Cancer-Related Bone Loss

Skeletal complications are among the most frequent and devastating morbidities that cancer patients face during the course of their illness. Cancer-related bone loss can be rapid and substantial, leaving patients at risk for:

Pathological fractures resulting in pain, impaired mobility and disability
Spinal compression from weakened vertebrae that impinge on nerves, causing pain and loss of basic autonomic functions, and often requiring surgery
Intractable bone pain, often requiring treatment with opioids or radiotherapy
Hypercalcemia, which can result in renal failure or cardiac arrhythmia if untreated

Thousands of cancer patients in the US are currently affected by cancer-related bone loss as a result of skeletal tumor proliferation or toxicities associated with treatment. One of the most aggressive causes of bone loss is multiple myeloma, a cancer that causes significant bone loss.

Multiple Myeloma

Multiple myeloma (MM) is a debilitating, fatal cancer that develops within the bone, as a result of the uncontrolled proliferation of malignant plasma cells. These tumor cells rapidly infiltrate and destroy the healthy components of bone marrow and skeleton, resulting in serious complications and fatality.

Approximately 50,000 patients in the U.S. have been diagnosed with myeloma
Median survival following diagnosis is 3 to 5 years

Several novel therapies were approved in recent years and response rates and remission rates are now improving. Despite these improved therapies, there remains significant need for treatments that can protect and repair damaged bone tissue that would improve patient quality of life and possibly alter the course of their disease.

Myeloma Bone Complications Cause Tremendous Suffering

A vicious cycle of destruction occurs, when proliferating myeloma cells direct the destruction of adjacent bone tissue, which, in turn, allows for the expansion of the myeloma cells. Myeloma cells drive the destruction of bone tissue by:

Stimulating osteoclasts (increasing bone resorption) and;
Inhibiting osteoblasts (preventing bone formation)

Regions surrounding areas of tumor growth where bone has been “dissolved”, called osteolytic lesions, are hallmarks of myeloma disease. The structural damage caused by these lesions is revealed by radiography as holes “punched” into the skeleton.

Nearly all myeloma patients exhibit some sign of bone disease at diagnosis, in the form of osteolytic lesions, fractures, or accelerated osteoporosis. Damage occurs most frequently in the spine, skull, pelvis, and ribs, and progressively worsens over time. The weakened skeleton causes tremendous suffering in myeloma patients:

75% of myeloma patients will suffer from bone pain
50% will experience a pathological fracture at some point during the course of MM
25% will have a vertebral fracture resulting in spinal compression

Significant Unmet Medical Needs Remains

Presently, the only drugs approved to treat myeloma bone disease are intravenous bisphosphonates (BPs). These agents help to slow the rate of bone resorption but do not form new bone needed to fill in the holes causes by the multiple myeloma tumors. Patients treated with these antiresorptive agents still have unmet medical needs such as:

Osteolytic lesions that do not heal with BP therapy
BPs reduce rate of skeletal related events by only 50%
Potential safety risk of osteonecrosis of the jaw from prolonged BP use

Reducing the rate of bone resorption alone is insufficient to treat myeloma bone disease. To fully prevent the risk of fractures and bone complications, it is critical to grow new bone to improve on the existing bone quality and to repair damage caused by myeloma.

ACE-011 for Multiple Myeloma and Other Cancer-related Bone Loss

Acceleron is developing a novel, bone forming agent, ACE-011, that harnesses the body’s own processes to stimulate the growth of new, high-quality bone. ACE-011 has the potential to improve physical function, overall health, and quality of life for patients with multiple myeloma, bone metastases of solid tumors, and cancer treatment-induced bone loss.

Learn about ACE-011 for Bone Growth and Repair