Relationships between the rate of bone resorption (measured by urinary N-telopeptide (Ntx) excretion) and a range of skeletal complications have been evaluated in patients with metastatic bone disease. A total of 121 patients had monthly measurements of Ntx during treatment with bisphosphonates. All skeletal-related events, plus hospital admissions for bone pain and death during the period of observation, were recorded. Data were available for 121 patients over the first 3-month period of monitoring (0 -3 months) and 95 patients over the second 3-month period (4 -6 months). N-telopeptide levels were correlated with the number of skeletal-related events and/or death (r ¼ 0.62, Po0.001 for 0 -3 months and r ¼ 0.46, Po0.001 for 4 -6 months, respectively). Patients with baseline Ntx values X100 nmol mmol À1 creatinine (representing clearly accelerated bone resorption) were 19.48 times (95% CI 7.55, 50.22) more likely to experience a skeletal-related event/death during the first 3 months than those with Ntx o100 (Po0.001). In a multivariate logistic regression model, Ntx was highly predictive for events/death. This study is the first to indicate a strong correlation between the rate of bone resorption and the frequency of skeletal complications in metastatic bone disease. N-telopeptide appears useful in the prediction of patients most likely to experience skeletal complications and thus benefit from bisphosphonate treatment.

Anterior pituitary extracts from intact and 4 week postcastration male and female rats were electrofocused in sucrose density gradients within the pH range 3.5-10. Column fractions were combined to cover this pH range in 0.5 pH units and assayed for LH by in vitro bioassay and RIA and for FSH by radioreceptor assay and RIA. The pH distribution of bioactive LH was altered after castration in both sexes, with the proportion of recovered activity in the alkaline pH range increasing (P less than 0.01) from 52-57% in the intact animal to 71-73% after castration. In addition, significantly more bioactivity was recovered in the pH range 7-9.5 with the male (37%) than with either of the female (diestrous, 30% or proestrous, 28%) groups (P less than 0.05). FSH receptor binding activity was located in the pH region 3.5-6.5. Significantly less receptor binding activity was recovered in the pH range 3.5-4.5 with the female groups (39% and 37% diestrous and proestrous, respectively) than the male group (61%; P less than 0.05, P less than 0.01). The distribution of immunoreactive LH and FSH was similar to that observed with the LH in vitro bioassay and FSH radioreceptor assay. It is concluded that the charge distribution of pituitary gonadotropins is altered according to the sex of the animal and after castration. These findings provide further evidence that the type of gonadotropin produced by the pituitary is under endocrine control.

Purpose: There are concerns over the late effects of cancer therapy, including accelerated bone loss leading to increased risk of osteoporosis. Treatment-related bone loss is well recognized in breast and prostate cancer, due to overt hypogonadism, but there has been little evaluation of the skeletal effects of chemotherapy alone in adults. This study assesses the extent of bone loss due to previous chemotherapy in men. Experimental Design: The bone mineral density (BMD) of men who had received previously chemotherapy with curative intent for lymphoma or testicular cancers was compared with that of an age-matched population of men from a cancer control population that had not received chemotherapy. BMD was measured by dual-energy X-ray scanning. Additionally, measurement of sex hormones and the bone turnover markers N-telopeptide fragment of type I collagen and bone-specific alkaline phosphatase were done. All statistical tests were two sided. Results: One hundred fifteen chemotherapy-treated patients and 102 cancer controls were recruited. There was no statistical difference in BMD between the chemotherapy and control groups at either spine or hip and the mean BMD values in both groups were no lower than that of a reference population. There were no significant differences in estradiol, luteinizing hormone, and testosterone, but follicle-stimulating hormone values were significantly higher in the chemotherapy group (P = 0.011). The mean values of NH 2 -terminal telopeptide fragment of type I collagen and bone-specific alkaline phosphatase were within the reference ranges. Conclusions: The absence of accelerated bone loss following chemotherapy is reassuring and suggests that standard dose cytotoxic chemotherapy has no lasting clinically important direct effects on bone metabolism.

PurposeSmoking is a major cause of lung cancer and continued smoking may compromise treatment efficacy and quality of life (HRQoL) in patients with advanced lung cancer.Our aims were to determine i) preference for treatments which promote quality over length of life depending on smoking status, ii) the relationship between HRQoL and smoking status at diagnosis (T1), after controlling for demographic and clinical variables and iii) changes in HRQoL 6 months after diagnosis (T2) depending on smoking status. Methods296 patients with advanced lung cancer were given questionnaires to assess HRQoL (EORTC-QLQ-C30), time-trade off for life quality versus quantity (QQQ) and smoking history (current, former or never smoker) at diagnosis (T1) and six months later (T2). Medical data were extracted from case records. ResultsQuestionnaires were returned by 202 (68.2%) patients at T1 and 114 (53.3%) at T2.Patients favoured treatments that would enhance quality of life over increased longevity. Those who continued smoking after diagnosis reported worse HRQoL than former smokers or those who never smoked. Smoking status was a significant independent predictor of coughing in T1 (worse in smokers), and Cognitive Functioning in T2 (better in never-smokers).3 ConclusionsSmoking by patients with advanced lung cancer is associated with worse symptoms on diagnosis and poorer HRQoL for those who continue smoking. The results have implications to help staff explain the consequences of smoking to patients.

We conclude that staff should give clearer advice about the adverse implications of continued smoking. We discuss the potential value of diagnosis as a teachable moment for promoting smoking cessation among patients and family members.