Validation of the global lung initiative 2012 multi-ethnic spirometric reference equations in healthy urban Zimbabwean 7-13 year-old school children: a cross-sectional observational study.

BACKGROUND: The 2012 Global Lung Function Initiative (GLI2012) provide multi-ethnic spirometric reference equations (SRE) for the 3-95 year-old age range, but Sub-Saharan African populations are not represented. This study aimed to evaluate the fit of the African-American GLI2012 SRE to a population of healthy urban and peri-urban Zimbabwean school-going children (7-13 years). METHODS: Spirometry and anthropometry were performed on black-Zimbabwean children recruited from three primary schools in urban and peri-urban Harare, with informed consent and assent. Individuals with a history or current symptoms of respiratory disease or with a body mass index-z score (BMI) < - 2 were excluded. Spirometry z-scores were generated from African-American GLI2012 SRE, which adjust for age, sex, ethnicity and height, after considering all GLI2012 modules. Anthropometry z-scores were generated using the British (1990) reference equations which adjust for age and sex. The African-American GLI2012 z-score distribution for the four spirometry measurements (FVC, FEV1, FEV1/FVC and MMEF) were evaluated across age, height, BMI and school (as a proxy for socioeconomic status) to assess for bias. Comparisons between the African-American GLI2012 SRE and Polgar equations (currently adopted in Zimbabwe) on the percent-predicted derived values were also performed. RESULTS: The validation dataset contained acceptable spirometry data from 712 children (344 girls, mean age: 10.5 years (SD 1.81)). The spirometry z-scores were reasonably normally distributed, with all means lower than zero but within the range of ±0.5, indicating a good fit to the African-American GLI2012 SRE. The African-American GLI2012 SRE produced z-scores closest to a normal distribution. Z-scores of girls deviated more than boys. Weak correlations (Pearson's correlation coefficient < 0.2) were observed between spirometry and anthropometry z-scores, and scatterplots demonstrated no systematic bias associated with age, height, BMI or socioeconomic status. The African-American GLI2012 SRE provided a better fit for Zimbabwean paediatric spirometry data than Polgar equations. CONCLUSION: The use of African-American GLI2012 SRE in this population could help in the interpretation of pulmonary function tests

Perinatal HIV infection is associated with deficits in muscle function in children and adolescents:a cross-sectional study 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 8–16years, taking ART for ≥2years, 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% female. 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 &lt; 0.001), long-jump distance (7.1[1.8,12.5]cm, P = 0.006), muscle density (0.58[0.12,1.05]mg/cm3, P = 0.018, but not lean mass 0.06[-1.08,1.21]kg, P = 0.891) versus boys without HIV; differences were consistent but smaller in females. Mediation analysis suggested the negative effect of HIV on jumping power in males 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/cm3, P = 0.049) independent of fat mass, than CWH on other ART.Conclusions: Perinatally-acquired HIV is associated, particularly in males, 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.</div

Menopausal symptoms by HIV status and association with health-related quality of life among women in Zimbabwe: a cross-sectional study.

BACKGROUND: The scale-up of antiretroviral therapy programmes has resulted in increased life expectancy of people with HIV in Africa. Little is known of the menopausal experiences of African women, including those living with HIV. We aimed to determine the prevalence and severity of self-reported menopause symptoms in women at different stages of menopause transition, by HIV status, and evaluate how symptoms are related to health-related quality of life (HRQoL). We further sought to understand factors associated with menopause symptoms. METHODS: A cross-sectional study recruited women resident in Harare, Zimbabwe, sampled by age group (40-44/45-49/50-54/55-60 years) and HIV status. Women recruited from public-sector HIV clinics identified two similarly aged female friends (irrespective of HIV status) with phone access. Socio-demographic and medical details were recorded and women staged as pre-, peri- or post-menopause. The Menopausal Rating Scale II (MRS), which classified symptom severity, was compared between those with and without HIV. Linear and logistic regression determined factors associated with menopause symptoms, and associations between symptoms and HRQoL. RESULTS: The 378 women recruited (193[51.1%] with HIV), had a mean (SD) age of 49.3 (5.7) years; 173 (45.8%), 51 (13.5%) and 154 (40.7%) were pre-, peri and post-menopausal respectively. Women with HIV reported more moderate (24.9% vs. 18.1%) and severe (9.7% vs. 2.6%) menopause symptoms than women without HIV. Peri-menopausal women with HIV reported higher MRS scores than those pre- and post-menopausal, whereas in HIV negative women menopausal stage was not associated with MRS score (interaction p-value = 0.014). With increasing severity of menopause symptoms, lower mean HRQoL scores were observed. HIV (OR 2.02[95% CI 1.28, 3.21]), mood disorders (8.80[2.77, 28.0]), ≥ 2 falls/year (4.29[1.18, 15.6]), early menarche (2.33[1.22, 4.48]), alcohol consumption (2.16[1.01, 4.62]), food insecurity (1.93[1.14, 3.26]) and unemployment (1.56[0.99, 2.46]), were all associated with moderate/severe menopause symptoms. No woman reported use of menopausal hormone therapy. CONCLUSIONS: Menopausal symptoms are common and negatively impact HRQoL. HIV infection is associated with more severe menopause symptoms, as are several modifiable factors, including unemployment, alcohol consumption, and food insecurity. Findings highlight an unmet health need in ageing women in Zimbabwean, especially among those living with HIV

