Osteoporotic Fractures: Diagnosis, Evaluation, and Significance From the International Working Group on DXA Best Practices.

Osteoporotic fractures, also known as fragility fractures, are reflective of compromised bone strength and are associated with significant morbidity and mortality. Such fractures may be clinically silent, and others may present clinically with pain and deformity at the time of the injury. Unfortunately, and even at the time of detection, most individuals sustaining fragility fractures are not identified as having underlying metabolic bone disease and are not evaluated or treated to reduce the incidence of future fractures. A multidisciplinary international working group with representation from international societies dedicated to advancing the care of patients with metabolic bone disease has developed best practice recommendations for the diagnosis and evaluation of individuals with fragility fractures. A comprehensive narrative review was conducted to identify key articles on fragility fractures and their impact on the incidence of further fractures, morbidity, and mortality. This document represents consensus among the supporting societies and harmonizes best practice recommendations consistent with advances in research. A fragility fracture in an adult is an important predictor of future fractures and requires further evaluation and treatment of the underlying osteoporosis. It is important to recognize that most fragility fractures occur in patients with bone mineral density T scores higher than -2.5, and these fractures confirm the presence of skeletal fragility even in the presence of a well-maintained bone mineral density. Fragility fractures require further evaluation with exclusion of contributing factors for osteoporosis and assessment of clinical risk factors for fracture followed by appropriate pharmacological intervention designed to reduce the risk of future fracture. Because most low-trauma vertebral fractures do not present with pain, dedicated vertebral imaging and review of past imaging is useful in identifying fractures in patients at high risk for vertebral fractures. Given the importance of fractures in confirming skeletal fragility and predicting future events, it is recommended that an established classification system be used for fracture identification and reporting.

Race-specific FRAX models are evidence-based and support equitable care: a response to the ASBMR Task Force report on Clinical Algorithms for Fracture Risk.

Task Force on 'Clinical Algorithms for Fracture Risk' commissioned by the American Society for Bone and Mineral Research (ASBMR) Professional Practice Committee has recommended that FRAX® models in the US do not include adjustment for race and ethnicity. This position paper finds that an agnostic model would unfairly discriminate against the Black, Asian and Hispanic communities and recommends the retention of ethnic and race-specific FRAX models for the US, preferably with updated data on fracture and death hazards. In contrast, the use of intervention thresholds based on a fixed bone mineral density unfairly discriminates against the Black, Asian and Hispanic communities in the US. This position of the Working Group on Epidemiology and Quality of Life of the International Osteoporosis Foundation (IOF) is endorsed both by the IOF and the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO).

Effects of maternal calcium supplementation on offspring blood pressure and growth in childhood and adolescence in a population with a low-calcium intake: follow-up study of a randomized controlled trial.

BACKGROUND: The World Health Organization recommends calcium supplementation (1500-2000 mg/d) during pregnancy for women with a low-calcium intake. OBJECTIVES: The purpose of this study was to investigate whether pregnancy calcium supplementation affects offspring blood pressure and growth in The Gambia where calcium intakes are low (300-400 mg/d). METHODS: Follow-up of offspring born during a randomized controlled trial of pregnancy calcium supplementation (ISRCTN96502494, 1996-2000) in which mothers were randomly assigned to 1500 mg Ca/d (Ca) or placebo (P) from 20 wk pregnancy to delivery. Offspring were enrolled at age 3 y in studies where blood pressure and anthropometry were measured under standardized conditions at approximately 2-yearly intervals. Mean blood pressure and growth curves were fitted for females and males separately, using the longitudinal SuperImposition by Translation and Rotation (SITAR) mixed effects model. This generates 3 individual-specific random effects: size, timing, and intensity, reflecting differences in size, age at peak velocity, and peak velocity through puberty relative to the mean curve, respectively. RESULTS: Five hundred twenty-three singleton infants were born during the trial (maternal group assignment: Ca/P = 259/264). Four hundred ninety-one were enrolled as children (females: F-Ca/F-P = 122/129 and males: M-Ca/M-P = 119/121) and measured regularly from 3.0 y to mean age 18.4 y; 90% were measured on ≥8 occasions. SITAR revealed differences in the systolic blood pressure and height curves between pregnancy supplement groups in females, but not in males. F-Ca had lower systolic blood pressure than F-P at all ages (size = -2.1 ± SE 0.8 mmHg; P = 0.005) and lower peak height velocity (intensity = -2.9 ± SE 1.1%, P = 0.009). No significant pregnancy supplement effects were seen for other measures. CONCLUSIONS: This study showed, in female offspring, that pregnancy calcium supplementation may lower systolic blood pressure and slow linear growth in childhood and adolescence, adding to evidence of offspring sexual dimorphism in responses to maternal supplementation. Further research is warranted on the long-term and intergenerational effects of antenatal supplementations. This trial was registered at ISRCTN Registry as ISRCTN96502494.

