Current Practice in Vitamin D Management in Allogeneic Hematopoietic Stem Cell Transplantation: A Survey by the Transplant Complications Working Party of the European Society for Blood and Marrow Transplantation.

Beyond its impact on bone health, numerous studies have investigated the immune-regulatory properties of vitamin D and shown how its deficiency can affect outcomes in allogeneic hematopoietic stem cell transplantation (HSCT), particularly in acute or chronic graft-versus-host disease. This survey, carried out by the Transplant Complications Working Party of the European Society for Blood and Marrow Transplantation (EBMT), describes the current clinical practice discrepancies across the EBMT HSCT programs. We therefore recommend the development of evidence-based guidelines to standardize evaluation criteria and to harmonize the management of vitamin D deficiency in patients undergoing allogeneic HSCT.

Late treatment effects following bone marrow transplant: Efficacy of implementing international guidelines.

An increasing cohort of haematopoietic cell transplantation (HCT) survivors has raised awareness of long-term and late effects. Updated recommendations for HCT late effects screening were published in 2012 [Majhail et al. Biology of Blood and Marrow Transplantation, 18 (2012):348]. We aimed to assess the clinical efficacy of a dedicated screening clinic to identify problems in HCT survivors using the international guidelines. Clinic letters and test results of the first 59 consecutive patients attending the screening clinic were evaluated. 30 females and 29 males (mean age of 49 years, range 22-74) were included. The mean time since transplant was 6 years (0.5-18). 49/65 transplants were allogeneic. Primary indications for HCT were myeloid (56%), lymphoid (37%), solid tumour (5%) and auto-immune diseases (2%). 134 complications were reported (mean 2, range 0-8), with 114 documented further actions/referrals. The most commonly reported concerns were pain 18/59 (31%), fatigue 14/59 (24%), sexual function 14/59 (24%) and sleep disturbance 11/59 (19%). Second primary malignancies were recorded in five cases. Implementation and audit of the international late effect screening guidelines confirm the need for systematic long-term physical and psychological screening and care, thus ensuring timely and efficient identification of problems and the opportunity to minimise morbidity effects and optimise health.

Experiences with perinatal death reviews in South Africa--the Perinatal Problem Identification Programme: scaling up from programme to province to country.

The Perinatal Problem Identification Programme (PPIP) was designed and developed in South Africa as a facility audit tool for perinatal deaths. It has been used by only a few hospitals since the late 1990s, but since the country's commitment to achieve Millennium Development Goal 4-the use of PPIP is now mandatory for all facilities delivering pregnant mothers and caring for newborns. To date 588 sites, representing 73% of the deliveries captured by the District Health Information System for South Africa, provide data to the national database at the Medical Research Council Unit for Maternal and Infant Health Care Strategies in Pretoria.

Holistic needs assessment in advanced, intensively treated multiple myeloma patients.

PURPOSE: It is recommended that patients with multiple myeloma should be assessed for unmet holistic needs at key times in their disease trajectory. The aim of this exploratory study was to characterise the holistic needs of advanced, intensively treated multiple myeloma using a structured assessment tool. METHODS: Patients with multiple myeloma who had undergone a haematopoietic stem cell transplantation and subsequent treatment for at least one episode of progressive disease but were in stable plateau phase were included in the study. Patients' holistic needs were assessed using the self-reporting tool, Sheffield Profile for Assessment and Referral for Care (SPARC). RESULTS: Thirty-two patients with a median age of 60 years at assessment and a median of 5.5 years from diagnosis were recruited. Using the SPARC, half of the patients reported tiredness as 'quite a bit/very much,' while one third complained that daytime somnolence and insomnia were 'quite a bit/very much.' Forty-four percent of patients reported pain. One third of patients were bothered and distressed by the side effects from their treatment and were worried about long-term effects of their treatment. Thirty-one percent of patients felt that the effect of their condition had an impact on their sexual life, and 40 % were worried about the effect that their illness was having on their family or other people. CONCLUSION: This is the first study to use a self-reported holistic needs assessment tool in multiple myeloma. A multidimensional structured questionnaire like the SPARC could provide a useful first step in the effective delivery of supportive and palliative care for patients with multiple myeloma.

