Double-blind, randomised, placebo-controlled, dose-finding study of oral ibandronate in patients with metastatic bone disease

Coleman, Robert E.; Purohit, O.P.; Black, CM; Vinholes, J.; Schlosser, K.; Huss, Hermann; Quinn, K. J.; Kanis, J. A.

doi:10.1023/a:1008386501738

Cited by 93 publications

(46 citation statements)

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“…We furthermore suggest that a urinary level of LP less than LP max in patients with OSCC may obviate the need for further investigations. The measurement of both LP and HP in the urine is recommended for the detection of bony metastases in a multitude of malignancies, indicating a higher specificity of LP for bone turnover, as compared to HP alone (Pecherstorfer et al, 1995;Takeuchi et al, 1996;Papatheofanis, 1997;Walne et al, 1997;Coleman et al, 1999;Marttunen et al, 1999;Tamura et al, 1999;Woitge et al, 1999Woitge et al, , 2001Demers et al, 2000;Liubimova et al, 2000;Tamada et al, 2001). Urinary HP is not specific for bony invasion, but may nevertheless be increased in the urine of patients with bony metastases as compared to patients without bony metastases.…”

Section: Discussionmentioning

confidence: 99%

“…Other possible causes for false positives are trauma, further malignancy or bone disease such as osteoporosis, rheumatoid arthritis, primary hyperparathyroidism, active Paget's disease of the bone, Ehlers -Danlos syndrome type VI and others (Eyre, 1992;Miyamoto et al, 1994;Acil et al, 1995;Chen et al, 1996;Coleman et al, 1999;Woitge et al, 1999). Urinary HP and LP are valuable trend markers of diseases with altered bone resorption as well as their treatment (Eyre, 1992;Acil et al, 1996;Coleman et al, 1997;Liubimova et al, 2000).…”

Section: Discussionmentioning

confidence: 99%

“…It has been suggested that the detection of LP in the serum or urine may be a helpful marker in establishing and possibly quantifying bone matrix resorption (Body and Delmas, 1992;Miyamoto et al, 1994;Vinholes et al, 1996;Papatheofanis, 1997;Tamada et al, 2001). The measurement of HP and, in particular, LP has been shown to be valuable in detecting the presence and/or extent of bony metastases in patients with multiple myeloma, carcinoma of the breast, lung, prostate gland, kidney, throat and digestive tract (Takeuchi et al, 1996;Papatheofanis, 1997;Walne et al, 1997;Yoshida et al, 1997;Coleman et al, 1999;Marttunen et al, 1999;Tamura et al, 1999;Woitge et al, 1999Woitge et al, , 2001Demers et al, 2000;Fontana and Delmas, 2000;Liubimova et al, 2000;Izumi et al, 2001;Tamada et al, 2001).…”

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confidence: 99%

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Collagen crosslink excretion and staging of oral cancer

et al. 2003

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Lysylpyridinoline (LP) and hydroxylysylpyridinoline (HP) are collagen crosslink residues of which the urinary concentration reflects the level of connective-tissue turnover. HP is ubiquitous in tissue, whereas LP is specific for bone. The purpose of this investigation was to assess the sensitivity and specificity of an increased urinary concentration of both HP and LP in indicating infiltration of mandibular bone by an oral squamous cell carcinoma (OSCC) or recurrence of the disease after successful therapy. We investigated the history and urine levels in 116 adult patients, who were divided into the following groups. Group 1: patients with OSCC with bone infiltration (n ¼ 17); group 2: patients with confirmed OSCC (n ¼ 12) without evidence of bone infiltration; group 3: patients with recurrence of an OSCC (n ¼ 13); group 4: patients without clinical evidence of disease (n ¼ 74). The range and upper limit of normal values (HP max and LP max ) were measured from the normal controls in group 4. Levels of LP and HP were measured by HPLC and fluorescence detection. There was a significant difference in the average urinary levels of LP and HP between groups 1 -4 (Po0.001). The presence of mandibular bone infiltration could be detected with a sensitivity and specificity of 100% when comparing groups 1 and 2. Presence of tumour tissue could be detected with a sensitivity of 90%. In conclusion, a normal LP concentration in patients with an OSCC strongly suggests that bone invasion by the disease has not taken place. If both urinary HP and LP are elevated, disease recurrence is highly likely.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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Collagen crosslink excretion and staging of oral cancer

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“…In addition, when the adverse events associated with an oral therapy can be directly attributed to the drug-for example, if adverse events occur in close temporal proximity to dosing-patients are less likely to comply. Oral bisphosphonate therapy has been associated with a fairly high rate of noncompliance and early study withdrawal because of its complicated treatment regimen and high rate of GI adverse events [40, [49][50][51][52].…”

Section: Compliance With Oral Bisphosphonate Therapymentioning

confidence: 99%

Safety of Intravenous and Oral Bisphosphonates and Compliance With Dosing Regimens

