Osteoporosis: Zemel BS

Gordon CM, Baim S, Bianchi ML, Bishop NJ, Hans DB, Kalkwarf H, Langman C, Leonard MB, Plotkin H, Rauch F, Zemel BS, Anonymous00043. · Children's Hospital Boston, Boston, MA 02115, USA. · South Med J. · Pubmed #18580718 No free full text.

Abstract: The International Society for Clinical Densitometry periodically holds Position Development Conferences (PDCs) for the purpose of establishing standards and guidelines for the assessment of skeletal health, including nomenclature, indications, acquisition, analysis, quality control, interpretation, and reporting of bone density tests. Topics are selected for consideration according to criteria that include clinical relevancy, uncertainty in the application of medical evidence to clinical practice, and the likelihood of the expert panel to reach a consensus agreement. The first Pediatric PDC was June 20 to 21, 2007 in Montreal, Quebec, Canada. Topics included fracture prediction and definition of osteoporosis in children; dual-energy x-ray absorptiometry (DXA) assessment in children with chronic disease that may affect the skeleton; DXA interpretation and reporting in children and adolescents; and the use of peripheral quantitative computed tomography in children and adolescents. This report describes the methodology and presents the results of this recent PDC.

Leonard MB, Zemel BS. · Department of Pediatrics, Departments of Biostatistics and Epidemiology, University of Pennsylvania School of Medicine, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA. · Pediatr Clin North Am. · Pubmed #11826803 No free full text.

Abstract: It is widely believed that osteoporosis prevention may be best accomplished during childhood and adolescence, when bones are growing rapidly and are most sensitive to environmental influences, such as diet and physical activity. For children with chronic diseases, a variety of factors may influence normal bone mineralization, including altered growth, delayed maturation, inflammation, malabsorption, reduced physical activity, glucocorticoid exposure, and poor dietary intake. In healthy children, maintaining adequate levels of calcium intake, serum vitamin D, and weightbearing physical activity may be sufficient to prevent osteoporosis later in life. Far less is known about effective prevention and treatment of poor bone mineralization in children with chronic illness, such as CF or CD. Osteoporosis prevention and intervention measures during childhood are limited by the paucity of reference data on bone mineralization. Although it is widely recognized that puberty, skeletal maturation, and body size influence BMC and bone density, no reference data for bone mineralization are scaled to these important measures. In children with chronic disease with delayed growth and maturation, the creation of such reference data is of paramount importance. In addition, the dynamic changes that occur during growth and maturation in the structural characteristics of trabecular and cortical bone and the development of the bone-muscle unit may influence current and future fracture risk. Further research is needed to characterize these changes and their use in the assessment of bone health and fracture risk in children. Only then can the impact of treatment strategies be appreciated fully.

Kramer RA, Zemel BS, Arvay-Nezu JL, Stallings VA, Leonard MB, Haber BA. · The Division of Gastroenterology, Hepatology & Nutrition, Children's Hospital of Philadelphia, PA 19104, USA. · Gastroenterol Res Pract. · Pubmed #19606216 links to  free full text

Abstract: Objectives. To assess bone health in a cohort of nonjaundiced children with biliary atresia (BA) and the effect of growth and development on bone outcomes. Methods. Children ages one to eighteen years receiving care from Children's Hospital of Philadelphia were recruited. Each child was seen once and assessed for growth, pubertal development, concurrent medications, bilirubin, ALT, albumin, vitamin D status, bone mineral density (BMD), and bone mineral content (BMC) of the lumbar spine and whole body. Results. BMD declined significantly with age, and upon further analysis with a well-phenotyped control cohort, it was found that BMC was significantly decreased for both lumbar spine and whole body, even after adjustment for confounding variables. An age interaction was identified, with older subjects having a significantly greater impairment in BMC. Conclusions. These preliminary results demonstrate that children with BA, including those without jaundice, are likely to have compromised bone health even when accounting for height and puberty, which are common confounding factors in chronic disease. Further investigation is needed to identify the determinants of poor bone mineral status and to develop strategies to prevent osteoporosis later in life.

Bergqvist AG, Schall JI, Stallings VA, Zemel BS. · Division of Neurology, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA. · Am J Clin Nutr. · Pubmed #19064531 No free full text.

