Search

Reduced bone mineral density (BMD) and altered bone metabolism are common findings in HIV-infected patients. Increased bone formation has been described both in HIV-infected adults and children. Wnt ligands promote bone formation by stimulating osteoblast differentiation and their survival. Sclerostin and dickkopf factor 1 (DKK-1), Wnt antagonists, are important negative regulators of bone formation. We studied 86 HIV-infected patients whose ages ranged from 5.7 to 27.9 years. Patients were all on antiretroviral therapy, but seven who were naïve to treatment. Bone alkaline phosphatase (BAP), sclerostin, and DKK-1 were measured in serum by enzyme immunoassay. BMD was measured by dual-energy X-ray absorptiometry at the lumbar spine and in the whole skeleton. Biochemical indexes were also measured in 143 healthy controls (age range 4.5-27.4 years). HIV-infected patients had lower than normal BMD (spine P < 0.005, and whole skeleton P < 0.03). BAP measurements were significantly higher in HIV-infected patients than controls (P ≤ 0.05). Sclerostin and DKK-1 concentrations were markedly lower than in controls (P ≤ 0.0006, and P ≤ 0.03, respectively). The serum concentration of both analytes of patients naïve to antiretroviral treatment was not different from that of treated patients. No correlations were found between sclerostin, DKK-1, and bone mineral measurements. Our data confirm the alteration of bone metabolism pathways in HIV-infected individuals. The lower concentration of Wnt antagonists is consistent with the increased bone formation markers.

The use of combined antiretroviral agents during pregnancy is important to prevent mother-to-child transmission of human immunodeficiency virus (HIV). Antiretroviral treatment (ARV) is associated with reduced bone mass and altered bone metabolism in HIV-infected patients. There are no data regarding the effect of ARV exposure during pregnancy on newborns and infants. We therefore studied 38 subjects born from HIV-infected mothers, and we measured the speed-of-sound (SOS) at the tibia by quantitative ultrasonography (QUS) just after birth. QUS measurements at mid-tibia is easily performed in infants with the appropriate probe. Nevertheless, at this skeletal site only cortical bone is present, and therefore QUS measurements reflect the status of only one kind of bone tissue. We also measured bone alkaline phosphatase (BAP) and C-terminal telopeptide of type I collagen (CTX) in the cord blood as bone formation and resorption markers, respectively. SOS measurements were repeated at 4 and 12 months of age. As a control group we studied 94 subjects born from HIV-negative mothers. At birth the median (range) SOS of ARV-exposed neonates was 3006 (2870-3168) m/s, while that of control subjects was 3007 (2757-3311) m/s. The difference was not significant. BAP concentration of ARV-exposed was 103.6 (31.6-182.8) U/L, not different from that of control subjects (104.4 [43.2-227.2] U/L). CTX concentrations were 1.07 (0.26-2.8) ng/mL, and 1.38 (0.34-4.2) ng/mL in ARV-exposed and control subjects, respectively. SOS measurements at 4 months and 12 months of age were available for 17 ARV-exposed subjects and for 57 control subjects. SOS values changed significantly over time in both groups (F=6.1; P<0.0001). No differences were present between ARV-exposed and control subjects at 4 and 12 months. Our study suggests that ARV exposure during intrauterine life does not affect negatively bone metabolism and bone development, and that the changes occurring in bone QUS measurements during the first year of life in ARV-exposed subjects are similar to those occurring in healthy control infants., (Copyright © 2011 Elsevier Inc. All rights reserved.)

There is evidence suggesting that early events in life may predispose the adult to osteoporosis. We assessed bone status by quantitative ultrasonography in healthy neonates, and we report the changes occurring during the first year of life, according to the type of early feeding. We measured the speed of sound (SOS) of the left tibia in 116 full-term infants (0-9 days of age) and in their mothers (21-42 years of age). SOS values did not correlate with gestational age of the study subjects (r = 0.08) or anthropometric measurements. The SOS measurements of the mothers did not correlate with those of their children (r = 0.01). Fifty-seven infants had SOS measurements performed at 4 and 12 months. Twenty-five infants were exclusively breast-fed, 12 received formula milk from birth, and 20 received human and formula milk. SOS measurements at 4 months were comparable with those at baseline, whereas at 12 months they were significantly higher. No effect of type of feeding was observed, indicating that SOS changes may be independent of the type of early diet.