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

The Impact of Human Immunodeficiency Virus and Menopause on Bone Mineral Density: A Longitudinal Study of Urban-Dwelling South African Women

An estimated 25% of South African women live with human immunodeficiency virus (HIV). Antiretroviral therapy roll-out has improved life expectancy, so many more women now reach menopause. We aimed to quantify changes in bone mineral density (BMD) during the menopausal transition in urban-dwelling South African women with and without HIV and determine whether HIV infection modified the effect of menopause on BMD changes. A 5-year population-based longitudinal study recruited women aged 40-60 years residing in Soweto and collected demographic and clinical data, including HIV status, anthropometry, and BMD, at baseline and at 5-year follow-up. All women were staged as pre-, peri-, or postmenopausal at both time points. Multivariable linear regression assessed relationships and interactions between HIV infection, menopause, and change in BMD. At baseline, 450 women had mean age 49.5 (SD 5.7) years, 65 (14.4%) had HIV, and 140 (31.1%), 119 (26.4%), and 191 (42.4%) were pre-, peri-, and postmenopausal, respectively; 34/205 (13.6%) women ≥50 years had a total hip (TH) or lumbar spine (LS) T-score ≤ -2.5. At follow-up 38 (8.4%), 84 (18.7%), and 328 (72.9%) were pre-, peri-, and postmenopausal. Those with HIV at baseline lost more total body (TB) BMD (mean difference -0.013 [95% confidence interval -0.026, -0.001] g/cm2 , p = 0.040) and gained more weight 1.96 [0.32, 3.60] kg; p = 0.019 than HIV-uninfected women. After adjusting for age, baseline weight, weight change, and follow-up time, the transition from pre- to postmenopause was associated with greater TB BMD losses in women with HIV (-0.092 [-0.042, -0.142] g/cm2 ; p = 0.001) than without HIV (-0.038 [-0.016, -0.060] g/cm2 , p = 0.001; interaction p = 0.034). Similarly, in women who were postmenopausal at both time points, those with HIV lost more TB BMD (-0.070 [-0.031, -0.108], p = 0.001) than women without HIV (-0.036 [-0.015, -0.057], p = 0.001, interaction p = 0.049). Findings were consistent but weaker at the LS and TH. Menopause-related bone loss is greater in women with HIV, suggesting women with HIV may be at greater risk of osteoporotic fractures. HIV services should consider routine bone health assessment in midlife women as part of long-term HIV care delivery. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR)

Osteoporosis, Rather Than Sarcopenia, Is the Predominant Musculoskeletal Disease in a Rural South African Community Where Human Immunodeficiency Virus Prevalence Is High: A Cross-Sectional Study.

The rollout of antiretroviral therapy globally has increased life expectancy across Southern Africa, where 20.6 million people now live with human immunodeficiency virus (HIV). We aimed to determine the prevalence of age-related osteoporosis and sarcopenia, and investigate the association between HIV, bone mineral density (BMD), muscle strength and lean mass, and gait speed. A cross-sectional community-based study of individuals aged 20-80 years in rural South Africa collected demographic and clinical data, including HIV status, grip strength, gait speed, body composition, and BMD. Sarcopenia was defined by the European Working Group on Sarcopenia in Older People 2 (EWGSOP2) guidelines, and osteoporosis as BMD T-score ≤ -2.5 (if age ≥50 years). The mean ± standard deviation (SD) age of 805 black South African participants was 44.6 ± 14.8 years, 547 (68.2%) were female; 34 (13.2%) were men, and 129 (23.6%) women had HIV, with 88% overall taking anti-retroviral therapy. A femoral neck T-score ≤ -2.5, seen in four of 95 (4.2%) men and 39 of 201 (19.4%) women age ≥50 years, was more common in women with than without HIV (13/35 [37.1%] versus 26/166 [15.7%]; p = 0.003). Although no participant had confirmed sarcopenia, probable sarcopenia affected more men than women (30/258 [11.6%] versus 24/547 [4.4%]; p = .001]. Although appendicular lean mass (ALM)/height2 index was lower in both men and women with HIV, there were no differences in grip strength, gait speed, or probable sarcopenia by HIV status. Older age, female sex, lower ALM/height2 index, slower gait speed, and HIV infection were all independently associated with lower femoral neck BMD. In conclusion, osteoporosis rather than sarcopenia is the common musculoskeletal disease of aging in rural South Africa; older women with HIV may experience greater bone losses than women without HIV. Findings raise concerns over future fracture risk in Southern Africa, where HIV clinics should consider routine bone health assessment, particularly in aging women. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR)