Health service accreditation reinforces a mindset of high-performance human resource management: lessons from an Australian study.

OBJECTIVE: To investigate whether an accreditation program facilitates healthcare organizations (HCOs) to evolve and maintain high-performance human resource management (HRM) systems. DESIGN: Cross-sectional multimethod study. SETTING AND PARTICIPANTS: Healthcare organizations participating in the Australian Council on Healthcare Standards Evaluation and Quality Improvement Program (EQuIP 4) between 2007 and 2011. MAIN OUTCOME MEASURES: Ratings across the EQuIP 4 HRM criteria, a clinical performance measure, surveyor reports (HRM information) and interview data (opinions and experiences regarding HRM and accreditation). RESULTS: Healthcare organizations identified as high performing on accreditation HRM criteria seek excellence primarily because of internal motivations linked to best practice. Participation in an accreditation program is a secondary and less significant influence. Notwithstanding, the accreditation program provides the HCO opportunity for internal and external review and assessment of their performance; the accreditation activities are reflective learning and feedback events. CONCLUSIONS: This study reveals that HCOs that pursue highly performing HRM systems use participation in an accreditation program as an opportunity. Their organizational mindset is to use the program as a tool by which to reflect and obtain feedback on their performance so to maintain or improve their management of staff and delivery of care.

An app with brief behavioural support to promote physical activity after a cancer diagnosis (APPROACH): study protocol for a pilot randomised controlled trial.

BACKGROUND: There are multiple health benefits from participating in physical activity after a cancer diagnosis, but many people living with and beyond cancer (LWBC) are not meeting physical activity guidelines. App-based interventions offer a promising platform for intervention delivery. This trial aims to pilot a theory-driven, app-based intervention that promotes brisk walking among people living with and beyond cancer. The primary aim is to investigate the feasibility and acceptability of study procedures before conducting a larger randomised controlled trial (RCT). METHODS: This is an individually randomised, two-armed pilot RCT. Patients with localised or metastatic breast, prostate, or colorectal cancer, who are aged 16 years or over, will be recruited from a single hospital site in South Yorkshire in the UK. The intervention includes an app designed to encourage brisk walking (Active 10) supplemented with habit-based behavioural support in the form of two brief telephone/video calls, an information leaflet, and walking planners. The primary outcomes will be feasibility and acceptability of the study procedures. Demographic and medical characteristics will be collected at baseline, through self-report and hospital records. Secondary outcomes for the pilot (assessed at 0 and 3 months) will be accelerometer measured and self-reported physical activity, body mass index (BMI) and waist circumference, and patient-reported outcomes of quality of life, fatigue, sleep, anxiety, depression, self-efficacy, and habit strength for walking. Qualitative interviews will explore experiences of participating or reasons for declining to participate. Parameters for the intended primary outcome measure (accelerometer measured average daily minutes of brisk walking (≥ 100 steps/min)) will inform a sample size calculation for the future RCT and a preliminary economic evaluation will be conducted. DISCUSSION: This pilot study will inform the design of a larger RCT to investigate the efficacy and cost-effectiveness of this intervention in people LWBC. TRIAL REGISTRATION: ISRCTN registry, ISRCTN18063498 . Registered 16 April 2021.

Gender differences in self-reported late effects, quality of life and satisfaction with clinic in survivors of lymphoma.

