The maternal skeleton rapidly demineralizes during lactation to provide calcium to milk, responding to the stimuli of estrogen deficiency and mammary-secreted PTH-related protein. We used calcitonin/calcitonin gene-related peptide-alpha (Ctcgrp) null mice to determine whether calcitonin also modulates lactational mineral metabolism. During 21 d of lactation, spine bone mineral content dropped 53.6% in Ctcgrp nulls vs. 23.6% in wild-type (WT) siblings (P < 0.0002). After weaning, bone mineral content returned fully to baseline in 18.1 d in Ctcgrp null vs. 13.1 d in WT (P < 0.01) mice. Daily treatment with salmon calcitonin from the onset of lactation normalized the losses in Ctcgrp null mice, whereas calcitonin gene-related peptide-alpha or vehicle was without effect. Compared with WT, Ctcgrp null mice had increased circulating levels of PTH and up-regulation of mammary gland PTH-related protein mRNA. In addition, lactation caused the Ctcgrp null skeleton to undergo more trabecular thinning and increased trabecular separation compared with WT. Our studies confirm that an important physiological role of calcitonin is to protect the maternal skeleton against excessive resorption and attendant fragility during lactation and reveal that the postweaning skeleton has the remarkable ability to rapidly recover even from losses of over 50% of skeletal mineral content.

Mice lose 20% to 25% of trabecular bone mineral content (BMC) during lactation and restore it after weaning through unknown mechanisms. We found that tibial Pthrp mRNA expression was upregulated fivefold by 7 days after weaning versus end of lactation in wild-type (WT) mice. To determine whether parathyroid hormone–related protein (PTHrP) stimulates bone formation after weaning, we studied a conditional knockout in which PTHrP is deleted from preosteoblasts and osteoblasts by collagen I promoter–driven Cre (CreColI). These mice are osteopenic as adults but have normal serum calcium, calcitriol, and parathyroid hormone (PTH). Pairs of Pthrpflox/flox;CreColI (null) and WT;CreColI (WT) females were mated and studied through pregnancy, lactation, and 3 weeks of postweaning recovery. By end of lactation, both genotypes lost lumbar spine BMC: WT declined by 20.6% ± 3.3%, and null decreased by 22.5% ± 3.5% (p < .0001 versus baseline; p = NS between genotypes). During postweaning recovery, both restored BMC to baseline: WT to –3.6% ± 3.7% and null to 0.3% ± 3.7% (p = NS versus baseline or between genotypes). Similar loss and full recovery of BMC were seen at the whole body and hind limb. Histomorphometry confirmed that nulls had lower bone mass at baseline and that this was equal to the value achieved after weaning. Osteocalcin, propeptide of type 1 collagen (P1NP), and deoxypyridinoline increased equally during recovery in WT and null mice; PTH decreased and calcitriol increased equally; serum calcium was unchanged. Urine calcium increased during recovery but remained no different between genotypes. Although osteoblast-derived PTHrP is required to maintain adult bone mass and Pthrp mRNA upregulates in bone after weaning, it is not required for recovery of bone mass after lactation. The factors that stimulate postweaning bone formation remain unknown. © 2011 American Society for Bone and Mineral Research.

BackgroundThe relationship between major dietary patterns and colorectal cancer (CRC) in other populations largely remains consistent across studies. The objective of the present study is to assess if dietary patterns are associated with the risk of CRC in the population of Newfoundland and Labrador (NL).MethodsData from a population based case–control study in the province of NL were analyzed, including 506 CRC patients (306 men and 200 women) and 673 controls (400 men and 273 women), aged 20–74 years. Dietary habits were assessed by a 169-item food frequency questionnaire (FFQ). Logistic regression analyses were performed to investigate the association between dietary patterns and the CRC risk.ResultsThree major dietary patterns were derived using factor analysis, namely a Meat-diet pattern, a Plant-based diet pattern and a Sugary-diet pattern. In combination the three dietary patterns explained 74% of the total variance in food intake. Results suggest that the Meat-diet and the Sugary-diet increased the risk of CRC with corresponding odds ratios (ORs) of 1.84 (95% CI: 1.19-2.86) and 2.26 (95% CI: 1.39-3.66) for people in the highest intake quintile compared to those in the lowest. Whereas plant-based diet pattern decreases the risk of CRC with a corresponding OR of 0.55 (95% CI: 0.35-0.87). Even though odds ratios (ORs) were not always statistically significant, largely similar associations across three cancer sites were found: the proximal colon, the distal colon, and the rectum.ConclusionThe finding that Meat-diet/Sugary-diet patterns increased and Plant-based diet pattern decreased the risk of CRC would guide the promotion of healthy eating for primary prevention of CRC in this population.

ObjectiveTo examine the association between dietary patterns and colorectal cancer (CRC) survival.DesignCohort study.SettingA familial CRC registry in Newfoundland.Participants529 newly diagnosed CRC patients from Newfoundland. They were recruited from 1999 to 2003 and followed up until April 2010.Outcome measureParticipants reported their dietary intake using a food frequency questionnaire. Dietary patterns were identified with factor analysis. Multivariable Cox proportional hazards models were employed to estimate HR and 95% CI for association of dietary patterns with CRC recurrence and death from all causes, after controlling for covariates.ResultsDisease-free survival (DFS) among CRC patients was significantly worsened among patients with a high processed meat dietary pattern (the highest vs the lowest quartile HR 1.82, 95% CI 1.07 to 3.09). No associations were observed with the prudent vegetable or the high-sugar patterns and DFS. The association between the processed meat pattern and DFS was restricted to patients diagnosed with colon cancer (the highest vs the lowest quartile: HR 2.29, 95% CI 1.19 to 4.40) whereas the relationship between overall survival (OS) and this pattern was observed among patients with colon cancer only (the highest vs the lowest quartile: HR 2.13, 95% CI 1.03 to 4.43). Potential effect modification was noted for sex (p value for interaction 0.04, HR 3.85 for women and 1.22 for men).ConclusionsThe processed meat dietary pattern prior to diagnosis is associated with higher risk of tumour recurrence, metastasis and death among patients with CRC.

A series of 36 patients who had been hospitalized following closed head injury (CHI) were followed up 4.06 (SD 3.71) years after the injury. Measures were taken of degree of psychosexual dysfunction (Golombok Rust Inventory of Sexual Satisfaction-GRISS), general psychiatric morbidity (General Health Questionnaire-GHQ), and clinical anxiety and depression (Hospital Anxiety and Depression Scale-HAD). These measures were completed by patients and partners. Resulting data revealed that 50% of male patients with current sexual partners produced psychosexual profiles that fell within the dysfunctional range. For both male patients and their partners, the chief psychosexual complaint was infrequency. Of the patients studied, 61% were classified (using the GHQ) as having degrees of emotional distress that would fall within the range of psychiatric 'caseness', while 25% of patients achieved HAD criteria for clinical anxiety and 22% met HAD criteria for depression. Of the partners, 41% met GHQ criteria for psychiatric 'caseness', 18% being classified using the HAD as anxiety cases and 6% as depression cases. No effects of severity of injury were observed on any of the main outcome measures. Age and time since injury were related to measures of psychosexual dysfunction. These results are discussed in relation to the existing literature on psychosocial outcome in closed head injury, and recommendations for therapeutic intervention are made.