Bone densitometry in pediatric populations: discrepancies in the diagnosis of osteoporosis by DXA and CT

OBJECTIVES: To test the hypothesis that because of errors associated with growth and development, osteoporosis is frequently overdiagnosed in children when using dual-energy x-ray absorptiometry (DXA). This study compared bone density values obtained by DXA with those from computed tomography (CT), which is not influenced by body or skeletal size. STUDY DESIGN: Vertebral bone density was measured by using both DXA and CT in 400 children (100 each, healthy and sick boys and girls). Regression analysis was used to compare DXA and CT Z scores, and the agreement between DXA and CT classifications of Z scores below -2.0 was examined. RESULTS: DXA and CT Z scores were moderately related (r2 = 0.55 after accounting for age and anthropometric measures). DXA Z scores predicted CT Z scores below -2.0 with reasonable sensitivity (72%), specificity (85%), and negative predictive value (98%), but positive predictive value was low (24%). Many more subjects were classified as having bone density lower by DXA (76/400) than by CT (25/400), particularly subjects below the 5 th percentile of height and/or weight for age. CONCLUSIONS: The inability of DXA to account for the large variability in skeletal size and body composition in growing children greatly diminishes the accuracy of this projection technique for assessing bone acquisition and diagnosing osteoporosis in pediatric populations.     

Effect of a novel procedure for limiting motion on body composition and bone estimates by dual-energy X-ray absorptiometry in children

We studied the effect of using the BodyFIX (Medical Intelligence Inc, Schwabmunchen, Germany) to immobilize children during a dual-energy X-ray absorptiometry scan on body composition and bone estimates. Overestimates of soft tissue and bone introduced by the BodyFIX were avoided by using a modified version of the system or were corrected by using mathematical models developed in this study.     

Bone measurements by peripheral quantitative computed tomography (pQCT) in children with cerebral palsy

OBJECTIVE: To use peripheral quantitative computed tomography (pQCT) to determine bone measurements in patients with cerebral palsy (CP) age 3 to 20 years and compare them with control subjects. STUDY DESIGN: A total of 13 (5 male) patients with CP, along with 2 sex- and age-matched controls for each, were included in a mixed-model analysis with matched pairs as random effects for pQCT bone measurements of the 20% distal tibia. RESULTS: Tibia length was similar in the CP and control groups (P = .57). Weight was marginally higher in the control group (P = .06). Cortical bone mineral content (BMC), area, thickness, polar strength-strain index (pSSI), and periosteal and endosteal circumferences were greater in the control group (P < .05 for all). Relationships between bone measurements and weight showed that cortical BMC, area, periosteal circumference, and pSSI were greater at higher weights in the control group (group-by-weight interaction, P < .05 for all). Cortical thickness was greater in the control group and was correlated with weight. Cortical volumetric bone mineral density (vBMD) was greater with higher weights in the CP group (group-by-weight interaction, P = .03). CONCLUSIONS: Bone strength, as indicated by pSSI, is compromised in children with CP due to smaller and thinner bones, not due to lower cortical bone density.     

Overdiagnosis of osteoporosis in children due to misinterpretation of dual-energy x-ray absorptiometry (DEXA)

OBJECTIVE: Dual-energy x-ray absorptiometry (DEXA) is increasingly used to evaluate children for osteoporosis. However, the interpretation of pediatric DEXA is complicated by growth and development. Because most DEXA scans are performed on adults, we hypothesized that physicians who interpret DEXA may not be aware of these pediatric issues, potentially leading to misdiagnosis. STUDY DESIGN: Children (n=34, aged 4-17 years) diagnosed with low bone mineral density (BMD) based on a DEXA scan were referred for possible inclusion in a childhood osteoporosis protocol. The referral DEXA scans were analyzed for accuracy. RESULTS: Thirty (88%) of the scans had at least one error in interpretation. The most frequent error (62%) was use of T-score (SD score compared with young adults) to diagnose osteoporosis, which is inappropriate for children. Other errors included use of a reference database that does not consider gender or ethnic differences (21%), incorrect bone map (21%), inattention to short stature (15%), and other measurement or statistical error (12%). After correcting for these errors, 53% had normal BMD, whereas only 26% retained the diagnosis of low BMD. The remaining 21% could not be given a definitive diagnosis. CONCLUSION: In children, the diagnosis of osteoporosis is often due to misinterpretation of a DEXA scan.     

