Maximizing Access and Minimizing Barriers to Research in Low- and Middle-Income Countries: Open Access and Health Equity.

Access to published research has always been difficult for researchers and clinicians in low- and middle-income countries, because of the cost of and lack of access to the relevant publications. The dramatic recent increase in electronic research publications has resulted in a marked improvement in reader access to these publications through their mainly Open Access policies, however the costs of processing of submissions and publication have now become the burden of the researchers wishing to publish, rather than the readers. For many researchers working in LMIC, the Article Processing Charges (APC) are prohibitive, hampering the publication of research being conducted in and relevant to these countries. A number of grant funding agencies and international not-for-profit organizations are trying to address these issues by including funding for article publications in their grants, or by supporting publishing entities by subsiding the cost of publication, but more needs to be done by major journal publishers through markedly reducing the APC being charged to researchers in LMIC for open access facilities.

The association between the timing, intensity and magnitude of adolescent growth and body composition in early adulthood.

OBJECTIVES: There's paucity of longitudinal studies assessing the role of adolescent growth on adult body composition in developing countries. The aims of this study were to assess the association between adolescent change in height, weight and BMI and early adult height, weight, body fat and lean mass. METHODS: Magnitude, timing and intensity of height, weight and BMI growth were modelled for participants from the Birth to Thirty (Bt30) cohort (7-23 years). Early adult height, weight, BMI and DXA-derived body composition were obtained 1881 black participants (21-24 years). Linear regression analyses were used to assess associations. RESULTS: Adolescents with an earlier onset of puberty were heavier in childhood and had an earlier timing and faster weight gain velocity in late adolescence. The intensity of adolescent weight gain was positively associated with adult BMI and fat mass index (FMI) in females. Early timing of adolescent BMI gain was associated with increased weight and BMI in adult females and FMI in adult males. Achieving peak weight velocity around age at peak height velocity was associated with lower BMI and fat mass in both sexes. CONCLUSION: This study confirms the adverse consequences of excessive weight gain prior to puberty, which is associated with an earlier and faster resurgence in weight gain velocity in early adulthood. Factors that contribute to an asynchronous timing of ages of peak weight and peak height velocities may accentuate the risk of adult obesity.

A Cross-Sectional Study of the Associations between Biomarkers of Vitamin D, Iron Status, and Hemoglobin in South African Women of Reproductive Age: the Healthy Life Trajectories Initiative, South Africa.

Background: Vitamin D deficiency and anemia impact the health of women of reproductive age. Evidence suggests an inverse relationship between serum vitamin D (25-hydroxyvitamin D [25(OH)D]) and anemia/iron deficiency, but less is known about these associations in women of reproductive age, in particular in a setting with a combined burden of micronutrient deficiency, food insecurity, and obesity. Objective: We aimed to assess the associations between 25(OH)D and biomarkers of iron and anemia in a cohort of women of reproductive age from Soweto, South Africa. The prevalence of vitamin D deficiency was also assessed. Methods: In this cross-sectional substudy of the Healthy Life Trajectories Initiative (HeLTI) South Africa pilot trial, 25(OH)D, iron markers (ferritin and soluble transferrin receptor [sTFR]), and altitude-adjusted hemoglobin (Hb) were measured in 493 women aged 18 to 25 years. Associations between iron deficiency/anemia and vitamin D status were evaluated using multivariable logistic regression, adjusting for confounders including fat mass index (FMI). Structural equation modeling (SEM) was performed to evaluate direct and indirect pathways between 25(OH)D, iron and anemia markers, and covariates. Results: Of 493 participants, 136 (27.6%) had vitamin D insufficiency (25(OH)D ≥12-20 ng/mL), whereas 28 (5.6%) had vitamin D deficiency (<12 ng/mL). Anemia and iron deficiency were not significantly associated with vitamin D category (25(OH)D<20 ng/mL compared with ≥20 ng/mL) in multivariable logistic regression analyses. In SEM, log-transformed 25(OH)D was not significantly associated with Hb, ferritin, or sTFR, but it was significantly associated with season of data collection, hormonal contraceptive use, and FMI (total effects: B = 0.17, 95% CI: 0.104, 0.236, P < 0.001; B: 0.10, 95% CI: 0.041, 0.154, P < 0.001; B: -0.01, 95%CI: -0.016, -0.003, P = 0.003, respectively). Conclusion: No significant association between vitamin D (25(OH)D), anemia (Hb), and iron markers was found. The inverse relationship between FMI and vitamin D status emphasizes the overlap between adiposity and micronutrient deficiencies in young South African women, exacerbating their risk of disease development.

