The findings of a recent study suggest that the progression of both multiple myeloma and myeloma-related bone disease may be determined by measuring the levels of key proteins commonly found in bones. The study was published in the European Journal of Haematology.

Myeloma cells not only stimulate the formation of cells that break down bone, but also inhibit cells responsible for bone formation.  As a result, multiple myeloma patients have a high rate of bone disease characterized by bone pain and fractures.

Patients are typically treated with bisphosphonates to protect against progressive bone disease; however, this treatment has recently been linked to bone disease of the jaw (known as osteonecrosis of the jaw) and kidney damage. Doctors are now more cautious in prescribing bisphosphonates to patients, and international guidelines recommend that patients in remission should only receive this treatment for a maximum of two years.

Additionally, doctors are advised to monitor disease progression with radiographs, CT scans, or MR scans only when clinically indicated after the patient’s initial staging. However, significant bone damage can occur before the patient exhibits symptoms of disease progression.

An alternative strategy to monitor disease progression is to track the activity of the biochemical markers for bone formation and resorption. Unlike conventional radiography, the markers can be measured with monthly monitoring, which allows for an immediate intervention as soon as the problem is detected.

In their study, researchers from Denmark evaluated the use of certain bone remodeling markers to determine their usefulness in detecting progression of both myeloma and myeloma-related bone disease. The protein bALP indicates the degree to which bone is formed in patients, whereas proteins CTX-1, 1CTP, and NTX-1 indicate the level of bone that is broken down to release minerals such as calcium (a process known as bone resorption).

The researchers recruited 93 patients who received monthly monitoring of the bone formation and bone degradation markers for a period of two years. During the study period, 29 patients relapsed. Of those 29 patients, 10 experienced two episodes of disease progression, and one patient experienced three episodes of disease progression for total of 40 cases of disease progression.

The researchers identified 26 cases in which a radiological evaluation was conducted at the time of disease progression. They found that 15 patients showed progressive bone disease in addition to myeloma progression.

For all 40 cases, researchers performed a retrospective analysis of the bone marker levels to see if any changes in the markers could have predicted relapse.

Analysis of the collected biochemical markers indicated that the bone degradation marker CTX-1 increased significantly in all 40 cases. The increase was more significant in patients with concurrent progression in bone disease.

The levels of the bone formation marker bALP were low in all 40 cases and remained low during the entire study period. Researchers observed an increase in the levels at the first sign of disease progression. The marker remained low in patients with progressive bone disease, while a small increase was observed in patients with no detectable bone disease progression.

Researchers also calculated a CTX-1/bALP ratio for each patient to see if it corresponded to disease progression detected with radiography. The ratio compares the number of bone-degrading proteins to the number of bone-forming proteins. The researchers found that an increase in the CTX-1/bALP ratio corresponded to detected bone disease progression, whereas the ratio remained constant if bone disease progression was not detected.

Based on these results, the authors of the study concluded that measuring bone formation and degradation markers can be used to detect myeloma progression and myeloma-related bone disease.

Furthermore, this strategy can help determine when treatment with bisphosphonates should be initiated before substantial bone destruction occurs.

However, in order to confirm the findings from the study, the researchers point out that prospective studies with pre-planned bone imaging are needed.

For more information, please read the original article in the European Journal of Haematology (abstract).