Could self-reported physical performance help predict individuals at the highest risk of mortality and hospital admission events in clinical practice? Findings from the Hertfordshire Cohort Study.

AIM: To consider how self-reported physical function measures relate to adverse clinical outcomes measured over 20 years of follow-up in a community-dwelling cohort (aged 59-73 at baseline) as compared with hand grip strength, a well-validated predictor of adverse events. BACKGROUND: Recent evidence has emphasized the significant association of physical activity, physical performance, and muscle strength with hospital admissions in older people. However, physical performance tests require staff availability, training, specialized equipment, and space to perform them, often not feasible or realistic in the context of a busy clinical setting. METHODS: In total, 2997 men and women were analyzed. Baseline predictors were measured grip strength (Jamar dynamometer) and the following self-reported measures: physical activity (Dallosso questionnaire); physical function score (SF-36 Health Survey); and walking speed. Participants were followed up from baseline (1998-2004) until December 2018 using UK Hospital Episode Statistics and mortality data, which report clinical outcomes using ICD-10 coding. Predictors in relation to the risk of mortality and hospital admission events were examined using Cox regression with and without adjustment for sociodemographic and lifestyle characteristics. FINDINGS: The mean age at baseline was 65.7 and 66.6 years among men and women, respectively. Over follow-up, 36% of men and 26% of women died, while 93% of men and 92% of women were admitted to hospital at least once. Physical activity, grip strength, SF-36 physical function, and walking speed were all strongly associated with adverse health outcomes in both sex- and fully adjusted analyses; poorer values for each of the predictors were related to greater risk of mortality (all-cause, cardiovascular-related) and any, neurological, cardiovascular, respiratory, any fracture, and falls admissions. SF-36 physical function and grip strength were similarly associated with the adverse health outcomes considered.

Fracture Risk and Health Profiles Differ According to Relationship Status: Findings from the Hertfordshire Cohort Study.

Registry studies have suggested associations between relationship status and fracture risk. We considered associations between relationship status and incident fracture in the Hertfordshire Cohort Study, comprising community-dwelling older adults, and explored associations between socioeconomic and lifestyle factors with relationship status. 2997 participants completed a baseline questionnaire (1998-2004) and clinic visit. Participants were followed up until December 2018 using Hospital Episode Statistics, which report clinical outcomes using codes from the 10th revision of the International Classification of Diseases (ICD-10); these codes were used to ascertain incident fractures. Relationship status (not currently married/cohabiting vs currently married/cohabiting) at baseline was examined in relation to incident fracture using Cox regression. Associations between baseline characteristics and relationship status were examined using logistic regression. Mean baseline age was 66.2 years. 80% were married/cohabiting at baseline; 15% had an incident fracture (mean (SD) follow-up duration: 14.4 (4.5) years). The following were related to greater likelihood of not being married/cohabiting: older age (women only); higher BMI (women only); current smoking; high alcohol consumption (men only); poorer diet quality (men only); lower physical activity; leaving school before age 15 (women only); and not owning one's home. Those not married/cohabiting had greater risk of incident fracture compared to those who were (age-adjusted hazard ratios (95% CI) 1.58 (1.06, 2.38) among men, 1.35 (1.06, 1.72) among women); associations were attenuated after accounting for the above factors associated with relationship status in the corresponding sex. This suggests that differences in health profiles and lifestyle according to relationship status may explain the association between relationship status and fracture risk.

Estimating the impact of test-trace-isolate-quarantine systems on SARS-CoV-2 transmission in Australia.

