Effects of Gestational Age, Maternal Diabetes, and Intrauterine Growth Retardation on Markers of Fetal Bone Turnover in Amniotic Fluid

Little is known about the dynamics of bone formation and bone resorption in utero, particularly the normal changes that occur throughout gestation and in clinical situations that result in low bone mass at birth. The objectives of this study were to describe the effects of gestational age on markers of fetal bone turnover, and to investigate whether the reported low bone mass at birth in small-for-gestational-age (SGA) infants and infants of diabetic mothers (IDMs) was associated with biochemical markers of decreased bone formation or increased bone resorption in utero. Bone formation and resorption were assessed by measurement of carboxyterminal propeptide of type I procollagen (PICP) and cross-linked carboxyterminal telopeptide of type I collagen (ICTP), respectively, in 201 amniotic fluid samples. These markers are by-products of type I collagen formation and degradation, respectively, and have been used in the assessment of bone metabolism ex utero. Both PICP and ICTP concentrations in amniotic fluid were inversely associated with gestational age (P < 0.0001). Amniotic fluid concentrations of PICP increased exponentially in relation to infant birthweight (P= 0.008), and SGA infants had lower amniotic fluid PICP concentrations than controls (P= 0.07). The presence of diabetes in the mother was not associated with alterations in amniotic fluid PICP or ICTP concentrations. Although maturational effects on clearance of bone markers from amniotic fluid cannot be excluded, these data are consistent with a high turnover of bone matrix early in fetal life, and a reduction in bone formation when fetal growth is compromised.     

Assisted Exercise and Bone Strength in Preterm Infants

Studies have previously demonstrated that brief (4 weeks) passive range-of-motion exercise is beneficial for bone development in very low birth weight (VLBW) preterm infants. However, the optimal duration of exercise for bone development in preterm infants is yet unknown. The aim of the present study was to examine the effect of 8 weeks of assisted exercise on bone strength and metabolism in VLBW premature infants. Sixteen infants (mean ± standard error of the mean birth weight 1,009 ± 55 g and gestational age 27.3 ± 0.3 weeks) were randomly assigned into exercise (n = 8) and control (n = 8) groups. The intervention started at the first week of life and involved 8 weeks of daily passive extension and flexion range-of-motion exercise of the upper and lower extremities. Biochemical markers of bone turnover were measured at enrollment and after 8 weeks. Bone strength was measured weekly by quantitative ultrasound measurement of tibial bone speed of sound (SOS). Bone SOS decreased significantly in the control group (−108.1 ± 33.7 m/second, P < 0.0001) during the study period, while remaining stable in the exercise group (11.3 ± 22.8 m/second). The main beneficial effect of exercise occurred in the first 4 weeks of the intervention. There were no significant differences in the bone turnover marker changes between the groups. There is a significant postnatal decrease in bone SOS in VLBW preterm infants. Eight weeks of assisted range-of-motion exercise attenuates the decrease in bone strength and may decrease the risk of osteopenia in premature infants.     

The postoperative response of the term and preterm newborn infant to sodium administration

Twenty surgical newborn infants aged less than 5 days were selected for study to determine the quantity of sodium administered during operation and the subsequent 48 hours, and to determine their response to this sodium load. There were 6 preterm infants with gestational age 35 weeks or less and 14 full-term infants aged more than 35 weeks. Measurements calculated at 12 hourly intervals for 48 hours after operation included sodium intake, sodium excretion, fractional excretion of sodium, and serum sodium. No special guidelines were utilized for fluid management. The mean sodium intake during the 48-hour study period for the term infants was 15.7 mEq/kg, of which 46% was given during the first 12 hours, and for the premature infants was 17.1 mEq/kg, of which 56% was given during the first 12 hours. In the two groups of patients, the amount of sodium given during the first 12 hours was 470% and 480% of their estimated maintenance requirements, respectively. The mean sodium output during the first 12 hours was low in the term group (1.2 mEq/L) and the premature group (1.3 mEq/L), and subsequently increased reaching maximum levels of 2.3 and 2.1 mEq/L, respectively, by 36 hours. The fractional excretion of sodium exceeded 1.0% in 53% of the term and 94% of the preterm infants. During the study period, the mean serum sodium levels exceeded 145 mEq/L (hypernatremia) in 64% of the term and 67% of the preterm infants.(ABSTRACT TRUNCATED AT 250 WORDS)     