Serum 1,25-dihydroxyvitamin D levels in the diagnosis and pathogenesis of nutritional rickets - a multivariable re-analysis of a case-control study.

BACKGROUND: A multivariable logistic regression model resulting from a case-control study of nutritional rickets in Nigerian children suggested that higher levels of serum 25(OH)D may be required to prevent nutritional rickets in populations with low-calcium intakes. OBJECTIVES: This current study evaluates if adding serum 1,25-dihydroxyvitamin D [1,25(OH)2D] to that model shows that increased levels of serum 1,25(OH)2D are independently associated with risk of children on low-calcium diets having nutritional rickets. METHODS: Multivariable logistic regression analysis was used to model the association between serum 1,25(OH)2D and risk of having nutritional rickets in cases (n = 108) and controls (n = 115) after adjusting for age, sex, weight-for age z-score, religion, phosphorus intake and age began walking and the interaction between serum 25(OH)D and dietary calcium intake (Full Model). RESULTS: Serum 1,25(OH)2D levels were significantly higher (320 pmol/L vs. 280 pmol/L) (P = 0.002), and 25(OH)D levels were lower (33 nmol/L vs. 52 nmol/L) (P < 0.0001) in children with rickets than in control children. Serum calcium levels were lower in children with rickets (1.9 mmol/L) than in control children (2.2 mmol/L) (P < 0.001). Dietary calcium intakes were similarly low in both groups (212 mg/d) (P = 0.973). In the multivariable logistic model, 1,25(OH)2D was independently associated with risk of having rickets [coefficient = 0.007 (95% confidence limits: 0.002-0.011)] after adjusting for all variables in the Full Model. CONCLUSIONS: Results confirmed theoretical models that in children with low dietary calcium intake, 1,25(OH)2D serum concentrations are higher in children with rickets than in children without rickets. The difference in 1,25(OH)2D levels is consistent with the hypothesis that children with rickets have lower serum calcium concentrations which prompt the elevation of PTH levels resulting in an elevation of 1,25(OH)2D levels. These results support the need for additional studies to identify dietary and environmental risks for nutritional rickets.

Calcium status assessment at the population level: Candidate approaches and challenges.

Inadequate dietary calcium intake is a global public health problem that disproportionately affects low- and middle-income countries. However, the calcium status of a population is challenging to measure, and there are no standard methods to identify high-risk communities even in settings with an elevated prevalence of a disease caused or exacerbated by low calcium intake (e.g., rickets). The calcium status of a population depends on numerous factors, including intake of calcium-rich foods; the bioavailability of the types of calcium consumed in foods and supplements; and population characteristics, including age, sex, vitamin D status, and genetic attributes that influence calcium retention and absorption. The aim of this narrative review was to assess candidate indicators of population-level calcium status based on a range of biomarkers and measurement methods, including dietary assessment, calcium balance studies, hormonal factors related to calcium, and health outcomes associated with low calcium status. Several promising approaches were identified, but there was insufficient evidence of the suitability of any single indicator to assess population calcium status. Further research is required to develop and validate specific indicators of calcium status that could be derived from the analysis of data or samples that are feasibly collected in population-based surveys.

Intramuscular depot medroxyprogesterone acetate accentuates bone loss associated with tenofovir disoproxil fumarate-containing antiretroviral therapy initiation in young women living with HIV (the BONE: CARE study): a prospective cohort study in Uganda.