Effect of HIV infection on growth and bone density in peripubertal children in the era of antiretroviral therapy: a cross-sectional study in Zimbabwe.

BACKGROUND: Faltered linear growth and pubertal delay, which are both common in children with HIV in sub-Saharan Africa, might affect adolescent bone accrual and future fragility fracture risk. We investigated the association of HIV with bone density adjusted for skeletal size in peripubertal children in Zimbabwe. METHODS: We did a cross-sectional study of baseline data from the IMVASK cohort, which enrolled children aged 8-16 years with HIV who had been taking antiretroviral therapy (ART) for at least 2 years, and children of the same age without HIV. Children with HIV were recruited from public sector HIV clinics at Parirenyatwa General Hospital and Harare Central Hospital (Harare, Zimbabwe), and children without HIV were recruited from six schools in the same suburbs that the hospitals serve. Sociodemographic, clinical, and anthropometric data were collected. Dual-energy X-ray absorptiometry (DXA) was used to measure the bone outcomes of total-body less-head bone mineral content for lean mass adjusted for height (TBLH-BMCLBM), and lumbar spine bone mineral apparent density (LS-BMAD), and we assessed the prevalence of low TBLH-BMCLBM and low LS-BMAD (defined by Z-scores of less than -2·0). Size adjustment techniques were used to overcome the size dependence of DXA measurement. We used linear regression models, with multiple imputation for missing data, to assess relationships between risk factors and TBLH-BMCLBM and LS-BMAD Z-scores in children with and without HIV. FINDINGS: We recruited 303 children with HIV (mean age 12·4 years [SD 2·5]; 151 [50%] girls) and 306 children without HIV (mean age 12·5 years [SD 2·5]; 155 [51%] girls). In children with HIV, median age of HIV diagnosis was 3·0 years (IQR 1·2-5·8), and median ART duration was 8·1 years (6·2-9·5); for 102 (34%) children, ART included tenofovir disoproxil fumarate (TDF). Children with HIV had a higher prevalence of low TBLH-BMCLBM Z-score than children without HIV (29 [10%] of 279 children with available data vs 18 [6%] of 292 with available data; p=0·066) and a higher prevalence of low LS-BMAD Z-score (40 [14%] of 279 vs 17 [6%] of 293 with available data; p=0·0007). HIV and male sex were associated with earlier pubertal (Tanner) stage. The negative associations between HIV and Z-scores for TBLH-BMCLBM and LS-BMAD were more pronounced with pubertal maturation, particularly in girls. Among children with HIV, TDF exposure and orphanhood were associated with lower TBLH-BMCLBM Z-score in confounder-adjusted analysis. Current TDF use (vs non-TDF-based ART) was associated with a reduction in TBLH-BMCLBM Z-score of 0·41 (95% CI 0·08-0·74; p=0·015) and in LS-BMAD Z-score of 0·31 (0·08-0·69; p=0·12). INTERPRETATION: Despite ART, HIV is associated with substantial skeletal deficits towards the end of puberty. The extent of bone deficits associated with TDF and its widespread use in children in sub-Saharan Africa are a concern for future adult fracture risk. FUNDING: Wellcome Trust

Disparities in fragility fracture and osteoporosis care in Africa.