BACKGROUND: Australian states and territories used test-trace-isolate-quarantine (TTIQ) systems extensively in their response to the COVID-19 pandemic in 2020-2021. We report on an analysis of Australian case data to estimate the impact of test-trace-isolate-quarantine systems on SARS-CoV-2 transmission. METHODS: Our analysis uses a novel mathematical modelling framework and detailed surveillance data on COVID-19 cases including dates of infection and dates of isolation. First, we directly translate an empirical distribution of times from infection to isolation into reductions in potential for onward transmission during periods of relatively low caseloads (tens to hundreds of reported cases per day). We then apply a simulation approach, validated against case data, to assess the impact of case-initiated contact tracing on transmission during a period of relatively higher caseloads and system stress (up to thousands of cases per day). RESULTS: We estimate that under relatively low caseloads in the state of New South Wales (tens of cases per day), TTIQ contributed to a 54% reduction in transmission. Under higher caseloads in the state of Victoria (hundreds of cases per day), TTIQ contributed to a 42% reduction in transmission. Our results also suggest that case-initiated contact tracing can support timely quarantine in times of system stress (thousands of cases per day). CONCLUSION: Contact tracing systems for COVID-19 in Australia were highly effective and adaptable in supporting the national suppression strategy from 2020-21, prior to the emergence of the Omicron variant in November 2021. TTIQ systems were critical to the maintenance of the strong suppression strategy and were more effective when caseloads were (relatively) low.

General self-efficacy, not musculoskeletal health, was associated with social isolation and loneliness in older adults during the COVID-19 pandemic: findings from the Hertfordshire Cohort Study.

BACKGROUND: Social isolation and loneliness are prevalent among older adults. This study investigated factors influencing worsening social isolation and loneliness in community-dwelling older adults during the COVID-19 pandemic, focusing on musculoskeletal conditions, falls, and fractures. METHODS: We studied 153 participants from the Hertfordshire Cohort Study. Baseline assessments (2019-20) included osteoporosis, clinical osteoarthritis, fractures after age 45 years, falls in previous year, and lifestyle factors. Self-efficacy was assessed using a shortened General Self-Efficacy Scale. Social isolation was assessed using the 6-item Lubben Social Network Scale. Follow-up (2020-21) assessments included social isolation and loneliness using the 6-item De Jong-Gierveld scale for emotional, social, and overall loneliness. RESULTS: Baseline median age was 83.1 years. A history of smoking predicted worsening social isolation (p = 0.046). Being married (p = 0.026) and higher self-efficacy scores (p = 0.03) predicted reduced social isolation at follow-up. Greater alcohol consumption was associated with higher overall loneliness (p = 0.026). Being married was related to a 36% (95% CI: 3%, 58%) reduction in emotional loneliness (p = 0.037). No musculoskeletal condition was associated with social isolation or loneliness. However, we observed a 22% (14%, 30%; p < 0.001) reduction in emotional loneliness and a 12% (4%, 20%; p = 0.003) reduction in overall loneliness per unit increase in self-efficacy score. CONCLUSIONS: No musculoskeletal condition was associated with increased social isolation or loneliness, but longitudinal studies in larger samples are required. Greater self-efficacy was associated with reduced social isolation and reduced loneliness. Interventions promoting self-efficacy in older adults may reduce isolation and loneliness in this age group.

Perinatal HIV infection is associated with deficits in muscle function in children and adolescents in Zimbabwe.

OBJECTIVES: To determine how muscle strength, power, mass, and density (i.e. quality) differ between children living with HIV (CWH) and those uninfected, and whether antiretroviral therapy (ART) regime is associated with muscle quality. DESIGN: A cross-sectional study in Harare, Zimbabwe. METHODS: The study recruited CWH aged 8-16 years, taking ART for at least 2 years, from HIV clinics, and HIV-uninfected children from local schools. Muscle outcomes comprised grip strength measured by hand-held Jamar dynamometer, lower limb power measured by standing long-jump distance, lean mass measured by dual-energy X-ray absorptiometry, and muscle density (reflecting intramuscular fat) by peripheral quantitative computed tomography. Linear regression calculated adjusted mean differences (aMD) by HIV status. RESULTS: Overall, 303 CWH and 306 without HIV, had mean (SD) age 12.5 (2.5) years, BMI 17.5 (2.8), with 50% girls. Height and fat mass were lower in CWH, mean differences (SE) 7.4 (1.1) cm and 2.7 (0.4)kgs, respectively. Male CWH had lower grip strength [aMD 2.5 (1.1-3.9) kg, P  < 0.001], long-jump distance [7.1 (1.8-12.5) cm, P  = 0.006], muscle density [0.58 (0.12-1.05) mg/cm 3 , P  = 0.018, but not lean mass 0.06 (-1.08 to 1.21) kg, P  = 0.891) versus boys without HIV; differences were consistent but smaller in girls. Mediation analysis suggested the negative effect of HIV on jumping power in boys was partially mediated by muscle density ( P  = 0.032). CWH taking tenofovir disoproxil fumarate (TDF) had lower muscle density [0.56 (0.00-1.13)mg/cm 3 , P  = 0.049] independent of fat mass, than CWH on other ART. CONCLUSION: Perinatally acquired HIV is associated, particularly in male individuals, with reduced upper and lower limb muscle function, not mass. Intra-muscular fat (poorer muscle quality) partially explained reductions in lower limb function. TDF is a novel risk factor for impaired muscle quality.

