Metabolic Bone Disease Of Prematurity Research Articles

Metabolic bone disease in low birth weight babies between 1500 and 2000 g on exclusive breast feeding

Background: Metabolic bone disease of prematurity due to reduced bone mineralization is mostly described in infants of less than 1500 g. Although various guidelines recommend calcium and phosphate supplementation for low birth weight (LBW) newborns less than 1500 g and on exclusive breast feeding but there are no guidelines for those weighing above 1500 g and on exclusive breast feeding. Moreover, there is insufficient data on incidence of rickets and serum biochemical status in these babies of birth weight more than 1500g and on unsupplemented breast feeding and among term growth retarded babies. Objectives: To determine the incidence of rickets and changes in biochemical profile including serum calcium, phosphate, and alkaline phosphatase in preterm appropriate for gestational age (PTAGA) and term small for date (TSFD) babies with birth weight between 1500 and 2000 g and on unsupplemented breast feeding. Materials and Methods: It is an observational cohort study done at a tertiary care centre in northern India over a period of one year, including LBW babies between 1500 and 2000 g and on unsupplemented breast feeds. In group I, 116 PTAGA babies with birth weight 1500-2000g and on unsupplemented breast feeds were enrolled and 100 PTAGA babies completed follow up till 6 months. In group II 124 TSFD babies with birth weight 1500-2000 g and on unsupplemented breast feeds were enrolled and 100 TSFD babies completed follow up till 6 months. Biochemical parameters were done at baseline (before discharge) and were followed-up for a period of 6 months. Radiological assessment was done if clinical features of rickets appeared or serum biochemistry was suggestive of rickets. Results: Both groups, of babies, developed progressive decrease in serum calcium and phosphate levels, which was statistically significant as shown by time trend. Serum alkaline phosphatase showed significant increase from baseline in both the groups. Fourteen out of 200 (7%) babies developed radiological rickets at end of 3 months, which increased to 34/200 (17%) at end of 6 months. Serum alkaline phosphatase showed most consistent correlation with occurrence of rickets. Conclusion: LBW babies 1500-2000 g and on exclusive breast feeding are at significant risk of developing metabolic bone disease including rickets and need extra supplementation with calcium and phosphate besides Vitamin D.

Metabolic Bone Disease and Bone Mineral Density in Very Preterm Infants

To evaluate bone mineral density (BMD) in preterm neonates at discharge and identify the optimum cutoff values for serum alkaline phosphatase (ALP) and phosphorus (P) concentrations to diagnose the severity of metabolic bone disease of prematurity. A total of 336 preterm neonates (≤ 31 weeks' gestation and birth weight ≤ 1500 g) were prospectively evaluated for BMD before discharge using dual-energy X-ray absorptiometry. BMD reference values (at ALP ≤ 500 IU/L) were measured in 279 patients. BMD was classified as poor (<10th percentile) at <0.068 g/cm(2), fair (10th-25th percentile) at 0.068-0.081 g/cm(2), good (25th-75th percentile) at 0.081-0.112 g/cm(2), and very good (>75th percentile) at >0.112 g/cm(2). Increased BMD was associated with a higher birth weight, short duration of parenteral nutrition, and the absence of small for gestational age status, patent ductus arteriosus, intraventricular hemorrhage, and other clinical variables. Metabolic bone disease of prematurity was absent (ALP ≤ 500 IU/L) in 279 cases (83.0%), mild (ALP >500 IU/L and P ≥ 4.5 mg/dL) in 46 cases (13.7%), and severe (ALP >500 IU/L and P <4.5 mg/dL) in 11 cases (3.3%). A BMD >0.068 g/cm(2) at discharge indicated a 90.3% probability of not developing metabolic bone disease of prematurity. The factors independently associated with increased BMD included higher birth weight, short duration of parenteral nutrition, absence of intraventricular hemorrhage, exclusive feeding of fortified breast milk, and older age at discharge.

Severe metabolic bone disease of prematurity following a brief period of continuous veno-veno haemofiltration (CVVH)

Severe metabolic bone disease of prematurity following a brief period of continuous veno-veno haemofiltration (CVVH)

Does transient hypothyroxinemia influence metabolic bone disease of prematurity?

