Metabolic bone disease in the preterm infant: Current state and future directions

Table 1 Suggested guidelines for the prevention, monitoring and management of neonatal metabolic bone disease

Infants at risk	Prevention	Monitoring	Management
Born with birth weight below 1500 g	Early enteral nutritional intervention	Biochemical	If the biomarkers of MBD do not normalize, consider either vitamin D supplementation with up to 600 IU/d (although not well supported by evidence) or initiate instead ergocalciferol or alphacalcidol therapy in which case regular monitoring of urinary calcium/creatinine ratio is necessary to detect hypercalciuria
Born before 28 wk of gestation	Maintain a sufficient supply of Ca and P. Start oral P supplements as soon as its feasible. The P absorption rate is very good in the presence of Ca, with absorption rates exceeding 90% with both human and formula milk. The Ca absorption rate increases from 35 to 60 mg/kg per day when both Ca and P are supplemented and to 90 mg/kg per day when the appropriate dietary Ca/P ratio is attained. High Ca and P retention rates are attained with high-mineral preterm milk formulae or with fortified human milk	Monitor weekly serum “bone profile” (Ca, P and ALP): maintain serum Ca concentration between 2.05-2.75 mmol/L and serum P between 1.87-2.91 mmol/L If serum P < 1.8 mmol/L and ALP > 500 IU/L, renal TRP should be measured and, if it exceeds 95%, P supplementation should be started If serum P levels fail to increase and if serum ALP levels keep on rising, consider ergocalciferol or alphacalcidol therapy
Having received total parenteral nutrition for more than four weeks	Vitamin D supplementation	DEXA
On long-term diuretics or corticosteroid therapy	Ensure a minimum daily supplement of 400 IU vitamin D. Doses above 400 IU/d do not improve Ca and P absorption	Being increasingly used for assessing BMD in neonates, but not recommended as yet as a clinical tool
Suffering from neuromuscular disorders	Parenteral nutrition	Monitor for metabolic acidosis and hypercalciuria which may result from an increase in parenteral mineral delivery during parenteral nutrition
	Preparations providing 1.45 to 1.9 mmol/kg per day of Ca and 1.23 to 1.74 mmol/kg per day of P result in Ca and P retention rates of 88%-94% and 83%-97% respectively. The optimal Ca/P ratio in the intravenous solution fluid is between 1.3:1 and 1.7:1.54
	If needed, parenteral P delivery can also be enhanced by using special preparations of organic P
	Exercises
	Daily exercises such as gentle compression and movements of the limbs
	Regular review of medications in use
	Discontinuation of diuretics and steroids when appropriate

ALP: Alkaline phosphatase; BMD: Bone mass density; Ca: Calcium; IU: International units; P: Phosphorus; TRP: Tubular reabsorption of phosphate. DEXA: Dual-energy X-ray absorptiometry.