BACKGROUND: Tenofovir disoproxil fumarate (TDF) and intramuscular depot medroxyprogesterone acetate (DMPA-IM) are independently associated with reduced bone mineral density (BMD). We aimed to assess the combined effects of DMPA-IM use and TDF initiation on BMD in young adult women living with HIV over two years, compared with age-matched people without HIV. METHODS: Th BONE: CARE study was a prospective cohort study that recruited women aged 18-35 years from 11 HIV care and general health facilities in Kampala, Uganda. The participants were classified into four groups on the basis of their combination of HIV status, TDF use, and DMPA-IM use, as follows: women living with HIV initiating TDF-containing antiretroviral therapy (ART) with DMPA-IM (HIV positive, DMPA positive, and TDF positive); women living with HIV using DMPA-IM but not eligible for ART as per local guidelines at the time of enrolment into the study (HIV positive, DMPA positive, and TDF negative); women living with HIV initiating TDF-containing ART without DMPA-IM (HIV positive, DMPA negative, and TDF positive); and controls without HIV using non-hormonal contraceptives (HIV negative, DMPA negative, and TDF negative). BMD of the lumbar spine, total hip, and femoral neck were measured using semiannual dual-energy x-ray absorptiometry at enrolment and at intervals every 6 months thereafter. We assessed percentage change in mean BMD. FINDINGS: Between March 30, 2016, and Oct 19, 2017, we enrolled 265 women living with HIV initiating ART (159 DMPA-IM users and 106 non-hormonal contraceptive users), 187 women living with HIV using DMPA-IM but not ART, and 69 controls without HIV. Mean age was 26·1 years (SD 4·2). BMD declined significantly from baseline in women living with HIV on TDF with versus without DMPA-IM at the lumbar spine (-3·406% [95% CI -3·969 to -2·844] vs -1·111% [-1·929 to -0·293]; p<0·0001), total hip (-3·856% [-4·449 to -3·264] vs -1·714% [-2·479 to -0·949]; p=0·0002), and femoral neck (-4·422% [-5·078 to -3·766] vs -1·999% [-3·022 to -0·976]; p=0·0002), increased in controls at the lumbar spine (1·5% change), and remained unchanged at total hip and femoral neck (-0·1% change). Concurrent use of TDF and DMPA-IM resulted in significantly greater BMD decline (p<0·0001) than TDF alone (lumbar spine -2·677% [95% CI -3·743 to -1·611]; p<0·0001; total hip -2·518% [-3·575 to -1·461]; p<0·0001; and femoral neck -2·907 [-4·132 to -1·683]; p<0·0001) or than controls (lumbar spine -4·970% [-6·391 to -3·549]; p<0·0001; total hip -4·151% [-5·579 to -2·724]; p<0.0001; and femoral neck -4·773% [-6·424 to -3·122]; p<0·0001) INTERPRETATION: Concomitant DMPA-IM use resulted in a doubling of BMD loss in women living with HIV initiating TDF-containing ART. Identification of safer contraceptive and bone-sparing ART options should be prioritised for optimal care of women living with HIV. FUNDING: National Institute of Allergy and Infectious Diseases of the US National Institutes of Health.

Vitamin D Deficiency and Its Association with Iron Deficiency in African Children.

Vitamin D regulates the master iron hormone hepcidin, and iron in turn alters vitamin D metabolism. Although vitamin D and iron deficiency are highly prevalent globally, little is known about their interactions in Africa. To evaluate associations between vitamin D and iron status we measured markers of iron status, inflammation, malaria parasitemia, and 25-hydroxyvitamin D (25(OH)D) concentrations in 4509 children aged 0.3 months to 8 years living in Kenya, Uganda, Burkina Faso, The Gambia, and South Africa. Prevalence of iron deficiency was 35.1%, and prevalence of vitamin D deficiency was 0.6% and 7.8% as defined by 25(OH)D concentrations of <30 nmol/L and <50 nmol/L, respectively. Children with 25(OH)D concentrations of <50 nmol/L had a 98% increased risk of iron deficiency (OR 1.98 [95% CI 1.52, 2.58]) compared to those with 25(OH)D concentrations >75 nmol/L. 25(OH)D concentrations variably influenced individual markers of iron status. Inflammation interacted with 25(OH)D concentrations to predict ferritin levels. The link between vitamin D and iron status should be considered in strategies to manage these nutrient deficiencies in African children.

Calcium deficiency worldwide: prevalence of inadequate intakes and associated health outcomes.

Dietary calcium deficiency is considered to be widespread globally, with published estimates suggesting that approximately half of the world's population has inadequate access to dietary calcium. Calcium is essential for bone health, but inadequate intakes have also been linked to other health outcomes, including pregnancy complications, cancers, and cardiovascular disease. Populations in low- and middle-income countries (LMICs) are at greatest risk of low calcium intakes, although many individuals in high-income countries (HICs) also do not meet recommendations. Paradoxically, many LMICs with lower calcium intakes show lower rates of osteoporotic fracture as compared with HICs, though data are sparse. Calcium intake recommendations vary across agencies and may need to be customized based on other dietary factors, health-related behaviors, or the risk of calcium-related health outcomes. The lack of standard methods to assess the calcium status of an individual or population has challenged efforts to estimate the prevalence of calcium deficiency and the global burden of related adverse health consequences. This paper aims to consolidate available evidence related to the global prevalence of inadequate calcium intakes and associated health outcomes, with the goal of providing a foundation for developing policies and population-level interventions to safely improve calcium intake and status where necessary.

