than 2 months in the onset of bone-related events with zoledronic acid. Zoledronic acid appears to provide clinical benefit to patients with bone metastases. Unfortunately, however, this benefit has not been demonstrated in patients with lung cancer, and the analysis may be due to the fact that the diagnosis of bone metastases in patients with lung cancer remains suboptimal and lacks an effective combination of therapies. Exerting antitumor activity bisphosphonate compounds are also effective against tumor cell growth. Both in vivo and in vitro preclinical evidence demonstrates that bisphosphonate compounds have antitumor activity and reduce bone or extraosseous tumor load. Many hypotheses on the mechanisms of tumor suppression by bisphosphonate compounds have been proposed, including indirect inhibition of bone resorption and osteoclast genes, direct induction of apoptosis in tumor cells, inhibition of tumor invasion into bone, and inhibition of angiogenic and immunomodulatory responses. Zoledronic acid may provide additional therapeutic benefits. Some trials have recently been conducted or are ready to evaluate its role as an adjuvant drug, but further follow-up of trial results is needed for its efficacy in lung cancer patients. The emergence of biologically targeted drugs has brought new hope to the treatment of advanced lung cancer. In recent years, EGFR-targeted therapy has become a hotspot in lung cancer research. Some biologically targeted drugs such as gefitinib have been gradually applied to the clinic as second- and third-line drugs, bringing new hope to the treatment of advanced non-small cell lung cancer patients. There is no controlled trial result on the application of targeted drugs in lung cancer bone metastasis. One trial found that the expression of EGFR in lung cancer bone metastases was similar to that in primary foci, and the up-regulation of the receptor level was more common than the down-regulation, but whether this result can guide the clinical treatment needs to be further explored. 4, the therapeutic role of radiopharmaceuticals is still to be further verified radiopharmaceuticals through the concentration in the metastatic foci and release rays to kill tumor cells and thus relieve pain. However, the conclusion of this treatment is still uncertain, and the therapeutic experience of metastatic nuclide associated with lung cancer is still limited. The main side effect is myelosuppression (thrombocytopenia), which is especially pronounced in patients who have received prior radiotherapy. Warm tips: the specific use of drugs, please combine with the clinical, by the doctor’s face-to-face guidance shall prevail.