Sustained response to intravenous alendronate in postmenopausal osteoporosis

We studied the effects of alendronate (amino-hydroxybutylidene bisphosphonate) on biochemical indices of bone turnover and on lumbar spinal bone mineral density in 15 postmenopausal women with vertebral osteoporosis. Alendronate 7.5 mg daily was administered intravenously as a slow infusion for four consecutive days. Treatment was associated with a significant decrease in serum calcium (p < 0.01), fasting urinary calcium excretion (p < 0.01) and hydroxyproline excretion within several days followed a later decrease in serum alkaline phosphatase activity that showed a significant reduction at two months after treatment (p < 0.05). Serum calcium reverted to pretreatment values by the second week after infusion, but the decrease in alkaline phosphatase, urinary calcium, and hydroxyproline excretion persisted to six months after infusion. There was a 3% mean increase in lumbar bone mineral density at six months (p < 0.01). A transient lymphopenia or leucopenia was noted in eight patients and a short-lived fever in six. No other side effects were observed. This study demonstrates that short-term exposure to high intravenous doses of alendronate induces suppression of bone resorption in osteoporosis that persists for at least 6 months after infusion. We conclude that a short exposure to high intravenous doses induces sustained effects on bone turnover in much the same manner as that observed in Paget's disease of bone.     

Longitudinal evaluation of a bone resorption marker in elderly subjects

The variability over time in the excretion of a hone resorption metabolite (collagen type I N-telopeptide crosslink, NTx) was evaluated in a cohort of community-dwelling elderly men and women (mean age 73 years). Three annual 24-h urine samples were collected. NTx concentration was measured using an established ELISA. Total (24-h) NTx excretion as well as NTx/creatinine concentration were compared. Men had a significantly lower excretion of NTx/creatinine than women who were not on hormone replacement therapy. Overall, the within-subject long-term coefficient of variability for NTx/creatinine was 26%. The correlation coefficient between the samples taken a year apart was higher for the 24-h NTx excretion (r=0.66) than for the 24-h creatinine excretion (r=0.51). The consistency of NTx excretion over time was also evaluated in all 93 subjects with three yearly samples using Kendall’s rank correlation method; the resulting coefficient of concordance was 0.78 (significant at the 0.01 level). These results indicate that while NTx excretion varies in subject samples collected over a period of 2 years, this variability is not much greater than the daily variation reported for NTx and other bone metabolism markers. The relative reproducibility of NTx excretion over time in this age group was also evident in the coefficient of concordance. The results provide support for stratifying subjects according to level of bone resorption and identifying those subjects with high turnover who may be at greater risk of osteoporotic fracture.     

Influence of nutrition on urinary oxalate and calcium in preterm and term infants

  Few data for normal urinary oxalate (Ox) and calcium (Ca) excretion related both to gestational age and nutritional factors have been reported in preterm or term infants. We therefore determined the molar Ox and Ca to creatinine (Cr) ratios in spot urines from 64 preterm and 37 term infants aged 1–60 days, either fed formula or human milk (HM). Only vitamin D was supplemented; renal or metabolic diseases were excluded. Urinary Ox/Cr ratio was higher in preterm than in term infants, both when formula fed (1st month 253 vs. 180 mmol/mol and 2nd month 306 vs. 212 mmol/mol; P<0.05) or HM fed (206 vs. 169 mmol/mol and 283^* vs. 232 mmol/mol; ^* P<0.05). Ox/Cr was also higher in formula- than HM-fed preterm infants. The ratio increased during the first 2 months of life irrespective of nutrition. Urinary Ca/Cr ratio was comparable in all groups during the 1st month of life, except for a lower (P<0.05) value in term infants fed HM (0.10 mol/mol). It increased in all groups during the 2nd month of life, being highest in HM-fed preterm infants (1.86 mol/mol). In conclusion, urinary Ox and Ca excretion is influenced by both gestational age and nutrient intake in preterm and term infants. Received October 2, 1996; received in revised form and accepted April 24, 1997     