Objective: To investigate the relationship between Metabolic Bone Disease (MBD) and Transient Hypothyroxinemia of Prematurity (THOP).Method: One hundred twenty-four infants, born in Marmara University Hospital with a gestational age ≤34 weeks, were enrolled. Clinical features were recorded. Serum TSH, free T4, total T4, calcium, phosphorus and total Alkaline Phosphatase (ALP) levels were determined in the first and third postnatal weeks. MBD was defined as a phosphorus level <4.5 mg/dl and/or ALP >900 IU/l. THOP was defined as a serum free and/or total thyroxine level lower than −1 SD for gestational age at the 7th postnatal day.Result: THOP was diagnosed in nineteen (15.3%) patients. MBD was diagnosed in 52 (41.9%) at the 3rd month. Low birth weight, low gestational age and prolonged parenteral nutrition were associated with MBD. Multivariate analysis documented a significant relationship solely between MBD and gestational age.Conclusion: The risk of MBD does not increase significantly in babies with THOP.

Severe metabolic bone disease of prematurity following continuous veno-veno haemofiltration

Searchable abstracts of presentations at key conferences on calcified tissues ISSN 2052-1219 (online)

Occult Rib Fractures: Defining the Cause

The probability of physical abuse (PA) is high in children with occult rib fractures. Other causes include non‐intentional trauma, post surgery and cardiopulmonary resuscitation. Bone fragility increases the risk of fractures, namely metabolic bone disease of prematurity (MBDP), osteogenesis imperfecta, rickets and rare metabolic bone diseases.‘Occult rib fractures have a high probability of physical abuse’This case series describes 61 children under two years of age with rib fractures and associations with clinical and radiological features and aetiology. There were 20 cases of PA, 11 post surgical and three non‐intentional trauma. Two cases had fractures following cardiopulmonary resuscitation, 18 MBDP and one metabolic bone disease. In six cases, the cause remained unknown. The number and distribution of rib fractures and the age of infants did not discriminate between MBDP and PA. Fractures were predominantly posterior, postero‐lateral or lateral. All cases of MBDP had a gestational age of 31 weeks or less and birth weight &lt; 1.25 kg. Each child with MBDP had at least one additional risk factor. Chronic lung disease was recorded in seven, prolonged total parenteral nutrition in ten, steroid use in four, furosemide medication in eight and necrotising enterocolitis in three. All PA cases had other associated injuries or signs of neglect.We recommend a comprehensive assessment of infants with occult rib fractures including an examination to exclude associated trauma, a child protection assessment and a full clinical assessment to exclude risk factors for co‐existing bone fragility. Copyright © 2013 John Wiley &amp; Sons, Ltd.Key Practitioner Messages: The number and distribution of rib fractures and the age of infants do not discriminate between PA and rib fractures seen in MBDP. Assessment of infants with occult rib fractures should include an examination to exclude associated trauma, a child protection assessment and a full clinical assessment to exclude risk factors for co‐existing bone fragility.‘An examination to exclude associated trauma, a child protection assessment and a full clinical assessment’

Metabolic Bone Disease of Prematurity

Preterm infants are at significant risk of reduced bone mineral content and subsequent bone disease, variably termed osteopenia of prematurity or neonatal rickets. The prevalence varies depending on gestation, occurs up to 30% of Korean extremely low birth weight infants (ELBW). The etiology is multifactoreal: inadequate nutrient intake, prolonged parenteral nutrition, chronic co-morbidities and immobilization. In Korean ELBW infants, rickets of prematurity was significantly increased by 18 times with severe parenteral nutrition associated cholestasis, and by 3 times with moderate/severe bronchopulmonary dysplasia. Prolonged hospitalization with ventilator care could lead to lack of physical activity and muscle contraction against resistance in preterm infants, which may increase bone resorption and demineralization, resulting in osteopenia. Low serum P and high alkaline phosphatase (ALP) are suggestive of metabolic bone disease. In Korean ELBW infants, increased serum ALP (>495 IU) at the age of 5 weeks has a 81% of sensitivity and 87% of specificity for radiographic rickets. An early nutritional intervention can reduce both the prevalence and the severity of osteopenia. Provision of adequate nutrition including energy, protein and minerals, and passive physical exercise during first weeks of life may prevent abnormal bone remodeling activity in preterm infants. Early detection by vigorous monitoring of bone homeostasis and prompt treatment of osteopenia are warranted in these high-risk infants. This review is to focus on the recent advances in the understanding of bone metabolism in preterm infants and on the therapeutic approach to prevent and to treat metabolic bone disease of prematurity.

