Bortezomib increases osteoblast activity in myeloma patients irrespective of response to treatment

Heider, Ulrike; Kaiser, Martin; Müller, Christian; Jakob, Christian; Zavrski, Ivana; Schulz, Carsten-Oliver; Fleissner, Claudia; Hecht, Monica; Sezer, Orhan

doi:10.1111/j.1600-0609.2006.00692.x

Cited by 138 publications

(112 citation statements)

References 32 publications

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“…20 Recent studies demonstrated that bone markers, which reflect osteoclast and osteoblast activity, can be modulated by novel agents such as proteasome inhibitors or immunmodulatory drugs. [21][22][23][24] Because of the clinical relevance of myeloma bone disease, we hypothesized that the bone resorption marker ICTP may add to the prognostic value of ISS. Thus, we evaluated the adverse prognostic impact of ICTP in combination with established prognostic factors in a patient cohort of 100 consecutive newly diagnosed patients with symptomatic MM.…”

Section: Introductionmentioning

confidence: 99%

Incorporation of the bone marker carboxy-terminal telopeptide of type-1 collagen improves prognostic information of the International Staging System in newly diagnosed symptomatic multiple myeloma

et al. 2008

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Section: Introductionmentioning

confidence: 99%

Incorporation of the bone marker carboxy-terminal telopeptide of type-1 collagen improves prognostic information of the International Staging System in newly diagnosed symptomatic multiple myeloma

et al. 2008

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“…93,94 As described by Heider et al, the combination of bortezomib ± dexamethasone produced significant increases in serum bALP and OC in both responders and non-responders. 95 Giuliani et al found significant increases in the number of osteoblasts per mm 2 of bone tissue in trephine biopsies of patients responding to bortezomib, but not in subjects who did not respond. 96 Terpos et al showed that, in 34 patients bortezomib monotherapy reduced serum Dkk-1 and RANKL levels.…”

Section: Bortezomibmentioning

confidence: 99%

“…Indeed, Heider et al found an attenuated increase in bALP in patients who received VD compared with those who received bortezomib monotherapy. 95 Thus, although different effective anti-myeloma regimens in combination with bisphosphonates can reduce bone resorption through reduction of tumor burden and inhibition of osteoclast function, 63 to-date only bortezomib has clearly shown an anabolic bone effect in MM.…”

Section: Bortezomibmentioning

confidence: 99%

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

et al. 2010

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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 antimyeloma 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.

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“…Osteoblast stimulation by bortezomib was also reported by Heider et al, 87 who measured changes in bALP and OC, in patients who received bortezomib7dexamethasone (n ¼ 25) and in a control group of patients who received adriamycin/ dexamethasone, melphalan/prednisone or thalidomide-containing therapy (n ¼ 58). Significant increases in bALP and OC following bortezomib treatment were observed in both responders and non-responders, irrespective of whether dexamethasone was included in the treatment regimen.…”

Section: Clinical Studiesmentioning

confidence: 93%

The effect of novel anti-myeloma agents on bone metabolism of patients with multiple myeloma

2007

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Immunomodulatory drugs (IMiDs) and bortezomib have been recently used in the management of patients with both newly diagnosed and relapsed/refractory multiple myeloma. Except of their direct anti-myeloma effect, these agents also alter the interactions between myeloma cells and marrow microenvironment. Several recent studies have investigated their potential effect on myeloma bone disease. Preclinical studies have demonstrated that IMiDs reduce osteoclast formation and function in vitro. Clinical studies have confirmed that thalidomide reduces markers of bone resorption, while lenalidomide induces osteoclast arrest in myeloma patients. However, IMiDs seem to have no effect on osteoblast exhaustion present in myeloma. The proteasome inhibitor bortezomib restores abnormal bone remodeling through the inhibition of osteoclast function and the increase in osteoblast differentiation and activity in vitro. In myeloma patients, bortezomib reduces biochemical markers of bone resorption and normalizes the RANKL/osteoprotegerin ratio, while at the same time increases bone formation markers reducing levels of dickkopf-1 protein.Whether these effects are direct and not only a consequence of the agents' antimyeloma activity is not totally clear. This review summarizes all available data for these attractive agents that combine potent anti-myeloma activity with beneficial effects on bone and may alter the way of management of myeloma-related bone disease.

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Bortezomib increases osteoblast activity in myeloma patients irrespective of response to treatment

Abstract: These data show that treatment with bortezomib leads to enhanced markers of osteoblast activity in patients with myeloma. The comparison with the control group suggests that the effect on osteoblasts is unique to the proteasome inhibitor.

Cited by 138 publications

References 32 publications

Incorporation of the bone marker carboxy-terminal telopeptide of type-1 collagen improves prognostic information of the International Staging System in newly diagnosed symptomatic multiple myeloma

Incorporation of the bone marker carboxy-terminal telopeptide of type-1 collagen improves prognostic information of the International Staging System in newly diagnosed symptomatic multiple myeloma

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

The effect of novel anti-myeloma agents on bone metabolism of patients with multiple myeloma

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