What works in engaging communities? Prioritising nutrition interventions in Burkina Faso, Ghana and South Africa.

BACKGROUND: "Choosing All Together" (CHAT), is a community engagement tool designed to give the public a voice in how best to allocate limited resources to improve population health. This process evaluation explored the mechanisms through which CHAT generates community engagement. METHOD: The CHAT tool was adapted and implemented for use in two rural communities (Nanoro, Burkina Faso, and Navrongo, Ghana) and one urban township (Soweto, South Africa) to prioritize maternal and child nutrition interventions. Community discussions were audio-recorded, transcribed, and translated into English. Twenty-two transcripts, including six each from Navrongo and Soweto and 10 from Nanoro, were analysed thematically to generate data driven codes and themes to explain mechanisms underlying the CHAT process. The process evaluation was based on the UK MRC process evaluation guidance. RESULTS: Seven themes describing the functions and outcomes of CHAT were identified. Themes described participants deliberating trade-offs, working together, agreeing on priorities, having a shared vision, and increasing their knowledge, also the skills of the facilitator, and a process of power sharing between participants and researchers. Participants came to an agreement of priorities when they had a shared vision. Trained facilitators are important to facilitate meaningful discussion between participants and those with lower levels of literacy to participate fully. CONCLUSION: CHAT has been shown to be adaptable and useful in prioritising maternal and child nutrition interventions in communities in Burkina Faso, Ghana, and South Africa. Conducting CHAT in communities over a longer period and involving policy-makers would increase trust, mutual respect and develop partnerships.

Undernutrition in children aged 0-59 months by region and over time: secondary analysis of the Burkina Faso 2012-2018 National Nutrition Surveys.

The global burden of undernutrition remains high, responsible for significant under-five mortality in resource-limited settings. Numerous sustainable development goals (SDGs) are linked to nutrition, and nationally representative nutrition surveillance is a key activity to track progress towards SDGs and guide efficient programmes. OBJECTIVES: The aim of this study is to look at spatial and temporal trends in undernutrition in children under 5 years age in Burkina Faso. SETTING: We used data from annual National Nutrition Surveys using Standardised Monitoring and Assessment of Relief and Transitions methodology (anthropometry, morbidity) over 7 years (2012-2018) in Burkina Faso. PARTICIPANTS: Children of under 5 years from households selected through systemic sampling at countrywide level. MAIN OUTCOME MEASURES: Prevalence of stunting (height-for-age z-score, <-2), underweight (weight-for-age z-score, <-2) and wasting (weight-for-height z-score, <-2) at regional and national. We used general linear mixed models, adjusted by age, survey year, sex, presence of fever and/or diarrhoea, and poverty index to quantify the risk of undernutrition over time and by region of residence. RESULTS: Between 2012 and 2018, decreases were observed overall in the prevalence of growth retardation (stunting) decreased from 33.0% (95% CI 32.3 to 33.8) in 2012 to 26.7% (95% CI 26.2 to 27.3) in 2018. Underweight reduced from 24.4% (95% CI 23.7 to 25.1) to 18.7% (95% CI 18.2 to 19.2) for the same period and wasting decreased from 10.8% (95% CI 10.3 to 11.3) in 2012 to 8.4% (95% CI 8.1 to 8.8) in 2018. However, there was substantial variation across the country, with increased risk of undernutrition in the regions of Sahel, East and Cascades primarily. High-risk regions were characterised by a lower poverty index and limited access to healthcare services. CONCLUSIONS: Our findings could inform national policymakers in refining and optimising resource allocation based on the identification of high-risk areas.

