Long-Term Controlled Trial With Diphosphonate in Patients With Osteolytic Bone Metastases

Elomaa, Inkeri; Blomqvist, Carl; Gröhn, Pentti; Porkka, L.; Kairento, Anna-Liisa; Selander, Katri S.; Lamberg‐Allardt, Christel; Holmström, Teddy

doi:10.1016/s0140-6736(83)92755-1

Cited by 197 publications

(62 citation statements)

References 18 publications

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“…ICTP was also superior to M protein, when these markers were correlated with survival. It is known that production of the M component predicts the stage of the disease with resonable accuracy, but as a single parameter it does not predict survival (Durie & Salmon, 1975 (Elomaa et al, 1983;Merlini et al, 1990). Since the number of patients in the present study is small, we will test the validity of this conclusion in a much larger group of patients, participating in a randomised study on the effect of clodronate, combined with the ordinary treatment with melphalan and prednisolon.…”

Section: Discussionmentioning

confidence: 84%

“…The effect of treatment was followed by determinating serum and urinary M protein, fasting urinary calcium/creatinine (Ca/Cr) and hydroxyproline/creatinine (OHP/Cr) ratios as well as serum calcium, creatinine, alkaline phosphatase (AP) and transaminase concentrations (Elomaa et al, 1983). The samples for serum PICP and ICTP, together with those for the other determinations, were collected one day before starting each treatment course, since corticosteroids have a negative effect on bone collagen formation.…”

Section: Methodsmentioning

confidence: 99%

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Serum concentration of the cross-linked carboxyterminal telopeptide of type I collagen (ICTP) is a useful prognostic indicator in multiple myeloma

Elomaa

Virkkunen²,

Risteli³

et al. 1992

Br J Cancer

136

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Summary Type I collagen is the main collagen type found in mineralised bone. Specific immunoassays for PICP (carboxyterminal propeptide of type I procollagen) and ICTP (cross-linked carboxyterminal telopeptide region of type I collagen) allow simultaneous assessment of the synthesis and degradation of type I collagen in serum samples, respectively. Our aim was to find out whether these metabolites of type I collagen are useful markers for following bone turnover and evaluating treatment response in multiple myeloma, which is a good model disease of excessive osteolysis. Fifteen consecutive patients were studied before and throughout their treatment. Samples for serum PICP and ICTP were collected before starting each treatment course of melphalan and prednisolon. Response to treatment was evaluated by following the changes in M protein and bone roentgenograms. The disease was progressing in four and regressive in 11 patients, but in four of these a recurrence occurred. In nonresponders the ICTP concentration was permanently elevated despite treatment. In responders both increased or normal levels of ICTP were initially observed, but they returned to or remained in the reference interval during treatment. The ICTP concentration increased upon recurring disease. There was a strong correlation between the extent of bone lesions and ICTP. There was no correlation between ICTP and PICP, the latter mainly remaining within the reference range, a finding that suggests no change in bone formation. ICTP was a significant predictor for survival in this patient group (P < 0.05). We conclude that ICTP is a specific and sensitive marker for bone resorption. Simultaneous use of serum ICTP and PICP offers an additional and easy means to follow bone turnover and evaluate the response to therapy in multiple myeloma.Skeletal disease is a major cause of morbidity in myeloma. Bone pain and fractures result from loss of bone. Bone resorption is increased due to osteoclast activating factors, which are elaborated by myeloma cells. One of the most potent factors is lymphotoxin (Garrett et al., 1987).The mainstay of long-term management in multiple myeloma is adequate chemotherapy. The response to treatment has been evaluated by measuring the M proteins. A decrease in or disappearance of the M proteins indicates reduction of tumour mass in the bone marrow, but it does not reflect healing of the skeletal disease (Durie & Salmon, 1975). Therefore measurements of bone metabolism have been used (Kraenzlin et al., 1989).Until recently the only assays available for bone turnover were serum alkaline phosphatase for monitoring bone formation and urinary calcium and hydroxyproline for monitoring bone resorption. None of these is specific for bone and all have been proven insensitive and unreliable. Nowadays more specific assays, namely osteocalcin for the assessment of bone formation and pyridinoline cross-links for the assessment of bone resorption, have been developed (Kraenzlin et al., 1989). Serum osteocalcin is the most abundant noncollageno...

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Section: Discussionmentioning

confidence: 84%

Section: Methodsmentioning

confidence: 99%

Serum concentration of the cross-linked carboxyterminal telopeptide of type I collagen (ICTP) is a useful prognostic indicator in multiple myeloma

Elomaa

Virkkunen²,

Risteli³

et al. 1992

Br J Cancer

136

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“…Therefore, breast cancer patients with extraskeletal metastatic disease and patients with locally advanced disease are at high risk of suffering during their limited survival time, from impairment of their quality of life due to events of skeletal morbidity such as bone pain, pathological fractures and hypercalcaemia. In previous studies, we and others have shown that long-term supportive bisphosphonate treatment reduces significantly skeletal morbidity in patients with breast cancer and established metastatic bone disease [5][6][7][8], and improves selective aspects of quality-of-life [9], The question arises whether bisphosphonate treatment, initiated in the bone metastases-free stage of disease, can prevent or delay the develop ment o f bone involvement.…”

Section: Introductionmentioning

confidence: 99%

Does supportive pamidronate treatment prevent or delay the first manifestation of bone metastases in breast cancer patients?

A¹,

Hermans

Beex

et al. 1996

European Journal of Cancer

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“…Older clinical trials provided initial evidence that patients who were treated with bisphosphonates developed fewer new metastases. In particular, Elomaa et al (1983Elomaa et al ( , 1987 observed this effect after administration of clodronate in a controlled non-randomized study in patients with breast cancer and osseous metastases, although it should be pointed out that the number of patients in each group was small. Following discontinuation of the bisphosphonate, the number of new metastases in the two groups became similar.…”

Section: First Clinical Trialsmentioning

confidence: 98%

Bisphosphonates in the adjuvant treatment of cancer: experimental evidence and first clinical results

Diel

Mundy²

2000

Br J Cancer

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Several animal models, as well as a number of cell culture experiments, indicate a prophylactic effect of bisphosphonates in respect of subsequent bone metastasis. Moreover, in preliminary clinical trials involving patients with advanced breast cancer and local or remote metastases, biophosphonates produced a reduction in new skeletal metastases. This overview summarizes and discusses the results of the latest investigations. It opens with a section on the pathophysiology of bone metastasis, which is followed by a report on animal models and first studies of bisphosphonate treatment as a new approach in systemic adjuvant therapy. © 2000 Cancer Research Campaign

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Long-Term Controlled Trial With Diphosphonate in Patients With Osteolytic Bone Metastases

Cited by 197 publications

References 18 publications

Serum concentration of the cross-linked carboxyterminal telopeptide of type I collagen (ICTP) is a useful prognostic indicator in multiple myeloma

Serum concentration of the cross-linked carboxyterminal telopeptide of type I collagen (ICTP) is a useful prognostic indicator in multiple myeloma

Does supportive pamidronate treatment prevent or delay the first manifestation of bone metastases in breast cancer patients?

Bisphosphonates in the adjuvant treatment of cancer: experimental evidence and first clinical results

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