Diagnosis, treatment, and response assessment in solitary plasmacytoma: updated recommendations from a European Expert Panel.

Solitary plasmacytoma is an infrequent form of plasma cell dyscrasia that presents as a single mass of monoclonal plasma cells, located either extramedullary or intraosseous. In some patients, a bone marrow aspiration can detect a low monoclonal plasma cell infiltration which indicates a high risk of early progression to an overt myeloma disease. Before treatment initiation, whole body positron emission tomography-computed tomography or magnetic resonance imaging should be performed to exclude the presence of additional malignant lesions. For decades, treatment has been based on high-dose radiation, but studies exploring the potential benefit of systemic therapies for high-risk patients are urgently needed. In this review, a panel of expert European hematologists updates the recommendations on the diagnosis and management of patients with solitary plasmacytoma.

Whole-body computed tomography versus conventional skeletal survey in patients with multiple myeloma: a study of the International Myeloma Working Group.

For decades, conventional skeletal survey (CSS) has been the standard imaging technique for multiple myeloma (MM). However, recently whole-body computed tomography (WBCT) has been implemented into the diagnostic criteria of MM. This analysis compares sensitivity and prognostic significance of WBCT and CSS in patients with smoldering MM (SMM) and MM. Fifty-four of 212 patients (25.5%) had a negative CSS and a positive WBCT for osteolytic lesions (P<0.0001). Of 66 patients with SMM based on CSS, 12 (22.2%) had osteolytic lesions on WBCT. In comparison, WBCT failed to detect some bone destructions in the appendicular skeleton possibly due to limitations of the field of view. Presence of lytic bone lesions in WBCT was of borderline prognostic significance (P=0.051) for SMM patients, with a median time to progression of 38 versus 82 months for those without bone destructions. In conclusion, WBCT identifies significantly more sites of bone destruction than CSS. More than 20% of patients with SMM according to CSS have in fact active MM detectable with WBCT. On the basis of this and other studies, WBCT (either computed tomography (CT) alone or as part of a positron emission tomography-CT protocol) should be considered the current standard for the detection of osteolytic lesions in MM.

Salvage bortezomib-dexamethasone and high-dose melphalan (HDM) and autologous stem cell support (ASCT) in myeloma patients at first relapse after HDM with ASCT. A phase-2 trial.

Until recently, only retrospective studies had been published on salvage high-dose melphalan (HDM) with autologous stem cell 'transplantation' (ASCT). In a prospective, nonrandomized phase-2 study, we treated 53 bortezomib-naïve patients with bortezomib-dexamethasone as induction and bortezomib included in the conditioning regimen along with the HDM. Median progression-free survival (PFS), time to next treatment (TNT) and overall survival (OS) after start of reinduction therapy were 21.6, 22.8 and 46.6 months, respectively. For 49 patients who completed salvage bortezomib-HDM(II) with ASCT, there was no significant difference of PFS and TNT after HDM (II) compared with after the initial HDM(I), and thus patients were their own controls (PFS (I: 20.1 vs II: 19.3 months (P=0.8)) or TNT (I: 24.4 vs II: 20.7 months (P=0.8)). No significant differences in the response rates after salvage ASCT compared with the initial ASCT. Bortezomib-HDM conditioning combo was feasible, and toxicity was as expected for patients treated with bortezomib and ASCT. In conclusion, in bortezomib-naïve patients treated at first relapse with salvage ASCT including bortezomib, PSF and TNT did not differ significantly from initial ASCT and median OS was almost 5.5 years with acceptable toxicity. A recent prospective randomized study confirms salvage ASCT to be an effective treatment.

Autologous stem cell transplantation versus novel drugs or conventional chemotherapy for patients with relapsed multiple myeloma after previous ASCT.

High-dose therapy (HDT) followed by autologous stem cell transplantation (ASCT) is the most common first-line treatment for patients with multiple myeloma (MM) under 65 years of age. A second ASCT at first relapse is frequently used but is challenged by the use of novel drugs. We retrospectively studied the outcome of second-line treatment in MM patients from the Nordic countries with relapse after first-line HDT and ASCT. Patients that underwent a second ASCT (n=111) were compared with patients re-treated with conventional cytotoxic drugs only (n=91) or with regimens including novel drugs (proteasome inhibitors and/or immunomodulatory drugs) (n=362) without a second ASCT. For patients receiving a second ASCT median overall survival was 4.0 years compared with 3.3 years (P<0.001) for the group treated with novel drugs and 2.5 years (P<0.001) for those receiving conventional cytotoxic drugs only. A second ASCT also resulted in a significantly longer second time to progression and a significantly longer time to next treatment. We conclude that, irrespective of the addition of novel drugs, MM patients in first relapse after ASCT still appear to benefit from a second ASCT. A second ASCT should be considered for all physically fit patients.