Alterations of fat distribution and insulin resistance are associated with increased risk of metabolic derangements and cardiovascular disease. HIV-infected adult patients on antiretroviral treatment often show lipodystrophy, insulin resistance and hypoadiponectinemia, but data in children are controversial. We investigated serum adiponectin concentration in a cohort of HIV-infected youths, and we assessed the relationships with lipodystrophy and insulin resistance. We studied 36 HIV-infected patients (aged 5.0 - 19.4 years), and 171 healthy subjects (aged 4.9 - 17.9 years) for adiponectin measurements. All patients underwent body composition assessment by dual-energy x-ray absorptiometry, and an oral glucose tolerance test to determine the fasting insulin concentration, the insulin area under the curve (AUC), and the HOMA index. Adiponectin serum concentration was measured by an immunoenzymatic assay. Sixteen patients had central fat accumulation, 6 had peripheral lipoatrophy, 5 had a mixed phenotype, and the remaining 9 were non-lipodystrophic. Fasting insulin, insulin AUC, and HOMA index were significantly higher in patients with central fat adiposity and mixed phenotype than in the other two groups. The patients of the former two groups had adiponectin concentration much lower than healthy controls, and patients with peripheral lipoatrophy or normal phenotype had normal concentration. Low adiponectin concentration is associated to central fat and mixed lipohypertrophy, and to signs of insulin resistance in HIV-infected youths. Strict monitoring of metabolic and cardiovascular evolution should be performed in these patients.

Background: Growth impairment and bone toxicity due to tenofovir disoproxil fumarate (TDF) fetal exposure has been described mainly in animals. We evaluated growth pattern and bone health in TDF-exposed HIV-uninfected children born to HIV-infected mothers, defined as seroreverters (SR)., Methods: This was a multicentre observational cross-sectional cohort study enrolling 68 SR who were in utero exposed to an antiretroviral regimen including (TDF+) or not including (TDF-) tenofovir. Neonatal data and duration of antiretroviral exposure were recorded. At enrolment, anthropometric measures, tibial speed of sound (SOS) by quantitative ultrasound and several parameters of bone metabolism were assessed., Results: Gestational age and median in utero antiretroviral exposure were similar in subjects exposed to TDF (n=33) and those non-exposed (n =35). Age at enrolment was comparable in the two groups (TDF-exposed range 11.8-76.2 months and TDF non-exposed range 11.8-77.9 months). The incidence of low weight and length measurements (<10th percentiles) at birth was similar in TDF-exposed and TDF non-exposed. Normal growth development was found in both groups of subjects at enrolment. The median (0.6; range -2.4-2.6) SOS z-score of TDF-exposed was similar to the median (0.8; range -2.2-4.4) SOS z-score of TDF non-exposed (Student's t=0.84; P=0.40). Parameters of bone metabolism were similar in the two groups., Conclusions: Exposure to TDF during pregnancy does not impair growth patterns, bone health and markers of bone metabolism in SR infants and young children born to HIV-infected women.

Mineral water may be a useful means to achieve optimal dietary calcium intake, but the effect of different mineral waters on calcium metabolism is unknown. We therefore evaluated calcium excretion in 24-hour urine in 10 healthy individuals (5 women and 5 men) after two weeks of drinking at least 1500 mL/day of mineral water with a low electrolyte content or 1500 mL/day of mineral water rich in calcium and bicarbonate but with a different sodium content. The low-sodium water Sangemini was one of these two mineral waters. Calcium excretion did not significantly increase after intake of the Sangemini mineral water in comparison with the baseline period of low-electrolyte mineral water intake. Conversely, the calcium excretion increased significantly after intake of the second mineral water. The plasma concentration of C-terminal telopeptide of type I collagen and the urinary phosphate excretion decreased after intake of the second mineral water in comparison with the baseline period, whereas they did not decrease after intake of Sangemini water. Therefore, phosphate excretion was higher after drinking Sangemini water than the other studied mineral water. Drinking Sangemini water may have a slight effect on calcium excretion and may not inhibit bone turnover in the short term. The lesser effect of Sangemini water on calcium excretion could be useful in the treatment of osteoporosis.