Abstract: BACKGROUND: The ketogenic diet (KD) is a high-fat, low-carbohydrate, and protein diet that effectively treats intractable epilepsy (IE). OBJECTIVE: The purpose of this study was to measure the change in bone mineral content (BMC) in children with IE treated with the KD for 15 mo. DESIGN: Prepubertal children >or=5 y of age with IE were eligible. A 4:1 ketogenic diet was maintained for 15 mo, and whole-body and spine BMCs were measured with dual-energy X-ray absorptiometry. Z scores were generated by comparing the children with IE with a cohort of 847 healthy children. Other measurements included demographics, anthropometry, serum 25-hydroxyvitamin D (25-OHD), intact parathyroid hormone, electrolytes, and dietary intake. All measurements were performed at baseline and at 3, 6, 12, and 15 mo. Longitudinal mixed effects models were used to analyze change in BMC over time. RESULTS: Twenty-five children (9 girls, 16 boys) with IE [age (x +/- SD): 7.3 +/- 1.9 y] participated. Growth and bone health status were suboptimal as were serum 25-OHD concentrations and dietary intake of calcium and vitamin D. Whole-body and spine BMC-for-age both declined by 0.6 z score/y and whole-body and spine BMC-for-height declined 0.7 z score/y and 0.4 z score/y, respectively. Height declined 0.5 z score/y. Body mass index (BMI; in kg/m(2)) z score, age, and ambulation were positive predictors of BMC, which declined sharply over 15 mo of KD treatment. CONCLUSION: Bone health in children with IE was poor, particularly for younger nonambulatory children with low BMI status. The KD resulted in progressive loss of BMC. The mechanism is unclear. Further studies are needed.

Lewiecki EM, Gordon CM, Baim S, Binkley N, Bilezikian JP, Kendler DL, Hans DB, Silverman S, Bishop NJ, Leonard MB, Bianchi ML, Kalkwarf HJ, Langman CB, Plotkin H, Rauch F, Zemel BS. · New Mexico Clinical Research & Osteoporosis Center, 300 Oak Street NE, Albuquerque, NM 87106, USA. · Osteoporos Int. · Pubmed #18633664 No free full text.

Abstract: The International Society for Clinical Densitometry (ISCD) conducts Position Development Conferences (PDCs) for the purpose of establishing standards and guidelines in the field of bone densitometry. Topics for consideration are selected according to clinical relevance, a perceived need for standardization, and the likelihood of achieving agreement. Questions regarding nomenclature, indications, acquisition, analysis, quality control, interpretation, and reporting of bone density tests for each topic area are assigned to task forces for a comprehensive review of the scientific literature. The findings of the review and recommendations are then presented to an international panel of experts at the PDC. The expert panel votes on potential Official Positions for appropriateness, necessity, quality of the evidence, strength of the recommendation, and applicability (worldwide or variable according to local requirements). Recommendations that are approved by the ISCD Board of Directors become Official Positions. The first Pediatric PDC was 20-21 June 2007 in Montreal, QC, Canada. The most recent Adult PDC was held 20-22 July 2007, in Lansdowne, VA, USA. This Special Report summarizes the methodology of the ISCD PDCs and presents selected Official Positions of general interest.

Ladinsky GA, Vasilic B, Popescu AM, Wald M, Zemel BS, Snyder PJ, Loh L, Song HK, Saha PK, Wright AC, Wehrli FW. · Division of Renal, Electrolytes and Hypertension, University of Pennsylvania Medical Center, Philadelphia, Pennsylvania, USA. · J Bone Miner Res. · Pubmed #17784842 links to  free full text

Abstract: In postmenopausal women with a wide range of vertebral deformities, MRI-based structural measures of topology and scale at the distal radius are shown to account for as much as 30% of vertebral deformity, independent of integral vertebral BMD. INTRODUCTION: Trabecular bone architecture has been postulated to contribute to overall bone strength independent of vertebral BMD measured by DXA. However, there has thus far been only sparse in vivo evidence to support this hypothesis. MATERIALS AND METHODS: Postmenopausal women, 60-80 yr of age, were screened by DXA, and those with T-scores at either the hip or spine falling within the range of -2.5 +/- 1.0 were studied with the MRI-based virtual bone biopsy, along with heel broadband ultrasound absorption and pQCT of the tibia. The data from 98 subjects meeting the enrollment criteria were subjected to microMRI at the distal tibia and radius, and measures of topology and scale of the trabecular bone network were computed. A spinal deformity index (SDI) was obtained from morphometric measurements in midline sagittal MR images of the thoracic and lumbar spine to evaluate associations between structure and deformity burden. RESULTS: A number of structural indices obtained at the distal radius were correlated with the SDI. Among these were the topological surface density (a measure of trabecular plates) and trabecular bone volume fraction, which were inversely correlated with SDI (p < 0.0001). Combinations of two structural parameters accounted for up to 30% of the variation in SDI (p < 0.0001) independent of spinal BMD, which was not significantly correlated. pQCT trabecular BMD was also weakly associated, whereas broadband ultrasound absorption was not. No significant association between SDI and structural indices were found at the tibia. CONCLUSIONS: Structural measures at the distal radius obtained in vivo by microMRI explained a significant portion of the variation in total spinal deformity burden in postmenopausal women independent of areal BMD.

