Mastectomy, body deconstruction, and impact on identity: a qualitative study.

OBJECTIVES: This qualitative study aims at understanding the consequences of body deconstruction through mastectomy on corporality and identity in women with breast cancer. DESIGN: Nineteen women were contacted through the hospital. All had to undergo mastectomy. Some were offered immediate breast reconstruction, others, because of cancer treatments, had no planned reconstruction. A qualitative reflexive methodological background was chosen. METHOD: Women were invited to participate in three semi-structured interviews, one shortly before or after mastectomy, and the other interviews later in their illness courses, after surgery. All interviews were transcribed verbatim. Thematic analysis was performed. The analysis of the first interview of each woman is presented in this article. RESULTS: Mastectomy provokes a painful experience of body deconstruction. Even when immediate reconstruction is proposed, contrasted feelings and dissonance are expressed when comparing the former healthy body to the present challenged body entity. Body transformations are accompanied with experiences of mutilation, strangeness, and modify the physical, emotional social, symbolic and relational dimensions of the woman's gendered identity. Although the opportunity of breast reconstruction is seen as a possible recovery of a lost physical symmetry and body integrity, grieving the past body and integrating a new corporality leads to a painful identity crisis. CONCLUSION: With mastectomy, the roots of the woman's identity are challenged, leading to a re-evaluation of her existential values. The consequences of mastectomy transform the woman's corporality and embodiment, and question her identity. Psychological support is discussed in the perspective of our results.

Influence of a vegetarian diet versus a diet with fishmeal on bone in growing pigs.

This study was conducted to examine if substantial bone loss occurs in growing pigs fed a vegetarian diet in comparison with a diet containing fishmeal. Twelve 6-week-old weaned pigs were assigned to two groups: group V [vegetarian diet; 0.61% phosphorus (P) in dry matter until 25 kg and 0.46% P until the end of the experiment] and group F (fishmeal diet; 0.61% P in dry matter until 25 kg and 0.46% P until the end of the experiment). Phytase was added to both diets. These two diets were fed to the two groups for a period of 6 weeks. Blood samples were collected weekly, faeces were collected three times a week. Concentrations of osteocalcin (OC) and carboxyterminal telopeptide of type I collagen (ICTP) were measured in serum, using a radioimmunoassay, and bone-specific alkaline phosphatase (bAP) was measured using an enzyme immunoassay. Bone mineral density (BMD) and content (BMC) were determined by peripheral quantitative computer tomography (pQCT) in the tibia and phalanx. In addition, 1,25-dihydroxyvitamin D (VitD) and parathyroid hormone (PTH) were measured in serum. The digestibility of P was significantly decreased in group V. Significant changes in bAP activities and OC concentrations occurred with time during the 6 weeks. ICTP concentrations were significantly higher in group V. Total BMC and BMD in the tibia and BMD in the phalanx significantly decreased in group V. The results show that a vegetarian diet induces a significant loss of bone and a higher bone formation in group V compared with group F, although phytase was added to both diets. The dietary requirements for P in pigs, especially in the context of feeding vegetarian diets and adding an appropriate amount of phytase, should be investigated further.

Influence of dietary phosphorus deficiency with or without addition of fumaric acid to a diet in pigs on bone parameters.

The purpose of this study was to examine if substantial bone loss occurs in weaned pigs by feeding a phosphorus-deficient diet with or without fumaric acid. Eighteen weaned pigs were used. The animals were assigned to three groups: group C (control; 0.65% P on DM basis), group LP (low phosphorus; 0.37% P on DM basis) and group LPF (low phosphorus plus fumaric acid; 0.35% P on DM basis plus 2% fumaric acid). These three diets were fed to the groups for a period of four weeks after a two-week adaptation period. Blood samples were collected once a week. Carboxyterminal telopeptide of type I collagen (ICTP) in serum was used as a bone resorption marker. Osteocalcin (OC) and bone-specific alkaline phosphatase (bAP) were used as bone formation markers. Bone mineral density (BMD) and content (BMC) were determined by peripheral quantitative computer tomography. BAP activities significantly increased (24%) in group LPF, and at the last sampling day group LPF had significantly increased activities in comparison to group C. In contrast, ICTP concentrations significantly increased with time in group LP and LPF, and at the last sampling day group LPF had significantly increased activities in comparison to group C. BMD and BMC in femur and tibia significantly decreased in group LP and LPF. The results show that P-deficient diets induce a bone loss. Fumaric acid did not influence the degree of bone loss. With a better understanding of its effect on bone, dietary phosphorus requirements in pigs could be more precisely defined.