Bone Mineral Density and Osteoporosis after Preterm Birth: The Role of Early Life Factors and Nutrition

The effects of preterm birth and perinatal events on bone health in later life remain largely unknown. Bone mineral density (BMD) and osteoporosis risk may be programmed by early life factors. We summarise the existing literature relating to the effects of prematurity on adult BMD and the Developmental Origins of Health and Disease hypothesis and programming of bone growth. Metabolic bone disease of prematurity and the influence of epigenetics on bone metabolism are discussed and current evidence regarding the effects of breastfeeding and aluminium exposure on bone metabolism is summarised. This review highlights the need for further research into modifiable early life factors and their effect on long-term bone health after preterm birth.

Physical Therapy Reduces Bone Resorption and Increases Bone Formation in Preterm Infants

To evaluate bone metabolism in newborn preterm infants before and after a physical therapy protocol. This randomized controlled clinical trial included 30 newborn preterm infants with gestational age ≤ 35 weeks and appropriate weight for gestational age, who were randomized into control group (CG) and physiotherapy group (PG). The PG protocol consisted of 15 minutes of daily passive movements with gentle joint compression 5 days a week. Daily data were obtained on feeding and body weight. Measurements of bone-specific alkaline phosphatase (BAP) and urinary deoxypyridinoline (DPD) were collected before and after intervention in both groups. The analysis of covariance test was performed to compare the means of both groups. At baseline, gestational age and corrected gestational age, birth weight, and gender were similar between both groups. Nutrient supply, length of total parenteral nutrition, and mechanical ventilation were also similar. BAP level increase in PG was 22.44 ± 3.49 U/L, whereas in CG was 2.87 ± 3.99 U/L (p = 0.003). There was a reduction of DPD levels in PG of 28.21 ± 11.05 nmol/mmol, and an increase of 49.95 ± 11.05 nmol/mmol (p < 0.001) in GC. The benefits of prevention and treatment of metabolic bone disease of prematurity, in addition to an adequate diet, should include these passive exercises with gentle joint compressions to improve the quality of premature infant's bones.

Three Different Causes of Hypercalciuria

Hypercalciuria is defined as urinary calcium excretion ≥0.1 mmol/kg/24 h, and can be a result of various disease states. The most frequent clinical signs of hypercalciuria include hematuria, abdominal pain, urolithiasis, nephrocalcinosis, dysuria, enuresis, and urinary tract infection. 3 case reports of children with hypercalciuria of different origin are presented, with final diagnoses of (1)idiopathic hypercalciuria, (2)familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC), and (3)metabolic bone disease of prematurity, respectively. Assessment of hypercalciuria is essential in all children with urolithiasis and nephrocalcinosis, or demineralization of bone. It should be also a part of differential diagnostic procedure in hematuria, recurrent abdominal pain, urinary tract infection and enuresis in childhood.

Metabolic bone disease of prematurity and secondary hyperparathyroidism

To illustrate, via case histories, the importance of laboratory investigations for the early diagnosis and management of metabolic bone disease (MBD). We report three cases of extreme premature infants with MBD. These three infants had several risk factors for MBD of prematurity: very low birthweight, delayed enteral feeds, cholestatic liver disease, intolerance of fortification, the use of glucocorticoids and diuretics. Serum alkaline phosphatase and parathyroid hormone (PTH) were elevated despite relatively normal calcium and phosphate levels. These parameters were corrected with additional supplementation of calcium, phosphate and vitamin D. Infants born extremely prematurely have significant calcium and phosphate depletion by the time they reach full term compared with the normal fetal accretion rate. This is exacerbated if there is poor tolerability to feeds where extra calcium and phosphate could not be added either by additives or via human milk fortifier. Serum calcium and phosphate levels may be normal despite inadequate intake or stores due to the counter-regulatory effect of PTH. In infants at risk of MBD, testing serum alkaline phosphatase, vitamin D and PTH with calcium and phosphate may assist in the monitoring and management of MBD.