Hospital admissions and mortality over 20 years in community-dwelling older people: findings from the Hertfordshire Cohort Study.

BACKGROUND: Demographic changes worldwide are leading to pressures on health services, with hospital admissions representing an important contributor. Here, we report admission types experienced by older people and examine baseline risk factors for subsequent admission/death, from the community-based Hertfordshire Cohort Study. METHODS: 2997 participants (1418 women) completed a baseline questionnaire and clinic visit to characterize their health. Participants were followed up from baseline (1998-2004, aged 59-73 years) until December 2018 using UK Hospital Episode Statistics and mortality data, which report clinical outcomes using ICD-10 coding. Baseline characteristics in relation to the risk of admission/death during follow-up were examined using sex-stratified univariate logistic regression. RESULTS: During follow-up, 36% of men and 26% of women died and 93% of men and 92% of women had at least one hospital admission; 6% of men and 7% of women had no admissions and were alive at end of follow-up. The most common types of admission during follow-up were cardiovascular (ever experienced: men 71%, women 68%) and respiratory (men 40%, women 34%). In both sexes, baseline risk factors that were associated (p < 0.05) with admission/death during follow-up were older age, poorer SF-36 physical function, and poorer self-rated health. In men, manual social class and a history of smoking, and in women, higher BMI, not owning one's home, and a minor trauma fracture since age 45, were also risk factors for admission/death. CONCLUSIONS: Sociodemographic factors were related to increased risk of admission/death but a small proportion experienced no admissions during this period, suggesting that healthy ageing is achievable.

DNA methylation at the suppressor of cytokine signaling 3 (SOCS3) gene influences height in childhood.

Human height is strongly influenced by genetics but the contribution of modifiable epigenetic factors is under-explored, particularly in low and middle-income countries (LMIC). We investigate links between blood DNA methylation and child height in four LMIC cohorts (n = 1927) and identify a robust association at three CpGs in the suppressor of cytokine signaling 3 (SOCS3) gene which replicates in a high-income country cohort (n = 879). SOCS3 methylation (SOCS3m)-height associations are independent of genetic effects. Mendelian randomization analysis confirms a causal effect of SOCS3m on height. In longitudinal analysis, SOCS3m explains a maximum 9.5% of height variance in mid-childhood while the variance explained by height polygenic risk score increases from birth to 21 years. Children's SOCS3m is associated with prenatal maternal folate and socio-economic status. In-vitro characterization confirms a regulatory effect of SOCS3m on gene expression. Our findings suggest epigenetic modifications may play an important role in driving child height in LMIC.

Men's motivations, barriers to and aspirations for their families' health in the first 1000 days in sub-Saharan Africa: a secondary qualitative analysis.

Introduction: The first 1000 days of life are a critical period of growth and development that have lasting implications for health, cognitive, educational and economic outcomes. In sub-Saharan Africa, gender and social norms are such that many men have little engagement with maternal and child health and nutrition during pregnancy and early childhood. This study explores how men perceive their role in three sites in sub-Saharan Africa. Methods: Secondary qualitative analysis of 10 focus group discussions with 76 men in Burkina Faso, Ghana and South Africa. Data were thematically analysed to explore men's perceptions of maternal and child health and nutrition. Results: Men considered themselves 'providers' and 'advisors' within their families, particularly of finances, food and medicines. They also indicated that this advice was out of care and concern for their families' health. There were similarities in how the men perceive their role. Differences between men living in rural and urban settings included health priorities, the advice and the manner in which it was provided. Across all settings, men wanted to be more involved with maternal and child health and nutrition. Challenges to doing so included stigma and proscribed social gender roles. Conclusion: Men want a greater engagement in improving maternal and child health and nutrition but felt that their ability to do so was limited by culture-specified gender roles, which are more focused on providing for and advising their families. Involving both men and women in intervention development alongside policymakers, health professionals and researchers is needed to improve maternal and child health and nutrition.

Disparities in the Prevalence of Osteoporosis and Osteopenia in Men and Women Living in Sub-Saharan Africa, the UK, and the USA.