Over coming decades, Africa is predicted to experience the greatest rise in the number of older people, who, in this region, spend longer living with disability and dependence than do those in high-income settings, impacting individuals, families, communities, and healthcare systems in some of the most resource-poor countries. As well as shifting demographics, rapid urbanisation, double and triple burdens of malnutrition, changing physical activity patterns, workplace environments, and climates change contribute to the growing prevalence of non-communicable diseases 1. NCDs include cardiometabolic and musculoskeletal diseases, which often coexist as multimorbidity, along with communicable diseases such as HIV – an emerging chronic disease of ageing. Growing evidence shows HIV and its treatment are important risk factors for fracture2. In the Global Burden of Disease study, fragility fractures and osteoporosis (defined as low bone mineral density (BMD) and structural deterioration of bone) contribute to ‘other’ musculoskeletal disorders, yet their important contribution to the rising prevalence of injury- and fracture-related disability, morbidity and mortality is increasingly recognised 3. To date, lack of awareness and hence healthcare prioritisation in Africa, plus a high income country-led focus on specialist techniques to assess BMD (that are unavailable across much of Africa), has likely led to wide-spread under-reporting of morbidity (e.g., disability) and mortality associated with fragility fractures, inevitably creating inequity in fracture prevention and care provision 3. Fractures of the proximal femur (hip) present a particular challenge to functional ability and survival. Hip fracture incidence is projected to double in South Africa between 2020-2050; a rise which will be seen across West, East and Southern African countries as populations continue to age and transition economically 4 5. In Black South African women and men, fracture outcomes are poorer, with much higher morbidity and mortality than is seen in other countries 6. Harmonisation of cohorts across South Africa, The Gambia, and Zimbabwe, confirmed that osteoporosis and osteopenia are just as common in ageing Black African populations, as their similarly aged US counterparts 1. Healthcare systems, increasingly managing age-related multimorbidity, need to adapt to manage osteoporosis and prevent fragility fractures, for example HIV services managing post-menopausal women should be routinely assessing fracture risk. Without such changes, exacerbating health inequities will continue to grow for ageing populations in these settings. Solutions lie in improving clinical awareness, primary care and specialist training, and expansion in access to potentially innovative diagnostic, treatment and rehabilitation services. Traditionally an osteoporosis diagnosis requires a dual energy X-ray absorptiometry (DXA) scan confirming a BMD T-Score ≤−2.5 (using internationally defined thresholds for diagnosis 1,7). Furthermore, DXA scanners are expensive, require specialist support, reliable electricity supply, and are very few (just three in Zimbabwe; population 15.2 million). Where they are available, costs can prove prohibitive to public healthcare users 8. Additionally, as most people who sustain a fragility fracture have a femoral neck BMD T-Score greater than −2.5, i.e., not in the osteoporotic range consideration of the many clinical risk factors besides BMD, for fragility fracture risk, is key. Widespread DXA scanning provision is not practical in resource-constrained public healthcare settings; hence, validation of methods for non-specialist fracture risk assessment should be a priority; options including FRAX®, Garvan and the vertebral fracture risk assessment calculator (VFRAC). Validation will necessitate collection of robust epidemiological data for fracture prevalence and incidence in different populations across Africa. Furthermore, evidence is lacking for the role of additional context-specific clinical risk factors such as HIV infection, which are likely to be important beyond age, BMD, prior fracture and alcohol intake (for men) 9. There will be few data regarding parental fracture in many populations due to historically low life expectancy. Further, research is needed to validate these new fracture risk assessment tools in African populations.A further inequality stems from differences in provision within public and private health care services where access to medicines, used commonly in high income countries for primary and secondary fracture prevention, is most often only possible in private healthcare systems. This largely reflects lack of prioritisation of osteoporosis medicines, as being ‘essential’, by the WHO. Where private healthcare plans exist in South Africa, osteoporosis is not considered a primary medical benefit, hence there is no incentive to assess and treat fracture risk, though those with more comprehensive medical insurance are reimbursed in the case of severe osteopenia, osteoporosis and fracture8. Medical pluralism is also common, particularly in West Africa where traditional bone setters are usually the first point-of-contact on a complex care pathway, which can result in treatment delays. Equitable access to affordable osteoporosis and fracture treatment should be a priority for health care providers and policy makers. The ultimate clinical manifestation of osteoporosis is a fragility fracture. Much of the available literature in Africa has been under powered to estimate fracture prevalence or incidence. Except for South Africa, there remains a paucity of robust epidemiological data to evidence the rise in fragility fractures and to determine context-specific clinical risk factors. Notably, of 131 fracture liaison services surveyed globally in 2020, only one was operational (in South Africa) across Western, Eastern and Southern Africa 10.In conclusion, ageing populations in Africa do not have equitable access to diagnostic and treatment options to reduce future fragility fracture risk and subsequent disability. Given the predicted exponential rise in demand placed by osteoporosis and fragility fractures on already stretched healthcare systems, this must be given attention. Awareness is certainly increasing, with recognition of the importance of appropriate diagnostic and management pathways. It will be important to ensure that communities and stakeholders are fully consulted, as pathways are co-developed, to ensure practical context-specific solutions are implemented. Focusing on equitable access to diagnostic services, creation of implementable tools for diagnosis and treatment monitoring, and building capacity in the provision of healthcare and specific expertise in osteoporosis care, should be key goals for healthcare services, policymakers and governments. <br/

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.” Summary: 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.</p