Overview
Definition:
Osteopenia of prematurity (OOP) is a metabolic bone disease characterized by a low bone mineral content in preterm infants, leading to increased risk of fractures and bone deformities
It results from an inadequate supply of calcium and phosphorus to meet the demands of rapid skeletal growth, especially in infants born before 30 weeks of gestation or with a birth weight less than 1000 grams.
Epidemiology:
Occurs in 20-40% of very low birth weight (VLBW) infants, with the incidence increasing with decreasing gestational age and birth weight
Infants requiring prolonged parenteral nutrition, those with chronic lung disease, or malabsorption syndromes are at higher risk.
Clinical Significance:
OOP poses significant challenges in neonatal intensive care units, impacting long-term skeletal development, growth, and potentially leading to rickets, fractures, and impaired motor development
Optimal calcium and phosphorus management is crucial for improving bone health outcomes in this vulnerable population.
Risk Factors
Gestational Age:
Infants born before 30 weeks gestation have insufficient intrauterine accretion of bone minerals.
Birth Weight:
Very low birth weight (VLBW) infants (<1000g) have limited mineral reserves.
Nutritional Intake:
Inadequate enteral or parenteral intake of calcium and phosphorus.
Medical Conditions:
Chronic lung disease (requiring ventilation, steroids), gastrointestinal disorders (NEC, cholestasis, short bowel syndrome), infections, and prolonged immobilization.
Medications:
Corticosteroids (inhibit osteoblast activity and calcium absorption), loop diuretics (increase urinary calcium and phosphorus excretion).
Clinical Presentation
Symptoms:
Often insidious onset
May present with poor weight gain
Irritability
Muscle weakness or hypotonia
Fractures (pathological, often long bones like femur, humerus) identified incidentally or following minor trauma
Respiratory distress may worsen due to rib fractures.
Signs:
Skeletal deformities (rachitic rosary, bowing of long bones) may be subtle in neonates
Epiphyseal enlargement is uncommon
Tenderness on palpation of bones
Signs of hypocalcemia (e.g., carpopedal spasm, stridor) if severe.
Diagnostic Criteria:
Diagnosis is often based on a combination of clinical suspicion, risk factors, laboratory findings, and imaging
Radiographic findings of decreased bone mineralization (generalized osteopenia, cortical thinning, fraying of metaphyses) are classic
Biochemical markers are supportive but not definitive for diagnosis.
Diagnostic Approach
History Taking:
Detailed history of gestational age, birth weight, postnatal feeding (enteral/parenteral), duration of ventilatory support, steroid use, and presence of gastrointestinal issues
Family history of bone disease.
Physical Examination:
Assess for signs of rickets, assess muscle tone and strength, palpate for bone tenderness
Examine for any signs of trauma or fracture.
Investigations:
Serum calcium (total and ionized), phosphorus, alkaline phosphatase (SAP), magnesium, and vitamin D levels (25-hydroxyvitamin D)
Serial monitoring is essential
Radiographs of long bones (e.g., tibia, femur) to assess bone mineralization, cortical thickness, and metaphyseal changes
Bone mineral density (BMD) measurements using DXA or quantitative ultrasound (QUS) can be used in older infants but are less common in neonates.
Differential Diagnosis:
Other causes of hypomineralization: Hypophosphatasia (genetic disorder with low SAP), severe malnutrition, chronic renal insufficiency, Albright's hereditary osteodystrophy, and calcium/phosphorus malabsorption syndromes.
Management
Initial Management:
Early identification of at-risk infants and initiation of appropriate nutritional support
Aim to provide adequate calcium and phosphorus to support bone growth, considering both enteral and parenteral routes.
Calcium And Phosphorus Supplementation:
Target serum phosphorus levels: 1.5-2.5 mmol/L (4.6-7.8 mg/dL)
Target serum calcium levels: 2.0-2.6 mmol/L (8-10.4 mg/dL) for total calcium, or 1.1-1.4 mmol/L (4.4-5.6 mg/dL) for ionized calcium
Recommended daily intake for preterm infants is approximately 100-150 mg/kg/day for calcium and 50-100 mg/kg/day for phosphorus, adjusted based on gestational age, birth weight, and feeding route.
Enteral Supplementation:
Provide calcium and phosphorus in fortified human milk or specialized preterm formula
Common forms: calcium gluconate, calcium lactate, dibasic calcium phosphate, potassium phosphate
Dosing is crucial to avoid precipitation in feeding tubes or gastrointestinal issues.
Parenteral Supplementation:
Administered via peripheral or central venous access
Calcium and phosphorus must be added to parenteral nutrition (PN) solutions carefully to prevent precipitation (calcium phosphate salt)
The order of addition (e.g., phosphate before calcium) and pH of PN are critical
Maximum solubility depends on PN formulation, osmolarity, and temperature
Refer to established PN guidelines for safe limits.
Vitamin D Supplementation:
Vitamin D is essential for calcium and phosphorus absorption
Administer cholecalciferol (D3) or ergocalciferol (D2)
Typical dose: 400-1000 IU/day
Monitor serum 25-hydroxyvitamin D levels.
Supportive Care:
Minimize corticosteroid use if possible
Optimize nutrition
Gentle handling of infants to prevent fractures
Physiotherapy may be considered for infants with muscle weakness or fractures.
Complications
Early Complications:
Fractures (especially long bones, ribs)
Hypocalcemia (symptomatic)
Hypophosphatemia
Precipitation of calcium phosphate in PN lines or kidneys.
Late Complications:
Delayed growth and development
Impaired motor milestones
Skeletal deformities (bowing of limbs)
Increased risk of osteoporosis later in life.
Prevention Strategies:
Proactive identification of high-risk infants
Timely and adequate enteral/parenteral calcium and phosphorus supplementation
Careful management of PN solutions to prevent precipitation
Judicious use of corticosteroids
Adequate vitamin D intake.
Prognosis
Factors Affecting Prognosis:
Severity of OOP, gestational age at birth, presence of associated comorbidities (e.g., chronic lung disease), adequacy and timing of nutritional management, and development of fractures.
Outcomes:
With appropriate management, bone mineralization improves, and fractures heal
Long-term skeletal outcomes depend on the severity and duration of the disease and the effectiveness of interventions
Most infants achieve normal bone density by term-equivalent age or later.
Follow Up:
Regular monitoring of growth, bone mineral status (biochemical markers and serial radiographs), and skeletal development
Continued nutritional support and vitamin D supplementation as needed
Physiotherapy and orthopedic follow-up may be required for infants with significant deformities or fractures.
Key Points
Exam Focus:
Risk stratification for OOP
Biochemical markers: high alkaline phosphatase (SAP), low phosphorus
Radiographic signs of osteopenia
Principles of calcium/phosphorus supplementation in enteral and parenteral nutrition
Prevention of calcium-phosphate precipitation in PN
Role of vitamin D.
Clinical Pearls:
Always consider OOP in VLBW infants with poor growth or fractures
Monitor serum electrolytes and SAP closely
Pay meticulous attention to the safe preparation of PN solutions to avoid calcium-phosphate precipitation
Consider adjusting mineral intake based on infant's growth trajectory and metabolic status.
Common Mistakes:
Underestimating the mineral needs of preterm infants
Inadequate monitoring of serum calcium, phosphorus, and SAP
Incorrect calculation or administration of PN solutions leading to precipitation
Delayed diagnosis and initiation of treatment.