PURPOSE: To review the rising prevalence of osteopenia and osteoporosis in sub-Saharan Africa and the challenges this poses to governments and healthcare services. Using existing studies, we compare the prevalence of osteopenia and osteoporosis in men and women from sub-Saharan Africa to US and UK cohorts. Context-specific disparities in healthcare are discussed particularly the challenges in diagnosis and treatment of osteoporosis. RECENT FINDINGS: There are few epidemiological data describing the burden of osteoporosis in sub-Saharan Africa. In the studies and cohorts presented here, osteoporosis prevalence varies by sex, country and area of residence, but is generally higher in African populations, than has previously been appreciated. Risk factors contributing to poorer bone health include HIV, malnutrition and "inflammaging." Reprioritization towards care of ageing populations is urgently required. Equitable access to implementable preventative strategies, diagnostic services, treatments and pathways of care for bone health (for example embedded within HIV services) need now to be recognized and addressed by policy makers.

What values drive communities' nutrition priorities in a resource constrained urban area in South Africa?

BACKGROUND: Voices of under-resourced communities are recognised as important yet are often unheard in decisions about healthcare resource allocation. Deliberative public engagement can serve as an effective mechanism for involving communities in establishing nutrition priorities. This study sought to identify the priorities of community members of a South African township, Soweto, and describe the underlying values driving their prioritisation process, to improve nutrition in the first 1000 days of life. METHODS: We engaged 54 community members (28 men and 26 women aged > 18 years) from Soweto. We conducted seven group discussions to determine how to allocate limited resources for prioritising nutrition interventions. We used a modified public engagement tool: CHAT (Choosing All Together) which presented 14 nutrition intervention options and their respective costs. Participants deliberated and collectively determined their nutritional priorities. Choices were captured quantitatively, while group discussions were audio-recorded. A thematic analysis was undertaken to identify the reasons and values associated with the selected priorities. RESULTS: All groups demonstrated a preference to allocate scarce resources towards three priority interventions-school breakfast provisioning, six-months paid maternity leave, and improved food safety. All but one group selected community gardens and clubs, and five groups prioritised decreasing the price of healthy food and receiving job search assistance. Participants' allocative decisions were guided by several values implicit in their choices, such as fairness and equity, efficiency, social justice, financial resilience, relational solidarity, and human development, with a strong focus on children. Priority interventions were deemed critical to supporting children's optimal development and well-being, interrupting the intergenerational cycle of poverty and poor human development in the community. CONCLUSION: Our study demonstrates how public engagement can facilitate the incorporation of community values and programmatic preferences into nutrition priority setting, enabling a responsive approach to local community needs, especially in resource constrained contexts. Findings could guide policy makers to facilitate more appropriate decisions and to improve nutrition in the first 1000 days of life.

Cross-Calibration of iDXA and pQCT Scanners at Rural and Urban Research Sites in The Gambia, West Africa.

Between-scanner differences in measures of bone and body composition can obscure or exaggerate physiological differences in multi-site studies or the magnitude of changes in longitudinal studies. We conducted a cross-calibration study at two bone imaging centres in The Gambia, West Africa where DXA (dual-energy X-ray absorptiometry) and pQCT (peripheral Quantitative-Computed Tomography) are routinely used. Repeat scans were obtained from 64 Gambian adults (58% Male) aged Mean(SD) 30.9 (13.5) years with Mean(SD) body mass index (BMI) 21.7 (4.0) kg/m2, using DXA (GE Lunar iDXA, whole body [WB], total hip [TH], lumbar spine [LS]) and pQCT (Stratec XCT2000L/XCT2000, tibia 4%, 50% sites). Between-scanner differences were tested using paired t tests (p < 0.05). Between-scanner correlation was explored with linear regression, and cross-calibration equations derived. Bland-Altman analysis investigated machine trend/bias. When differences were detected (p < 0.05), cross-calibration equations were applied to urban values, with t tests and Bland Altman analysis repeated. Between-scanner differences exceeded the predefined level of statistical significance (p < 0.05) for WB aBMD and BA; all pQCT measures vBMD, BMC, cortical cross-sectional area (CSA) and stress-strain index (SSI). Between-scanner correlation was high (R2:0.92-0.99), except pQCT Mu.Den (R2 = 0.51). Bland Altman plots indicated bias increased with increasing BMD. Cross-calibration equations attenuated all between-scanner differences and systematic bias. Cross-calibration, particularly of pQCT scanners, is an important consideration in multi-site studies particularly where between population comparisons are intended. Our experiences and findings may be generalisable to other resource-limited settings where the logistics of sourcing parts and in-country repair may result in lengthy scanner downtime.

