Fractures Associated with Metabolic Bone Disease in Extremely Preterm and Extremely Low Birth Weight Infants Before...

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.

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.

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).

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.