The use of biochemical markers of bone remodeling in multiple myeloma: a report of the International Myeloma Working Group.

Lytic bone disease is a frequent complication of multiple myeloma (MM). Lytic lesions rarely heal and X-rays are of limited value in monitoring bone destruction during anti-myeloma or anti-resorptive treatment. Biochemical markers of bone resorption (amino- and carboxy-terminal cross-linking telopeptide of type I collagen (NTX and CTX, respectively) or CTX generated by matrix metalloproteinases (ICTP)) and bone formation provide information on bone dynamics and reflect disease activity in bone. These markers have been investigated as tools for evaluating the extent of bone disease, risk of skeletal morbidity and response to anti-resorptive treatment in MM. Urinary NTX, serum CTX and serum ICTP are elevated in myeloma patients with osteolytic lesions and correlate with advanced disease stage. Furthermore, urinary NTX and serum ICTP correlate with risk for skeletal complications, disease progression and overall survival. Bone markers have also been used for the early diagnosis of bone lesions. This International Myeloma Working Group report summarizes the existing data for the role of bone markers in assessing the extent of MM bone disease and in monitoring bone turnover during anti-myeloma therapies and provides information on novel markers that may be of particular interest in the near future.

The polymorphism IL-1beta T-31C is associated with a longer overall survival in patients with multiple myeloma undergoing auto-SCT.

Proinflammatory cytokines are suspected to play a role in the pathogenesis of multiple myeloma (MM). Therefore, it is possible that inborn genetic variations leading to a modified expression of these cytokines will influence the outcome for these patients. We investigated 348 MM patients undergoing high-dose melphalan treatment followed by Auto-SCT and examined the influence of single nucleotide polymorphisms (SNPs) in genes involved in the inflammatory response. We found that the polymorphism IL-1beta T-31C significantly influenced overall survival (OS; P=0.02) and that carriers of the variant C-allele had a significantly longer survival than homozygous wild-type allele TT-carriers (relative risk 0.6 (95% CI=0.5-0.9); P=0.008). The polymorphisms IL-6 G-174C, IL-10 C592A, PPARgamma2 Pro(12)Ala, COX-2 A-1195G, COX-2 T8473C and NFKB1 ins/del did not influence the OS in this group of patients. Furthermore, homozygous carriers of the variant allele of IL-1beta T-31C were at 1.37-fold (CI=1.05-1.80) increased risk of MM as compared with population-based controls (P=0.02). Our results indicate that IL-1beta is involved in the pathogenesis of MM.

Serum osteoprotegerin levels are reduced in patients with multiple myeloma with lytic bone disease.

Osteoprotegerin (OPG), the neutralizing decoy receptor for the osteoclast activator RANK ligand, was measured in serum taken from patients with multiple myeloma at the time of diagnosis. Median OPG was lower in the patients with myeloma (7.4 ng/mL; range, 2.6-80; n = 225) than in healthy age- and sex-matched controls (9.0 ng/mL; range 5.1-130; n = 40; P =.02). Importantly, OPG levels were associated with degree of radiographically assessed skeletal destruction (P =.01). The median OPG level in patients lacking osteolytic lesions was 9.1 ng/mL, as compared with 7.6 ng/mL and 7.0 ng/mL, respectively, in patients with minor or advanced osteolytic disease. Furthermore, OPG levels were associated with World Health Organization performance status (P =.003) and correlated to serum levels of carboxy-terminal propeptide of type I procollagen (PICP; P <.001) but not with clinical stage or survival. These findings suggest impaired OPG function in myeloma and give a rationale for OPG as a therapeutic agent against myeloma bone disease.

High levels of soluble syndecan-1 in myeloma-derived bone marrow: modulation of hepatocyte growth factor activity.