OBJECTIVES: Gender differences in perceived vulnerability to late effects and views about follow-up among cancer survivors have received little attention. As lymphoma affects both genders similarly, we compared the consequences of cancer (late effects, perceived vulnerability and quality of life (health-related quality of life (HRQoL)), and satisfaction with clinic visits between genders. METHODS: A cohort of 115 younger adults (18-45 years, >5 years disease-free survival), who had been treated for lymphoma participated. Questionnaires (n = 91) were completed before and after (n = 62) routine consultant-led appointments. Survivors (n = 24) without appointments were recruited by post. Questionnaires included HRQoL, late effects, perceived vulnerability, issues survivors wanted to discuss and reported discussing in clinic, time waiting in clinic and consultation satisfaction. RESULTS: There were no gender differences in number of self-reported late effects or perceived vulnerability. Men with more late effects reported worse psychological HRQoL (r = 0.50, p<0.001). While men wanted to discuss more topics than they did, women were able to discuss the topics they wanted (ANOVA, p = 0.01). Multiple regression analyses showed a shorter wait in clinic (r = -0.46, p = 0.009) and discussing more topics (r = 0.34, p = 0.06) explained 30.6% of the variance in consultation satisfaction for men. CONCLUSIONS: Issues surrounding follow-up provision are increasingly important given the length of survival in young adults following treatment for lymphoma. Men may experience poor psychological well-being due to distress about unanswered concerns. Consideration of their concerns should be prioritised, given that satisfaction and ultimately continued attendance at clinic and HRQoL may be dependent on the extent to which follow-up meets survivors' expectations.

Systematic review of the use of translated patient-reported outcome measures in cancer trials.

BACKGROUND: Patient-reported outcomes (PROs) are used in clinical trials to assess the effectiveness and tolerability of interventions. Inclusion of participants from different ethnic backgrounds is essential for generalisability of cancer trial results. PRO data collection should include appropriately translated patient-reported outcome measures (PROMs) to minimise missing data and sample attrition. METHODS: Protocols and/or publications from cancer clinical trials using a PRO endpoint and registered on the National Institute for Health Research Portfolio were systematically reviewed for information on recruitment, inclusion of ethnicity data, and use of appropriately translated PROMs. Semi-structured interviews were conducted with key stakeholders to explore barriers and facilitators for optimal PRO trial design, diverse recruitment and reporting, and use of appropriately translated PROMs. RESULTS: Eighty-four trials met the inclusion criteria, only 14 (17%) (n = 4754) reported ethnic group data, and ethnic group recruitment was low, 611 (13%). Although 8 (57%) studies were multi-centred and multi-national, none reported using translated PROMs, although available for 7 (88%) of the studies. Interviews with 44 international stakeholders identified a number of perceived barriers to ethnically diverse recruitment including diverse participant engagement, relevance of ethnicity to research question, prominence of PROs, and need to minimise investigator burden. Stakeholders had differing opinions on the use of translated PROMs, the impact of trial designs, and recruitment strategies on diverse recruitment. Facilitators of inclusive research were described and examples of good practice identified. CONCLUSIONS: Greater transparency is required when PROs are used as primary or secondary outcomes in clinical trials. Protocols and publications should demonstrate that recruitment was accessible to diverse populations and facilitated by trial design, recruitment strategies, and appropriate PROM usage. The use of translated PROMs should be made explicit when used in cancer clinical trials.

Metabolic syndrome and cardiovascular disease after haematopoietic cell transplantation (HCT) in adults: an EBMT cross-sectional non-interventional study.

Metabolic syndrome (MetS) is associated with cardiovascular disease in the general population and is also a potential cardiovascular risk factor in survivors of haematopoietic cell transplantation (HCT). We report an EBMT cross-sectional, multi-centre, non-interventional study of 453 adult HCT patients surviving a minimum of 2 years post-transplant attending routine follow-up HCT and/or late effects clinics in 9 centres. The overall prevalence of MetS was 37.5% rising to 53% in patients >50 years of age at follow-up. There were no differences in rates of MetS between autologous and allogeneic HCT survivors, nor any association with graft-versus-host disease (GvHD) or current immunosuppressant therapy. Notably, there was a significantly higher occurrence of cardiovascular events (CVE, defined as cerebrovascular accident, coronary heart disease or peripheral vascular disease) in those with MetS than in those without MetS (26.7% versus 9%, p < 0.001, OR 3.69, 95% CI 2.09-6.54, p < 0.001), and, as expected, MetS and CVE were age-related. Unexpectedly, CVE were associated with occurrence of second malignancy. Screening for and management of MetS should be integrated within routine HCT long-term follow-up care for both allogeneic and autologous HCT survivors. Further research is warranted, including randomised controlled trials of interventional strategies and mechanistic studies of cardiovascular risk in HCT survivors.

