According to a report published in eJHaem, a loss of balance along with associated falls appears to be a triggering factor for skeletal-related events in patients with multiple myeloma (MM) with bone disease, especially in those who are frail and those with amyloid light-chain (AL) amyloidosis.

The researchers conducted a retrospective analysis to identify baseline conditions and triggering factors for skeletal-related events in patients with MM treated with denosumab. Skeletal-related events were defined as a pathologic fracture, radiation therapy to bone, surgery to bone, or spinal cord compression.

The team assessed the time to the first skeletal-related event after denosumab treatment based on patients’ medical charts. They also conducted univariate and multivariate analyses of risk factors for skeletal-related events.

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A total of 75 patients with MM (newly diagnosed MM [NDMM], n=52; 69%; relapsed/refractory MM [RRMM], n=23; 31%) who received a subcutaneous injection of 120 mg denosumab for bone disease between June 2012 and December 2020 were included in the study. Patients had a median age of 69 years (range, 44-88). All patients had been treated with proteasome inhibitor-based regimens. Patients received denosumab a median of 7 times (range, 1-35).

At a median follow-up duration of 17 months (interquartile range, 1-86), the researchers found that skeletal-related events occurred in 6 of 52 patients (11.5%) with NDMM and 5 of 23 with RRMM (21.7%).

Using Kaplan-Meier analysis, they found that patients with RRMM had a significantly shorter time to first skeletal-related event than those with NDMM; at 3 years, the proportion of patients without a skeletal-related event was 89.6% in NDMM and 55.7% in RRMM (log-rank test P =.02).

In a univariate analysis, the team found that an Eastern Cooperative Oncology Group performance status of ≥3 (odds ratio [OR], 4.50; 95% CI, 1.15-17.63; P =.037) and the coexistence of AL amyloidosis (OR, 23.63; 95% CI, 2.19-255.21; P =.009) were correlated with the occurrence of skeletal-related events. In a multivariate analysis, they found that coexistence of AL amyloidosis remained an independent risk factor for the occurrence of skeletal-related events (OR, 14.62; 95% CI, 1.20-177.50; P =.035).

The team reported that in 3 of 4 cases with AL amyloidosis, bone fractures occurred by patients falling down due to orthostatic hypotension and/or muscle weakness.

Limitations of the study included the single-center, retrospective design, small sample sizes, and no objective estimation of physical functions.

Disclosure: One study author declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures. 


Miki H, Nakamura S, Oura M, et al. The importance of retaining physical functions to prevent skeletal-related events in multiple myeloma patients with bone disease. EJHaem. 2022;3(2):480-483. doi:10.1002/jha2.402