Authored by Dr. Brian Koffman
Bottom Line:
Chronic lymphocytic leukemia / small lymphocytic lymphoma (CLL / SLL) patients with abnormal bone health are at high risk for fragility fractures (FF), fractures that occur with minimal trauma. This is true even for those with normal bone density and, surprisingly, is more common in men.
Who Performed the Research and Where Was it Published:
Dr. Deborah Stephens was one of three authors of Risk Factors for Fragility Fractures in Chronic Lymphocytic Leukemia, published online in Cureus in February 2024 with free access.
Background:
Those with CLL / SLL are living longer and issues beyond CLL progression are becoming increasingly important. While infections and second cancers are well-recognized complications, others, such as bone health and fractures, remain underrecognized, undertreated, and not well-understood.
Methods and Participants:
This retrospective study interrogated the Huntsman Cancer Institute (HCI) CLL electronic medical record database. This search compiled all patients diagnosed with CLL and abnormal bone health, defined as diagnoses of osteopenia (low bone density), osteoporosis, and/or a history of Fragility Fractures, from January 1, 2000, to July 31, 2020, who received care at the HCI. The review included demographic, clinical, laboratory, and radiologic data. An FF was defined as a fracture of the spine, wrist, or hip that occurred spontaneously or with minimal trauma.
Results:
- 89 patients with CLL and abnormal bone health were identified and included in the study. Nearly two of three, or 59, had at least one fragility fracture.
- 62% were female, and 83% Caucasian ethnicity. The mean age was 68.
- Participants with an FF were more likely to be male and to have smoked.
- Only 53 (60%) patients had bone density testing (DXA scan).
- Surprisingly, those with an FF were less likely to be diagnosed with osteoporosis by a DXA scan than those without an FF. Also, surprisingly, those with an FF received less treatment for osteoporosis.
- 48 (81%) of the FFs were fractures of the (low back) vertebral bones.
Discussion:
Almost two out of every three of those with a diagnosis of both CLL and abnormal bone health experienced an FF despite most not having proven osteoporosis. Male gender and smoking history increased the risk. This highlights a significant gap in the screening and treatment of osteoporosis in our patients with CLL / SLL.
Fractures of the vertebral bones were by far the most common. This suggests the problem may be how CLL alters how bone is constructed. We know a crucial binding molecule for bone remodeling, RANKL, is released by CLL cells, leading to weaker bones, which further suggests that blocking this with a RANKL inhibitor such as denosumab might make more sense than using the more commonly prescribed bisphosphonates to prevent fractures. Dr. Stephen is studying how bone is formed in CLL with the help of a structural engineer and micro-CT scans of bone marrow biopsies.
Conclusions:
Patients with CLL are living longer, and many are having to deal with poor bone health and resultant fractures. Unlike those without CLL / SLL, these fractures are more common in men, though the other risk factors are similar. Discuss appropriate screening and management with your healthcare team, including adequate Vitamin D3 and calcium intake.
The significant unmet need for understanding and managing bone health and preventing painful and disabling fractures is just one part of our increasing awareness of the need to develop a more comprehensive approach to all the issues related to survivorship.
Links and Resources:
Access the article Risk Factors for Fragility Fractures in Chronic Lymphocytic Leukemia to learn more about the research, including more information on other risk factors.
Watch my interview with Dr. Stephens for more background information.
Stay strong; we are all in this together
Brian Koffman, MDCM (retired), MS Ed
Co-Founder, Executive VP and Chief Medical Officer
CLL Society
