Table 1

Summary of study measurements to be quantified at baseline and follow-up

MeasurementMeasurement methodOutcome
Interview-based questionnaireSociodemographic characteristicsQuestionnaireAge, sex, school attendance, orphanhood, guardianship
Clinical historyQuestionnaire*History of fractures and trauma (modified Landin classification55)
HIV history: age at diagnosis, WHO disease stage, nadir CD4 count, opportunistic infections†
ART regimen/duration†
Exposures: steroid use, smoking, alcohol, recreational drugs
Family history of musculoskeletal disease and fractures
Other comorbidities
Physical activityThe International Physical Activity Questionnaire (IPAQ)45 questionnaire
(short form)
Median MET-minutes‡ of physical activity/week
  1. Inactive (<600 MET-minutes/week)

  2. Minimally active (600–1499 MET-minutes/week)

  3. Highly active (≥1500 MET-minutes/week)

Nutrition‡Dietary assessment tool (Modified Short Food Frequency Questionnaire46)Daily dietary calcium and vitamin D intake
Prevalence of vitamin supplementation
Sun exposure
Quality of life and disabilityWashington Disability Score56 Functioning and disability score
Standardised examinationMusculoskeletal examinationPaediatric Gait, Arms, Legs and Spine (pGALS)48
±regional clinical examination
Joint, spine and gait abnormalities
Pubertal stageTanner’s staging57 58 Prepubertal (stage 1)
Pubertal (stage 2–3)
Postpubertal (stage 4 and 5)
AnthropometryHeight (standing and sitting)
Weight
Mid-upper arm circumference (MUAC)§
Standing height-for-age (Z-score)¶59
Weight-for-age (Z-score)¶59
Body mass index (BMI) (Z-score)¶59
MUAC (Z-score)¶59
Muscle strengthJamar dynamometer
standing long jump¶
Hand grip strength (kg, Z-score)¶60
Jumping distance (cm, Z-score)**61
RadiologySkeletal maturityHand/wrist radiographBone age (years)
Bone and muscle compositionDual-energy X-ray absorptiometry (DXA) of total body, lumbar spine and hip††Size corrected DXA measures of TBLH BMCLBM (g), LS BMAD (g/cm3) and Z-scores <−2.¶
Lean mass
Bone architecturePeripheral quantitative computed tomography (pQCT)Trabecular and cortical vBMD (g/cm3),
total and cortical CSA (mm²), cortical thickness (mm), periosteal and endosteal circumference (mm), SSI (mm3), PMI (mm4) and CSMI (mm4)
Blood
tests
Bone markers and DNABlood test (DNA extraction and serum saved)Future testing e.g. Vitamin D, alkaline phosphotase, C-terminal telopeptide (CTX)‡‡
HIV markersBlood testCD4 count, HIV viral load†
  • *Details of treatment and comorbidities will be confirmed by patient-held medical records where available.

  • †Denotes assessments to be carried out in HIV-infected participants only.

  • ‡Energy requirements defined in METS (multiples of the resting metabolic rate that give a score in MET-minutes).

  • §Nutritional indicator to include composite information from history (usual diet last month, sun exposure–vitamin D status) and clinical examination (MUAC). Similar methods have been used in other low-income contexts.46

  • ¶Age-specific and sex-specific Z-scores for (1) anthropometric measures will be determined using the WHO child growth standards.59 (2) Hand grip strength will be determined with reference to the uninfected comparison group and European normative data.60 (3) Jumping distance will be determined using normative data from South Africa.61 (4) Low BMD will be determined with reference to published paediatric Hologic DXA reference databases for LS BMAD and TBLH BMCLBM Z-scores.36

  • **Standing long jump; the longest distance after two attempts will be recorded.

  • ††Pregnancy urine dipstick in female participants prior to DXA if uncertain pregnancy status.

  • ‡‡Tests to be carried out on stored blood when further funding is secured.

  • CSA, cross-sectional area; CSMI, cross-sectional moment of inertia; DXA, dual-energy X-ray absorptiometry; LS BMAD, lumbar spine bone mineral apparent density; PMI, polar moment of inertia; SSI, Strength Strain Index; TBLH BMCLBM, total-body less-head bone mineral content for lean mass adjusted for height.