Bone status assessment in preterm and term infants by dual-energy X-ray absorptiometry

We assessed the bone status of preterm and term infants by measuring their bone mineral density (BMD) by dual-energy X-ray absorptiometry (DXA). Thirty neonates weighing 699–3590 g were selected as subjects. Infants with multiple anomalies or severe chronic lung disease were excluded. Using the corrected term age (35–48 weeks), we measured their lumbar spinal BMD (L1–L4) by DXA. Alkaline phosphatase (ALP) and skeletal alkaline phosphatase (B-ALP) were measured at the same time. In addition, we compared the BMD values with growth parameters and chemical markers. The term BMD correlated significantly with the birth weight (r = .90), height (r = .85), and gestational age (r = .76). The birth weight correlated more closely with the BMD than with the weight at the time of BMD measurement. The B-ALP level showed an inverse correlation with BMD (r = −0.41). The preterm infants apparently acquired lower BMDs during intrauterine life. The inverse correlation of B-ALP with BMD may be found only in the neonatal period. The BMD measured by DXA and the B-ALP level are very useful parameters for assessing bone status in infants, including extremely low birth weight infants. Received: Aug. 21, 1997 / Accepted: Nov. 6, 1997     

Quantitative Ultrasound Measurements in Premature Infants at 1 Year of Age: The Effects of Antenatal Administered Corticosteroids

The aim of this study was to evaluate the effects of antenatally administered glucocorticoids on bone status of preterm infants at 1 year corrected age. The study population consisted of 32 preterm infants with a gestational age of 24-34 weeks. The infants were divided into two groups according to antenatal exposure to corticosteroids. Quantitative ultrasound (QUS) assessment of bone was performed in the study infants at the corrected age of 1 year. Blood levels of carboxy-terminal propeptide of type I procollagen (PICP) and carboxy-terminal telopeptide of type I collagen (ICTP) were measured at birth and at 1 year corrected age. Levels of PICP and ICTP were significantly lower at birth in corticosteroid-exposed neonates (P < 0.05). At corrected age of 12 months ICTP levels remained significantly lower in corticosteroid-exposed infants, but we found no significant difference in levels of the bone-formation marker PICP between corticosteroid-exposed and nonexposed infants. In the majority of participant preterm infants bone speed of sound (SOS) was within age-adjusted normal values of full-term infants. There was no significant difference in bone SOS between exposed and nonexposed infants at corrected age of 12 months. There was no correlation between SOS and levels of bone markers. The results of our study indicate that, despite the suppression of fetal bone turnover at birth in corticosteroid-exposed infants, antenatal glucocorticoid treatment seems to have no long-term impact on bone status of preterm infants assessed by QUS complementary to measurement of bone-turnover markers at 1 year corrected age.     

婴儿早期骨代谢生化指标与声波速度值和出生后年龄间的关系

目的 探讨婴儿早期骨代谢生化指标与声波速度值和出生后年龄间的关系.方法 采用骨定量超声(QUS)仪对167例出生3月内的婴儿进行胫骨声波速度(SOS)测量.其中包括53例早产儿(胎龄:32.6±2.7周)和114例足月儿(胎龄:39.1±1.2周);同时在部分婴儿中测量血钙、磷、碱性磷酸酶(ALP)和骨碱性磷酸酶(BALP).结果 ①早产儿和足月儿的血钙、磷、ALP和BALP值之间均差异无显著性.②婴儿骨SOS值与ALP呈显著负相关(n=167,r=-0.139,P=0.036)、与BALP也显著负相关(n=32,r=-0.410,P=0.010);SOS值与血钙、血磷及血钙磷乘积无显著性相关.在早产儿中,ALP和BALP与日龄均显著相关,相关系数r分别为0.286(n=53,P=0.019)和0.946(n=7,P=0.001);在足月儿中未发现显著相关性.血磷与日龄呈显著负相关(n=24,r=-0.509,P=0.005).③ALP与BALP高度相关(n=32,r=0.958,P=0.001),BALP占ALP活力的47.3%.早产儿在出生时BALP和Ⅰ型胶原羧基端肽(IcTP)显著正相关(n=36,r=0.768,P=0.001).结论 定量超声技术测量SOS有助于我们评估婴儿早期骨状况;在此横向研究中我们发现骨SOS与骨代谢生化指标之间存在相关性,然而,二者间的纵向关系有待于进一步研究.     

