Studies investigating MBD and ALP
| Study | Population | N | Intervention/Comparison | Outcome | Comments |
|---|---|---|---|---|---|
| Lucas et al 15 | Preterm infants; birth weight <1850 g | 857 | Randomised to either: breast milk alone or preterm formula alone; or breast milk (banked) plus maternal milk or preterm formula plus maternal milk. ALP measured with other serum variables. Growth followed until 18 months | Infants stratified as to peak ALP levels; infants ≥1200 IU/l had lower phosphate and reduced stature at 9 and 18 months | Observational study from larger nutritional intervention trial: no formal/direct measurement of bone density |
| Backström et al 19 | Preterm infants <33 weeks, appropriate weight for gestation (median 1490 g) | 43 | ALP and bone-ALP measured at 3weeks, 12 weeks chronological age; DEXA at 3 and 6 months corrected gestational age | No clear correlation between ALP and bone-ALP with bone density. Peak ALP ‘cut-off’ of >900 IU/l was only 88% sensitive and 71% specific, for subsequent low bone density | Low bone density as proxy for MBD defined as <95 mg/cm3 |
| Faerk et al 16 | Preterm infants <32 weeks, mean birth weight 1129 g | 108 | Part of larger nutritional intervention RCT (randomised to either: mother's milk or breast milk+phosphate or breast milk+fortifier or preterm formula). ALP measured from 1 week of age until 37 weeks corrected gestation, DEXA scans at term corrected | No association between ALP levels and measured bone mineralisation. No difference in bone mineralisation between those with peak ALP<600 and ALP>1200 | |
| Hung et al 20 | Preterm infants ≤34 weeks, Mean GA 29+2 weeks; mean birthweight 1224 g | 46 | Samples collected fortnightly from 3 weeks old until term for ALP, BoneALP, Ca, P; Radiographic assessment at term equivalent to look for osteopenia. Infants given preterm formula or breast milk (fortifier incl. Ca/P added once intake 80 ml/kg/day) | ALP and Bone ALP levels closely correlated. ALP> 700 IU/l at 3 weeks after delivery was 73% sensitive and 74% specific for osteopenia assessed radiographically at term equivalent. Bone-specific ALP 73% sensitive, 80% specific at same interval | Infants without osteopenia were significantly older; only 75% of infants completed study. Infants without osteopenia had significantly higher Pi at 3 weeks. Radiographic scoring used not DEXA |
| Walters et al 21 | Infants <38 weeks | 84 | 3 or more measurements of ALP and contemporary radiographs. Cut-off of 10× local upper limit of adult ‘normal’ as proposed predictor of bone disease | Variable times to peak ALP level noticed. Only one infant with ALP>10×ULN had radiological evidence of bone disease | Observational; inclusion of quite mature infants |
| Glass et al 14 | Infants 26–40 weeks gestation | 349 | ALP and bone-ALP measured at 5-10d after birth (to establish ‘normal range’ for these infants). Subset analysis of those who had radiographs done for clinical reasons | ALP reached higher peak in more preterm infants, peak predated radiograph change by 2–4 weeks. Radiographic change only seen if ALP>500 IU/l | Cohort study, observational and not powered for radiographic comparison |
| James et al 22 | Preterm infants (28–32 weeks, 650–2000 g); Comparison group of term infants | 17; 15 | ALP measurements plus radiographs and photon absorptiometry of radius/ulna compared between two groups at term corrected age | Preterm infants have lower bone mineralisation at term. Weak correlation between radiograph appearances of demineralisation and directly measured. No relationship found between mineralisation and ALP levels | Comparative cohort study. ALP measured at term CGA therefore association with mineralisation at term rather than an examination of predictive value |
ALP, alkaline phosphatase; CGA, corrected gestational age; DEXA, dual-energy absorptiometry; MBD, metabolic bone disease.