Follow-up care for cancer survivors: views of the younger adult.

BACKGROUND: Since the launch of the National Cancer Survivorship Initiative, there has been a surge of interest surrounding the value and organisation of long-term follow-up care after cancer treatment. We report the views of 309 adult cancer survivors (aged 18-45 years) on provision of follow-up and preferences for care. METHODS: A total of 207 survivors completed questionnaires before and after routine consultant-led follow-up appointments and 102 were recruited by post. Measures of health status (including late effects, perceived vulnerability to late effects and quality of life), reasons for attending follow-up (clinical and supportive), issues to be discussed at follow-up and preferences for different models of care were assessed. RESULTS: In all, 59% of the survivors reported experiencing one or more cancer-related health problems. Survivors rated clinical reasons for attending follow-up more highly than supportive reasons (P<0.001), although nutritional advice and counselling were considered useful (60 and 47%, respectively). Those still receiving scheduled follow-up appointments did not discuss the range of issues intended with 'late effects' and 'fertility', which were particularly under-discussed. Hospital rather than GP follow-up was more highly rated. CONCLUSION: Survivors value the clinical reassurance currently provided by consultant-led care. However, supportive needs are not systematically addressed. Multi-disciplinary services are recommended to meet supportive needs in addition to clinical care.

Follow-up care for cancer survivors: the views of clinicians.

BACKGROUND: Evidence for the efficacy of late effects surveillance in adult cancer survivors is lacking and there is little agreement among clinicians on appropriate follow-up care. METHODS: We report the views of both cancer experts and general practitioners (GPs) on long-term follow-up provision for cancer survivors, focussing on the 18-45 years age group. A total of 421 cancer experts (36% haematologists, 33% oncologists, 18% surgeons, 10% nurses, 2% other) and 54 GPs responded to a structured online survey. Reasons for follow-up care (clinical or supportive); advantages and disadvantages of follow-up in primary care; current practice; and resources required for a quality follow-up service were assessed. RESULTS: Clinicians valued clinical reasons for follow-up more highly than supportive reasons (P<0.001). Learning more about late effects and checking for cancer recurrence were rated as the most important reasons for follow-up by cancer experts and GPs. A total of 85% of cancer specialists hold follow-up consultations alongside patients on active treatment. Cancer experts agreed that primary care follow-up would increase their availability for acute oncological care, but reduce information on late effects. The most important resource to provide a quality follow-up service was specialist nursing support (91%). CONCLUSIONS: Follow-up guidelines that include late effects surveillance are needed. Where and who should deliver this care requires further debate.

Prevalence and consequences of androgen deficiency in young male cancer survivors in a controlled cross-sectional study.

BACKGROUND: Testosterone replacement in hypogonadal males improves body composition, sexual function, and health-related quality of life. Male cancer survivors are at risk of androgen deficiency; however, when and in whom testosterone should be replaced remain unanswered questions. OBJECTIVE: The aim of our study was to define the prevalence of androgen deficiency in this patient group through assessment of testosterone levels and related measures. DESIGN: This was a cross-sectional, observational study of cases and controls. We recruited 176 cancer survivors and 213 controls, aged 25-45 yr. RESULTS: Of cancer survivors, 97% had received chemotherapy and 40% radiotherapy. Cancer survivors had lower total testosterone (tT) levels than controls (mean difference 2.67 nmol/liter; 95% confidence interval 1.58-3.76; P = 0.003), and 24 of 176 (13.6%; 95% confidence interval 9.3-19.5) had a tT less than 10 nmol/liter, which was less than 2.5% centile for controls. Cancer survivors had a greater fat mass, higher fasting insulin and glucose levels, increased fatigue, and reduced sexual function and health-related quality of life. In both cohorts, the tT correlated negatively with insulin levels and negatively with body fat mass; however, the difference in tT between them was independent of fat mass. We measured tT and SHBG and calculated bioavailable testosterone. The changes in calculated bioavailable testosterone were similar to tT. CONCLUSIONS: A significant proportion of young male cancer survivors had a frankly low tT associated with an increased fat mass and insulin level compared with controls. These factors would be predicted to improve in response to testosterone replacement therapy and provide a powerful argument for an interventional study of testosterone therapy in young male cancer survivors.