Dose-response effect of short-term calcitriol treatment on bone and mineral metabolism in normal males

To evaluate the effects of short-term treatment with calcitriol on biochemical markers of calcium and bone metabolism, 36 normal male volunteers (aged 21–54 years) were randomized to oral treatment for 7 days with either (A) calcitriol, 1 μg twice daily, (B) calcitrol, 0.5 μg twice daily, or (C) placebo twice daily. Serum calcium increased slightly in a dose-dependent manner (maximal increase 2.5%, p < 0.05) followed by a heavy increase in both 24 h (max. 156.1%, p < 0.001) and fasting urinary calcium excretion (max. 123.1%, p < 0.001), and a striking reduction in serum PTH (max. −43.1%, p < 0.001). Biochemical markers of osteoblast activity and bone formation increased immediately in a dose-dependent manner [serum osteocalcin (max. 37.8%, p < 0.03) and serum procollagen type I C-terminal propeptide (PICP) (max. 26.0%, p < 0.05)], whereas there was no effect on serum bone alkaline phosphatase. Calcitriol treatment had no effect on biochemical markers of bone resorption [serum C-terminal telopeptide of type I collagen (ICTP) and fasting urinary excretion of hydroxyproline/creatinine (OHP)]. Extraosseous collagen matrix synthesis was not affected evaluated by serum procollagen type III N-terminal propeptide (PIIINP). In the follow-up period (15 weeks) no unequivocal changes were observed. The fast and protracted increase in biochemical markers of osteoblast activity and bone formation, without affecting bone resorption and extraosseous connective tissue metabolism points toward a selective effect of calcitriol on bone matrix formation.     

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.     

The response of rat tibiae to incremental bouts of mechanical loading: A quantum concept for bone formation

To investigate the minimum number of loading bouts necessary to produce new lamellar or woven bone formation, and the time required for its initiation, bone formation was measured in 32 retired breeder female Sprague-Dawley rats following one, two, three, or five bouts of applied loading. Bending forces of 54 N were applied to right tibiae using a four-point loading apparatus, and left tibiae served as contralateral controls. Loading was applied as a sine wave with a frequency of 2 Hz for 18 s (36 cycles) per loading bout. Rats were injected with alizarin on day 1 and calcein on days 5 and 12, and were killed on day 19. One bout of loading was sufficient to increase the periosteal woven bone surface (Wb.Pm/B.Pm) from 0% to 40% (p < 0.01), and to 80% after five bouts of loading (p < 0.01), with a dose-response relationship for increases in Wb.Pm/B.Pm (p < 0.0001), mineral apposition rate (Wb.AR; p = 0.002), and bone formation rate (Wb.BFR/BS; p = 0.0001). In the first labeling period (days 1–5), the endocortical lamellar bone forming surface (BS_f/BS) was increased slightly (p < 0.05), but no significant differences were shown for BFR/BS or MAR. From days 5 to 19, right tibiae showed a dose-response increase in BFR/BS (p = 0.002) and BS_f/BS (p = 0.008), but not MAR. These results are consistent with a “quantum” model of bone formation such that a “quantum” of bone cells is activated in response to the loading bout and the strain magnitude dictate the size or microstructural organization of a given packet of new bone. Conversely, the distributed nature of loading may define the recruitment, rather than size, of new packets of bone.     