Syndecan-1 is a heparan sulfate proteoglycan expressed on the surface of, and actively shed by, myeloma cells. Hepatocyte growth factor (HGF) is a cytokine produced by myeloma cells. Previous studies have demonstrated elevated levels of syndecan-1 and HGF in the serum of patients with myeloma, both of negative prognostic value for the disease. Here we show that the median concentrations of syndecan-1 (900 ng/mL) and HGF (6 ng/mL) in the marrow compartment of patients with myeloma are highly elevated compared with healthy controls and controls with other diseases. We show that syndecan-1 isolated from the marrow of patients with myeloma seems to exist in an intact form, with glucosaminoglycan chains. Because HGF is a heparan-sulfate binding cytokine, we examined whether it interacted with soluble syndecan-1. In supernatants from myeloma cells in culture as well as in pleural effusions from patients with myeloma, HGF existed in a complex with soluble syndecan-1. Washing myeloma cells with purified soluble syndecan-1 could effectively displace HGF from the cell surface, suggesting that soluble syndecan-1 can act as a carrier for HGF in vivo. Finally, using a sensitive HGF bioassay (interleukin-11 production from the osteosarcoma cell line Saos-2) and intact syndecan-1 isolated from the U-266 myeloma cell line, we found that the presence of high concentrations of syndecan-1 (more than 3 microg/mL) inhibited the HGF effect, whereas lower concentrations potentiated it. HGF is only one of several heparin-binding cytokines associated with myeloma. These data indicate that soluble syndecan-1 may participate in the pathology of myeloma by modulating cytokine activity within the bone marrow.

Biochemical markers of bone metabolism reflect osteoclastic and osteoblastic activity in multiple myeloma.

In order to evaluate the use of recently developed assays of bone metabolism in multiple myeloma we performed a histomorphometric study of bone biopsies in 16 myeloma patients. Furthermore, we measured the levels of interleukin-6 (IL-6), soluble IL-6 receptor (IL-6sR), IL-1beta, tumour necrosis factor (TNF) alpha, TNFbeta, and transforming growth factor (TGF) beta in marrow plasma aspirated from the biopsy area. MARKERS OF BONE RESORPTION: The N-terminal telopeptide of collagen I (Ntx) in urine showed a strong positive correlation with the dynamic histomorphometric indices of bone resorption (r=0.68-0.72). Slightly weaker correlations were observed between the dynamic indices of bone resorption and the C-terminal telopeptide of collagen I (ICTP) in serum (r= 0.57-0.62) and deoxypyridinoline (Dpyr) in urine (r= 0.54), whereas urinary pyridinoline (Pyr) did not correlate with the histomorphometric findings. MARKERS OF BONE FORMATION: Serum C-terminal propeptide of procollagen I (PICP) and serum bone-specific alkaline phosphatase (bAP) showed significant correlations with the dynamic parameters of bone formation (r=0.57-0.58), whereas serum osteocalcin and serum total AP did not. CYTOKINES: Highly significant correlations were observed between marrow IL-6 and rates of bone resorption and activation frequency (r=0.76-0.82) and with serum ICTP (r=0.63). Minor, but also significant correlations were observed between the resorptive indices and IL-6sR and IL-1beta. The data indicate that measurements of the biochemical markers of bone metabolism may be useful in monitoring myeloma bone disease, and might thus be of use for dose titration of bisphosphonate therapy.

Serum syndecan-1: a new independent prognostic marker in multiple myeloma.

Serum samples drawn at diagnosis from 174 myeloma patients were analyzed for the presence of the heparan [corrected] sulfate proteoglycan, syndecan-1. Syndecan-1 was elevated in 79% of patients (median, 643 units/mL) compared with 40 healthy controls (median, 128 units/mL), P <.0001. Serum syndecan-1 correlated with the following: serum creatinine, secretion of urine M-component over the course of 24 hours, soluble interleukin-6 (IL-6) receptor, C-terminal telopeptide of type I collagen, beta(2)-microglobulin, percentage of plasma cells in the bone marrow, disease stage, and serum M-component concentration. In order to evaluate syndecan-1 as a prognostic marker in multiple myeloma, it was entered into a multivariate Cox regression model. Data from 138 patients were available for this analysis. As a continuous variable, syndecan-1 was an independent prognostic parameter in addition to serum beta(2)-microglobulin and World Health Organization performance status. When syndecan-1 was dichotomized by the best cutoff (66th percentile, 1170 units/mL), the survival difference between the groups was highly significant: "high" syndecan-1 group had a median survival of 20 months, and the "low" syndecan-1 group had a median of 44 months (P <.0001). We conclude that syndecan-1 is a new independent prognostic parameter in multiple myeloma, and its role in prognostic classification systems should be further investigated. (Blood. 2000;95:388-392)

Danish patients with untreated multiple myeloma do not harbour human herpesvirus 8.