Background: Decreased bone mineral density (BMD) has been associated with the use of tenofovir disoproxil fumarate (TDF) in HIV-infected adults. The data in HIV-infected children are conflicting. The aim of this study was to assess the safety of a TDF-containing antiretroviral (ARV) regimen on BMD in paediatric patients. We report the results of a longitudinal 60-month follow-up study., Methods: A total of 21 vertically HIV-infected Caucasian youths (10 male and 11 female) on ARV treatment containing lamivudine, efavirenz and TDF were enrolled (age range 4.9-17.9 years at baseline). BMD was measured at the lumbar spine and in the whole skeleton by DXA. Bone-specific alkaline phosphatase (BAP) was measured as a bone formation marker and urinary N-telopeptide of type-I collagen (NTx) was measured as a bone resorption index., Results: Baseline mean (±sd) BMD measurements of HIV-infected patients expressed as z-scores were -0.7 (±0.9) for lumbar spine and -0.13 (±1.0) for the whole skeleton. BMD measurements did not change significantly during the 60-month observation period. Both BAP and NTx concentrations were higher than a reference group of controls at baseline and remained unchanged throughout the study., Conclusions: Our data indicate that a TDF-containing regimen does not decrease the BMD of HIV-infected youths.

Bones undergo intensive modeling during growth, a process involving both formation and resorption processes. Bone formation can be accurately monitored by measurements of bone-specific alkaline phosphatase (BAP) in serum. The lack of appropriate reference values has hampered the use of BAP in pediatric subjects. The purposes of the present study were to verify the effect of age, gender, and puberty on BAP concentration in healthy children, and to generate reference curves. Morning blood samples were collected from 239 healthy children and adolescents (113 boys), aged 4.5-20.9 years. Anthropometric measurements and pubertal stage were recorded. Blood samples were also obtained from 37 healthy young adults (13 men), aged 21.5-30.2 years. BAP concentration varied significantly with age, showing a peak at age 10-12 years in girls and 12-14 years in boys. Prepubertal concentration of BAP was six- to sevenfold higher than in healthy adults. We observed significantly higher BAP values at the beginning of puberty (stage II) compared to prepubertal stage in both sexes. The effect of puberty was independent from age and gender. We demonstrated that BAP serum concentration varies with age in children and adolescents, and we provided equations to calculate reference values. Because BAP concentrations vary markedly according to the pubertal stage, the values of BAP obtained in single patients should be compared to reference considering not only age and sex, but also the stage of pubertal development.

New markers have been used to monitor the changes of bone turnover occurring during growth. Data on bone turnover rate during the perinatal period are, however, very scarce. In the present study we evaluated bone turnover rate, assessed by the measurement of urinary N-terminal telopeptide of type I collagen (NTx) concentrations, at different gestational ages, and we documented the trend of bone turnover rate occurring in the first days after birth. Urine samples were obtained from 83 healthy full term newborn infants, 16 preterm, and 17 infants of diabetic mothers (IDMs). The first miction after birth was collected. Urine samples were also collected 24 and 48 h after birth. NTx was measured by an enzyme-linked immunosorbent assay (Osteomark, Ostex International, Inc. Seattle, WA). The relationship between NTx at birth and all the other variables has been evaluated using multiple regression analysis. The changes of NTx excretion over time and the effect of the groups were studied by multivariate analysis of variance (MANOVA) for repeated measures. We found a remarkable association between gestational age and NTx concentrations at birth (R = 0.56; p < 0.00001). NTx concentrations showed a progressive decrement, reaching a nadir between the 38th and the 42nd week of gestation. The NTx concentrations changed significantly during the first 48 h of life in the three groups. Moreover, preterm infants had NTx excretion values at birth significantly higher than full term infants (p < 0.001), whereas NTx excretion rates of IDMs were not different from those of the other two groups of subjects. In conclusion, gestational age seems to be the major determinant of bone turnover in neonates; NTx excretion rate is higher before term, it slows in proximity of delivery, and it increases significantly during the first 48 h of life. Preterm infants have higher bone turnover rate than full term infants. NTx excretion rate of IDMs was comparable with those of the control subjects.

