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CLINICAL STUDIES

Bone Densitometry in Patients With Multiple Myeloma XAVIERMARIETTE,M.D., PIERREKHALIFA,M.D., PHILIPPERAVAUD,M.D., JACQUESFRIJA, M.D., MAURICELAVAL-JEANTET,M.D., CLAUDECHASTANG,M.D., Ph.D., JEANCLAUDEBROUET,M.D., Ph.D., JEANPAULFERMAND,M.D., faris, France

PURPOSE,PATIENTS,ANDlWEl'HO~weperformed dual-energy x-ray abeorptiometry in 10 selected patients with aggressive multiple myeloma in whom substantial tumor mass reduction was achieved after high-dose chemoradiotherapy followed by autologow blood stem cell transphlntatiolL RI%XJLT& In moat cases, bone mineral density (BMD) of the spine was initially low (Mean Z scorn -2.69, SEM 0.76) and dramatically increased after treatment (mean increase 16.4%; 7.7% with 95% confidence interval 2.2 to 12.2, excluding one patient whose spine BMD increased by 94.8%). In contrast, skeletal roentgenograms, computed tomographic scans, and magnetic resonance imaging did not reveal any significant improvement of patients’ bone 1esionJL CONCLUSIONs:hpatientswith mukiplemyeloma, bone densitometry could be a useful way to asse68 the efficacy of treatment on bone status.

From the Services d’lmmuno-h&matologie (XM. JCB. JPF), de Radiologie (JF. MU). et de Biostatistique (CC), Mpital Saint-Louis; Laboratoire d’Ost6odensitom&rie (PK), LOS; and Service de Rhumatologie (PR). Mpital Cochin, Paris, France. Requests for reprints should be addressed to J.P. Fermand, M.D., Service d’lmmuno-h6matologie. H6pital Saint-Louis, 1, avenue Claude Vellefaux. 75475 Paris cedex 10, France. Manuscript submitted October 3, 1991, and accepted in revised form March 11, 1992.

D

emineralization and lytic bone lesions (LBL) are common features of patients with multiple myeloma and are usually assessed by conventional radiography, computed tomography (CT), and magnetic resonance imaging (MRI). MRI is the most sensitive imaging technique for detecting LBL, but the technique lacks specificity [l]. Bone mass can now be measured by dual-energy X-ray absorptiometry (DXA), which provides useful information for the management of patients with various bone diseases [2]. To evaluate bone densitometry in multiple myeloma, we performed DXA in 10 patients before and 1 year after treatment with high-dose chemotherapy, total body irradiation (TBI), and autologous blood stem cell transplantation. In most cases, we observed a dramatic increase of lumbar bone mass, whereas imaging techniques did not reveal any significant improvement of bone lesions.

PATIENTS AND METHODS Ten patients (eight men and two women) with stage III multiple myeloma were treated with highdose chemotherapy (melphalan, carmustine, cyclophosphamide, and etoposide) and total body irradiation followed by autografting using blood stem cells [3]. These were collected at diagnosis by leukaphereses performed at hematologic recovery of a cytotoxic drug-induced aplasia [3]. Between blood stem cell collection and autografting, patients received three monthly courses of vincristine, Adriamycin, and methylprednisolone. All patients were white except for one black male patient (Patient I, Figure 1). The mean age was 44.7 years (range: 35 to 54 years). After high-dose chemotherapy, total body irradiation, and autografting, all 10 patients had a minimal residual disease characterized by fewer than 5% plasma cells on bone marrow smears and by a low level of the monoclonal component. In six patients, the monoclonal component was detected only by sensitive immunochemical techniques. No additional treatment was delivered. Current median follow-up is 25.5 months (range: 20.4 to 28.9 months). One patient experienced a relapse and died at 19 months, whereas all other

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PATIENTS Figure 1. Spine bone mineral (Patients A through J).

patients disease.

are well with

density

(BMD)

(g/cm2)

stable minimal

before

(dark

residual

Measurement of Bone Mineral Density Bone mineral density (BMD) was measured at the lumbar spine (anteroposterior view Ll through L4) and left femoral neck by DXA using a standard single QDR-1000 X-ray bone densitometer (Hologic Inc., Waltham, MA). The long-term precision on a hydroxyapatite spine phantom was 0.5%. As assessed by in vivo control studies, reproducibility was 0.4% for the lumbar spine and 1.7% for the femoral neck [4]. For each patient, two series of measurements were performed by the same observer in identical regions, one at diagnosis and the other 8 to 12 months after high-dose chemotherapy, total body irradiation, and grafting. In all 10 patients, radiographic, CT, and MRI studies of the lumbar spine were performed at the same time as DXA. Results were expressed as g/cm2 and as a Z score. Z score values were calculated for each patient, representing the number of standard deviations above or below the statistical mean for age- and sexmatched healthy men or women. For men’s spine and hip BMD, normal reference values provided by the manufacturer (Hologic) were used and showed a mean 0.2% per year decrease between 30 and 60 years of age. Normal women’s values were established in 400 French women of different ages; mean 596

December 1992 The American Journal of Medicine

bars)

and after

(hatched

bars)

treatment

in the

10 patients

decreases before and after menopause were 0.5% to 1% and 2% to 4% per year, respectively [5,6, and P. Khalifa, unpublished data]. Absolute and relative differences of BMD were calculated and compared to zero using parametric and nonparametric (Wilcoxon) tests.

RESULTS At diagnosis, skeletal radiographs, CT scans, and MRI showed multiple LBL in all patients but two: one patient (Patient J) had normal skeletal imagery, whereas the other (Patient I) had only a few cranial lesions. Lumbar vertebral fractures were obvious in two patients (Patients B and H). During follow-up, a lumbar vertebral fracture did not occur in any case, and comparative analysis of lateral radiographs of lumbar spine did not show any significant change in the posterior heights of Ll through L4. Furthermore, sequential imaging studies did not disclose either improvement or further deterioration of vertebral integrity and of LBL. Mean initial lumbar BMD was 0.757 g/cm2 @EM 0.077). The mean Z-score was -2.69 (SEM 0.76). Only two patients (Patients I and J) had a positive Z-score. The mean initial value of femoral neck BMD was 0.759 g/cm2 (SEM 0.046), and the mean Z-score was -0.89 (SEM 0.47). Treatment-induced changes in spine BMD are shown in Figure 1. BMD increased in all patients except for the two women (Patients D and J). The

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BONE DENSITOMETRY AND MULTIPLE MYELOMA / MARIETTE ET AL

mean increase was 0.080 g/cm2 (SEM 0.027; p

Bone densitometry in patients with multiple myeloma.

We performed dual-energy x-ray absorptiometry in 10 selected patients with aggressive multiple myeloma in whom substantial tumor mass reduction was ac...
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