Parathyroid hormone,calcitonin and vitamin D metabolites in beta-thalassaemia major

Serum calcium (Ca), phosphorus (P), alkaline phosphatase (Al-P), parathyroid hormone (PTH), calcitonin (CT), 25-hydroxyvitamin D₃ (25OHD₃), 1,25-dihydroxyvitamin D₃ (1,25(OH)₂D₃) levels and urinary excretion of Ca, P, hydroxyproline (OH-P) and cyclic AMP (cAMP) were determined in summer and in winter in 13 thalassaemic children (7 aged 3–5 years-group 1-; and 6 aged 10–13 years-group 2-), who had never taken vitamin D supplements or therapy, and in two groups of 14 controls of the same age.In thalassacmics of group 1 only serum AL-P levels and OH-P urinary excretion were higher than in controls (P<0.01). In thalassaemics of group 2 Ca (P<0.05), P (P<0.05), PTH (P<0.001), CT (P<0.001), 25 OHD₃ (P<0.05), 1,25(OH)₂D₃ (P<0.001) levels and cAMP urinary excretion (P<0.001) were lower, whereas Al-P (P<0.001) and CT (P<0.001) levels and urinary excretion of P (P<0.05) and of OH-P (P<0.001) were higher than in controls, both in summer and in winter.Advancing age induces in thalassaemic patients a decrease in PTH secretion and a consequent deficit in synthesis of 1,25(OH)₂D₃ that may explain some aspects of bone changes, which CT hypersecretion may tend to counteract.Abbreviations Ca calcium - P phosphorus - Al-P alkaline phosphatase - PTH parathyroid hormone - CT calcitonin - 250HD₃ 25-hydroxyvitamin D₃ - 1,25(OH)₂D₃ 1,25-dihydroxyvitamin D₃ - OH-P hydroxyproline - cAMP cyclic AMP Presented in part at the 23rd annual meeting of the European Society for Paediatric Endocrinology, Heidelberg, September 2–5, 1984     

Decreased bone mineral density with off-label use of tenofovir in children and adolescents infected with human immunodeficiency virus

5 of 6 children infected with human immunodeficiency virus (HIV) receiving Tenofovir disoproxil fumarate (TDF) experienced absolute decreases in bone mineral density (BMD). 2 pre-pubertal subjects experienced >6% BMD decreases. 1 subject was the smallest child and experienced a 27% decrease, necessitating withdrawal of TDF. Subsequently, her BMD recovered. Monitoring of children infected with HIV who require treatment with TDF is warranted.     

Alterations in bone characteristics associated with glycemic control in adolescents with type 1 diabetes mellitus

OBJECTIVE: To determine whether bone characteristics in adolescents with type 1 diabetes mellitus (DM) are influenced by blood glucose regulation and disease duration. The subjects were adolescents with type 1 DM (n=55) recruited from the University of Utah's Primary Children's Pediatric Diabetes Treatment Center. A reference database consisting of 95 healthy adolescents from the same geographic area was used for comparison.Study design Measurements of the tibia by peripheral quantitative computed tomography were made to assess cortical and trabecular bone characteristics. Hip, spine, and whole body characteristics were measured by dual-energy x-ray absorptiometry. Height, weight, health histories, Tanner stage, disease duration, insulin regimen, and glycosylated hemoglobin values were recorded. RESULTS: Age, maturation, and body size and composition values were similar between the subjects with type 1 DM and reference. Subjects with type 1 DM had lower tibia trabecular and femoral neck density and whole body mineral content and density. The mean glycosylated hemoglobin value was inversely related to tibia trabecular bone density (R(2)=-0.30) and whole body bone mineral content (R(2)=-0.25) and accounted for 3.0% to 8.9% of the variance. CONCLUSIONS: Altered bone mineral acquisition in adolescents with type 1 DM may limit peak bone mass acquisition and increase the risk of osteoporosis in later life.     