2004

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Patients with advanced cancers-particularly breast and prostate cancers-are at high risk for bone metastasis, leading to accelerated bone resorption and clinically significant skeletal morbidity. Bisphosphonates are effective inhibitors of bone resorption and reduce the risk of skeletal complications in patients with bone metastases. The standard routes of administration for bisphosphonates used in clinical practice are either oral or i.v. infusion. Oral administration of bisphosphonates is complicated by poor bioavailability (generally <5%) and poor gastrointestinal tolerability. First-generation bisphosphonates, such as clodronate (Bonefos ® ; Anthra Pharmaceuticals; Princeton, NJ), must be administered at high oral doses (1,600-3,200 mg/day) to achieve therapeutic effects, which leads to poor tolerability and compliance with oral dosing regimens. Infusion of bisphosphonates is associated with dose-and infusionrate-dependent effects on renal function. In particular, high bisphosphonate doses (e.g., 1,500 mg clodronate) can cause severe renal toxicity unless infused slowly over many hours. In contrast, the newer, more potent bisphosphonates effectively inhibit bone resorption at micromolar concentrations, and the small doses required can be administered via relatively short i. The Oncologist 2004;9(suppl 4):28-37 www.TheOncologist.com

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“…The presence of such tissue could be detected with a sensitivity of 90% and specificity of 65% whether bone was infiltrated or not (Springer et al, 2003a). The urinary levels of HP and, in particular, LP have been shown to be increased in patients with bony metastases from multiple myeloma, carcinoma of the breast, lung, prostate gland, kidney, throat and digestive tract (Takeuchi et al, 1996;Papatheofanis, 1997;Walne et al, 1997;Yoshida et al, 1997;Coleman et al, 1999;Marttunen et al, 1999;Tamura et al, 1999;Woitge et al, 1999Woitge et al, , 2001Demers et al, 2000;Fontana and Delmas, 2000;Liubimova et al, 2000;Izumi et al, 2001;Tamada et al, 2001).…”

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Follow-up of collagen crosslink excretion in patients with oral squamous cell carcinoma and analysis of tissue samples

et al. 2003

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The presence of an oral squamous cell carcinoma (OSCC) may be associated with increased urinary excretion of the markers of collagen degradation, hydroxylysylpyridinoline (HP) and lysylpyridinoline (LP). We investigated the possibility of these markers predicting the presence of active disease. Patients from a current study on HP and LP were included as follows: Group 1a (OSCC with confirmed mandibular bony infiltration, n ¼ 12), group 1b (group 1a patients 46 months after successful treatment), group 2a (OSCC without evidence of mandibular bone infiltration, n ¼ 8), group 2b (group 2a patients 46 months after successful treatment), group 3a (recurrent OSCC, n ¼ 8), group 3b (group 3a patients 46 weeks later, symptoms unchanged) and group 4 (control group, n ¼ 74). Tissue samples from tumour tissue and adjacent healthy mucosa were additionally investigated for HP and LP concentrations (n ¼ 8). The decrease in the urinary concentrations of HP and LP was statistically significant between groups 1a and 1b (Po0.001 for HP and LP), but not between groups 2a and 2b (P ¼ 0.07 for HP and LP), while values in groups 1b and 2b were within the normal range. When comparing groups 3a and 3b, a significant increase was observed for LP (P ¼ 0.050), but not HP (P ¼ 0.208). In conclusion, successful treatment of OSCC with bony involvement may be associated with a reduction of urinary HP and LP, whereas ongoing disease may result in an increase of LP. HP and LP may both be useful markers of tumour progression in patients with OSCC. British Journal of Cancer (2003) Hydroxylysylpyridinoline (HP) and lysylpyridinoline (LP) are two nonreducible crosslinks of mature collagen, which are formed by a sequence of post-translational modifications. HP is a derivative of three residues of hydroxylysine, and is present in virtually all mature tissues (tendon, vessel wall, cartilage, dentine and bone). LP is a derivative of two residues of hydroxylysine and one residue of lysine, and is found primarily in dentine and bone (Body and Delmas, 1992;Eyre, 1992;Miyamoto et al, 1994;Acil et al, 1996Acil et al, , 2002aPapatheofanis, 1997;Tamada et al, 2001;Jepsen et al, 2003; Springer et al, 2003a, b).It has been suggested that the detection of LP in the serum or urine may be a helpful marker in establishing and possibly quantifying bone matrix resorption (Body and Delmas, 1992;Miyamoto et al, 1994;Vinholes et al, 1996;Papatheofanis, 1997;Tamada et al, 2001;Springer et al, 2003a). In a previous study, we were able to assess the range and upper limit (HP max and LP max ) of normal values. We were able to show that the measurement of LP in the urine was able to separate a group of patients with oral squamous cell carcinoma (OSCC) with bone infiltration from patients with OSCC without bone infiltration with a sensitivity of 100% and a specificity of 100% (Springer et al, 2003a). In that paper, we suggested that when the level of LP exceeds LP max in a patient with a confirmed OSCC, bony invasion by the malignant process is highly likely and further inve...

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Double-blind, randomised, placebo-controlled, dose-finding study of oral ibandronate in patients with metastatic bone disease

Cited by 93 publications

References 23 publications

Collagen crosslink excretion and staging of oral cancer

Collagen crosslink excretion and staging of oral cancer

Safety of Intravenous and Oral Bisphosphonates and Compliance With Dosing Regimens

Follow-up of collagen crosslink excretion in patients with oral squamous cell carcinoma and analysis of tissue samples

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