Urinary vitamin A excretion in very low birth weight infants

Vitamin A (VA) deficiency in very low birth weight (VLBW) infants is associated with an increased risk for disorders related to kidney and lung maturation and function. VA losses through increased urinary retinol (ROH) excretion might contribute to this deficiency risk. The mechanism accounting for ROH loss in the urine has not yet been clarified. The aim of this study was to assess the excretion of ROH, retinol-binding protein 4 (RBP4) and transthyretin (TTR) in urine from VLBW infants in comparison with that in term infants in relation to kidney function. Urine specimens were collected from 15 VLBW infants (birth weight < 1,500 g) as well as from 20 term infants during the first 2 days after birth. ROH in urine was detectable in 14 of the 15 VLBW infants at a median concentration of 234 nmol/g creatinine. In the group of term infants, 17 of the 20 excreted ROH, but at an approximately five-times lower concentration (P < 0.001). Excretion of RBP4 and TTR was also much higher in VLBW infants (both P< 0.001). The urinary ROH excretion in VLBW infants may be related to the impaired tubular handling of its carrier proteins RBP4 and TTR. Thus, ROH excretion might contribute to an increased risk of VA deficiency, especially in VLBW infants.     

Inguinal herniorrhaphy in young infants: Perianesthetic complications and associated preanesthetic risk factors

Study Objectives: (1) To prospectively observe and tabulate all preaanesthetic complications in young infants undergoing herniorrhaphy with general anesthesia and (2) to identify all major postnatal complications and determine which, if any, might be significant risk factors for perianesthetic complications.

Design: Prospective case control study.

Setting: Columbus, Ohio, Children's Hospital, a teaching and tertiary referral center.

Patients: One hundred two consecutive infants 60 weeks postconceptual age (PCA) or younger undergoing herniorrhaphy with general anesthesia.

Interventions: None

Measurements and Main Results: All perionesthetic complications occurring during anesthesia, in the postanesthesia care unit (PACU), during the remaining hospital stay, and within 30 days of anesthesia were recorded, and a detailed postnatal history was compiled. Fifty-five percent of 60 preterm infants [37 weeks gestational age (GA) or younger] and 50% of 42 term infants (older than 37 weeks GA) experienced at least one perianesthetic complication. Following discharge from the PACU, in-house complications were confined to the preterm group. Significant risk factors included a history of apnea, bradycardia, and ventilatory support for at least 24 hours after birth, mainly for respiratory distress syndrome.

Conclusions: In a teaching hospital, prospectively observed preaanesthetic complications can occur in more than 50% of infants 60 weeks PCA or younger undergoing herniorrhaphy with inhalation anesthesia. Infants younger than 49 weeks PCA with a significant preanesthetic risk factor should be monitored overnight for apnea and bradycardia.     

Effect of slow-release sodium fluoride on cancellous bone histology and connectivity in osteoporosis

We have previously demonstrated that a treatment regimen of slow-release sodium fluoride (SRNaF) and continuous calcium citrate increases lumbar bone mass, improves cancellous bone material quality, and significantly reduces vertebral fracture rate in osteoporotic patients. In order to assess whether such treatment also improves trabecular structure, we quantitated cancellous bone connectivity before and following 2 years of therapy with SRNaF in 23 patients with osteoporosis and vertebral fractures. In addition, we performed bone histomorphometry on the same sections used for connectivity measurements. There was a significant increase in L2-L4 bone mineral density during therapy (0.827 ± 0.176 g/cm² SD to 0.872 ± 0.166, p = 0.0004). Significant histomorphometric changes were represented by increases in mineral apposition rate (0.6 ± 0.4μm/d to 1.1 ± 0.7, p = 0.0078) and adjusted apposition rate (0.4 ± 0.3 μm/d to 0.6 ± 0.4, p = 0.016). On the other hand, trabecular spacing significantly declined (from 1375 ± 878 μm to 1052 ± 541, p = 0.05). Two-dimensional quantitation of trabecular struts on iliac crest histological sections disclosed significant increases in mean node number per mm² of cancellous tissue area (0.22 ± 0.12 vs. 0.39 ± 0.27, p = 0.0077), the mean node to free-end ratio (0.23 ± 0.21 vs. 0.41 ± 0.46, p < 0.05), and in the mean node to node strut length per mm² of cancellous area (0.098 ± 0.101 vs. 0.212 ± 0.183, p < 0.01). There were no significant changes in any of the measurements associated with free-end number or free-end to free-end strut length. When patients were divided into those with severe and mild-modest spinal bone loss (based upon initial lumbar bone density) the significant changes in connectivity occurred in patients with mild-moderate bone loss, but not in those with severe bone loss, suggesting that fluoride's effect is in part dependent on the presence of a certain critical amount of bone. This finding in combination with the previously reported increases in bone mass and bone material quality may explain the significant reduction in vertebral fracture rate observed with this particular fluoride regimen.     

