Osteopenia//Rickets of Prematurity (OOP)
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Osteopenia//Rickets of Prematurity Articles:

• Osteopenia//Rickets of Prematurity (OOP)
  
  
  1) Osteopenia of prematurity
  Annu Rev Nutr. 1994;14:169-85, Greer FR Departments of Pediatrics and Nutritional Sciences, University of Wisconsin, Madison, Wisconsin, 53792
  
  Page 169: "In growing low birth-weight (LBW) infants (birth weight less than 1500 g and less than 32 weeks gestational age), it occurs almost always without exception. This high incidence is not surprising since considering that 80% of fetal skeletal mineralization takes place during the last trimester of pregnancy. Thus one would expect an increasing degree of osteopenia in premature infants with decreasing gestational age. Page 170: "Fractures may also occur in osteopenic premature infants, with or without radiologic features of rickets." Page 173: "The incidence of rickets or fractures is also incresed in infants fed unsupplemented human milk or soy formulas." Page 176: "Because these infants are non-weight bearing, the more obvious clinical signs of rickets are not evident." They report on a few clinical cases of OOP.
  
  Case 1: Page 170: "An xray of the arm revealed cupping and flaring of the distal left radial and ulnar metaphases diagnostic of rickets but found no indication of trauma." Case 2: Page 171: "A routine chest x-ray revealed 11 healing rib fractures as well as severely dimineralized bones." Case 3: Page 172: "A routine postoperative chest radiograph revealed multiple rib fractures." "At 13 weeks a left tibial fracture as well as a healing fracture of the right radius were diagnosed with Xray." Laboratory blood serum results: All 3 cases had high elevations of 1,25-dihydroxyvitamin D and Alkaline Phosphatase and a moderate deficiency in Phosphorus. They were all diagnosed with OOP and were given calcium and phosphate supplements and did not experience further fractures.
  
  Page 173: "Even term infants may have decreased stores owing to maternal complications such as severe preeclampsia with fetal growth retardation and placental insufficiency." "This problem is present even in the stable, relatively healthy, growing premature infant. For these infants, mature human milk containing 25-35 mg/dl of calcium and 10-15 mg/dl of phosphorus simply does not contain enough minerals to support skeletal growth at the intrauterine rate." Page 176: "Several medicines have been associated with increased calcium losses in premature infants. These include the diuretics furosemide and aldactone.
  
  2) Osteopenia of Prematurity: A Preventable Disease
  J of Perinatology Vol. VI No. 1, 1984, pages 27-32, Alkaly A, Pomerance J, Edelstein S Division of Neonatology, Department of Pediatrics, Cedars-Sinai Medical Center, Los Angeles, California
  
  Page 27: "Osteopenia of Prematurity (OOP) is a metabolic bone disease, associated with decreased bone mineral content (BMC) in premature infants. Although in ,most cases OOP is subclinical, overt rickets and or bone fractures may develop. The disease may occur as a result of three main causes: 1) deficient intake of vitamin D; 2) decreased hydroxylation of vitamin D to 25-hydroxy vitamin D and 1.25-dihydroxy vitamin D; and 3) decreased intake of calcium and phosphorus." "Maternal deficiency of vitamin D as well as toxemia od pregnancy. May contribute to the development of osteopenia in the infant due to a reduced supply of calcium, phosphorus, and Vitamin D to the fetus." Page 28: "Decreased absorption of vitamin D secondary to impaired absorption of fat or inability to maintain adequate intestinal bbile acid concentration in preterm infants may also lead to vitamin D deficiency. The American Academy of Pediatrics recommends an additional 400 IU of vitamin D be given daily to premature infants irrespective of growth rate and mineral and vitamin D content of the formula." "Balance studies of Similac Special Care indicate that Ca retention rates are comparable to fetal accretion rates and approximate it for P." "It appears that the major cause of osteopenia in VLBW infants receiving adequate daily vitamin D supplementation is deficient Ca and P."
  
  Page 29: "A useful and simple grading of skeletal radiographic rangings in preterms with osteopenia is as follows: Grade 1. Loss of dense white line of metaphyses, increased submetaphyseal lucency, and thinning of cortex. Grade 2. Changes of Grade 1 plus irregularity and fraying of metaphyses, with splaying and cupping. Grade 3. Changes of Grade 2 plus evidence of fractures. Optimally to achieve greater objectivity, the above assessment should be done by two radiologists who have no knowledge of the clinical and biochemical data of the infants. Most preterms with osteopenia have skeletal changes consistent with Grade 1."
  
