# Fractures Associated with Metabolic Bone Disease in Extremely Preterm and Extremely Low Birth Weight Infants Before and After a Bone Health Program

**Authors:** Saif Alsaif, Lina Alsherbini, Talal Aljarbou, Manal Alshareef, Kamal Ali

PMC · DOI: 10.3390/children12111574 · 2025-11-19

## TL;DR

A bone health program significantly reduced fractures in extremely preterm and low birth weight infants and improved their hospital outcomes.

## Contribution

The study demonstrates the effectiveness of a structured bone health bundle in reducing fractures among high-risk infants.

## Key findings

- Fracture incidence dropped from 9.5% to 1.64% after implementing the bone health program.
- Post-program fracture cases had lower peak ALP/PTH levels, earlier detection, and shorter hospital stays.
- The fracture burden per infant decreased significantly following the program implementation.

## Abstract

What are the main findings?
Fracture incidence decreased from 9.5% to 1.64% after program implementation (RR 0.17; NNT ≈ 13).Among infants who fractured, post-program cases had lower peak ALP/PTH, earlier detection, and shorter LOS.

Fracture incidence decreased from 9.5% to 1.64% after program implementation (RR 0.17; NNT ≈ 13).

Among infants who fractured, post-program cases had lower peak ALP/PTH, earlier detection, and shorter LOS.

What is the implication of the main finding?
A protocolized bone health bundle can reduce fractures in extremely preterm/ELBW infants and is feasible for routine NICU practice.Results support multicenter evaluation to confirm generalizability, define core bundle components, and set quality benchmarks.

A protocolized bone health bundle can reduce fractures in extremely preterm/ELBW infants and is feasible for routine NICU practice.

Results support multicenter evaluation to confirm generalizability, define core bundle components, and set quality benchmarks.

Background: Metabolic bone disease (MBD) of prematurity predisposes extremely preterm and extremely low birth weight (ELBW) infants to atraumatic fractures. Evidence on fracture reduction after structured Bone Health Programs (BHPs) remains limited. Methods: We conducted a single-center retrospective cohort of NICU admissions (2014–2024) with gestational age < 28 weeks and/or birth weight < 1000 g, comparing a pre-program era with a standardized BHP that incorporated protocolized biochemical surveillance, a week 4 screening radiograph, optimized mineral targets, pharmacist review of parenteral minerals, and “handle-with-care” practices. The study aimed to evaluate whether implementation of a structured BHP reduced fracture incidence and improved biochemical and clinical outcomes in extremely preterm and ELBW infants. Prespecified effect measures were risk ratio (RR), risk difference (RD) with 95% confidence intervals, Fisher’s exact p values, and number needed to treat (NNT). Among infants with fractures, we compared clinical course and biochemical context across eras. Results: Of 708 eligible infants, 221 were born pre-program and 487 post-program with similar baseline characteristics. Fracture incidence decreased from 9.5% (21/221) to 1.64% (8/487); RR 0.17 (95% CI 0.08–0.38); RD −7.86 percentage points; p < 0.001; NNT ≈ 13. Among infants who fractured, length of stay was lower post-program (104.1 ± 28.3 vs. 172.0 ± 91.5 days). Peak alkaline phosphatase and parathyroid hormone were also lower in the post-program era (ALP 501.3 ± 71.2 vs. 972.5 ± 93.5 IU/L, p = 0.032; PTH 23.1 ± 12.5 vs. 38.4 ± 21.7 pmol/L, p = 0.027), whereas serum phosphate and 25 OH vitamin D did not differ significantly. The fracture burden per infant decreased following the BHP (1.50 ± 0.53 vs. 3.19 ± 3.08, p = 0.024). Age at first fracture was earlier post-program, consistent with scheduled imaging (48.4 ± 34.9 vs. 83.9 ± 37.3 days, p = 0.031). Conclusions: A structured BHP was associated with a large reduction in fracture incidence and more favorable biochemical profiles, together with shorter hospitalization among fracture cases. Program elements that combine scheduled imaging, biochemical triggers, nutritional optimization, parenteral mineral stewardship, and standardized handling may improve skeletal outcomes. Multicenter prospective evaluations should confirm generalizability and define core components.

## Full-text entities

- **Genes:** PTH (parathyroid hormone) [NCBI Gene 5741] {aka FIH1, PTH1}, ALPP (alkaline phosphatase, placental) [NCBI Gene 250] {aka ALP, PALP, PLAP, PLAP-1}
- **Diseases:** Fracture (MESH:D050723), MBD (MESH:D001851)
- **Chemicals:** 25 OH vitamin D (-), phosphate (MESH:D010710)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Figures

2 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12651200/full.md

---
Source: https://tomesphere.com/paper/PMC12651200