Routine vaccination practice after adult and paediatric allogeneic haematopoietic stem cell transplant: a survey of UK NHS programmes.

This corrects the article DOI: 10.1038/bmt.2016.362.

Temporal and Environmental Factors Driving Vibrio Vulnificus and V. Parahaemolyticus Populations and Their Associations With Harmful Algal Blooms in South Carolina Detention Ponds and Receiving Tidal Creeks.

Incidences of harmful algal blooms (HABs) and Vibrio infections have increased over recent decades. Numerous studies have tried to identify environmental factors driving HABs and pathogenic Vibrio populations separately. Few have considered the two simultaneously, though emerging evidence suggests that algal blooms enhance Vibrio growth and survival. This study examined various physical, nutrient, and temporal factors associated with incidences of HABs, V. vulnificus, and V. parahaemolyticus in South Carolina coastal stormwater detention ponds, managed systems where HABs often proliferate, and their receiving tidal creek waters. Five blooms occurred during the study (2008-2009): two during relatively warmer months (an August 2008 cyanobacteria bloom and a November 2008 dinoflagellate bloom) followed by increases in both Vibrio species and V. parahaemolyticus, respectively, and three during cooler months (December 2008 through February 2009) caused by dinoflagellates and euglenophytes that were not associated with marked changes in Vibrio abundances. Vibrio concentrations were positively and significantly associated with temperature and dissolved organic matter, dinoflagellate blooms, negatively and significantly associated with suspended solids, but not significantly correlated with chlorophyll or nitrogen. While more research involving longer time series is needed to increase robustness, findings herein suggest that certain HAB species may augment Vibrio occurrences during warmer months.

Provision of long-term monitoring and late effects services following adult allogeneic haematopoietic stem cell transplant: a survey of UK NHS-based programmes.

Despite international guidelines, optimal delivery models of late effects (LE) services for HSCT patients are unclear from the clinical, organizational and economic viewpoints. To scope current LE service delivery models within the UK NHS (National Health Service), in 2014, we surveyed the 27 adult allogeneic HSCT centres using a 30-question online tool, achieving a 100% response rate. Most LE services were led and delivered by senior physicians (>80% centres). Follow-up was usually provided in a dedicated allograft or LE clinic for the first year (>90% centres), but thereafter attrition meant that only ~50% of patients were followed after 5 years. Most centres (69%) had a standard operating procedure for long-term monitoring but access to a LE Multi-Disciplinary Team was rare (19% centres). Access to medical specialities necessary for LE management was good, but specialist interest in long-term HSCT complications was uncommon. Some screening (endocrinopathy, cardiovascular) was near universal, but other areas were more limited (mammography, cervical smears). Funding of extra staff and investigations were the most commonly perceived barriers to implementation of LE services. This survey shows variation in the long-term follow-up of allogeneic HSCT survivors within the UK NHS and further work is warranted to optimize effective, sustainable and affordable models of LE service delivery among this group.

Observational study of the development and evaluation of a fertility preservation patient decision aid for teenage and adult women diagnosed with cancer: the Cancer, Fertility and Me research protocol.

