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P31. Biochemical markers of bone turnover in women who had received Tamoxifen for breast cancer
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metabolites calculated from the specific activity of plasma 25(OH)D. E significantly reduced plasma 25(OH)D (mean f SEM) compared to controls (21.4kl.6 vs 27.1H.9 ng/ml; P
P30. Investigation of pyridinoline excretion in women with breast cancer M Arora and I Dickson Department of Biology 6 Biochemistry, Brunel University, Uxbridge UBS 3PH Hydroxylysyl(HI’) and lysyl-pyridinoline (LP) are more specific urinary indicators of bone resorption than currently used biochemical tirkers. They may therefore have application to the investigation of bone metastases in breast cancer. To assess this and to determine the best type of specimen to collect, HP and LP were measured in early morning fasting and in overnight urine specimens from women with breast cancer, classified into one of three groups: primary (PBC); secondary, non-bony tietastases present (NBM); bone metastases present (BM+). HP and LP were measured by reverse phase HPLC, using fluorimetric detection, following acid hydrolysis of the urine and partial purification of the pyridinolines on CF-I cellulose columns. Data were normalised using creatinine (Cr). Values of HP/Cr and LP/Cr for early morning specimens in the BM+ group showed great spread, the means being about 3X higher than those in NBM and PBC groups; LP/Cr was slightly better than HP/Cr at discriminating between BM+ and the other groups. Although levels of pyridinolines were usually much high&i in overnight urine specimens the increase was similar in all groups and there appeared to be no advantage over fasting urine specimens.
P31. Biochemical markers of bone turnover in women who had received Tamoxifen for breast cancer F Li, I’ Pitt’, J Houghton** and C Moniz Departments of Clinical Biochemistry, *Rheumatology and the “Cancer Research Trial Centre, Kings College Hospital, London In a double blind placebo controlled study of 100 women (mean age 60yrs) receiving adjuvant Tamoxifen vs placebo for breast cancer, there was no significant difference in bone mineral density, spine BMD 0.976 vs 0.0980 g/cm2 and hip BMD 0.670 vs 0.653 g/cm2 measured by Dual Energy X-Ray Absorptiometry (NorlandXR26), between treated and untreated women matched for age, weight and height. Biochemical markers of bone turnover in 40 women, 20 treated and 20 placebo were not significantly different from normal controls, except for urinary pyridinoline (P) and deoxypyridinoline CD). In these women, mean (SD) in nmol/mmol creatinine of P and D, were elevated. P was 44.7 (11.2) and D was 11.2c4.6) vs 26.4t8.9) and 6.3c2.8) for P and D respectively. In this group 6 were diagnosed as having a recurrence of breast carcinoma. Thirteen additional stored fasting urine samples were randomly selected from the originai group of 100 women and P and D measured by HPLC. Both P 36.1 (range 18.4- 71.7) and D 16.4 (range 3.5-18.6) nmol/mmol/creat. were above the reference values and the range of results indicated that in some patients there was increased bone resorption. Elevated levels of bone collagen markers may reflect an ongoing underlying humoral effect of breast cancer on bone despite treatment, and measurement of these markers may be useful in predicting those who will relapse before the onset of clinical disease.
