Does chronic lymphocytic
leukemia increase the risk of
osteoporosis?
Amrita Desai, MD Internal Medicine Residency Program
Adam Olszewski, MD Department of Hematology and Oncology
Memorial Hospital of Rhode Island
Alpert Medical School of Brown University
Outline
„
Introduction
„
Aims
„
Methodology
„
Results
„
Limitations
„
Conclusions
Chronic Lymphocytic Leukemia (CLL)
„
Most common lymphoproliferative disorder seen in
the elderly
„
Incidence rates are 6.7 and 3.6 cases per 100,000
population/year
„
Indolent course
„
Excessive osteoclastic resorption leading to bone
demineraliztion
Cancer Causes Control 2008; 19:379.
Osteoporosis
„
Skeletal disorder characterized by compromised
bone strength predisposing to an increased risk of
fractures.
„
Prevalence is estimated to increase from 10 million
to >14 million people in 2020
„
Current medical costs are estimated at $13.7–20.3
billion.
Journal of Bone and Mineral Research
Volume 22, Issue 3, March 2007
Literature Search
Osteoporosis is a known complication:
„ Treated pediatric lymphomas.
J Clin Oncol. 1998;16(12):3752-3760.
„
Post- chemotherapy for non-Hodgkin lymphoma
ASH Annual Meeting Abstracts. 2006;108(11):4607
„
Unknown whether presence of a bone marrowreplacing process such as CLL is a significant risk
factor for osteopenia or osteoporosis
Aims
„
Investigate the prevalence of osteoporosis,
osteopenia and compression fractures in
patients with CLL treated at MHRI + RIH
„
Identify risk factors for compression fractures
„
Investigate if patients with CLL have increased
risk of osteoporosis
Methodology
„
A retrospective cohort study
Inclusion Criteria
Case selection:
- Patients at RIH and the MHRI Cancer Center
- Diagnosis of CLL on the basis of flow cytometry/bone
marrow biopsy
- Adequate medical information (follow up, physician
problem list or radiology evaluations)
- Patients with absolute lymphocyte count<5000/mm3
were excluded
Controls:
- Family Medicine Practice and Internal Medicine patients
at MHRI.
- ( 2:1)matched on age, gender, race and BMI
Data Collection
„
Demographics:
‰
‰
‰
‰
Age at diagnosis and last follow up
Ethnicity – not available in majority of cases
Height, weight and calculated BMI
Tobacco use status (current, past, never smoker)
Data Collection
„
Clinical/Laboratory data:
‰
‰
‰
‰
‰
‰
‰
‰
‰
‰
‰
Confirmation with flow cytometry
CD38 status
Available CLL FISH studies
Adenopathy
Splenomegaly
White blood cell count (WBC)
Absolute lymphocyte count (ALC)
Hemoglobin
Platelets
Beta-2-microglobulin
Lactate dehydrogenase (LDH)
Endpoints:
‰
DEXA (dual-energy x-ray absorptiometry) bone density
scan results.
‰
Evidence of osteoporosis (physician notation, CT scan
result)
‰
Evidence of osteopenia (physician notation, CT scan result)
‰
Evidence of compression fracture (physician notation,
report of the CT scan)
‰
Composite endpoint (any of the above)
Results
Controls
cases
MHRI
(120)
MHRI
(87)
Excluded
27
RIH
(53)
Included
60
4: ALC < 5000
10: Different diagnosis (“rule out
CLL”, “family history of CLL”, “LGL
leukemia”, leukocytosis)
12: inadequate follow up
information
1: prisoner
Excluded
17
Included
36
9: ALC < 5000
2: Different diagnosis (“rule out
CLL”, “family history of CLL”,
“LGL leukemia”, leukocytosis)
6: inadequate follow up
information
Results for:
„
The prevalence of osteoporosis, osteopenia
and compression fractures in patients with CLL
treated at MHRI Cancer Center and at RIH
Demographics
Cases N= 96
Age (median)
71yrs
Gender( Females)
48%
BMI (median)
Absolute Lymphocyte Count
(median)
Hemoglobin (mean)
LDH (mean)
Vitamin D level (mean)
Median follow up time
26
40,850/mm3
12.4 g/dL
202 IU/L
30.7 ng/mL
2.9 yrs
Prevalence of osteoporosis in CLL
patients
osteoporosis
12, 11%
96, 89%
Prevalence of osteoporosis +osteopenia
in CLL patients
5, 5%
osteoporosis
osteopenia
12, 13%
79, 82%
Prevalance of compression fractures in
CLL patients
7, 7%
96, 93%
Compression
fractures
Discussion
„
Low prevalence of osteoporosis
„
High prevalence of compression fractures
Results for:
„
Identification of risk factors for compression
fractures
Risk factors for Compression Fractures in
CLL patients
HR
CI
p
Osteopenia/osteoporosis
12.8
95%CI 1.5-109, p=0.004
Anemia
8.9
95%CI 1.1-74
P=0.01
ALC> 100,000/mm3
5.1
95%CI 1.1-23.7
P=0.04
Risk factors for compression fractures in
CLL patients
Discussion
„
More disease burden increases risk of
compression fracture
„
Need for early screening
Results for:
„
Do patients with CLL have increased risk of
osteoporosis?
CT scans
Fisher's exact = 0.327
DEXA scans
p<0.001
Prevalence of osteoporosis
Fisher's exact = 0.107
Compression Fracture
odds ratio 1.0, 95%CI 0.32-2.84, p=1.0
Discussion
„
More DEXA scans in controls
„
In some cases men got fewer DEXA scans
compared to women
„
Informant bias?
„
More CT scans in cases
Limitations
„
Retrospective study
„
Small cohort
„
Single centre study
„
Paucity of data available on imaging studies
Conclusion
„
The incidence of osteoporosis in CLL patients
was 12%
„
The incidence of compression fractures was 7%
„
Compression fractures were higher with
osteoporosis/osteopenia and with heavier
burden of disease.
References
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