Burnham JM, Shults J, Petit MA, Semeao E, Beck TJ, Zemel BS, Leonard MB. · The Children's Hospital of Philadelphia, Philadelphia PA 19104, USA. · J Bone Miner Res. · Pubmed #17243860 No free full text.

Abstract: Proximal femur geometry was assessed in children and young adults treated with chronic GCs for CD or SSNS. Subperiosteal width and section modulus were significantly lower in CD and greater in SSNS compared with controls, highlighting the importance of the underlying disease, persistent inflammation, and alterations in lean mass. INTRODUCTION: The impact of glucocorticoid (GC) therapy on bone structure during growth is unknown. Our objective was to characterize proximal femur geometry in children and young adults with Crohn disease (CD) or steroid-sensitive nephrotic syndrome (SSNS) compared with controls and to evaluate the influence of lean mass and GC therapy on bone parameters. MATERIALS AND METHODS: DXA scans of the hip and whole body were obtained in 88 subjects with CD, 65 subjects with SSNS, and 128 controls (4-26 years of age). Hip structural analysis parameters (subperiosteal width, cross-sectional area [CSA], and section modulus in the narrow neck [NN], intertrochanteric region [IT], and femoral shaft [FS]), areal BMD, and whole body lean mass were expressed as Z scores compared with controls. Multivariable linear regression was used to adjust outcomes for group differences in age, sex, race, and height. RESULTS: Mean lean mass Z scores were lower in CD (-0.63, p < 0.001) and greater in SSNS (0.36, p = 0.03) compared with controls. Hip areal BMD Z scores were lower in CD (-0.73, p < 0.001) but not SSNS (-0.02, p > 0.2) compared with controls. In CD, Z scores for subperiosteal width (NN: -1.66, p < 0.001; FS: -0.86, p < 0.001) and section modulus (NN: -0.60, p = 0.003; FS: -0.36, p = 0.03) were significantly lower than controls. In contrast, in SSNS, Z scores were greater for IT subperiosteal width (0.39, p = 0.02), FS CSA (0.47, p = 0.005), and FS section modulus (0.49, p = 0.004). Alterations in section modulus in CD and SSNS were eliminated after adjustment for lean mass. Cumulative GC dose was inversely associated with FS subperiosteal width and section modulus only in CD. CONCLUSIONS: These data show that the effects of GC on proximal femur geometry during growth are influenced by the underlying disease, persistent inflammation, and alterations in lean mass. These data also provide insight into the structural basis of hip fragility in CD.

Fung EB, Kawchak DA, Zemel BS, Rovner AJ, Ohene-Frempong K, Stallings VA. · Department of Hematology, The Children's Hospital & Research Center, Oakland, California, USA. · Pediatr Blood Cancer. · Pubmed #17243130 links to  free full text

Abstract: Children with sickle cell anemia (SCA) have low bone mass though bone turnover has not been well described. In this study, growth and pubertal development were assessed twice, 1 year apart, in 80 young subjects with type-SS SCA, while whole body bone mineral content (BMC) and density where measured in a subset (n = 46). Markers of bone turnover were measured at the second visit. Bone formation (alkaline phosphatase) was elevated, whereas bone resorption (deoxypyridinoline) was decreased compared to published data in healthy children. Markers of bone turnover correlated with growth velocity and pubertal development but not with changes in bone mass.

Burnham JM, Shults J, Semeao E, Foster B, Zemel BS, Stallings VA, Leonard MB. · Children's Hospital of Philadelphia, Department of Pediatrics, University of Pennsylvania, 34th Street and Civic Center Boulevard, Philadelphia, PA 19104, USA. · J Bone Miner Res. · Pubmed #15537438 No free full text.

