Osteopenia of Prematurity: Primary Treatment
The primary treatment for osteopenia of prematurity is optimized calcium and phosphorus supplementation, with growing premature infants requiring 1.6-3.5 mmol/kg/day (64-140 mg/kg/day) of calcium and 1.6-3.5 mmol/kg/day (50-108 mg/kg/day) of phosphorus via parenteral nutrition, maintaining a molar Ca:P ratio around 1.3. 1
Nutritional Supplementation Strategy
Parenteral Nutrition Requirements
For growing premature infants, the ESPGHAN/ESPEN/ESPR/CSPEN guidelines establish specific mineral targets that directly prevent and treat osteopenia:
- Calcium: 1.6-3.5 mmol/kg/day (64-140 mg/kg/day) 1
- Phosphorus: 1.6-3.5 mmol/kg/day (50-108 mg/kg/day) 1
- Magnesium: 0.2-0.3 mmol/kg/day (5.0-7.5 mg/kg/day) 1
- Molar Ca:P ratio: Approximately 1.3 (mass ratio 1.7) 1
Critical early management caveat: During the first days of life, very low birth weight infants are at high risk for hypophosphatemia due to their extreme phosphorus needs for growth. 1 In this early period, use 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 that can cause muscle weakness, respiratory failure, cardiac dysfunction, and death. 1
Enteral Nutrition Requirements
When transitioning to enteral feeds, calcium and phosphorus should be supplemented at 90-150 mg/kg/day (2.25-3.7 mmol/kg/day) and 45-80 mg/kg/day (1.5-2.6 mmol/kg/day) respectively. 2 Breast milk fortifier is recommended until corrected age of 40 weeks, and up to 52 weeks in growth-retarded infants. 2
Vitamin D Supplementation
Vitamin D should be supplemented at 400-800 IU daily, particularly in breastfed infants, accounting for vitamin content already present in formula or fortifier. 2 Active metabolites of vitamin D are not recommended. 2
Monitoring Protocol
Regular biochemical monitoring every 2 weeks starting from the 6th week of life is essential, measuring:
- Serum calcium and phosphorus 2
- Alkaline phosphatase (elevated levels >900 IU/L suggest osteopenia) 3
- Urinary calcium 1
- Parathyroid hormone 1
- 25-OH vitamin D concentrations 1
The adequacy of calcium and phosphorus intake can be assessed when both minerals start being excreted simultaneously in urine with low concentrations (>1 mmol/L), indicating a slight surplus. 1
Adjunctive Physical Activity
Physical activity protocols combining passive range of motion and gentle joint compression, when combined with adequate nutritional supplementation, reduce osteopenia of prematurity. 4 Weight-bearing activities should be incorporated as tolerated. 4
Prevention of Aluminum Toxicity
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 Ingredients with the lowest aluminum content should be prioritized for parenteral nutrition preparation. 1
Special Considerations
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
For infants with intrauterine growth restriction on parenteral nutrition, careful monitoring of plasma phosphate concentration within the first days of life is required to prevent severe hypophosphatemia. 1
Bisphosphonate treatment has limited published experience in infants and should only be considered in severe cases with fractures, prescribed by specialists knowledgeable in pediatric osteoporosis management. 1, 5
Common Pitfalls to Avoid
- Do not use neutral potassium phosphate (K2HPO4) as it induces precipitation risk that limits its use. 1
- Avoid chloride-containing calcium salts (calcium chloride) as they may increase anion gap and lead to metabolic acidosis. 1
- Do not delay phosphorus supplementation in very low birth weight infants, as early hypophosphatemia is the primary metabolic derangement. 1
- Monitor for hypercalciuria and nephrocalcinosis when calcium and phosphorus are not balanced appropriately. 1