Early response to vitamin D2 in children with calcium deficiency rickets

OBJECTIVE: To assess the effect of vitamin D(2) administration on serum vitamin D metabolite concentrations in calcium deficiency rickets. STUDY DESIGN: We administered vitamin D(2), 50,000 IU orally to 16 Nigerian children 15 to 48 months of age with radiographically active rickets. We measured calcium and vitamin D metabolites at baseline and at 1, 3, 7, and 14 days. RESULTS: At baseline, ranges of serum 25-hydroxyvitamin D (25(OH)D) concentrations were 18 to 40 nmol/L (7-16 ng/mL), and 1,25-dihydroxyvitamin D (1,25-(OH)(2)D) concentrations were 290 to 790 pmol/L (120-330 pg/mL). After vitamin D administration, serum 25(OH)D and 1,25(OH)(2)D concentrations rapidly rose and peaked at 2.8 and 1.9 times the baseline values (P < .001), respectively, at 3 days. Positive correlations between 1,25(OH)(2)D and 25(OH)D were strongest at day 3 (r = 0.84, P < .001) and weakest at day 14 (r = 0.41, P = .11). The relationship of 1,25(OH)(2)D with 25(OH)D at baseline and the increase in 1,25(OH)(2)D in response to vitamin D were similar to those described in children with vitamin D deficiency. However, unlike the pattern in vitamin D deficiency, 1,25(OH)(2)D remained positively correlated with 25(OH)D after administration of vitamin D. CONCLUSION: Dietary calcium deficiency increases the demand for 25(OH)D above that required in vitamin D deficiency to optimize 1,25(OH)(2)D concentrations. Assessment of vitamin D sufficiency in persons or communities may need to be adjusted for habitual dietary calcium intake.     

Speed of sound: relation to geometric characteristics of bone in children, adolescents, and adults

OBJECTIVES: To investigate the relation between volumetric bone mineral density (vBMD) and speed of sound (SOS). STUDY DESIGN: Total and trabecular vBMD were measured by peripheral quantitative computed tomography at the forearm in a population of 216 individuals of a pediatric outpatient clinic. Moreover, SOS was measured by a quantitative ultrasound device (QUS) at the thumb, patella, and os calcis. RESULTS: Linear regression analysis revealed that the prediction of SOS by vBMD is relatively weak (R2 < 0.1). Moreover, body height and measures of bone size have a stronger influence on SOS than vBMD. The influence of bone size on SOS also depends on the location of measurement (highest prediction of SOS by body height at patella with R2 = 0.56). Anthropometric characteristics have a stronger influence on SOS than measures of bone mineral density at the thumb and patella in comparison to os calcis (body height predicts SOS at os calcis, with R2 = 0.03). Conclusions QUS is not a suitable method to assess bone density. If QUS is applied for the assessment of bone development and of bone fracture risk, the measurement should be performed with consideration of anthropometric measurements.     

Dual energy X-ray absorptiometry of the hand and wrist–a possible technique to assess skeletal maturation: methodology and data in normal youths

Ninety five normal Caucasian subjects (51F, 44 M) aged from 2 to 25 y were measured at the hand and wrist level with a small DXA system (pDEXA™) in order to obtain the normal values of the bone mineral content (BMC), density (BMD) and projected area (A) of carpal (c) and metacarpal (m) bones. BMDc ranged from 0.065 ± 0.007 g/cm to 0.365 ± 0.035 g/cm in females and 0.425 ± 0.040 g/cm in males. It presented a sharp change of increase rate at 15.5 and 17 y of age in girls and boys, respectively. Ac presented the same kind of evolution as BMDc, but had a larger value dispersion. The second metacarpal bone had the highest BMCm value in 85% of females and 90% of males. The sum of BMCmi or Ami values (i = 1–5) and the projected mean density of the 5 metacarpal bones was well correlated with BMCc, Ac and BMDc, respectively ( r > 0.90). A volumetric mineral density, dmi, calculated for each of these bones, approximated to a cylinder, was correlated with age ( r > 0.85).     

Bone mineral acquisition in adolescents with type 1 diabetes

OBJECTIVE: To track bone mineral acquisition in adolescents with type 1 diabetes (DM). STUDY DESIGN: Subjects were adolescents, ages 12 to 18 years, with DM (n=42) and a healthy regional reference (n=199). Measurements of tibia bone characteristics by peripheral quantitative computed tomography (pQCT) and spine and whole body (WB) by dual-energy x-ray absorptiometry (DEXA), anthropometrics, and lifestyle questionnaires were obtained during a 12-month period. Disease duration, insulin dose, renal function, and glycosylated hemoglobin (HbA1c) values for the previous 12 months were recorded. RESULTS: Body size and maturation were similar between groups. DM had lower tibia, spine, and WB bone characteristics but greater muscle mass (LBM) and lower bone mineral content (BMC)/LBM at baseline and 12 months. Annual gains for tibia cortical bone and WB BMC/LBM were lower and inversely related to HbA1c levels (R=-0.36 to -0.51), whereas spine area and density and WBLBM were greater and were predicted by pubertal-driven growth. Overall, the DM cohort had 8.5% less WB BMC/LBM, suggesting that bone mineral deposition was not adequately adapted to muscle gains. CONCLUSIONS: Adolescents with type 1 diabetes continue to have smaller bone mass and bone size despite normal growth and maturation. Poor metabolic control appears to negatively influence bone mineral acquisition.