  Page 30: "In recent years, rickets of prematurity frequently have been prevented by use of formulas fortified with Ca and P. Balance studies of Similac Special Care, and to a lesser extent Enfamil Premature Formula, have shown them to meet the theoretic requirements of Ca, and to approximate it for P." Iif breast milk is used, supplementation of Ca and P should be provided."
  
  Page 31: "Furosemide therapy is known to casue hypercalciuria and renal calcification in preterm infants." "Therefore it may be of value, in infants receiving furosemide therapy, to add chlorothiazide treatment, because of its anticalcuric effect. Abdominal ultrasonography for early detection od renal calcification may be indicated in these infants." (Page 2 of 3)
  
  3) Reports of osteopenia/rickets of prematurity are on the increase because of improved survival rates of low birthweight infants.
  J Emerg Med. 2002 Oct;23(3):305-6, Caksen H, Ozturk A, Kurtoglu S, Tuncel M.
  
  Page 305: "The main etiologic factor is insufficient phosphorus supplementation. However, the etiology is multifactorial and also includes calcium deficiency, vitamin D deficiency, certain drugs, aluminum loading, and immobilization." "A 2 month-old boy was admitted to our emergency Department with respiratory distress, dyspnea, and cyanosis. He was the product of a 30-week preterm gestation and labor." "The extremity X-ray showed osteopenia, and cupping and fraying of the distal ends of the radius and ulna, and fracture of the middle one-third of the right femur." "Clinical rickets has been a recognized complication of prematurity for over 40 years, and now has a reported incidence of up to 13% in infants weighing less than 1500 g at birth and born before the 35th week of gestation." Page 306: "Also, 24% of infants with a birth weight less than 1500 g have fractures." "Amir et. Al noted that fractures not related to birth trauma were diagnosed in 1.2% of preterm infants between the 24th and 160th day of life. In their study they reviewed 12 preterm infants with fracture and observed that most of the infants may have suffered from bone loss associated with low intake of calcium and phosphorus." "We thought that rickets of prematurity developed because of insufficient phosphorus and vitamin D supplementation in our infant. Based on this case, we would like to emphasize that routine vitamin D and mineral supplements should be given routinely to premature infants."
  
  4) A 3-month-old baby with multiple fractures.
  Am J Orthop 1997 Oct;26(10):713-5, Peh WC, Brockwell J, Gilula LA
  
  Page 713: "A 3-month old baby boy was incidentally noted to have multiple rib fractures on his chest radiograph. He was born prematurely at 31 weeks gestation, weighing only 980 g at birth." Page 714: "The chest radiograph shows multiple right-sided rub fractures with expansion of the anterior ends of all the ribs." "There is periosteal reaction at the right humeral shaft. The proximal metaphyses of both humeri are flared and indistinct in outline, with metaphyseal spurring. Radiographs of the right forearm and left femur show similar features of flared and indistinct metaphyses, general blurring of the bony cortices, and transverse midshaft fractures." "Calcium and phosphorus supplements were added to his parental diet. The fractures healed three weeks later."
  
  "The characteristic radiographic features of rickets are most apparent in the regions of the most active growth ­ that is, around the growth plate." "The earliest specific change is slight axial widening of the growth plate, followed by decrease in density at the zone of provisional calcification of the metaphysis." "Disorganized cartilage cell growth in the zone of the maturation produces joint swelling because of bulky growth plates, as well as the "rachitic rosary" deformity at the costochondral junctionsof the middle ribs. Other typical sites affected include the distal femur, proximal humerus, both ends of the tibia, and the distal ends of the radius and ulna."
  
  5) Increments in whole body bone mineral content associated with weight and length in pre-term and full-term infants during the first 6 months of life.
  Arch Med Res 2001 Jul-Aug;32(4):288-92, Avila-Diaz M, Flores-Huerta S, Martinez-Muniz I, Amato D.
  