Abstracts
from the Joint Meeting,
September
1992
P32. The effect of Tamoxifen on resorption cavity characteristics in women with breast cancer CDP Wright, NJ Garrahan’, M Stanton*, R Mansell”, J-C Gazet+ and JE Compston Dept of Medicine, University of Cambridge Clinical School, Addenbrooke’s Hospital, Cambridge, *Department of Pathology, University of Wales, College of Medicine, Cardiff, “‘Department of Surgery, Manchester University and +St George’s Hospital, London Tamoxifen is a non-steroidal ant&estrogen widely used in the treatment of breast cancer. Densitometric studies indicate that it has a beneficial effect on bone mass, but there are no data on its effect on bone remodelling in man. We have studied resorption cavity characteristics in 34 women with breast cancer, 19 treated with tamoxifen for a mean of 33 months and 15 untreated. Cavities were measured using image analysis on toluidine bluestained sections from iliac crest bone biopsies. Mean and maximum cavity depth and cavity area were significantly lower in the tamoxifen-treated patients compared to the untreated group (p
P33. Multiple myeloma, a bone-resorbing tumour counteracts cell adhesion in vitro CE Evans and J Parker University of Manchester Bone Research Centre, Department of Orthopaedic Surgery, CSB, Hope Hospital, Salford M6 8HD Bone-resorbing tumours invade bone by a variety of mechanisms, including protease production and stimulation of osteoclastic bone resorption. We have previously demonstrated that bone-resorbing tumours (breast cancer and multiple myeloma (MM)), had inhibitory effects on human osteoblast-like cells (hOB) in vitro (12). We now present preliminary results which demonstrate that MM cells secrete factors which interfere with the normal in vitro process of attachment of hOB to their substrate. These factors are also able to cause the hOB to detach from the culture vessel after the cells have attached and spread. We looked at these effects using three human myeloma cell lines, GM1500, Karpas 707 and RPMl8226, and in hOB derived by the explant technique, which possesses osteoblast-like characteristics. Incubation of the hOB with conditioned medium (CM) from the myeloma upon seeding caused 42% inhibition of cell attachment; exposure to the CM after attachment inhibited attachment 50%. The detached cells were viable & upon removal of the CM, were able to re-attach & replicate. This pilot study suggests that one of the mechanisms by which MM exerts its osteolytic effect on bone is interference with the attachment of osteoblask to the bone surface, thereby hindering bone repair. 1. Evans et a1,1991, J Endocrino1,128:125-128 2. Evans et a1,1992, Clin Exp Met,D:33-38
Psychiatric changes after the correction of primary P34. hyperparathyroidism SJ McAllion, A Gunn’ and CR Paterson Departments of Biochemical Medicine and ‘Surgery Ninewells Hospital and Medical School, Dundee DDI 9.W
It has long been recognised may be associated affective symptoms
that primary hyperparathyroidism with psychiatric problems, particularly or organic confusional states. Occasionally
metabolites calculated from the specific activity of plasma 25(OH)D. E significantly reduced plasma 25(OH)D (mean f SEM) compared to controls (21.4kl.6 vs 27.1H.9 ng/ml; P
P30. Investigation of pyridinoline excretion in women with breast cancer M Arora and I Dickson Department of Biology 6 Biochemistry, Brunel University, Uxbridge UBS 3PH Hydroxylysyl(HI’) and lysyl-pyridinoline (LP) are more specific urinary indicators of bone resorption than currently used biochemical tirkers. They may therefore have application to the investigation of bone metastases in breast cancer. To assess this and to determine the best type of specimen to collect, HP and LP were measured in early morning fasting and in overnight urine specimens from women with breast cancer, classified into one of three groups: primary (PBC); secondary, non-bony tietastases present (NBM); bone metastases present (BM+). HP and LP were measured by reverse phase HPLC, using fluorimetric detection, following acid hydrolysis of the urine and partial purification of the pyridinolines on CF-I cellulose columns. Data were normalised using creatinine (Cr). Values of HP/Cr and LP/Cr for early morning specimens in the BM+ group showed great spread, the means being about 3X higher than those in NBM and PBC groups; LP/Cr was slightly better than HP/Cr at discriminating between BM+ and the other groups. Although levels of pyridinolines were usually much high&i in overnight urine specimens the increase was similar in all groups and there appeared to be no advantage over fasting urine specimens.