Estrogen reduces the depth of resorption pits by disturbing the organic bone matrix degradation activity of mature osteoclasts.

Decreased E2 levels after menopause cause bone loss through increased penetrative resorption. The reversal effect of E2 substitution therapy is well documented in vivo, although the detailed mechanism of action is not fully understood. To study the effects of E2 on bone resorption, we developed a novel in vitro bone resorption assay in which degradation of inorganic and organic matrix could be measured separately. E2 treatment significantly decreased the depth of resorption pits, although the area resorbed was not changed. Electron microscopy further revealed that the resorption pits were filled with nondegraded collagen, suggesting that E2 disturbed the organic matrix degradation. Two major groups of proteinases, matrix metalloproteinases (MMPs) and cysteine proteinases, have been suggested to participate in organic matrix degradation by osteoclasts. We show here that MMP-9 released a cross-linked carboxyl-terminal telopeptide of type I collagen from bone collagen, and cathepsin K released another C-terminal fragment, the C-terminal cross-linked peptide of type I collagen. E2 significantly inhibited the release of the C-terminal cross-linked peptide of type I collagen into the culture medium without affecting the release of cross-linked carboxyl-terminal telopeptide of type I collagen in osteoclast cultures. These results suggest that organic matrix degradation is initiated by MMPs and continued by cysteine proteases; the latter event is regulated by E2.

The course of selected bone resorption marker concentrations in response to short-term hypocalcemia experimentally induced with disodium EDTA infusions in dairy cows.

The collagen metabolites hydroxyproline (HYP), deoxypyridinoline (DPD), and the carboxyterminal telopeptide of type I collagen (ICTP) are suitable markers for bone resorption in humans and several animal species. The purpose of this study was to describe the course of bone resorption markers during short-term hypocalcemia induced with disodium ethylenediaminetetraacetic acid (Na2EDTA) and to investigate whether bone resorption is increased in dairy cows under these conditions. EDTA infusions have been used as a model for periparturient paresis in dairy cows and to estimate the calcium mobilization rate from body reserves in ruminants. In this study, hypocalcemia was induced by means of a 5% Na2EDTA infusion (0.55 mg/kg/min Na2EDTA for 5 h = total dose of 100.6 g). Two experiments were conducted: (1) Six 4-11 years-old Brown Swiss cows were infused intravenously with EDTA for 5 h. Blood and urine samples were taken repeatedly from 1 day before until 10 days after infusion. (2) Towards the end of the lactation, the experiment was repeated with the same animals after a 14-day-period of feeding a low calcium diet (26 g/animal per day). The EDTA-infusion induced hypocalcemia and hypophosphatemia. The HYP-, DPD- and ICTP-concentration remained mainly unaffected during both infusions. Only DPD showed an increase during infusion and HYP an increase 2 days after the infusion. In conclusion, the EDTA infusion had little effect on the concentrations of the measured bone markers, which may be due to the fact that the serum calcium pool was refilled by increased absorption of Ca via the gastrointestinal tract. From these results, it can be concluded that bone resorption was not influenced by EDTA infusion.

Biochemical markers of bone formation and resorption around parturition and during lactation in dairy cows with high and low standard milk yields.

Substantial changes occur in skeletal metabolism during lactation. These dynamic changes are monitored with biochemical bone markers. The goal of the present study was to follow these changes in lactating cows and to investigate whether cows with a higher milk yield have a higher mobilization rate of calcium from bone. Hydroxyproline, deoxypyridinoline, pyridinoline, and the carboxyterminal telopeptide of type I collagen (ICTP) were chosen as markers for bone resorption, whereas osteocalcin was used as a bone formation marker. Urine and blood samples were collected from cows with a mean standard milk yield of 4900 and 6500 kg, respectively, 14 d before, and 14 d, 1 mo, 1.5 mo, and monthly after parturition. Urinary hydroxyproline, deoxypyridinoline, and pyridinoline concentrations increased with time, but no differences between the two groups were evident. Concentrations of 1,25-dihydroxy vitamin D and ICTP of the two groups showed an increase 14 d after parturition. Furthermore, using multivariate regression models with age and milk yield as covariates, ICTP concentrations were higher in the group with a higher milk yield. In contrast, osteocalcin concentrations decreased 14 d after parturition and returned to prepartum values 1 mo after parturition. The increase of ICTP concentrations in both groups indicates that bone was substantially resorbed. At the same time, probably less Ca was embedded in bone, as indicated by the decrease of the osteocalcin concentrations. In conclusion, cows showed increased bone resorption around parturition, and cows with higher milk yield mobilize calcium more actively from bone than cows with lower milk yield.

