Chapter 21: Low Bone Mass in Very Preterm or Other High-Risk Infants

I. Intensive care

1. Definition

   1. There is no clear definition of this condition.

   2. It is referred to by multiple names, most commonly osteopenia of prematurity, metabolic bone disease of prematurity, or rickets of prematurity.

   3. Each of these names implies somewhat different characteristics of the clinical (rickets), laboratory (metabolic bone disease), or radiological (osteopenia and rickets) findings.

   4. In practical terms, it is the presence of radiological rickets or fractures that determines the clinical symptomatology. However, markedly abnormal laboratory values, including a very high alkaline phosphatase activity are concerning and may require clinical intervention.

2. Incidence

   1. As this is not a reportable condition, the incidence is unknown and would depend on which type of definition is used.

   2. For example, an elevated alkaline phosphatase, indicative of metabolic bone disease is nearly universal in very low birthweight infants and as such it is not really possible to identify a true upper limit of normal for the serum alkaline phosphatase activity in preterm infants.

   3. Clinically apparent fractures are uncommon.

   4. In general, it has been suggested that low bone mass is present in about half of all VLBW infants, but true rickets is likely much less common in this population except in infants <600 g birthweight, where it may reach 50%. Using modern nutritional methods of providing minerals to infants, the incidence of clinically significant low bone mass is probably about 10% of VLBW infants but this number cannot readily be verified.

3. Pathophysiology

   1. VLBW infants have an extremely high requirement of calcium and phosphorus, the principal components of bone mineral. This need cannot be met using unfortified human milk.

   2. Vitamin D deficiency is not a primary cause of LBM in VLBW infants.

   3. However, in full-term infants with malabsorptive problems, such as intestinal failure/short gut and/or cholestatic liver disease, vitamin D deficiency may play an important role in inadequate mineral absorption and bone mass growth.

   4. The rare preterm infant with significant renal failure may also present with multiple problems related to bone minerals, including low serum calcium, high serum phosphorus, low vitamin D status, and bone demineralization.

4. Risk factors

   1. Clinically important risk factors during hospitalization are those that might decrease mineral intake or absorption or increase mineral excretion.

   2. Specifically, these primarily include

      • The use of unfortified or inadequately fortified human milk

      • Frequent use of loop diuretics

      • Use of steroids

      • Fluid restriction

      It is impossible in many circumstances to be certain about the most important of these factors, but infants in the NICU frequently encounter more than one of these risks.

   3. In many cases, it is lower mineral intake, not bioavailability or even increased renal calcium excretion by loop diuretics (eg, furosemide), which is the principal problem.

5. Clinical presentation

   1. Signs and symptoms

      1. There are often few if any clinical signs in high-risk neonates.

      2. Physical signs of rickets or fractures can be present, however, and are similar to those seen in older children. Specifically, bone or joint swelling can occur.

      3. Classic signs such as bowing of the legs, frontal bossing, rachitic rosary, ...