P31. Biochemical markers of bone turnover in women who had received Tamoxifen for breast cancer F Li, I’ Pitt’, J Houghton** and C Moniz Departments of Clinical Biochemistry, *Rheumatology and the “Cancer Research Trial Centre, Kings College Hospital, London In a double blind placebo controlled study of 100 women (mean age 60yrs) receiving adjuvant Tamoxifen vs placebo for breast cancer, there was no significant difference in bone mineral density, spine BMD 0.976 vs 0.0980 g/cm2 and hip BMD 0.670 vs 0.653 g/cm2 measured by Dual Energy X-Ray Absorptiometry (NorlandXR26), between treated and untreated women matched for age, weight and height. Biochemical markers of bone turnover in 40 women, 20 treated and 20 placebo were not significantly different from normal controls, except for urinary pyridinoline (P) and deoxypyridinoline CD). In these women, mean (SD) in nmol/mmol creatinine of P and D, were elevated. P was 44.7 (11.2) and D was 11.2c4.6) vs 26.4t8.9) and 6.3c2.8) for P and D respectively. In this group 6 were diagnosed as having a recurrence of breast carcinoma. Thirteen additional stored fasting urine samples were randomly selected from the originai group of 100 women and P and D measured by HPLC. Both P 36.1 (range 18.4- 71.7) and D 16.4 (range 3.5-18.6) nmol/mmol/creat. were above the reference values and the range of results indicated that in some patients there was increased bone resorption. Elevated levels of bone collagen markers may reflect an ongoing underlying humoral effect of breast cancer on bone despite treatment, and measurement of these markers may be useful in predicting those who will relapse before the onset of clinical disease.
Abstracts
from the Joint Meeting,
September
1992
P32. The effect of Tamoxifen on resorption cavity characteristics in women with breast cancer CDP Wright, NJ Garrahan’, M Stanton*, R Mansell”, J-C Gazet+ and JE Compston Dept of Medicine, University of Cambridge Clinical School, Addenbrooke’s Hospital, Cambridge, *Department of Pathology, University of Wales, College of Medicine, Cardiff, “‘Department of Surgery, Manchester University and +St George’s Hospital, London Tamoxifen is a non-steroidal ant&estrogen widely used in the treatment of breast cancer. Densitometric studies indicate that it has a beneficial effect on bone mass, but there are no data on its effect on bone remodelling in man. We have studied resorption cavity characteristics in 34 women with breast cancer, 19 treated with tamoxifen for a mean of 33 months and 15 untreated. Cavities were measured using image analysis on toluidine bluestained sections from iliac crest bone biopsies. Mean and maximum cavity depth and cavity area were significantly lower in the tamoxifen-treated patients compared to the untreated group (p
P33. Multiple myeloma, a bone-resorbing tumour counteracts cell adhesion in vitro CE Evans and J Parker University of Manchester Bone Research Centre, Department of Orthopaedic Surgery, CSB, Hope Hospital, Salford M6 8HD Bone-resorbing tumours invade bone by a variety of mechanisms, including protease production and stimulation of osteoclastic bone resorption. We have previously demonstrated that bone-resorbing tumours (breast cancer and multiple myeloma (MM)), had inhibitory effects on human osteoblast-like cells (hOB) in vitro (12). We now present preliminary results which demonstrate that MM cells secrete factors which interfere with the normal in vitro process of attachment of hOB to their substrate. These factors are also able to cause the hOB to detach from the culture vessel after the cells have attached and spread. We looked at these effects using three human myeloma cell lines, GM1500, Karpas 707 and RPMl8226, and in hOB derived by the explant technique, which possesses osteoblast-like characteristics. Incubation of the hOB with conditioned medium (CM) from the myeloma upon seeding caused 42% inhibition of cell attachment; exposure to the CM after attachment inhibited attachment 50%. The detached cells were viable & upon removal of the CM, were able to re-attach & replicate. This pilot study suggests that one of the mechanisms by which MM exerts its osteolytic effect on bone is interference with the attachment of osteoblask to the bone surface, thereby hindering bone repair. 1. Evans et a1,1991, J Endocrino1,128:125-128 2. Evans et a1,1992, Clin Exp Met,D:33-38
Psychiatric changes after the correction of primary P34. hyperparathyroidism SJ McAllion, A Gunn’ and CR Paterson Departments of Biochemical Medicine and ‘Surgery Ninewells Hospital and Medical School, Dundee DDI 9.W
It has long been recognised may be associated affective symptoms
that primary hyperparathyroidism with psychiatric problems, particularly or organic confusional states. Occasionally