  Abstract: BACKGROUND: The objective of the present study was to assess bone mineral content (BMC) of the whole skeleton in pre-term and full-term healthy infants and the factors influencing BMC, such as bone area, birth weight, birth length, current weight, current length, gender, and gestational age. METHODS: Forty-eight healthy full-term infants and 34 healthy premature infants fed predominantly with intact human milk were studied. BMC was measured monthly with dual energy X-ray absorptiometry (DEXA). At the same time, length and weight were measured and registered. Pre-term infants were studied at 60-day intervals. RESULTS: For both full-term and pre-term infants, BMC increased during the first months of life. However, the values of pre-term infants never reached the values of full-term infants, even after correcting for age and weight. For both full-term and pre-term infants, BMC was significantly correlated at the second month with birth weight (r = 0.901), birth length (r = 0.860), gestational age (r = 0.803), bone area (r = 0.960), current weight (r = 0.920), and current length (r = 0.840, p <0.001 for all correlation coefficients). Multivariate analysis revealed that bone area was the most important factor in predicting BMC. CONCLUSIONS: Pre-term children have lower BMC than full-term children. The main factor explaining this apparent osteopenia is bone area. Pre-term children have a higher daily mineralization rate than full-term children, but this catch-up mineralization is not enough to reach BMC levels seen in full-term children.
  
  6) The bone disease of preterm birth: a biomechanical perspective.
  Pediatr Res 2003 Jan;53(1):10-5, Miller ME. Department of Pediatrics, Wright State University School of Medicine, Dayton, OH 45404, U.S.A. srmmem@aol.com
  
  Abstract: "The bone disease of preterm birth has traditionally been explained by a decrease in bone formation from insufficient availability of calcium and phosphorus. However, there is emerging evidence that there is increased bone resorption in the bone disease of preterm birth, an observation that indicates some other explanation for this condition. The biomechanical model of postnatal bone formation states that, through a regulatory feedback system in the bone called the mechanostat, bone is able to respond to increased bone loading by increasing bone strength and to decreased bone loading by decreas ing bone strength. It is suggested that this increased bone resorption in the markedly preterm infant compared with the term infant is secondary to decreased bone loading. Application of this model to the fetus and preterm infant suggests that intrauterine bone loading of the fetus from movement and kicking against the uterus is critical for normal fetal bone formation. The associated muscle growth from this activity also contributes to bone loading. The markedly preterm infant is deprived of much of this critical time period of intrauterine bone accretion, and bone formation occurs in the less favorable extrauterine environment, where there is significantly less bone loading."
  
  Page 10: "The mean age of diagnosis of fractures in one series of preterm infants with fractures was 76 days and the types of fractures included long bone, rib, and metaphyseal fractures." "Contributing factors to the bone disease of preterm birth include chronic illness, prolonged hyperalimentation, bronchopulmonary dysplasia, and the use of hypercalciuric drugs such as furosemide for treatment of bronchopulmonary dysplasia,methylxanthines for treatment of apnea and bradycardia, both of which increase calcium losses."
  
  7) Osteopenia of prematurity: the cause and possible treatment.
  J Pediatr 1980 Mar;96(3 Pt 2):528-34 , Steichen JJ, Gratton TL, Tsang RC.
  
  Abstract: By photon absorptiometry, extrauterine bone mineralization in low-birth-weight infants fed a standard commercial formula lags significantly behind intrauterine bone mineralization. In the present study, infants of 28- to 32-week and 33- to 35-week gestational age were studied. The calcium content in a standard formula was increased to provide a daily calcium intake of 220 to 250 mg/kg/day. Phosphate intake was 110 to 125 mg/kg/day. Extrauterine bone mineralization by photon absorptiometry appeared to approximate the intrauterine bone mineralization rate.
  
  Page 528: A recent study at the University of Cincinnati College of Medicine has shown that extrauterine bone mineralization lags significantly behind intrauterine bone mineralization in low-birth-weight infants fed currently available propietary formula." "It is suggested that currently available infant formulas or breast milk fail to supply adequate mineral for optimal bone mineralization in the low-birth-weight premature infant." Page 533: "Osteopenia appears to be due mainly to mineral deficiency. By increasing the calcium and phosphorus content in formulas for low birth weight infants to provide about 220 to 250 mg of Ca/100 cal (and half the amount as P), the calcium intake in about double the estimated intrauterine calcium accretion rate during the last trimeser. The increased Ca and P intake appears to provide suficient mineral to allow for postnatal bone mineralization to approximate the intrauterine bone mineralization rate."