Modulation of skin collagen metabolism by irradiation: collagen synthesis is increased in irradiated human skin.

Radiation-induced fibrosis is a common side-effect of cancer treatment. The pathophysiological events leading to fibrosis are not known in detail. We analysed the effect of therapeutic irradiation on human skin collagen synthesis, skin thickness, gelatinases and their inhibitors. Twenty randomly chosen women who had been treated for breast cancer with surgery and radiation therapy participated in the study. In each patient, the irradiated skin area was compared with a corresponding non-treated skin area. Suction blister fluid (SBF) and serum samples were analysed for the aminoterminal propeptides of type I and type III procollagens (PINP and PIIINP), tissue inhibitors of matrix metalloproteinases (MMPs) 1 and 2 (TIMP-1 and TIMP-2) and MMP-9 and MMP-2/TIMP-2 complex. Skin biopsies were analysed for PINP and immunohistochemical staining was used for PIIINP. In irradiated skin, PINP, PIIINP, TIMP-1 and MMP-2/TIMP-2 complex levels in SBF and the number of PINP-positive fibroblasts in tissue sections were significantly higher in comparison with non-treated skin. The levels of TIMP-2 in irradiated and non-irradiated skin were similar. MMP-9 could not be detected in SBF with the assay used. The serum levels of MMP-9 were higher in the treated subjects than the reference values. The serum values of PINP, PIIINP, TIMP-1, TIMP-2 and MMP-2/TIMP-2 complex were not significantly affected. These results indicate increased local collagen synthesis and accumulation of connective tissue in irradiated skin. The marked upregulation of collagen synthesis as a result of irradiation offers a possibility to treat this complication with compounds such as topical steroids which downregulate collagen synthesis.

Immunochemical characterization of assay for carboxyterminal telopeptide of human type I collagen: loss of antigenicity by treatment with cathepsin K.

The assay for the cross-linked carboxyterminal telopeptide of type I collagen (ICTP) has been shown to reflect increased type I collagen degradation in such pathological conditions as bone metastases and rheumatoid arthritis, but to be rather insensitive to the changes in physiological bone collagen turnover (e.g., induced by estrogen or bisphosphonate treatment). To determine the reasons for this discrepancy we localized the antigenic determinant recognized by the ICTP assay and studied the effects of two major osteoclastic proteinases, cathepsin K (EC 3.4.22.38) and matrix metalloproteinase-9 (MMP-9; gelatinase B; EC 3.4.24.35), on immunoreactivity. The antigenic determinant was shown to reside within the hydrophobic phenylalanine-rich regions of the carboxyterminal telopeptides of the two alpha1 chains of human type I collagen, situated between the triple helical domain and the lysine-derived trivalent cross-link. This conclusion was based on differences between the amino acid sequences and cross reactivities of the corresponding human and bovine antigens before and after proteolytic treatments with chymotrypsin. A trivalent cross-link is necessary for providing such a structure, because the divalently cross-linked and monomeric natural and synthetic peptides from the same region, but containing only one phenylalanine-rich sequence, showed poor immunoreaction. Recombinant human cathepsin K cleaved the trivalently cross-linked ICTP structure at two sites between the phenylalanine-rich region and the cross-link, destroying the reactivity with ICTP antibodies. On the contrary, the treatment of isolated ICTP by the matrix metalloproteinases MMP-9 (gelatinase B), MMP-1 (collagenase 1), or MMP-13 (collagenase 3) had no effect on the immunoreaction. Our results indicate that the increased circulating concentrations of ICTP found in several clinical situations are most likely produced by matrix metalloproteinases, whereas cathepsin K-mediated, osteoclastic bone resorption destroys ICTP antigenicity.

Diurnal variation in concentrations of various markers of bone metabolism in dogs.