The role of human herpesvirus 8 (HHV-8) in multiple myeloma (MM) remains controversial. We examined 15 Danish MM patients before cytoreductive therapy. Mononuclear cells isolated from peripheral blood and bone marrow aspirates, as well as long-term cultured bone marrow stromal cells, were assayed for the presence of HHV-8 DNA. All material was tested by three simple unnested polymerase chain reaction (PCR) assays (amplifying regions of ORF26, ORFK1 and ORF75) and two nested PCR assays (amplifying regions of ORF26). HHV-8 was not demonstrated in any of the samples. Our findings do not suggest an association between HHV-8 and MM in the Danish population.

Prognostic evaluation in multiple myeloma: an analysis of the impact of new prognostic factors.

We have analysed the prognostic information for survival of presenting features in an unselected series of 394 myeloma patients. 15 variables with significant prognostic information were identified, among these were some not previously or only recently reported: serum levels of hepatocyte growth factor (HGF), interleukin-6 (IL-6), C-terminal cross-linked telopeptide of collagen I (ICTP) and soluble interleukin-6 receptor (sIL-6R). In a multivariate Cox analysis six variables were significantly and independently associated with poor survival: high age, low W.H.O.-performance status (PS), high serum levels of calcium, beta-2-microglobulin (beta-2M), IL-6 and sIL-6R. A risk score formed to predict survival for each percentile of the patient population allowed an efficient separation of prognostic groups. The discriminating power of the model compared favourably with three other previously published staging systems applied to the study population. Exclusion of IL-6 and sIL-6R from the model only marginally decreased the efficacy of the separation. The predictive value of some variables (sIL-6R, beta-2M and W.H.O.-PS) decreased significantly over time. We conclude that formation of a risk score based on independent variables is an efficient way to separate prognostic groups, that the contribution of new and not easily available parameters should be thoroughly evaluated before inclusion in prognostic models for clinical use and that the predictive value of parameters may decrease over time.

Long-term oral pamidronate treatment inhibits osteoclastic bone resorption and bone turnover without affecting osteoblastic function in multiple myeloma.

This study was performed as a cross-sectional substudy to the Danish-Swedish Pamidronate Study, a randomized placebo-controlled multicentre trial in multiple myeloma. The purpose was to evaluate the biological effects of long-term treatment with oral pamidronate 300 mg daily on bone metabolism by using histomorphometry and analysis of cytokines and biochemical markers of bone turnover. Sixteen patients were included after median 27.5 months of protocolized treatment; 10 patients received active treatment and 6 patients placebo. When compared with placebo, pamidronate treatment was associated with: (a) marked decreased osteoclastic resorption rate (0.86+/-0.59 microm/d vs. 5.7+/-5.0 microm/d, p=0.002), and diminished activation frequency (0.20+/-0.18 yr(-1) vs. 0.72+/-0.55 yr(-1), p=0.014); (b) compensatory reduced volume referent bone formation rate (0.17+/-0.21 yr(-1) vs. 0.71+/-0.54 yr(-1), p=0.007), but unaltered mineral appositional rate; (c) neutral (-0.66+/-5.6 mm) vs. negative (-2.15+/-2.2 microm, p=0.013) bone balance per remodelling cycle; (d) higher trabecular bone volume (21.0+/-6.2% vs. 13.0+/-3.7%, p=0.01); (e) suppressed urinary excretion and serum levels of some of the biochemical markers of bone metabolism; and (f) significant reduction of circulating soluble interleukin-6 receptor (IL-6sR) (25.9+/-4.1 ng/ml vs. 32.1+/-6.6 ng/ml, p=0.04), and (g) a uniform tendency of lower serum and marrow plasma levels of IL-6, IL-1beta, and TNFalpha. Thus oral pamidronate was absorbed in biologically active amounts, and reduced overall bone resorption and bone turnover without impairing osteoblastic bone formation. The observation that cytokine and cytokine receptor levels were reduced extends the possible and potential beneficial actions of bisphosphonates in multiple myeloma.

Failure of oral pamidronate to reduce skeletal morbidity in multiple myeloma: a double-blind placebo-controlled trial. Danish-Swedish co-operative study group.