The Validity of Serum Alkaline Phosphatase to Identify Nutritional Rickets in Nigerian Children on a Calcium-Deprived Diet.

CONTEXT: Nutritional rickets results from the interaction of low vitamin D status and limited calcium intake. Serum alkaline phosphatase (AP) activity is a biomarker of impaired mineralization in rickets. OBJECTIVE: To assess the performance of serum AP activity in identifying nutritional rickets in calcium-deprived Nigerian children. METHODS: We reanalyzed data from a case-control study of children with active rickets and matched control subjects without rickets, using a multivariate logistic regression to assess the odds of rickets associated with AP activity, adjusting for age, sex, and weight-for-age z-score. RESULTS: A total of 122 children with rickets and 119 controls were included. Rachitic children had a mean (±SD) age of 54 ±â€…29 months, and 55 (45.1%) were male. Cases and controls had low dietary calcium intakes (216 ±â€…87 and 214 ±â€…96 mg/day, respectively). Serum AP activity levels in cases and controls were 812 ±â€…415 and 245 ±â€…78 U/L, respectively (P < 0.001). AP was negatively associated with 25-hydroxyvitamin D values (r = -0.34; P < 0.001). In the adjusted model, the odds ratio (95% CI) receiver operating characteristic curve was 0.978. AP > 350 U/L identified nutritional rickets in Nigerian children with sensitivity 0.93, specificity 0.92, positive likelihood ratio 11.3, and negative likelihood ratio 0.07. CONCLUSION: An AP > 350 U/L effectively discriminated between Nigerian children with and without nutritional rickets. AP is a low-cost biochemical test that could be used to screen for nutritional rickets, but cutoff values require validation in other populations, and laboratory values need to be standardized for widespread population studies.

Prevalence and predictors of vitamin D deficiency in young African children.

BACKGROUND: Children living in sub-Saharan Africa have a high burden of rickets and infectious diseases, conditions that are linked to vitamin D deficiency. However, data on the vitamin D status of young African children and its environmental and genetic predictors are limited. We aimed to examine the prevalence and predictors of vitamin D deficiency in young African children. METHODS: We measured 25-hydroxyvitamin D (25(OH)D) and typed the single nucleotide polymorphisms, rs4588 and rs7041, in the GC gene encoding the vitamin D binding protein (DBP) in 4509 children aged 0-8 years living in Kenya, Uganda, Burkina Faso, The Gambia and South Africa. We evaluated associations between vitamin D status and country, age, sex, season, anthropometric indices, inflammation, malaria and DBP haplotypes in regression analyses. RESULTS: Median age was 23.9 months (interquartile range [IQR] 12.3, 35.9). Prevalence of vitamin D deficiency using 25(OH)D cut-offs of < 30 nmol/L and < 50 nmol/L was 0.6% (95% CI 0.4, 0.9) and 7.8% (95% CI 7.0, 8.5), respectively. Overall median 25(OH)D level was 77.6 nmol/L (IQR 63.6, 94.2). 25(OH)D levels were lower in South Africa, in older children, during winter or the long rains, and in those with afebrile malaria, and higher in children with inflammation. 25(OH)D levels did not vary by stunting, wasting or underweight in adjusted regression models. The distribution of Gc variants was Gc1f 83.3%, Gc1s 8.5% and Gc2 8.2% overall and varied by country. Individuals carrying the Gc2 variant had lower median 25(OH)D levels (72.4 nmol/L (IQR 59.4, 86.5) than those carrying the Gc1f (77.3 nmol/L (IQR 63.5, 92.8)) or Gc1s (78.9 nmol/L (IQR 63.8, 95.5)) variants. CONCLUSIONS: Approximately 0.6% and 7.8% of young African children were vitamin D deficient as defined by 25(OH)D levels < 30 nmol/L and < 50 nmol/L, respectively. Latitude, age, season, and prevalence of inflammation and malaria should be considered in strategies to assess and manage vitamin D deficiency in young children living in Africa.

