Osteopenia of Prematurity: Primary Treatment
The primary treatment for osteopenia of prematurity is optimized calcium and phosphorus supplementation, with calcium intake of 1.6-3.5 mmol/kg/day (64-140 mg/kg/day) and phosphorus intake of 1.6-3.5 mmol/kg/day (50-108 mg/kg/day), maintaining a molar Ca:P ratio around 1.3, as recommended by ESPGHAN. 1
Nutritional Supplementation: The Cornerstone of Treatment
Parenteral Nutrition Phase
During the first days of life, very low birth weight infants require lower Ca:P ratios (0.8-1.0) with calcium 0.8-2.0 mmol/kg/day and phosphorus 1.0-2.0 mmol/kg/day to prevent severe hypophosphatemia, which is the primary metabolic derangement in this critical period. 1
Phosphorus supplementation must not be delayed in very low birth weight infants, as early hypophosphatemia poses the greatest immediate risk. 1
Magnesium intake should be maintained at 0.2-0.3 mmol/kg/day (5.0-7.5 mg/kg/day) for growing premature infants. 1
Transition to Enteral Nutrition
Once enteral feeding is established, calcium and phosphorus targets shift to the higher range of 1.6-3.5 mmol/kg/day for both minerals, with the molar Ca:P ratio returning to approximately 1.3. 1
Breast milk fortifier should be used to achieve these mineral targets, as unfortified breast milk is insufficient for premature infant bone mineralization needs. 1
Vitamin D Supplementation
Vitamin D supplementation at 400-800 IU/day is recommended, particularly in breast-fed infants, with vitamin content in formula or fortifier taken into account. 2
Evidence suggests that even low-dose vitamin D (200 IU/day) may be sufficient for prevention when combined with adequate calcium and phosphorus intake. 3
Monitoring Protocol: Early Detection is Critical
Biochemical monitoring should begin every 2 weeks starting from the 6th week of life, measuring serum calcium, phosphorus, alkaline phosphatase, parathyroid hormone, and 25-OH vitamin D concentrations. 1
Hypophosphatemia (P < 1.6 mmol/L) at 2 weeks is an early warning sign requiring immediate intervention with increased phosphorus supplementation. 4
Elevated parathyroid hormone at 8 weeks, particularly when correlated with low vitamin D levels, indicates developing osteopenia requiring treatment intensification. 4
The adequacy of calcium and phosphorus intake is confirmed when both minerals begin appearing simultaneously in urine with low concentrations (>1 mmol/L), indicating a slight surplus. 1
Critical Pitfalls to Avoid
Never use neutral potassium phosphate (K2HPO4) as it induces precipitation risk that limits its clinical utility. 1
Avoid chloride-containing calcium salts (calcium chloride) as they increase anion gap and lead to metabolic acidosis. 1
Do not delay phosphorus supplementation in very low birth weight infants—early hypophosphatemia is the primary metabolic derangement requiring immediate correction. 1
Monitor for hypercalciuria and nephrocalcinosis when calcium and phosphorus are not balanced appropriately, as excessive calcium without adequate phosphorus can cause renal complications. 1
Aluminum Toxicity Prevention
Use calcium gluconate packaged in polyethylene rather than glass vials to reduce aluminum contamination, as aluminum intake should not exceed 5 mg/kg/day. 1
Prioritize ingredients with the lowest aluminum content when preparing parenteral nutrition solutions. 1
Special Populations Requiring Heightened Vigilance
Infants with intrauterine growth restriction on parenteral nutrition require careful monitoring of plasma phosphate concentration within the first days of life to prevent severe hypophosphatemia. 1
Very premature newborns have increased risk of low bone mass, and short-term decline in bone strength may be prevented by higher calcium and phosphorus intake via parenteral nutrition or early initiation of PN. 1
When to Consider Bisphosphonates
Bisphosphonate treatment has limited published experience in infants and should only be considered in severe cases with fractures, prescribed exclusively by specialists knowledgeable in pediatric osteoporosis management. 1
This represents a last-resort intervention, not a primary treatment strategy for osteopenia of prematurity. 1