Fisioterapia motora no tratamento do prematuro com doença metabólica óssea

OBJETIVO: Revisar o papel da fisioterapia motora no prematuro com risco de desenvolver doença metabólica óssea. FONTES DE DADOS: Trata-se de uma revisão de literatura publicada entre 1986 e 2009, utilizando as seguintes palavras-chave: prematuro, calcificação fisiológica, modalidades de fisioterapia, doenças ósseas metabólicas e os respectivos descritores no idioma inglês. Foram selecionados 29 artigos científicos, via PubMed e ISI Web, além de um capítulo de livro nacional. SÍNTESE DOS DADOS: As doenças ósseas metabólicas compreendem um conjunto de condições relacionadas a alterações no processo de calcificação fisiológica, levando desde à fragilidade estrutural até ao desenvolvimento de fraturas. A aplicação rotineira de exercícios de mobilização passiva articular, massagem e posicionamento está relacionada ao ganho ponderal, ao aumento na densidade e no conteúdo mineral ósseo. CONCLUSÕES: A implementação de exercícios de fisioterapia motora parece proporcionar estabilidade ou estímulo para a formação óssea, podendo, consequentemente, prevenir e/ou minimizar as complicações decorrentes da doença metabólica óssea.

Metabolic Bone Disease of Prematurity

The incidence of metabolic bone disease (MBD) in preterm infants has been declining due to advances in nutritional care. Although the terms osteopenia and rickets have been used in the literature, MBD of prematurity is the preferred terminology for this condition. Despite the use of human milk fortifiers and commercial infant formulas specified for this population, MBD remains an important cause of morbidity in preterm infants. This review focuses on the physiology of intrauterine bone growth, the development of MBD in preterm infants, the various risk factors for MBD, pitfalls in diagnosis, prevention, and treatment of MBD. The use of speed of sound (SOS) ultrasonography and dual-energy X-ray absorptiometry (DXA) in the diagnosis, management, and prognosis also is discussed.

Effect of different doses of vitamin D on osteocalcin and deoxypyridinoline in preterm infants

Metabolic bone disease of prematurity is a common problem in preterm infants. The aim of the present paper was to measure the effect of vitamin D, in order to see the relation between vitamin D and urinary excretion of deoxypyridinoline (DPD), serum osteocalcin (OC), calcium (Ca), inorganic phosphorus (P), and alkaline phosphatase (ALP). Three different doses of vitamin D, 200 IU/kg (group 1, 11 infants), 400 IU/kg (group 2, 15 infants) and 800 IU/kg bodyweight/day (group 3, 11 infants), were administered to a total of 37 preterm infants between 15th day of birth until the 30th day of birth. There were no significant differences in levels of serum Ca and P before and after vitamin D supplementation in all groups. Serum ALP levels were increased in all but significantly only in groups 1 and 3. Serum OC levels were also increased in each group by the treatment. Urinary DPD excretion was increased gradually by the increase in vitamin D intake, but it was significant only in group 3. High dose of vitamin D supplementation might accelerate bone turnover and increased urinary DPD levels might reflect increased bone resorption. To the best of the authors' knowledge this is the first study comparing the effects of different vitamin D dose, by the means of urinary collagen cross-links, on bone turnover in preterm infants.

Bone disease in preterm

The survival rate of premature infants has significantly increased during the last few decades. As a consequence, new disorders such as osteopenia of prematurity have been emerging. We report 6 month evolution from diagnosis to recovery of a patient with metabolic bone disease of prematurity who showed a remarkable improvement on therapy with phosphate, calcium and vitamin D.