In order to study whether oral bisphosphonate therapy might prevent or reduce skeletal-related morbidity in patients with newly diagnosed multiple myeloma who required chemotherapy, 300 patients were included in a randomized multi-centre trial. Patients were given oral pamidronate at a dose of 300 mg daily, or placebo, in addition to conventional intermittent melphalan/prednisolone (and in some cases alpha-interferon) treatment. With a median treatment duration of about 550d, no statistically significant reduction in skeletal-related morbidity (defined as bone fracture, related surgery, vertebral collapse, or increase in number and/or size of bone lesions) could be demonstrated. Pamidronate treatment also did not have any influence on patient survival or on the frequency of hypercalcaemia. However, in patients treated with pamidronate there were fewer episodes of severe pain (P=0.02) and a decreased reduction of body height of 1.5 cm (P= 0.02). The overall negative result of the study is attributed to the very low absorption of orally administered bisphosphonates in general.

Elevated serum concentrations of hepatocyte growth factor in patients with multiple myeloma. The Nordic Myeloma Study Group.

Serum from 398 myeloma patients at diagnosis and serial samples from 29 patients were analysed for hepatocyte growth factor (HGF). HGF was elevated at diagnosis in 43% of myeloma patients compared with healthy controls (median 1.00 ng/mL and 0.44 ng/mL, respectively; P < .00001). In the group with elevated HGF levels 46% of the patients reached plateau phase, as compared with 60% of the patients with low HGF levels (P = .005), and the median survival time was 21 and 32 months, respectively (P = .002). In a univariate Cox regression analysis, HGF was a significant predictor of mortality (P = .02). In the subgroup of patients with beta 2-microglobulin levels less than or equal to 6 mg/L, high versus low HGF was a prognostic factor when a multivariate Cox regression analysis was performed. In serial samples HGF was higher at the time of diagnosis and relapse (median 0.57 ng/mL and 0.52 ng/mL, respectively; P = .0018) than at response (median 0.24 ng/mL, P = .008). We conclude that HGF may be a useful follow-up parameter in myeloma patients. Measurement of HGF may identify a group of patients with poor response to melphalan-prednisone treatment and short survival. HGF was a prognostic factor in patients with high levels of beta 2-microglobulin.

Bone marrow fibrosis and disease activity in multiple myeloma monitored by the aminoterminal propeptide of procollagen III in serum.

Simple bone marrow fibrosis is seen in 10-30% of multiple myeloma (MM) patients. We investigated the incidence and characteristics of the bone marrow stromal alterations, in order to characterize the collagens involved by immunohistochemistry, and to evaluate the use of serum aminoterminal propeptide of type III procollagen (PIIINP) as a marker of marrow fibrogenesis and disease activity in MM. 34 consecutive patients with newly diagnosed MM were included prospectively, and followed for 12-30 months. Compared with the findings in 15 normal individuals we found increased interstitial deposits of collagen III in 48% of MM patients, whereas deposits of collagen I were not increased. Interstitial fibrosis appeared to be restricted to areas of severe plasma cell infiltration, but it could also have a more dispersed presentation in the severely infiltrated marrow. There was a high co-distribution of collagen III fibrils and reticulin fibres. Serum PIIINP levels were elevated in most patients, and in the follow-up study serum PIIINP showed a good correlation with the response to treatment. Patients with resistant or progressive disease had continually elevated levels of PIIINP. In most patients with responsive disease serum PIIINP normalized, and we observed no relapses in patients who had normal serum PIIINP levels. Other patients who responded to treatment by reduced M-component level, but had persistently elevated serum levels of PIIINP, had either early relapses or developed progression of osteolytic lesions in spite of unchanged M-component levels. Therefore an elevated serum PIIINP during treatment might indicate an active malignant clone. Serum PIIINP does not simply follow the M-component, but gives further information of potential therapeutic value.

Abnormal bone turnover in monoclonal gammopathy of undetermined significance: analyses of type I collagen telopeptide, osteocalcin, bone-specific alkaline phosphatase and propeptides of type I and type III procollagens.

