Several Factors—but Not Osteoporosis—Increase Risk of Fractures in People With CLL

A new study shows multiple factors are associated with fragility fracture risk among people with chronic lymphocytic leukemia (CLL), but osteoporosis status is not one of them.

The findings were based on a single-center retrospective study, but the investigators said the report highlights the need for additional research. The study was published in the journal Cureus.

Corresponding author Lloyd Petty, DO, MPH, of the University of Utah, and colleagues, noted that both CLL and osteoporosis are prominent concerns among elderly patients. Osteoporosis involves disruption in the bone architecture, they said, and in CLL, malignant cells infiltrate the bone marrow, leading to bone resorption and demineralization.

“CLL, therefore, can cause bone loss and can exacerbate previously existing osteoporosis,” the authors wrote. “Despite this, there are limited clinical data describing the association of CLL with osteoporosis and fracture risk."

Broken bone in cast | Image credit: VadimGuzhva - stock.adobe.com

The investigators conducted a search of the Huntsman Cancer Institute’s database of patients with CLL treated between January 1, 2000, and July 31, 2020, identifying all patients with both CLL and a diagnostic code associated with abnormal bone health (osteopenia, osteoporosis, or fragility fractures). They found a total of 89 patients who met the inclusion criteria, most of whom were female (62%). The cohort had a mean age of 68 years (±11 years). Of those patients, two-thirds (66%) had at least one fragility fracture; the remaining 30 did not.

When investigators compared the 2 groups for fragility fracture risk factors, they found no differences in immunoglobulin heavy chain variable region gene mutation status between the fracture and no-fracture groups. Similarly, neither chromosomal abnormalities nor the presence of a complex karyotype was found to be associated with fracture risk.

However, other factors did appear to increase risk of fragility fractures. Men had a higher relative risk (RR; 8.1, 95% CI 2.1-31.7), as did patients with diabetes mellitus (RR 1.4, 95% CI 1.04-1.8), those who smoked (RR 1.3, 95% CI 1.02-1.8), patients with Rai staging scores greater than 0 (RR 1.4, 95% CI 1.04-1.9), and those with T-scores greater than -2.5 (RR 1.8, 95% CI 1.1-3.1).

The authors noted that they defined osteoporosis as having a T-score of less than -2.5. Thus, they said, the risk of fragility fractures was actually higher among patients without osteoporosis.

They added, however, that they did not have access to dual-energy X-ray absorptiometry (DXA) bone-density analysis for 40% of patients. They said the lack of such scans, even in patients who qualified for them, represents a significant screening and treatment gap.

Petty and colleagues also found that the large majority of fragility fractures (81%) were located in the spine. That finding is consistent with previous research, they said.

“Vertebral fractures are likely more frequent due to the high trabecular bone content in the vertebrae, potentially reflecting increased disease activity found in the spine compared to other large bones,” they wrote. “There is increased bone marrow activity in the axial skeleton in people with CLL.”

The investigators noted that CLL and osteoporosis already share common demographic risk factors, including older age and European ethnicity. They added that diabetes mellitus and smoking are also known risk factors for osteoporosis, and both were found in this study to increase the risk of fragility fractures.

The authors said further research into this issue is warranted, including larger, multi-center studies. They said such studies may help determine whether spine imaging and trabecular bone scoring ought to become standard components of initial evaluation of patients with CLL.

“There is a large gap in bone health assessment for our patients with CLL, highlighting the need for a more comprehensive, multidisciplinary approach to our care for those with CLL,” they concluded.

Reference

Petty L, Stephens D, Sharma A. Risk factors for fragility fractures in chronic lymphocytic leukemia. Cureus. Published online February 23, 2024. doi:10.7759/cureus.54774