INTRODUCTION: Women diagnosed with cancer and facing potentially sterilising cancer treatment have to make time-pressured decisions regarding fertility preservation with specialist fertility services while undergoing treatment of their cancer with oncology services. Oncologists identify a need for resources enabling them to support women's fertility preservation decisions more effectively; women report wanting more specialist information to make these decisions. The overall aim of the 'Cancer, Fertility and Me' study is to develop and evaluate a new evidence-based patient decision aid (PtDA) for women with any cancer considering fertility preservation to address this unmet need. METHODS AND ANALYSIS: This is a prospective mixed-method observational study including women of reproductive age (16 years +) with a new diagnosis of any cancer across two regional cancer and fertility centres in Yorkshire, UK. The research involves three stages. In stage 1, the aim is to develop the PtDA using a systematic method of evidence synthesis and multidisciplinary expert review of current clinical practice and patient information. In stage 2, the aim is to assess the face validity of the PtDA. Feedback on its content and format will be ascertained using questionnaires and interviews with patients, user groups and key stakeholders. Finally, in stage 3 the acceptability of using this resource when integrated into usual cancer care pathways at the point of cancer diagnosis and treatment planning will be evaluated. This will involve a quantitative and qualitative evaluation of the PtDA in clinical practice. Measures chosen include using count data of the PtDAs administered in clinics and accessed online, decisional and patient-reported outcome measures and qualitative feedback. Quantitative data will be analysed using descriptive statistics, paired sample t-tests and CIs; interviews will be analysed using thematic analysis. ETHICS AND DISSEMINATION: Research Ethics Committee approval (Ref: 16/EM/0122) and Health Research Authority approval (Ref: 194751) has been granted. Findings will be published in open access peer-reviewed journals, presented at conferences for academic and health professional audiences, with feedback to health professionals and program managers. The Cancer, Fertility and Me patient decision aid (PtDA) will be disseminated via a diverse range of open-access media, study and charity websites, professional organisations and academic sources. External endorsement will be sought from the International Patient Decision Aid Standards (IPDAS) Collaboration inventory of PtDAs and other relevant professional organisations, for example, the British Fertility Society. TRIAL REGISTRATION NUMBER: NCT02753296; pre-results.

Metabolic syndrome and cardiovascular disease following hematopoietic cell transplantation: screening and preventive practice recommendations from CIBMTR and EBMT.

Metabolic syndrome (MetS) is a constellation of cardiovascular risk factors that increases the risk of cardiovascular disease, diabetes mellitus and all cause mortality. Long-term survivors of hematopoietic cell transplantation (HCT) have a substantial risk of developing MetS and cardiovascular disease, with the estimated prevalence of MetS being 31-49% among HCT recipients. Although MetS has not yet been proven to impact cardiovascular risk after HCT, an understanding of the incidence and risk factors for MetS in HCT recipients can provide the foundation to evaluate screening guidelines and develop interventions that may mitigate cardiovascular-related mortality. A working group was established through the Center for International Blood and Marrow Transplant Research and the European Group for Blood and Marrow Transplantation with the goal of reviewing literature and recommend practices appropriate to HCT recipients. Here we deliver consensus recommendations to help clinicians provide screening and preventive care for MetS and cardiovascular disease among HCT recipients. All HCT survivors should be advised of the risks of MetS and encouraged to undergo recommended screening based on their predisposition and ongoing risk factors.

An enhancement module to improve the atypical birefringence pattern using scanning laser polarimetry with variable corneal compensation.

AIM: To examine the repeatability and effect of an enhancement module on the severity of atypical birefringence patterns (ABP) using scanning laser polarimetery (SLP) with variable corneal compensation (VCC). METHODS: 16 patients with perimetric glaucoma (PG), 24 glaucoma suspect and pre-perimetric glaucoma (GSPPG), and 12 normal volunteers (N) were included. One randomly selected eye of each volunteer was scanned three times using VCC and enhanced corneal compensation (ECC) at the same session by the same examiner. Typical scan scores (TSS) were calculated to evaluate the ABP. Coefficients of variability (CoV), coefficients of repeatability (CoR), and intraclass correlation coefficients (ICC) were calculated. RESULTS: The mean TSS using ECC (n = 97.3 (5.5), GSPPG = 98.3 (3.5), PG = 99.2 (2.3)) was significantly higher (p = 0.02, 0.01, and 0.006, respectively) compared with VCC (86.5 (14.4), 88.2 (18.2), and 83.4 (2.2), respectively). VCC parameters had a CoR of 1.2-6.5, CoV of 1.9%-8.6%, and ICC of 0.8-0.9. ECC parameters had a CoR of 0.5-4.0, CoV of 0.3%-5.1%, and ICC of 0.2-0.9. TSNIT average was the overall best performing parameter with the highest repeatability and least variability using both techniques (CoR<2.1, CoV<2%). CONCLUSION: The enhancement module significantly reduced the severity of ABP and maintained a high level of repeatability of retardation measurements.