Serum 25-hydroxyvitamin D requirements to prevent nutritional rickets in Nigerian children on a low-calcium diet-a multivariable reanalysis.

BACKGROUND: Nutritional rickets is believed to result from the interaction of inadequate serum 25-hydroxyvitamin D [25(OH)D] concentration and dietary calcium intake, but this interaction has not been confirmed in children with rickets. Determining the vitamin D requirements to prevent nutritional rickets has been thwarted by inconsistent case definition, inadequate adjustment for calcium intake and other confounders, and 25(OH)D assay variability. OBJECTIVES: To model the 25(OH)D concentration associated with nutritional rickets in calcium-deprived Nigerian children, adjusted for confounding factors, and develop a general approach to define vitamin D status while accounting for calcium intake. METHODS: Logistic regression was used to model the association of serum 25(OH)D with having rickets adjusted for calcium intake in a reanalysis of a case-control study in Nigerian children. The matching variables age, sex, weight-for-age z score, and 4 additional significant variables were selected [religion, age began walking, phosphorus intake, and the 25(OH)D × calcium intake interaction] using a rigorous 7-step algorithm. RESULTS: Cases had significantly (P < 0.0001) lower mean ± SD 25(OH)D than controls (33 ± 13 compared with 51 ± 16 nmol/L, respectively), whereas cases and controls had similarly (P = 0.81) low mean dietary calcium intakes (216 ± 88 and 213 ± 95 mg/d, respectively). There was a significant interaction between 25(OH)D and calcium intake [coefficient (95% CI): -0.0006 (-0.0009, -0.0002)]. Accordingly, as calcium intake increased from 130 to 300 mg/d, the adjusted odds of having rickets decreased dramatically with increasing 25(OH)D such that at 200 mg/d, the adjusted odds of having rickets at 47.5 nmol/L was 0.80, whereas it was 0.2 at 62.5 nmol/L. Moreover, at a calcium intake of 300 mg/d, the adjusted odds was 0.16 at a 25(OH)D concentration of 47.5 nmol/L and 0.02 at 62.5 nmol/L. CONCLUSIONS: The vitamin D requirement to prevent nutritional rickets varies inversely with calcium intake and vice versa. Also, application of multivariable modeling is essential in defining vitamin D requirements.

Bone Mineral Density in Antiretroviral Therapy-Naïve HIV-1-Infected Young Adult -Women Using Depot Medroxyprogesterone Acetate or Nonhormonal Contraceptives in Uganda.

Most studies evaluating BMD in human immunodeficiency virus (HIV)-infected populations have focused on antiretroviral therapy (ART)-experienced patients. In this study, the association between HIV-1 and/or depot medroxyprogesterone acetate (DMPA) and BMD among untreated HIV-1-infected women in a resource-limited setting was assessed before long-term exposure to ART. The data were then compared with that of the 2005-2008 United States National Health and Nutrition Examination Survey data for non-Hispanic White and Black women. Women aged 18-35 years, recruited from health facilities in Kampala, Uganda, were classified based on their combination of HIV-1 status and DMPA use: (i) HIV-1-infected current DMPA users, (ii) HIV-1-infected previous DMPA users, (iii) HIV-1-infected nonhormonal-contraceptive users, and (iv) HIV-uninfected nonhormonal-contraceptive users. All HIV-1-infected women reported being ART-naïve at baseline. BMD was measured at the lumbar spine, total hip, and femoral neck using DXA. Multivariate linear regression was used to assess the association between HIV-1 and/or DMPA and BMD Z-scores. Baseline data were analyzed for 452 HIV-1-infected (220 nonhormonal users, and 177 current and 55 previous DMPA users) and 69 HIV-1-uninfected nonhormonal-contraceptive users. The mean age was 26.1 years (SD, 4.2) with a median duration of DMPA use among current users of 24.0 months [medians (interquartile range), 12-48]. A higher proportion of HIV-1-infected previous (12.7%) or current DMPA users (20.3%) and nonhormonal users (15.0%) had low BMD (Z-score ≤-2 at any of the three sites) compared with age-matched HIV-1-uninfected women (2.9%). HIV-1 infection and DMPA use were independently associated with significantly lower mean BMD Z-scores at all sites, with the greatest difference being among HIV-1-infected current DMPA users (5.6%-8.0%) versus uninfected nonhormonal users. Compared with non-Hispanic White and Black women, the Ugandan local reference population had generally lower mean BMD at all sites. Newer treatment interventions are needed to mitigate BMD loss in HIV-1-infected women in resource-limited settings. © 2020 The Authors. JBMR Plus published by Wiley Periodicals LLC. on behalf of American Society for Bone and Mineral Research.