Insulin-dependent diabetes mellitus is associated to important micro and macro vascular complications. A good metabolic control can reduce the risk of complications. Aim of the study was to evaluate the metabolic control in adolescent diabetic patients using an educational system with graphic visualisation of capillary glycaemia. 40 (22 males, 18 females) insulin-dependent diabetic patients (age: 16.9 +/- 3.5 yrs; duration of diabetes: 6.7 +/- 4.6 yrs) were divided in two groups matched for age, sex, duration of diabetes and metabolic control. Patients of group 1 used One Touch II Video for three months. One Touch II Video is an educational program for diabetes mellitus linked to a meter for glycaemia assessment. Patients of group 2 were used as control group. All data were expressed as a mean +/- SD and were analysed by parametric t-Student test. In group 1 HbA1c at the end of the study was significantly reduced compared to the initial value: 8.58 +/- 1.65% vs 7.9 +/- 1.0% (p < 0.05). In group 2 HbA1c at end of the study was no different from the initial value. At short term One Touch II Video could be a useful instrument to improve metabolic control in insulin-dependent diabetic adolescents.

We studied the effects of recombinant human growth hormone (GH) treatment in 6 prepubertal children with achondroplasia. The patients' age ranged from 2 11/12 to 8 5/12 years and the GH dose was of 0.1 IU/kg/day subcutaneously. Auxological assessments and bone age determinations were performed 6 months before, at the beginning, and after 6 and 12 months of therapy. The growth velocity increase during the whole year of treatment ranged from 1.1 to 2.6 cm/year in 3 patients while in the others no variation was detected. No side effects were observed during the trial apart from a slight advancement of bone age in two patients. MRI at the cervicomedullary junction and CT scan of the base of the skull did not show any variation of the dimensions of the foramen magnum at the end of the trial compared to baseline. Our study shows that r-hGH can safely increase short-term growth velocity in some but not all prepubertal children with achondroplasia. Our data confirm the individual variability in the response to the GH treatment.

Urinary growth hormone (uGH) excretion was evaluated in 96 type-1 insulin-dependent diabetic patients and 37 age-matched healthy subjects. The growth hormone concentration was measured by a solid-phase immunoradiometric assay on 3 consecutive overnight urine collections. uGH excretion was comparable between diabetic patients and healthy subjects: 10.9 (0.1-34.8) vs. 9.1 (2.6-34.5) pg/min. In both groups uGH excretion was lower in prepubertal than in pubescent or pubertal individuals (diabetic patients, H = 29.7, p = 0.001; healthy subjects, H = 10.4, p = 0.006). In diabetic patients uGH excretion was related to beta 2-microglobulin excretion (r = 0.308; p = 0.005) and to urinary albumin excretion (r = 0.230; p = 0.02) but it was independent of HbA1c and overnight glycemic values. The coefficient of variation of uGH excretion was higher in diabetic patients with respect to healthy subjects: 50 (3-141) vs. 28(3-100)% (p = 0.002). Among diabetic patients it was greater in prepubertal than in pubescent or pubertal patients (H = 13.7; p = 0.002); in contrast, it was independent of pubertal stage in healthy individuals (H = 2.4; NS). The coefficient of variation of uGH was not related to HbA1c, the duration of diabetes, the coefficient of variation of urinary albumin excretion and the coefficient of variation of beta 2-microglobulin excretion. In conclusion uGH excretion is comparable among diabetic patients and healthy subjects, but its day-to-day fluctuation is greater in the former than in the latter group. Renal function but not metabolic control can influence uGH excretion. The day-to-day fluctuation in uGH excretion is independent of metabolic control and renal function.

The extent and the clinical significance of residual beta cell function has been evaluated by radioimmunoassay of C-peptide in 41 diabetic children in different stages of evolution, using an arginine tolerance test. In control subjects a significant rise of C-peptide levels occurred after the infusion with arginine. In patients at the onset of the disease and in patients not in the remission stage, C-peptide levels showed no increment and basal values were significantly lower than in healthy control children. Children during the remission phase showed basal and peak values not significantly different from controls. A positive correlation was found between highest CPR levels compared to basal CPR values and to the age at onset of diabetes; a negative correlation was found between the duration of the disease and insulin requirement.