droperidol The prevalence of pathological fracture was in th

The prevalence of pathological fracture was 32.9% in this study, and a significantly higher prevalence of simple fracture was observed in women (26.3%) than in men (15.2%). This sex difference may be partly explained by the lower weights of bones in women than in men. Indeed, we observed that the female patients were more likely to have thin droperidol of bone, lower bone mineral density, and few bone trabeculae. Moreover, the pulmonary metastasis rate of GCTs around the knee was 0.7%, while the overall metastasis rate was 1.3%, lower than rates reported previously [6,7].
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Introduction Maintenance of bone health relies on a balance between bone formation by osteoblasts and bone resorption by osteoclasts. Under normal physiological circumstances, these two processes are tightly regulated to ensure preservation of the structural integrity of bone. However, cancer therapies can disrupt this delicate balance, leading to bone loss and subsequent increased fracture risk [1]. The pathophysiology of cancer treatment induced bone loss (CTIBL) is ascribed to either the direct effects of adjuvant treatments on bone turnover i.e. chemotherapy and endocrine therapy, or indirect effects via suppression of ovarian function with the subsequent low oestrogen environment causing clinically relevant bone loss [2]. Suppression of ovarian function in premenopausal women can be temporary or permanent dependent on the type of cancer treatment. The risk of POI is higher in women >40 years compared to 40 years or under [3] as loss of primordial follicles from direct chemotherapy toxicity depletes an already lowered ovarian reserve secondary to age [4]. Chemotherapy induces permanent primary ovarian insufficiency (POI) in 63–85% of patients receiving cyclophosphamide, methotrexate and fluorouracil (CMF) regimens and up to 50% with use of anthracycline containing regimens [5,6] with effects on bone metabolism and bone mineral density (BMD) as a consequence. For example, following induction of permanent ovarian suppression by six cycles of doxorubicin and cyclophosphamide chemotherapy, BMD fell at 6 months by 5.2% at the lumbar spine and by 2.8% at the femoral neck compared to baseline [7]. Bone loss associated with treatment induced ovarian failure appears to be more rapid and severe than the bone loss that occurs during a natural menopause, and therefore carries an increased risk of skeletal morbidity in long term survivors of premenopausal breast cancer [8] Gonadotrophin-releasing hormone (GnRH) analogues, such as goserelin, induce a rapid but reversible suppression of ovarian function with serum levels of oestradiol and follicle stimulating hormone (FSH) reaching postmenopausal levels within 2 weeks of administration [9,10]. In addition to the adjuvant use of goserelin in endocrine sensitive breast cancer, GnRH analogues have been evaluated in prospective randomized trials as a possible protection against chemotherapy induced POI in premenopausal women receiving adjuvant chemotherapy. Conflicting results have been reported with some studies demonstrating a reduction in chemotherapy induced early menopause of between 17% and 56% with addition of goserelin [11,12], while others showed no statistical difference in resumption of menses post chemotherapy between those treated with or without goserelin [13,14]. The impact of combined GnRH and chemotherapy on acute bone loss during therapy, and the delayed effects on bone post treatment have not been reported to date. Herein we present the secondary endpoint of bone turnover marker changes (serum bone alkaline phosphatase [BALP] and urine N-terminal telopeptide [NTX]) in the OPTION trial. The preliminary primary endpoint data of amenorrhoea rates at 12 months post chemotherapy were not statistically different between those treated with or without goserelin [14], although final data have not been reported yet.
Patients and methods
Discussion In this secondary endpoint analysis of the OPTION trial, we have shown that the addition of goserelin to neo(adjuvant) chemotherapy temporarily increased bone turnover during treatment and that this reverses over the next 6–12 months after completion of treatment. This is probably mediated by the effects on ovarian function, with a rapid and profound fall in oestradiol levels but, once the drug is stopped, ovarian function resumes to a level that is sufficient to maintain normal bone turnover, even if this is not manifested by a demonstrable difference in the frequency of chemotherapy induced amenorrhoea. We found no acute direct effect of chemotherapy on bone turnover markers, but there was a delayed effect on bone with increased bone turnover starting at 6 months after completion of chemotherapy and continuing throughout the 36 months of observation. This was predominantly in women aged >40 years and in those women who developed chemotherapy induced amenorrhoea, suggesting there may not be a direct toxic effect of chemotherapy on bone but that the BMD loss is driven predominantly by POI. Our study however has limitations that include a lack of ovarian function information beyond 12 months, which limits the interpretation of the association between bone markers and POI after this time point. In addition the number of serum/urine samples available for the bone marker analysis decreased during follow up thus limiting the interpretation of data at later time points.