A spatial assessment of baseline nutrient and water quality values in the Ashepoo-Combahee-Edisto (ACE) Basin, South Carolina, USA.

The Ashepoo-Combahee-Edisto (ACE) Basin (South Carolina, USA) National Estuarine Research Reserve System (NERRS) encompasses some of the least developed USA coastline. Yet, periodic sampling showed that certain regions have higher nutrient, fecal coliform, and chlorophyll a levels, often with lower dissolved oxygen, than other South Carolina estuaries. To evaluate the spatial extent of these issues, a summer (2008) baseline study was conducted. Physical water quality, total nitrogen and phosphorus, chlorophyll a, dissolved organic carbon, and suspended solids were measured from surface waters of 67 stations (30 tidal creek, 37 open water). Nutrient and chlorophyll a levels were significantly (p<0.01) and negatively correlated with the extent of open water (% land cover), and chlorophyll a and nitrogen levels were, at times, elevated relative to concentrations typical of other estuaries in the state, reinforcing previous findings. This survey also identified several creeks not previously monitored that exhibited elevated nutrients.

Circulating estradiol and osteoprotegerin as determinants of bone turnover and bone density in postmenopausal women.

Osteoprotegerin (OPG) is a recently identified cytokine that acts as a decoy receptor for the receptor activator of NF kappa B ligand. OPG has been shown to be an important inhibitor of osteoclast differentiation and activation in rodent models. Estrogen is known to suppress bone resorption, and the action of estrogen on bone may be mediated by OPG. The relationship between endogenous estrogen and circulating OPG levels and bone status in human populations is unclear. Thus, the aim of this study was to investigate the relationship between biochemical markers of bone turnover and bone density and circulating OPG and endogenous estradiol levels in a population-based cohort of postmenopausal women. Subjects were 180 women ages 55-91 yr (mean age, 67 yr). Serum estradiol was measured using an auto-analyzer. Serum concentrations of OPG were determined by ELISA. Markers of bone formation and resorption were measured by standard methods. Bone mineral density at total body, total hip, femoral neck, and lumbar spine was measured by dual energy x-ray absorptiometry. There was a significant inverse relationship between estradiol and all bone turnover markers (r-values from -0.46 to -0.23; P < 0.05). Serum estradiol was positively related to absolute bone density at all sites and to change in bone density at the hip and femoral neck by univariate analysis (r-values from 0.15-0.29; P < 0.05). We observed a weak inverse association between OPG and serum-based bone turnover markers (r-values -0.18 and -0.16; P < 0.05). There was a significant positive relationship between OPG and bone mineral density at total body, total hip, and femoral neck (r-values from 0.17-0.2; P < 0.05) by univariate analysis, which was lost after adjustment for age and body mass index. There was a significant weak positive relationship between circulating OPG and serum estradiol (r = 0.18; P < 0.02). We observed no significant relationships between OPG and bone turnover markers measured in urine. We conclude that the variation in circulating endogenous estradiol levels is an important factor contributing to levels of bone turnover and bone density at the menopause. Our observations also suggest that circulating levels of OPG may reflect OPG activity in bone and are related to circulating endogenous levels of estradiol. We have previously reported high levels of variability in urine markers of bone resorption, and we suggest that this could account for the absence of a significant association between these markers and circulating OPG.