Evaluation of two methods of bone age assessment in peripubertal children in Zimbabwe.

OBJECTIVES: Bone age (BA) measurement in children is used to evaluate skeletal maturity and helps in the diagnosis of growth disorders in children. The two most used methods are Greulich and Pyle (GP), and Tanner and Whitehouse 3 (TW3), both based upon assessment of a hand-wrist radiograph. To our knowledge no study has compared and validated the two methods in sub-Saharan Africa (SSA), and only a few have determined BA despite it being a region where skeletal maturity is often impaired for example by HIV and malnutrition. This study aimed to compare BA as measured by two methods (GP and TW3) against chronological age (CA) and determine which method is most applicable in peripubertal children in Zimbabwe. METHODS: We conducted a cross-sectional study of boys and girls who tested negative for HIV. Children and adolescents were recruited by stratified random sampling from six schools in Harare, Zimbabwe. Non-dominant hand-wrist radiographs were taken, and BA assessed manually using both GP and TW3. Paired sample Student t-tests were used to calculate the mean differences between BA and chronological age (CA) in boys and girls. Bland-Altman plots compared CA to BA as determined by both methods, and agreement between GP and TW3 BA. All radiographs were graded by a second radiographer and 20 % of participants of each sex were randomly selected and re-graded by the first observer. Intraclass correlation coefficient assessed intra- and inter-rater reliability and coefficient of variation assessed precision. RESULTS: We recruited 252 children (111 [44 %] girls) aged 8.0-16.5 years. The boys and girls were of similar mean ± SD CA (12.2 ± 2.4 and 11.7 ± 1.9 years) and BA whether assessed by GP (11.5 ± 2.8 and 11.5 ± 2.1 years) or TW3 (11.8 ± 2.5 and 11.8 ± 2.1 years). In boys BA was lower than CA by 0.76 years (95 % CI: -0.95, -0.57) when using GP, and by 0.43 years (95 % CI: -0.61, -0.24) when using TW3. Among the girls there was no difference between BA and CA by either GP [-0.19 years (95 % CI: -0.40, 0.03)] or TW3 [0.07 years (95 % CI: -0.16, 0.29)]. In both boys and girls, there were no systematic differences between CA and TW3 BA across age groups whereas agreement improved between CA and GP BA as children got older. Inter-operator precision was 1.5 % for TW3 and 3.7 % for GP (n = 252) and intra-operator precision was 1.5 % for TW3 and 2.4 % for GP (n = 52). CONCLUSION: The TW3 BA method had better precision than GP and did not systematically differ from CA, meaning that TW3 is the preferred method of assessment of skeletal maturity in Zimbabwean children and adolescents. TW3 and GP methods do not agree for estimates of BA and therefore cannot be used interchangeably. The systematic differences in GP BA assessments over age means it is not appropriate for use in all age groups or stages of maturity in this population.

Investing in human development and building state resilience in fragile contexts: A case study of early nutrition investments in Burkina Faso.

Maternal and early malnutrition have negative health and developmental impacts over the life-course. Consequently, early nutrition support can provide significant benefits into later life, provided the later life contexts allow. This study examines the limits of siloed investments in nutrition and illustrates how ignoring life-course contextual constraints limits human development benefits and exacerbates inequality, particularly in fragile contexts. This case study focuses on Burkina Faso, a country with high rates of early malnutrition and a fragile state. We modelled the impact of scaling up 10 nutrition interventions to 80% coverage for a single year cohort on stunting, nationally and sub-nationally, using the Lives Saved Tool (LiST), and the consequent impact on earnings, without and with a complementary cash-transfer in later life. The impact on earnings was modelled utilising the well-established pathway between early nutrition, years of completed schooling and, consequent adult earnings. Productivity returns were estimated as the present value of increased income over individuals' working lives, then compared to estimates of the present value of providing the cost of nutrition interventions and cash-transfers. The cost benefit ratio at the national level for scaled nutrition alone is 1:1. Sub-nationally the worst-off region yields the lowest ratio < 0.2 for every dollar spent. The combination of nutrition and cash-transfers national cost benefit is 1:12, still with regional variation but with great improvement in the poorest region. This study shows that early nutrition support alone may not be enough to address inequality and may add to state fragility. Taking a life-course perspective when priority-setting in contexts with multiple constraints on development can help to identify interventions that maximizing returns, without worsening inequality.