Adolescent growth and BMI and their associations with early childhood growth in an urban South African cohort.

OBJECTIVES: The timing and magnitude of adolescent growth may be influenced by ethnicity and early life factors. We aimed to (a) characterize ethnic differences in the magnitude, timing, and intensity of adolescent growth in height, weight, and BMI; (b) assess the effect of early childhood growth on adolescent growth in black children. METHODS: Data were from the Birth to Twenty Plus cohort (Bt20+) in Johannesburg, South Africa (n = 3273). Height, weight, and BMI were modeled with ethnic comparisons using the SuperImposition by Translation and Rotation for 2089 participants who had data from 7 to 23 years. Relative weight gain and relative linear growth between 0 and 24 months and 24 and 60 months were generated. Multiple regression analyses were used to assess associations between childhood and adolescent growth. RESULTS: White children were 5 cm (SE: 0.7) taller than black children through adolescence. Black boys had a later timing of adolescent height (0.65 years ±0.12) than white boys, which in black girls was 0.24 years (0.11) earlier than in white girls. Black girls had faster BMI velocity than white girls. Among black children, birth weight and both relative weight gain 0 to 24 and relative linear growth between 3 and 24 months and 24 and 60 months were positively associated with the magnitude of adolescent growth and negatively associated with timing. CONCLUSION: Sex dimorphism in ethnic differences in timing of adolescent height growth may reflect some yet unexplained drivers for rapid weight gain and obesity in black females but not black males. Rapid weight gain in early life may contribute to faster adiposity accrual in adolescence.

Renal dysfunction, rod-cone dystrophy, and sensorineural hearing loss caused by a mutation in RRM2B.

More than two decades ago, a recessive syndromic phenotype affecting kidneys, eyes, and ears, was first described in the endogamous Afrikaner population of South Africa. Using whole-exome sequencing of DNA from two affected siblings (and their carrier parents), we identified the novel RRM2B c.786G>T variant as a plausible disease-causing mutation. The RRM2B gene is involved in mitochondrial integrity, and the observed change was not previously reported in any genomic database. The subsequent screening revealed the variant in two newly presenting unrelated patients, as well as two patients in our registry with rod-cone dystrophy, hearing loss, and Fanconi-type renal disease. All patients with the c.786G>T variant share an identical 1.5 Mb haplotype around this gene, suggesting a founder effect in the Afrikaner population. We present ultrastructural evidence of mitochondrial impairment in one patient, to support our thesis that this RRM2B variant is associated with the renal, ophthalmological, and auditory phenotype.

Vitamin D Status Is Not Associated with Cognitive or Motor Function in Pre-School Ugandan Children.

Vitamin D deficiency is common worldwide and young children are among the most affected groups. Animal studies suggest a key role for vitamin D in brain development. However, studies investigating the effects of vitamin D on neurobehavioural outcomes in children are inconclusive and evidence is limited in sub-Saharan Africa. We evaluated the effect of vitamin D status on cognitive and motor outcomes using prospective data from the Entebbe Mother and Baby Study birth cohort. We analysed data from 302 Ugandan children with 25-hydroxyvitamin D (25(OH)D) measurements below five years and developmental measures at five years of age. We used multivariable linear regression, adjusted for potential confounders, to estimate the effect of 25(OH)D on cognitive and motor outcomes. Of 302 children, eight (2.7%) had 25(OH)D levels <50 nmol/L, 105 (35.8%) had levels 50-75 nmol/L and 189 (62.6%) had levels >75 nmol/L. There was no evidence that earlier vitamin D status was associated with cognitive and motor outcomes in five-year-old Ugandan children. This study adds to the sparse literature and highlights the need for further longitudinal studies on vitamin D and neurobehavioural outcomes in children living in sub-Saharan Africa.

Bone Mineral Density, Body Composition, and Mineral Homeostasis Over 24 Months in Urban South African Women With HIV Exposed to Antiretroviral Therapy.