Abstract: Whole body BMC was assessed in 104 children and young adults with CD and 233 healthy controls. CD was associated with significant deficits in BMC and lean mass, relative to height. Adjustment for lean mass eliminated the bone deficit in CD. Steroid exposure was associated with short stature but not bone deficits relative to height. INTRODUCTION: Children with Crohn disease (CD) have multiple risk factors for impaired bone accrual. The confounding effects of poor growth and delayed maturation limit the interpretation of prior studies of bone health in CD. The objective of this study was to assess BMC relative to growth, body composition, and maturation in CD compared with controls. MATERIALS AND METHODS: Whole body BMC and lean mass were assessed by DXA in 104 CD subjects and 233 healthy controls, 4-26 years of age. Multivariable linear regression models were developed to sequentially adjust for differences in skeletal size, pubertal maturation, and muscle mass. BMC-for-height z scores were derived to determine CD-specific covariates associated with bone deficits. RESULTS: Subjects with CD had significantly lower height z score, body mass index z score, and lean mass relative to height compared with controls (all p < 0.0001). After adjustment for group differences in age, height, and race, the ratio of BMC in CD relative to controls was significantly reduced in males (0.86; 95% CI, 0.83, 0.94) and females (0.91; 95% CI, 0.85, 0.98) with CD. Adjustment for pubertal maturation did not alter the estimate; however, addition of lean mass to the model eliminated the bone deficit. Steroid exposure was associated with short stature but not bone deficits. CONCLUSION: This study shows the importance of considering differences in body size and composition when interpreting DXA data in children with chronic inflammatory conditions and shows an association between deficits in muscle mass and bone in pediatric CD.

Takahashi M, Wehrli FW, Hilaire L, Zemel BS, Hwang SN. · Department of Radiology, University of Pennsylvania Medical Center, 1 Silverstein, 3400 Spruce Street, Philadelphia, PA 19104, USA. · Proc Natl Acad Sci U S A. · Pubmed #11904367 links to  free full text

Abstract: Corticosteroids are in widespread clinical use but are known to have adverse skeletal side effects. Moreover, it is not known how soon these effects become apparent. Here, we describe a longitudinal approach to evaluate the short-term implications of excess corticosteroid exposure by quantitative in vivo magnetic resonance imaging and spectroscopy in conjunction with digital image processing and analysis in a rabbit model. Two-week treatment with dexamethasone induced a significant reduction in trabecular bone volume, which occurred at the expense of uniform trabecular thinning without affecting network architecture. Paralleling the loss in bone volume was conversion of hematopoietic to yellow marrow in the femoral metaphysis and atrophy of the femoral epiphyseal growth plate. This work demonstrates that detailed quantitative morphometric and physiological information can be obtained noninvasively at multiple skeletal locations. The method is likely to eventually replace invasive histomorphometry in that it obviates the need to sacrifice groups of animals at multiple time points. Finally, this work, which was performed on a clinical scanner, has implications for evaluating patients on high-dose steroid treatment.

Lewiecki EM, Gordon CM, Baim S, Leonard MB, Bishop NJ, Bianchi ML, Kalkwarf HJ, Langman CB, Plotkin H, Rauch F, Zemel BS, Binkley N, Bilezikian JP, Kendler DL, Hans DB, Silverman S. · New Mexico Clinical Research &Osteoporosis Center, 300 Oak Street NE, Albuquerque, NM 87106, USA. · Bone. · Pubmed #18793764 No free full text.

Abstract: The International Society for Clinical Densitometry (ISCD) periodically convenes Position Development Conferences (PDCs) in order to establish standards and guidelines for the assessment of skeletal health. The most recent Adult PDC was held July 20-22, 2007, in Lansdowne, Virginia, USA; the first Pediatric PDC was June 20-21, 2007 in Montreal, Quebec, Canada. PDC topics were selected according to clinical relevancy, perceived need for standardization, and likelihood of achieving agreement. Each topic area was assigned to a task force for a comprehensive review of the scientific literature. The findings of the review and recommendations were presented to adult and pediatric international panels of experts. The panels voted on the appropriateness, necessity, quality of the evidence, strength, and applicability (worldwide or variable according to local requirements) of each recommendation. Those recommendations that were approved by the ISCD Board of Directors become Official Positions. This is a review of the methodology of the PDCs and selected ISCD Official Positions.