Bone Abnormalities in Patients with Lymphoid Malignancy.

Background: Lymphoid malignancies can affect bone by direct invasion, bone marrow expansion and possibly by humoral factors causing demineralization. In addition to many individual case reports of patients with lytic lesions or hypercalcemia, two series of 9 and 8 patients, respectively, have been published. {Rossi, 1987; Marcelli, 1988} A prospective series of 65 patients with B-cell malignancies identified 8 with lytic lesions or hypercalcemia, and 40 with increased bone resorption by quantitative bone histology. {Rossi, 1990} The purpose of this study was to determine the frequency of bone abnormalities in patients with newly diagnosed or previously treated lymphocytic malignancies.

Methods: Patients from a single hematology-oncology practice were identified by ICD-9 billing codes and manual chart review. After giving informed consent, patients completed a questionnaire assessing bone symptoms and osteoporosis risk factors of prior fractures, family history for osteoporosis, late menarche, chronic renal disease, alcohol consumption, tobacco use and weight loss. Medical histories, medications, prior bone imaging and bone marrow pathology were obtained by chart review. Imaging studies were performed -- nuclear bone scan, Xrays of skull, spine, pelvis, humeri and femurs, CT scan of pelvis and bone mineral densitometry.

Results: Of 61 patients giving informed consent, 50 completed all parts of the study. Reasons for withdrawal included scheduling conflicts and intercurrent illness. There were 32 males and 18 females, with median age 66 (range 28 to 94). All but 1 were white. Performance status was 0 in 35, 1 in 13 and 2 in 2. Diagnoses were non-Hodgkins lymphoma in 23, chronic lymphocytic leukemia in 16, Hodgkins’ disease in 4, hairy cell leukemia in 3, mantle cell lymphoma in 2 and Waldenstrom’s macroglobulinemia in 2. None had hypercalcemia, but 8 had clinically significant bone destruction due to direct tumor extension, 1 had additional asymptomatic “metastases” on bone scan, distant from the biopsy-proven bone lesion, 2 had clinically “silent” lytic bone lesions on Xray and 4 had previously undiagnosed vertebral or rib fractures, associated with diminished bone mineral density (BMD). T-scores were low in 30, with 7 having osteoporosis and 23 having osteopenia. Patients with all diagnoses were affected, unrelated to time since diagnosis or treatment.

Conclusion: Patients with lymphoid malignancies are frequently at risk for bone abnormalities, especially demineralization. Decreased BMD is seen in most patients, regardless of age, osteoporotic risk factors, age or time since diagnosis or treatment. Patients with current or prior lymphoid malignancies should be offered bone densitometry, with appropriate therapy to reverse bone damage. Mechanisms might include osteoclast activation, possibly mediated by IL-6 or RANK-L. Prospective studies should be conducted to elucidate mechanisms and to find treatments to improve bone mineral density.