Quantitative Ultrasound in the Evaluation of Bone Status in Premature and Full-Term Infants

Metabolic bone disease of prematurity (MBDP) is a common and significant problem that often gives rise to osteopenia, fractures, osteomalacia, and osteoporosis. The purpose of our study is to establish normative data on bone status in premature and full-term infants to help future studies on MBDP. Bone status was prospectively determined as part of a multicenter study among newborns within 96 hours of life. The patients were divided into 2 groups: group 1 included those neonates 25-36 wk gestational age (premature), and group 2 neonates were born at 37-42 wk gestational age (full term). Demographic data were collected. The Omnisense 7000 Bone Sonometer (Sunlight Medical Ltd., Tel-Aviv, Israel) was used to determine the speed of sound (SOS) through the mid tibia, which reflects bone strength. A total of 235 patients were enrolled in this study. Group 1 (i.e., the premature infants) had a statistically lower age-adjusted SOS as compared with group 2 (i.e., the full-term infants) (analysis of variance; p=0.001). There was also a correlation between SOS and birth weight (r=0.3; p<001). This study represents the largest database of normative data for bone status measuring in preterm and term infants.

Tibial Speed of Sound in Term and Preterm Infants

The tibial speed of sound (SOS) was measured in 91 healthy singleton infants between 31 and 42 weeks of gestation and 12 sick preterm infants. In healthy infants, the tibial SOS was associated with corrected gestational age (r = 0.40, p < 0.001) but not birth weight. The median tibial SOS in 12 sick preterm infants (2,772, range 2,566–2,934 m/s), whose corrected gestational age was between 31 and 42 weeks, was lower (p < 0.001) than that of 69 healthy gestation-matched healthy infants (3,100, range 2,870–3,381 m/s). Tibial SOS measurements may allow radiation-free assessment of metabolic bone disease of prematurity.

Bone isoenzyme of serum alkaline phosphatase and serum inorganic phosphate in metabolic bone disease of prematurity

We wanted to improve detection of low bone mineral density in preterm infants by combining serum measurements of total alkaline phosphatase, its bone-type isoenzyme and serum inorganic phosphate in a prospective design. The subjects were 43 preterm infants. Total and bone isoenzyme activity of alkaline phosphatase was determined at 3 wk chronological age and at 3 and 6 mo corrected age. The main outcome measure, apparent bone mineral density (BMAD) at the distal forearm and forearm shaft, was assessed by dual energy X-ray absorptiometry at 3 and 6 mo corrected age. An apparent density below 95 mg/cm3 at 3 mo corrected age was considered to indicate bone disease, based on the distribution of BMAD values of children with non-complicated courses of prematurity. At 3 mo corrected age, total alkaline phosphatase activities exceeding 900 IU/l revealed low bone mineral density with 88% sensitivity and 71% specificity. Measurements of bone isoenzyme activity did not improve diagnostic performance. Serum inorganic phosphate levels below 1.8 mmol/l reflected low bone density with high specificity (96%), but the sensitivity was only 50%. A combination of the criteria "serum total alkaline phosphatase activity above 900 IU/l" and "serum inorganic phosphate concentrations below 1.8 mmol/l" yielded a sensitivity of 100% at a specificity of 70%. This was the best available screening method for low bone mineral density in preterms.

Bone isoenzyme of serum alkaline phosphatase and serum inorganic phosphate in metabolic bone disease of prematurity

Bone isoenzyme of serum alkaline phosphatase and serum inorganic phosphate in metabolic bone disease of prematurity

Metabolic bone disease of prematurity.

Metabolic bone disease is recognized with increasing frequency in very-low-birth-weight infants. Radiological changes characteristic of rickets have been found in 55% of infants with a birth weight of less than 1000 g and in 23% of infants weighing less than 1500 g at birth. Twenty-four per cent of infants with a birth weight of less than 1500 g have fractures. The main aetiological factor is insufficient phosphorus supplementation. The aetiology is, however, multifactorial and also includes calcium deficiency, vitamin D deficiency, certain drugs, aluminium loading and immobilisation. The method of choice in detecting subclinical mineral bone disease of prematurity is measurement of bone mineral density, but there is as yet no single good diagnostic method available for premature infants. The optimal mineral and vitamin D requirement of the premature infant must be established so that proper recommendations can be given. The current recommended vitamin D dose in Europe (ESPGAN 800-1000 IU/day) is probably too high when extra minerals are supplied. Moreover, the duration of mineral supplementation may need to be continued until the infant has reached a body weight of 3.5 kg. This article deals with the aetiology, pathogenesis, diagnosis and future prospects of metabolic bone disease of prematurity.