There is Nothing “Humerus” about Metabolic Bone Disease in High-Risk Infants

PowerPoint PresentationThere is Nothing “Humerus” about
Metabolic Bone Disease in High-Risk Infants
• Describe metabolic bone disease of prematurity (MBDP)
• Discuss causes and risk factors for MBDP
• Review biochemical markers with emphasis on parathyroid hormone (PTH)
• Show radiographic evidence of MBDP and fractures
• List intervention and monitoring strategies
• Case study
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Objectives
Definition: Bone disease in infants and children that stem from hereditary, genetic and/or acquired conditions of various etiologies that lead to disturbance in bone metabolism
Major consequences: reduced linear growth, bone deformities, non-traumatic fractures leading to bone pain, deterioration of motor development and disabilities
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preterm infants
Extremely Low Birth Weight (ELBW) will develop
osteopenia
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Lack of universal consensus on screening, diagnosis, treatment, or monitoring
Presence of guidance for risk factors and nutritionally focused preventative strategies
Often MBDP is clinically unknown until complications have already occurred like radiological changes including
fractures, or poor linear growth
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MBDP
Phosphorus) accretion
enteral or parenteral delivery to match intrauterine mineral
accretion rate or provide baseline mineral needs
• Conditions and medications impacting nutrient delivery, bone
metabolism and vitamin/mineral needs
transported across the
Between 32-36wks,
calcium
phosphate
provide sufficient amounts of minerals,
further complicated by medical conditions and
medications.
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Gestational age less than 34 weeks
Birthweight <1500 grams
Small for gestational age and intrauterine growth restriction
Inability to fortify breastmilk feeds with optimal fortifier for gestational age
Inability to provide appropriate preterm formula
Parenteral Nutrition for greater than 4 weeks 7
Causes and Risk Factors of MBDP
Medications:
Postnatal comorbidities:
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Congenital Heart Disease (CHD)
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Causes and Risk Factors of MBDP
A known complication of poor bone health stemming in part from
MBDP or MBD in general
Fracture Risk Reduction
– Previous fracture (not trauma related like clavicular fracture)
– Radiographic evidence of osteopenia placing infant at risk for fractures
– Genetic disease like Osteogenesis Imperfecta (Brittle Bones)
2. Creating universal awareness
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• Calcium (Ca): often normal (goal 9-100mg/dl)
• Phosphorus (P): typically low (goal 5.5-7 mg/dl)
– Could represent a true P deficiency or Ca deficit
• Magnesium (Mg): usually normal
• Vitamin D: low or normal (goal >30 nl/dl)
• Parathyroid Hormone (PTH): goal for infants is < 80pg/ml (normal
range for intact PTH 10-65pg/ml)
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Biochemical Levels seen in MBDP
• Ca: multiple roles in the body including building bone and supporting brain
and heart function via myocyte activity
• Phos: component of bones, teeth, cell membranes, DNA, RNA, ATP; plays
a role in regulation in gene transcription, activation of enzymes,
maintenance of normal pH in extracellular fluid, and intracellular energy
storage
• Alk phos is found primarily in bone, liver and intestines (isoenzymes)
– Elevated Alk phos seen in bone demineralization or bone turnover
– If Alk phos is over 1000 U/L with other abnormal liver function tests or
acute GI complications like perforation, the rise is related to the liver or
intestinal isoenzymes
Biochemical Markers
• Vitamin D: multiple roles and benefits in the body (focus here on
bones)
– Need enough for body to absorb Ca properly
– Vitamin D regulates the intestinal absorption of Ca
– Too much or too little vitamin D can cause an imbalance in
calcium metabolism.
metabolism in the body:
– PTH has the greatest action in the kidney for regulating calcium
metabolism
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In UK, study set out to investigate practices of MBDP among neonatologist and
endocrinologist. Survey inquired about biochemical monitoring and interventions
Majority of neonatologists look at Ca, P and Alk phos and typically supplement extra phos
and sometimes Ca with optimal Vit D
Higher percentage of endocrinologists focus more on PTH as a screening tool and
tend to supplement with Ca with or without P supplementation
Takeaway: underutilization of plasma PTH as a screening, diagnostic and
monitoring tool to guide appropriate supplementation of mineral for MBDP by
neonatologists.