Tracheotomy in the first year of life: outcomes in term infants, the Vanderbilt experience.

OBJECTIVE: In an era emphasizing critical care of preterm infants, we characterize the indications and outcomes of tracheotomies performed in the first year of life in term infants compared to preterm infants. METHODS: Retrospective study of 127 tracheotomies performed in the first year of life at a tertiary-care children's hospital between 1988-2004. RESULTS: Mean gestational ages of the term and preterm groups were 38.97 and 29.71 weeks, respectively (P < 0.001). Indications for tracheotomy were upper airway abnormalities in 53% for the term group. The number of subsequent airway procedures required was 1.39 in the term group, achieving decannulation in 36.3%, with a 20.5% mortality rate. CONCLUSION: Compared to preterm infants, the term decannulation rate was favorable, as chronic lung disease was uncommon. However, non-tracheotomy-related mortalities remained high. SIGNIFICANCE: Tracheotomies are often performed for relief of upper airway obstruction, and congenital and acquired comorbidities not related to tracheotomy are associated with adverse outcomes in term infants. EBM rating: C-4.     

Hypercalciuria in ex-preterm children, aged 7-8 years

In a previous study, 8 of 28 ex-preterm infants, aged 4–5 years, had increased urinary calcium excretion. The aim of this study was to confirm this finding and to determine if raised urinary calcium excretion is associated with reduced bone mineralisation. Forty-six ex-preterm children, aged 7–9 years, and 40 age- and sex-matched controls were recruited. The calcium excretion measured from 3 separate 24-h urine collections was recorded and a dietary assessment made from a diary record. Data were retrieved from the neonatal case notes and included aminoglycoside usage. Dual energy X-ray absorptiometry was used to measure bone mineral content and bone mineral density (BMD) in all children. The mean maximum 24-h urinary calcium was significantly higher in the preterm group than the term group (P=0.01). Increased calcium excretion was associated with raised neonatal aminoglycoside levels (P=0.0013). Height standard deviation score and hip BMD were significantly lower in the 21 preterm children with a 24-h urinary calcium above 4 mg/kg per day than term controls (P=0.04 and P=0.004, respectively). Urinary calcium excretion had a negative relationship with hip BMD in the preterm group (P=0.004). This difference in BMD was not observed in the 25 preterm children with normocalciuria. In the 10 preterm girls with hypercalciuria, hip BMD was lower than in control females (P=0.01). This difference in hip BMD between the 11 preterm boys with hypercalciuria and term boys was not significant (P=0.05). In conclusion, preterm children are shorter and have a lower hip BMD than those with normocalciuria. Further prospective studies are required to assess this risk and its influence on subsequent impaired bone mineralisation. Received: 28 September 2000 / Revised: 2 April 2001 / Accepted: 2 April 2001     

Early response in biochemical markers predicts long-term response in bone mass during hormone replacement therapy in early postmenopausal women