The main difference between monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma (MM) is the presence of lytic bone destructions in the latter. About 20% of MGUS patients develop MM, and histomorphometric studies have shown disturbed bone turnover rates in some of these patients. This study was performed in order to evaluate whether serum analyses of the C-terminal telopeptide of type I collagen (ICTP), as a reflector of bone degradation, and of osteocalcin, bone-specific alkaline phosphatase (bAP) and the C-terminal propeptide of type I procollagen (PICP), as markers of bone formation, might give information on disturbances of bone metabolism in MGUS. Furthermore, serum N-terminal propeptide of procollagen III (PIIINP) might give information on disturbances in collagen III metabolism in the bone marrow. In the 35 patients examined, serum ICTP was elevated in 12 patients (34%), serum PIIINP elevated in 6 patients (17%), serum osteocalcin elevated in 11 patients (31%), serum bAP elevated in 6 patients (17%), and serum PICP elevated in 4 patients (11%). Serum ICTP correlated significantly with PIIINP (r = 0.72, p < 0.001), and with serum osteocalcin (r = 0.57, p < 0.001) and serum bAP (r = 0.51, p = 0.002). These findings indicate disturbances of bone turnover and affected collagen metabolism in some MGUS patients. Follow-up observation may reveal any prognostic value of these findings.

Serum markers of bone metabolism in multiple myeloma: prognostic value of the carboxy-terminal telopeptide of type I collagen (ICTP). Nordic Myeloma Study Group (NMSG).

This study was performed to evaluate the prognostic significance of serum markers of bone and collagen metabolism in multiple myeloma. Serum C-terminal telopeptide of type I collagen (ICTP) reflects degradation of bone, whereas serum osteocalcin, together with serum C-terminal propeptide of procollagen type I (PICP) and serum bone-specific alkaline phosphatase (bAP) reflect synthesis of bone matrix. The N-terminal propeptide of procollagen type III (PIIINP) in serum reflects synthesis of type III collagen. We analysed frozen sera from 109 patients with newly diagnosed multiple myeloma. Serum ICTP was elevated (> 5.0 micrograms/l) in most patients (median 6.6 micrograms/l range 1.4-29.4 micrograms/l). Serum PIIINP was elevated (> 4.2 micrograms/l) in 46% (median 4.0 micrograms/l, range 1.4-20.1 micrograms/l). Serum PICP was generally within the reference limits, whereas serum osteocalcin and serum bAP were elevated in 19% and 37%, respectively. Serum ICTP correlated with serum PIIINP, serum beta 2-microglobulin (beta 2m), serum calcium, performance status, and stage. In univariate analysis, the test variables serum ICTP (P = 0.026) and serum osteocalcin (P = 0.036) were found to be of prognostic value, but PIIINP, PICP, or bAP in serum were not. Serum ICTP and serum beta 2m had a similar prognostic value. In multivariate analysis, serum calcium showed the highest prognostic significance, and serum beta 2m was the only other variable of independent prognostic value. However, in normocalcaemic patients, serum ICTP showed the highest prognostic significance, followed by serum osteocalcin. Thus, the serum levels of ICTP and osteocalcin seem related to bone turnover and calcium metabolism, and provide further information about myeloma activity, particularly in normocalcaemic patients.

Assessment of bone involvement in patients with multiple myeloma using bone densitometry.

To evaluate the use of dual energy X-ray absorptiometry (DXA) in multiple myeloma (MM) we performed a prospective study of 34 patients with newly diagnosed MM. Most patients had advanced disease and all but two patients had osteolytic bone destructions and/or pathological fractures. Bone mineral content (BMC) and bone mineral density (BMD) of the lumbar spine (L1-L4) and hip were measured using a Hologic QDR-1000 scanner. Collapsed vertebrae were not excluded from analysis. Data from 289 healthy Danish volunteers aged 21-79 yr were used for calculation of Z-scores. Lumbar spine BMC (Z-score -0.46 +/- 0.23, p = 0.05) and lumbar spine BMD (Z-score -0.56 +/- 0.23, p = 0.02) were significantly reduced in MM patients, whereas no reduction was seen in hip BMC or BMD. Collapsed vertebrae had marked reduced BMD (Z-score -1.34 +/- 0.22, p < 0.001), as had non-fractured vertebrae in the same individuals (Z-score -1.42 +/- 0.25, p < 0.001). Lumbar spine BMD correlated with radiologically assessed bone morbidity (r -0.37, p = 0.03) and stronger with the incidence of vertebral fractures (r -0.64, p < 0.001). Thus, osteopenia of the back is common in multiple myeloma and correlates with an increased incidence of fractures. DXA may identify subjects with increased risk of vertebral fractures for more intensive chemotherapeutic or anti-resorptive treatment.