What is the recommended treatment for metabolic bone disease of prematurity in premature infants born before 32 weeks of gestation or weighing less than 1500 grams at birth?

Metabolic Bone Disease of Prematurity: Treatment Recommendations

Primary Treatment Strategy

For premature infants born before 32 weeks gestation or weighing less than 1500 grams, optimize calcium and phosphorus supplementation immediately, targeting 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) with a molar Ca:P ratio around 1.3 for growing infants. 1, 2

Initial Management During First Days of Life

• Use lower Ca:P ratios (0.8-1.0) during the first days of life to prevent early postnatal hypophosphatemia, which is the primary metabolic derangement in very low birth weight infants due to their extreme phosphorus needs for growth. 1, 2

• Provide calcium 0.8-2.0 mmol/kg/day (32-80 mg/kg/day) and phosphorus 1.0-2.0 mmol/kg/day (31-62 mg/kg/day) during this early period when protein and energy intakes are being optimized. 1, 2

• Monitor plasma phosphate concentration carefully within the first days of life, particularly in infants with intrauterine growth restriction, as early hypophosphatemia can lead to hypercalcemia, hypercalciuria, and if prolonged, bone demineralization and nephrocalcinosis. 1, 2

Ongoing Nutritional Management for Growing Premature Infants

• Transition to higher mineral intake after the first few days, with calcium 1.6-3.5 mmol/kg/day (64-140 mg/kg/day) and phosphorus 1.6-3.5 mmol/kg/day (50-108 mg/kg/day), maintaining a molar Ca:P ratio around 1.3. 1, 2

• Provide magnesium 0.2-0.3 mmol/kg/day (5.0-7.5 mg/kg/day) for growing premature infants. 1, 2

• Individual requirements strongly depend on growth velocity and may range from 1-4 mmol/kg/day of calcium (40-160 mg/kg/day) and 0.75-3 mmol/kg/day of phosphorus (23-93 mg/kg/day). 1

Route of Administration and Formulation

• Prioritize early establishment of full enteral feeding as optimization of total parenteral nutrition and early achievement of full enteral feeding are critical goals for prevention and management of metabolic bone disease of prematurity. 3

• 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, 2

• Select ingredients with the lowest aluminum content for parenteral nutrition preparation, as aluminum toxicity contributes to metabolic bone disease in infants on long-term parenteral nutrition. 1, 2

Monitoring Protocol

• Begin biochemical monitoring at 6 weeks of life and repeat every 2 weeks, measuring serum calcium, phosphorus, alkaline phosphatase, urinary calcium, parathyroid hormone, and 25-OH vitamin D concentrations. 2, 4, 5

• Assess adequacy of calcium and phosphorus intake by checking for simultaneous urinary excretion of both minerals with low concentrations (>1 mmol/L), indicating a slight surplus and appropriate balance. 2

• If first-tier screening (serum calcium, phosphorus, alkaline phosphatase) is abnormal, obtain parathyroid hormone and/or tubular resorption of phosphate to differentiate between calcium and phosphate deficiency as primary etiologies. 4

Physical Activity Component

• Instruct caregivers to facilitate enhanced physical activity in preterm infants, as this promotes bone mineralization and weight gain while preventing the development of metabolic bone disease. 6, 3

• Ensure all uninvolved joints move regularly through complete range of motion to prevent disuse osteopenia. 7

Critical Pitfalls to Avoid

• Never use neutral potassium phosphate (K2HPO4) as it induces precipitation risk that limits its use in parenteral nutrition. 2

• Avoid chloride-containing calcium salts (calcium chloride) as they may increase anion gap and lead to metabolic acidosis. 2

• Do not delay phosphorus supplementation in very low birth weight infants, as early hypophosphatemia is the primary metabolic derangement requiring immediate correction. 2

• Monitor for hypercalciuria and nephrocalcinosis when calcium and phosphorus are not balanced appropriately, as prolonged imbalance can cause renal complications. 1, 2

Special Considerations for Severe Cases

• Reserve bisphosphonate treatment only for severe cases with fractures, prescribed exclusively by specialists knowledgeable in pediatric osteoporosis management, as there is limited published experience with bisphosphonates in infants. 2

• For infants on long-term parenteral nutrition, consider using an inverse Ca:P ratio of 0.5 with higher phosphorus intake (0.7 mmol/kg/day) and calcium intake (0.35 mmol/kg/day) in absence of vitamin D administration, as this approach has empirically shown benefit in reversing hypercalciuria and preventing painful bone disease. 1