Bone metastasis

# Overview
Bone metastases, or metastatic bone disease, is a class of cancer metastases that results from primary tumor invasion to bone.  Bone-originating cancers like osteosarcoma, chondrosarcoma, and Ewing's sarcoma are rare.  And, unlike hematological malignancies that originate in the blood and form non-solid tumors, bone metastases generally arise from epithelial tumors and form a solid mass inside the bone.  Bone metastases cause severe pain, characterized by a dull, constant ache with periodic spikes of incident pain.

# Sources of bone metastases
Bone is one of the most common locations for metastasis. While any type of cancer is capable of forming metastatic tumors within bone, the microenvironment of the marrow tends to favor particular types of cancer, including prostate, breast, and lung cancers. Particularly in prostate cancer, bone metastases tend to be the only site of metastasis.
- Breast cancer
- Prostate cancer
- Lung cancer

# Phenotypes
Under normal conditions, bone undergoes a continuous remodeling through osteoclast-mediated bone resorption and osteoblast-mediated bone deposition.  These processes are normally tightly regulated within bone to maintain bone structure and calcium homeostasis in the body.  Disregulation of these processes by tumor cells leads to either osteoblastic or osteolytic phenotypes. Regardless of the phenotype, though, bone metastases show osteoclast proliferation and hypertrophy.

# Symptoms
Bone metastases are a major clinical concern that can cause severe pain, bone fractures, spinal cord compression, hypercalcemia, anemia, spinal instability, decreased mobility, and rapid degradation in the quality of life for patients.  Patients have described the pain as a dull ache that grows worse over time, with intermittent periods of sharp, jagged pain.  Even under controlled pain management, these periods of breakthrough pain can occur rapidly, without warning, several times a day.
- severe pain
- bone fractures
- spinal cord compression
- hypercalcemia
- anemia
- spinal instability
- decreased mobility

## Causes of symptoms
Acidosis is the increased acidity in a given location, whether it is blood, urine, or tissues.  Osteoclasts generate extracellular protons, lowering the pH of the extracellular matrix (ECM) around the osteoclast to approximately 4.5.  Nociceptors in the bone trigger a pain response in the brain in response to this acidosis.  It is thought that this is the primary source of the dull, chronic pain experienced by patients with bone metastasis.
The uncoupled regulation of the osteoclasts and osteoblasts leads to malformation of the bone. Malformed bones are unable to withstand the normal mechanical stresses placed on them in day-to-day activity, leading to fractures, spinal compression, and spinal instability.  Malformed bones may also mechanically trigger pain receptors both within the bone and in the surrounding tissue.

# Treatment
The traditional treatments for cancer are Radiotherapy and chemotherapy, usually in combination with one another.  Scientists and pharmaceutical companies are researching drugs to target different types of cancer, including metastatic bone disease.
High-intensity focused ultrasound (HIFU) has CE approval for palliative care for bone metastasis. As an entirely side-effect free and non-invasive treatment, HIFU has been successfully applied in the treatment of cancer to destroy tumours of the bone, brain, breast, liver, pancreas, rectum, kidney, testes, and prostate. HIFU treatments are still in investigatory phases as more information is needed to study effectiveness in order to obtain full approval in countries such as the USA. In China HIFU has CDFA approval since 2001 and over 180 treatment centres have been established in China, Hong Kong, and Korea. It is expected that HIFU may become one of the fastest, most effective, and safest methods to treat some cancers. No anesthetic is required. The focused hyperthermia response of body tissue to HIFU is easily guided using MRI to yield a very precise technique.
One treatment that has been considered is bisphosphonates. Bisphosphonates have shown great promise in reducing bone cancer pain, bone destruction, and tumor growth.  However, they have exhibited side effect such as the induction of arthralgias and osteonecrosis of the jaw.
Monthly injections of radium-223 chloride (as Xofigo, formerly called Alpharadin) have
been approved by the FDA in May 2013 for castration-resistant prostate cancer (CRPC) with bone metastases.

## Pain management
The World Health Organization's pain ladder was designed for the management of cancer-associated pain, and mainly involves various strength of opioids.
Other treatments include bisphosphonates, corticosteroids, radiotherapy, and radionucleotides.
Percutaneous osteoplasty involves the use of bone cement to reduce pain and improve mobility.
In palliative therapy, the main options are external radiation and radiopharmaceuticals.