Based on data from 153 early postmenopausal women who completed a double-blind, randomized 3 year study of graded hormone replacement therapy (HRT) doses or placebo, we investigated the value of bone markers to predict prevention of bone loss. Absolute values of serum and urinary CrossLaps (S-CTX and U-CTX) after 2 weeks of treatment were significantly correlated to 3 year bone mass response (r = −0.28/−0.35; p < 0.001). These associations were fully expressed at 6 months (r = −0.61/−0.64; p < 0.001). Receiver operating characteristic analyses revealed that the predictive capacity of one measurement of a resorption marker after 6 months’ treatment performed similarly as assessment of hip bone mass over 3 years in predicting preservation of spinal bone mass over 3 years. Comparable results were obtained using percent change from baseline in resorption markers at both 6 and 12 months, whereas for formation markers percent change was superior to absolute value at 6 months but not at 12 months. Values of accuracy for S-CTX for a cutoff of 1881 pmol/L at 6 months were 85.2% (sensitivity), 74.3% (specificity), 90.5% (positive predictive value), and 63.4% (negative predictive value); U-CTX performed similarly, whereas the values for the formation markers were slightly lower. A cutoff for S-CTX of 1245 pmol/L eliminated false-positive individuals (those who had a decrease below the cutoff but lost bone). In the false-negative group, which was composed of individuals whose S-CTX did not decrease below the cutoff but had preserved bone mass, S-CTX was significantly associated with spinal bone mass response (r = −0.41; p < 0.01), indicating these women had been treated with a dose that was not at its optimum for their individual bone turnover. For this cutoff, the values were 49.5% (sensitivity), 97.1% (specificity), 98% (positive predictive value), and 40% (negative predictive value). In conclusion, early bone marker measurements predict long-term preservation of bone mass during HRT. Resorption markers seem superior to formation markers, which reflects that the primary effect of HRT is on bone resorption. A strategy with two cutoff levels may optimize the use of bone markers to predict bone mass response. Whether resorption markers can be used to guide individualized treatment remains to be investigated.     

Rotational deformities of the tibia and foot in preterm infants

Metatarsus adductus and medial tibial torsion are common in term infants. Our study shows that metatarsus adductus is rare, whereas medial tibial torsion does not occur in preterm infants with gestational ages of less than or equal to 30 weeks. These preterm infants have lateral rotation of the legs, external tibial rotation, and everted or normal feet at birth. This posture may explain the rarity of metatarsus adductus and medial tibial torsion in preterm infants.     

Effect of ammonium-chloride-induced metabolic acidosis on renal electrolyte handling in human neonates

The present study was undertaken to determine the relative contribution of altered glomerular and tubular functions to the metabolic-acidosis-induced increase of renal electrolyte excretion in healthy preterm and full-term neonates and in older infants. Studies were performed in 10 premature infants (mean birth weight 1618 g, gestational age 30.8 weeks) weekly for 6 consecutive weeks, in 11 full-term neonates (mean birth weight 3085 g, gestational age 38.6 weeks) on the 7th day of life and in 25 older control infants (mean age 6.5 months, body weight 6802 g), before and after NH₄Cl loading. Blood acid-base parameters, plasma and urine electrolyte and creatinine concentrations were measured, endogenous creatinine clearance and fractional electrolyte excretion (FE) calculated. It was demonstrated that the significant reduction in blood pH and total CO₂ content induced by NH₄Cl administration was associated with significant increases in glomerular filtration rate (GFR), urine flow rate, FE_Na and FE_Cl, in each group studied, irrespective of maturity, postnatal age or pre-load values. FE_K also tended to increase, but the change reached statistical significance only in older infants and in premature babies during the 1st, 2nd and 5th week of post-natal life. FE_Ca and FE_PO4 increased slightly in preterm and full-term newborns and became significant in older infants. Prior to NH₄Cl administration, FE_Ca correlated positively with FE_Na in each group. NH₄Cl metabolic acidosis, however, dissociated FE_Ca from FE_Na in the full-term newborns and older infants but not in the preterm neonates. We conclude that changes in urinary excretory response of human neonates to NH₄Cl administration may be accounted for by the combined effect of increased GFR and decreased electrolyte reabsorption.