Dietitians should become comfortable asking for PTH levels and interpreting PTH levels and
communicate with endocrine and neonatal colleagues
Chinoy A, Mughal MZ, Padidela R. Metabolic bone disease of prematurity-National survey of current neonatal and paediatric endocrine approaches. Acta Paediatr. 2020.
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Focus on Parathyroid Hormone (PTH) and balance of Ca and P
• After birth (regardless of gestational age) → fall in Ca, with nadir attained
24-30hours postnatally
• Leads to surge in PTH → PTH enhances calcium reabsorption in the kidney
and results in urinary phosphate wasting.
• PTH aids in the production of calcitriol [1,25(OH)2D] by activating renal
25(OH)D3-1-alpha-hydroxylase → tells the intestines to absorb Ca and P
• PTH promotes bone resorption and subsequent release of Ca and P from
the bones to keep serum levels normal
• If there is insufficient Ca intake for prolonged periods → metabolic
changes occur
17Metabolic bone disease of prematurity. Rustico SE, Calabria AC, Garber SJ. J Clin Transl Endocrinol. 2014 Sep; 1(3):85-91.
PTH
phosphorus levels. Hypophosphatemia is an early indicator of
disrupted calcium metabolism and manifests by 7-14 days of life.
• This can occur either due to isolated phosphate deficiency or to
elevated PTH levels.
• Phosphate reabsorption is increased by the kidney and thus tubular
reabsorption of phosphate is also a useful measure of phosphate
homeostasis.
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Chacham S, Pasi R, Chegondi M, Ahmad N, Mohanty SB. Metabolic Bone Disease in Premature Neonates: An Unmet
Challenge. J Clin Res Pediatr Endocrinol. 2020;12(4):332-339. doi:10.4274/jcrpe.galenos.2019.2019.0091
Low P levels
phosphorus excretion;
hypercalcemia which suppresses PTH levels.
So, plasma PTH helps
regulation and maintenance of normal blood levels
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• Compensatory response to hypocalcemia
• Anticonvulsants
• Steroids
• Isoniazid
• Lithium
• Rifampin
• Cimetidine
• Propranolol
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defined cortex, zone of provisional
calcification is present.
provisional calcification, edge of the
metaphysis is irregular and indistinct.
Severe—grossly demineralized bone, no
zone of provisional calcification, brush
border exists at edge of metaphysis.
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old former ELBW
preterm infant with
Janet Reid, The Children’s
Hospital of Philadelphia.
"disappearing" bones (vertebral
bodies barely visible)
Healing humeral fracture
preterm formula
provide adequate supplementation to
adjust pending condition or serum
markers
Aluminum)
– Approach with Interdisciplinary team including neonatologist, physical therapist, nurse, radiologist, endocrinologist (higher level involvement when possible)
– Include bone health or review of bones on XR (medical team, radiology)
– Minimize osteolytic meds that impair bone health (based on medical need)
– Maximize range of motion and ensure physical boundaries for preemies (PT)
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• Address mineral deficits appropriately: Calcium with or without Phos supplements
• Adjust Ca:P ratio in both enteral or parenteral nutrition for optimal bone mineralization
• Provide adequate amount of Vitamin D supplementation and adjust pending levels of Vit D 25-OH
• Pay attention to other non-nutritional factors and the patient’s course → advocate for your patient (therapies, minimize use of osteolytic medications)
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• Biochemical markers: Ca, P, Mg, Alk phos, PTH, Vit D
• Pay close attention to radiological reports
• Trend growth on appropriate growth curve with emphasis on liner
growth and correct length measurements
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• Former 24 +6/7 ELBW (<1000g) preemie with history of feeding
issues, resp failure, persistent thrombocytopenia, poor postnatal
growth, transfer for higher level of care at just over 1 month of age
• Phos level at admission of 1mg/dl → bolus x 2 of Naphos
• Ca level normal
• Caffeine since birth
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– GA <34wks and BW <1500g
– More than 2 weeks on caffeine
– Inability to use GI tract/provide appropriate enteral mineral
delivery
• Also noted to have insufficient provision of vitamin D, Ca and phos
and poor parenteral Ca:P ratio based on outside hospital PN
• HIGH RISK FOR FRACTURES and likely has early MBDP
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2. Obtain Vit D 25-OH first
3. Since pt was on PN, improved Ca:P ratio
4. Ask for all XRs to be reviewed moving forward
Improving phos levels noted. Vit D actually came back at 35ng/dl. Since on PN and pt was critically ill and needing blood, held off on getting PTH in the first few weeks because I knew what I had to do and would not be able to do much more
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Initial recs- based on clinical status
• After less than one month, XR noted concern for altered bone
mineralization with metaphyseal irregularities which commented
may relate to rickets
• First fracture identified a few weeks later in upper extremities with
fraying
cupping/fraying at growth plates. concern for underlying bone
disorder; noted mild periosteal reaction of left ulna and possibly
distal humeri
healing fracture). Periosteal
reaction bilateral distal humeri.
