Does chronic lymphocytic leukemia increase the risk of osteoporosis?Amrita Desai, MD Internal Medicine Residency ProgramAdam Olszewski, MD Department of Hematology and OncologyMemorial Hospital of Rhode IslandAlpert 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 ResearchVolume 22, Issue 3, March 2007

Literature Search

Osteoporosis is a known complication: Treated pediatric lymphomas.

Post- chemotherapy for non-Hodgkin lymphoma

Unknown whether presence of a bone marrow-replacing process such as CLL is a significant risk factor for osteopenia or osteoporosis

J Clin Oncol. 1998;16(12):3752-3760.

ASH Annual Meeting Abstracts. 2006;108(11):4607

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 CriteriaCase 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 upEthnicity – not available in majority of casesHeight, weight and calculated BMITobacco use status (current, past, never smoker)

Data Collection

Clinical/Laboratory data:Confirmation with flow cytometryCD38 statusAvailable CLL FISH studiesAdenopathySplenomegalyWhite blood cell count (WBC)Absolute lymphocyte count (ALC)HemoglobinPlateletsBeta-2-microglobulinLactate 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)

cases

MHRI(87)

RIH(53)

Excluded 27

Included 60

Excluded 17

Included 36

Controls

MHRI(120)

4: ALC < 500010: Different diagnosis (“rule out CLL”, “family history of CLL”, “LGL leukemia”, leukocytosis) 12: inadequate follow up information 1: prisoner

Results

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) 26Absolute Lymphocyte Count (median) 40,850/mm3

Hemoglobin (mean) 12.4 g/dLLDH (mean) 202 IU/LVitamin D level (mean) 30.7 ng/mLMedian follow up time 2.9 yrs

12, 11%

96, 89%

Prevalence of osteoporosis in CLL patients

osteoporosis

Prevalence of osteoporosis +osteopenia in CLL patients

79, 82%

12, 13%5, 5% osteopenia

osteoporosis

7, 7%

96, 93%

Prevalance of compression fractures in CLL patients

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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