OBJECTIVE: To evaluate diurnal variation in concentrations of selected markers of bone metabolism in dogs. ANIMALS: Ten 3- to 4-year-old ovariectomized Beagles. PROCEDURE: Blood and urine samples were obtained in the morning before dogs were fed (8 AM) and then at 2-hour intervals for 24 hours. This procedure was repeated 2 weeks later. Concentrations of osteocalcin (OC) and carboxy terminal telopeptide of type-I collagen (ICTP) were measured in serum, using a radioimmunoassay; concentrations of hydroxyproline (HYP), pyridinoline (PYD), and deoxypyridinoline (DPD) were analyzed in urine. Hydroxyproline concentration was measured by means of a colorimetric test, whereas PYD and DPD concentrations were quantified by use of high-performance liquid chromatography. RESULTS: In both parts of the study, HYP concentrations increased significantly, compared with values before feeding, until 8 hours after feeding; HYP concentrations then returned to prefeeding values. Concentrations of DPD and PYD decreased from before feeding until 2 PM and then increased until 8 PM. The ICTP concentrations slowly decreased until 4 PM but returned to prefeeding values thereafter. In both parts of the study, concentrations of OC decreased during the day and then increased to reach values similar to those obtained before feeding. CONCLUSIONS: Changes in the concentrations of bone markers were detected throughout the day in the dogs of this study. Increase in HYP concentration most likely was related to feeding. As documented for bone resorption and formation in other species, circadian rhythms were evident for concentrations of DPD, PYD, and OC. Investigators should consider the time of sample collection when measuring these markers.

Annual serum PICP and ICTP and antler growth in female reindeer (Rangifer tarandus tarandus).

Annual cycle of type I collagen formation and degradation and antler growth was studied in six adult female reindeer, Rangifer tarandus tarandus. Blood samples were collected twice a week during 1 year. Antler length was measured weekly during the antler growth period. An assay for human PICP, the carboxyterminal propeptide of type I procollagen, was used as an indicator of type I collagen formation and an assay for bovine ICTP, the carboxyterminal telopeptide of type I collagen, as an indicator of type I collagen degradation. PICP was clearly increased during the antler growth period. Also ICTP was slightly elevated during antler growth, but the highest values were found in autumn and winter. Our statistical analysis revealed that changes in lagged values (from 3 to 6 weeks) of PICP could be linked to the subsequent changes in the growth rate of the antler, although the highest values of PICP were found during the final third of antler growth. ICTP had significant predictive power as well, but the connection with the growth rate seemed more immediate than that of PICP. In conclusion, antler collagen synthesis can be predicted by PICP, but also ICTP was related to the antler growth.

Serum type I collagen degradation markers, ICTP and CrossLaps, are factors for poor survival in lung cancer.

We investigated the prognostic value of the serum markers of type I collagen synthesis (PINP and PICP) and degradation (ICTP and CrossLaps) in 143 lung cancer patients with a local or locally advanced disease or a metastatic disease. The mean values of ICTP, CrossLaps, PINP and PICP were significantly higher in patients with bone metastases than in those without metastases or with only soft tissue metastases. The patients with ICTP < or = 5.0 micrograms/l or CrossLaps < or = 5000 pmol/l had a better prognosis. The histopathological type, the site of metastases or the stage of the disease had no influence on these results. In multivariate regression analysis, both ICTP and CrossLaps in contrast to PINP or PICP, were prognostic factors for poor survival in lung cancer patients. ICTP, CrossLaps, sedimentation rate, hemoglobin and AFOS reached separately weaker, but statistically significant values as predictors of survival with stage and operation.

Comparison of bone resorption markers during hypocalcemia in dairy cows.

This study investigated whether hydroxyproline, deoxypyridinoline, or the carboxyterminal telopeptide of type I collagen could be used as markers to provide evidence of bone resorption during hypocalcemia of dairy cows. Serum concentrations of the amino-terminal propeptide of type III procollagen were also analyzed to study the effect of parturition on type III collagen, which is a component of soft connective tissues. Urine and blood samples were collected on d 1 to 5, on d 9, and d 14 after parturition from 18 cows with symptoms of periparturient paresis (group 1) and 19 healthy control cows without symptoms (group 2). Urine concentrations of hydroxyproline and deoxypyridinoline were measured with a colorimetric assay and an enzyme immunoassay, respectively. Serum concentrations of the amino-terminal propeptide of type III procollagen were measured using a commercially available radioimmunoassay. A radioimmunoassay was developed to analyze serum concentrations of the carboxyterminal telopeptide of bovine type I collagen. The mean corrected urinary hydroxyproline concentrations in group 1 increased from parturition to d 14; concentrations in group 1 were significantly higher for group 2 after d 5. Mean corrected deoxypyridinoline concentrations in urine increased after parturition to reach a peak at d 9, and serum concentrations of the carboxyterminal telopeptide of type I collagen peaked at d 5. However, mean concentrations of deoxypyridinoline and the carboxyterminal telopeptide of type I collagen did not differ significantly between groups. The variation in the behavior of the three markers is likely a reflection of the different phases and aspects of the bone collagen degradation. In conclusion, assays for urinary deoxypyridinoline and serum carboxyterminal telopeptide of type I collagen determinations are useful tools to follow the course of degradation of bone collagen in dairy cows.