• Finally reached enough enteral feeds of fortified donor breastmilk to start enteral Ca (20-40mg/kg) and phos (15-25mg/kg)
• Once over 35 weeks and growth still challenging despite giving 27cal/oz → transitioned to preterm formula and off Donor breastmilk entirely (why?)
• Increased Ca supplements twice based on PTH but did not need to increase Phos.
• Increase vit D delivery to account for repeated insufficient levels
• Recently able to discontinue Phos supplement but continued Ca
• Vit D supplementation increased from 1200 units to 1600 units after 8/30 Vit D level not improved (formula providing just over 1000 units) → total of 2600 units
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Lab Ref range
Ca 9 - 11 mg/dL 9.1 8.5 9.6 9.1 9.1 9.8 10.2 10.4
Phos 5.5-6.5 mg/dL 1.0 4.2 4.9 5.2 5.8 5.9 6.2
Alk phos 150-420 U/L 520 424 376 433
(7/30)
Vit D25OH > 30 ng/dL 43 22 22
• While here, continue to follow labs weekly or every 2 weeks
• Follow up on Vit D level
• Inquire about XRs
closer to d/c
• Determine if Ca supplementation still needed and when to reduce
Vit D supplements
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and aggressive nutrition interventions when decreased
mineralization is noted, MBD can be attenuated
• PTH levels should be considered when dealing with altered
bone health or metabolic bone disease in high risk infants
• Dietitians have an obligation to move our field forward and
learn more about labs we may not be comfortable/familiar
with
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Takeaways
Ehrenkranz RA, Dusick AM, Vohr BR, et al. Growth in the neonatal intensive care unit influences neurodevelopmental and growth outcomes of
extremely low birth weight infants. Pediatrics 2006; 117:1253–1261.
Miller J, Makrides M, Gibson RA, et al. Effect of increasing protein content of human milk fortifier on growth in preterm infantsborn at <31 wk
gestation: a randomized controlled trial. Am J Clin Nutr 2012; 95:648–655.
Finch C. Review of trace mineral requirements for preterm infants: what are the current recommendations for clinical practice? Nutr Clin Pract.
2015;30:44–58
Arslanoglu S, Moro GE, Ziegler EE. Preterm infants fed fortified human milk receive less protein than they need. J Perinatol2009; 29:489–492
Texas Children’s Hospital. Texas Children’s Hospital Pediatric Nutrition Reference Guide. 11th ed. Houston, TX: Texas Children’s Hospital; 2016
Abrams, S. A. and the Committee on Nutrition. Pediatrics 2013; 131;e1676
Bozzetti, V., Tagliabue, P. Metabolic Bone Disease in Preterm Newborn: an update on nutritional issues. Italian Journal of Pediatrics 2009 , 35:20
Moreira, A, Jacob, R., Lavender, L., Escaname, E. Metabolic Bone Disease of Prematurity. NeoReviews 2015; 16; e631
Rustico, S. E., Calabria, A. C. and Garber, S. J. (2014). Metabolic bone disease of prematurity. Journal Of Clinical & Translational Endocrinology, 1(3),
85-91
Gómez-Alonso, C. Paediatric Metabolic Bone Disease: A Lifetime Ahead. Adv Ther 37, 38–46 (2020). https://doi.org/10.1007/s12325-019-01174-3
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