Human immunodeficiency virus- (HIV-) infection and antiretroviral therapy (ART) exposure are associated with bone loss. African data are limited despite the region's HIV burden. Of 247 ART-naïve, premenopausal, urban, black African women aged 33.9 ± 6.6 years from Soweto, South Africa, measured at baseline, 110 underwent anthropometry, DXA, and blood and urine collections at 12 and 24 months; 39 were HIV-negative (Nref), 28 were people with HIV (PWH) not ART-exposed for the duration of the study (ART-N), and 43 were PWH who were ART-exposed within the first 12 months (ART-Y). At baseline, the ART-Y group had lower BMI and fat mass than the Nref group. Within 12 months of ART initiation, areal bone mineral density (aBMD) had decreased at the lumbar spine and at the whole body less head, despite increased weight, and hip aBMD had not increased in line with the Nref group. There was no evidence of further bone changes between 12 and 24 months. By 24 months, the ART-Y women had gained weight and fat mass, but remained lighter with less fat than the Nref women. ART initiation normalized the low serum albumin of the ART-Y group at baseline, but was associated with elevated bone turnover markers at 12 and 24 months. Vitamin D status and renal phosphate handling were normal. ART-N had similar aBMD and other characteristics to the Nref group throughout, except unlike the Nref group, weight and fat mass did not increase and serum albumin decreased. This study in African women of childbearing age demonstrated that the bone loss that had occurred in these PWH after ART initiation did not continue after 12 months and that bone loss did not occur in ART-unexposed PWH over 2 years. At 24 months, despite gains in weight and fat mass, ART-exposed women remained lighter, with lower aBMD, fat mass, and higher bone turnover than women without HIV. More studies are required to establish if the bone loss and fat gain reverse, stabilize, or continue with further ART exposure, particularly during and after menopause. © 2020 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.

Aetiology of nutritional rickets in rural Bangladeshi children.

OBJECTIVES: A high prevalence of rickets of unknown aetiology has been reported in Chakaria, Bangladesh. Classically, rickets is caused by vitamin D deficiency but increasing evidence from Africa and Asia points towards other nutritional deficiencies or excessive exposure to some metals. The aim of this study was to investigate the aetiology of rickets in rural Bangladeshi children. METHODS: 64 cases with rickets-like deformities were recruited at first presentation together with age-sex-village matched controls. Data and sample acquisition included anthropometry, radiographs, fasted plasma and urinary samples, 24 h weighed dietary intake together with a 24 h urine collection, and 13C-breath tests to detect Helicobacter (H.) pylori infection. RESULTS: One child had active rickets and frank hypovitaminosis D (F, n = 1) and one had deformities with radiological features of Blount disease (M, n = 1). The remaining cases were grouped into those with active rickets, defined as a radiographic Thacher score ≥1.5 (Group A, n = 24, 12M, 12F) and rickets-like bone deformities but not active rickets (Group B, n = 38, 28M, 10F). All children had a low dietary calcium intake, but this was lower in Group A than their controls (mean (SD): 156 (80) versus 323 (249) mg/day, p = 0.005). Plasma 25-hydroxyvitamin D (25OHD) was lower in Group A compared to controls; 63% of Group A and 8% of controls had a concentration <25 nmol/L (p ≤ 0.0001). There was, however, no evidence of differences in skin sunshine exposure. Group A had lower plasma calcium and phosphate and higher 1,25-dihydroxyvitamin D (1,25(OH)2D) and parathyroid hormone (PTH). 88% of Group A and 0% of controls had undetectable plasma intact fibroblast growth factor (iFGF23), with c-terminal FGF23 (cFGF23) concentrations in the normal range. Urinary phosphate and daily outputs of environmental metals relative to creatinine were higher and tubular maximal phosphate reabsorption per unit glomerular filtration rate (TmP/GFR) was lower in Group A compared to controls. Although less pronounced than Group A, Group B had higher alkaline phosphatase, 1,25(OH)2D and PTH concentrations than controls but similar calcium intake, TmP/GFR, iFGF23 and cFGF23 concentrations. Mean 25OHD concentrations were also similar to controls and there was no significant difference in the percentage <25 nmol/L (Group B: 13%, controls: 5%, p = 0.2) No group differences were seen in prevalence of anaemia, iron deficiency or H. pylori infection. CONCLUSION: Nutritional rickets in this region is likely to be predominantly due to low calcium intake in the context of poor vitamin D status and exposure to environmental metals, but not H. pylori infection, anaemia or iron deficiency.