Search

Introduction: With increasing healthcare costs, it is important to quantify the number of total knee arthroplasty (TKA) patients who have MRIs that are not considered clinically necessary. The purpose of this study was to determine the number of unnecessary preconsultation MRIs done among TKA patients at our institution., Methods: Eight hundred and sixty-nine patients who underwent a primary TKA were identified. Review of medical records and imaging results was conducted to determine which patients had received preconsult MRIs and whether they were necessary or unnecessary., Results: Of the 869 TKA, 177 (20.4%) presented with a preconsultation MRI, of which, 112 met the study inclusion criteria. Of the 112 MRIs, 18 (20.7%) were done without radiographic imaging, and 69 (79.3%) were completed after radiographically evident moderate-to-severe arthritis. Overall, 87 MRIs (10.0%) were deemed clinically unnecessary., Conclusions: Referring physicians are overusing MRIs before consultation with an orthopaedic surgeon. The 87 patients who had unnecessary MRIs at our institution over a one-year period represented a cost of $20,706. Extrapolating that number to the scale of patients affected by arthritis each year is potentially a staggering amount of money. Evidence-based guidelines should be put into place to optimize healthcare utilization., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Orthopaedic Surgeons.)

Background: Lack of paediatric reference data limits the utility of handgrip strength as a measure of fitness and well-being., Aim: To develop paediatric handgrip reference curves and evaluate associations with body size and composition and race/ethnicity group., Subjects and Methods: Handgrip, body size and composition data were obtained from National Health and Nutrition Examination Survey 2011-2014 participants aged 6-20 years. Densitometry-derived fat and appendicular lean soft tissue mass index Z-scores (FMIZ, ALSTMIZ) were generated in participants >8 years. Dominant and non-dominant handgrip reference curves were created using the LMS method. Analyses included sample weights to produce nationally representative estimates., Results: Differences in handgrip strength according to hand dominance increased with age. Handgrip strength was associated with height and arm length Z-scores ( R  = 0.42 to 0.47) and ALSTMIZ ( R  = 0.54). Handgrip strength was higher in the non-Hispanic Black group and lower in the Mexican American compared to non-Hispanic White group. Group differences were attenuated when adjusted for height, arm length or ALSTMIZ., Conclusion: Paediatric handgrip reference curves were generated from which individual Z-scores can be calculated separately for dominant versus non-dominant hand and adjusted for body size. Association with ALSTMIZ suggests handgrip Z-score may be used as a measure of functional body composition.

MAGEC rods (NuVasive) provide distraction growth in early-onset scoliosis. Pedicle screw use with MAGEC rods can lead to anchor failure. Sublaminar bands offer superior fixation points for the MAGEC system while preserving pedicles and facets, avoiding spinal cord injury, and eliminating the need for fluoroscopy. Sublaminar bands can be safely used up to cervical vertebra four (C4), substantially decreasing the risk of complications such as anchor pull-out, rod breakage, and proximal junctional kyphosis that typically occurs with pedicle screws and hooks. This case demonstrates the viable option of sublaminar band fixation as an anchor system for MAGEC rods. This is a retrospective case review of one patient with early-onset scoliosis who underwent multiple osteotomies, spinal cord decompression, and placement of MAGEC rods with sublaminar bands. The patient had successful distraction procedures conducted routinely throughout a 44-month period with no associated implant complications or neurologic sequelae during that period. The patient had achieved maximal distraction with the implanted rods and thereafter underwent removal of the MAGEC rods and replacement implantation with longer MAGEC rods. The purpose of this case review was to demonstrate the superior fixation results provided with sublaminar band fixation for MAGEC rod distraction systems., (Copyright © 2023 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Orthopaedic Surgeons.)

Objective: To evaluate the impact of a diagnostic stewardship intervention on Clostridioides difficile healthcare-associated infections (HAI)., Design: Quality improvement study., Setting: Two urban acute care hospitals., Interventions: All inpatient stool testing for C. difficile required review and approval prior to specimen processing in the laboratory. An infection preventionist reviewed all orders daily through chart review and conversations with nursing; orders meeting clinical criteria for testing were approved, orders not meeting clinical criteria were discussed with the ordering provider. The proportion of completed tests meeting clinical criteria for testing and the primary outcome of C. difficile HAI were compared before and after the intervention., Results: The frequency of completed C. difficile orders not meeting criteria was lower [146 (7.5%) of 1,958] in the intervention period (January 10, 2022-October 14, 2022) than in the sampled 3-month preintervention period [26 (21.0%) of 124; P < .001]. C. difficile HAI rates were 8.80 per 10,000 patient days prior to the intervention (March 1, 2021-January 9, 2022) and 7.69 per 10,000 patient days during the intervention period (incidence rate ratio, 0.87; 95% confidence interval, 0.73-1.05; P = .13)., Conclusions: A stringent order-approval process reduced clinically nonindicated testing for C. difficile but did not significantly decrease HAIs., Competing Interests: All authors report no conflicts of interest relevant to this article., (© The Author(s) 2023.)

Objective: We determined associations between adipokines and abnormal body composition in patients with rheumatoid arthritis (RA)., Methods: Combining data from three RA cohorts, whole-body dual-energy absorptiometry measures of appendicular lean mass and fat mass indices were converted to age-, sex-, and race- and ethnicity-specific Z scores. Lean mass relative to fat mass was determined based on prior methods. Independent associations between body composition profiles and circulating levels of adiponectin, leptin, and fibroblast growth factor (FGF)-21 were assessed using linear and logistic regression models adjusting for demographic characteristics and study cohort. We also determined the improvement in the area under the curve (AUC) for prediction of low lean mass when adipokines were added to predictive models that included clinical factors such as demographic characteristics, study, and body mass index (BMI)., Results: Among 419 participants, older age was associated with higher levels of all adipokines, whereas higher C-reactive protein level was associated with lower adiponectin levels and higher FGF-21 levels. Greater fat mass was strongly associated with lower adiponectin levels and higher leptin and FGF-21 levels. Higher levels of adiponectin, leptin, and FGF-21 were independently associated with low lean mass. The addition of adiponectin and leptin levels to regression models improved prediction of low lean mass when combined with demographic characteristics, study, and BMI (AUC 0.75 vs. 0.66)., Conclusion: Adipokines are associated with both excess adiposity and low lean mass in patients with RA. Improvements in the prediction of body composition abnormalities suggest that laboratory screening could help identify patients with altered body composition who may be at greater risk of adverse outcomes., (© 2021 American College of Rheumatology. This article has been contributed to by US Government employees and their work is in the public domain in the USA.)

Objective: Controversy remains as to whether low serum urate or uric acid (UA) levels contribute to adverse outcomes. We evaluated the relation between low serum UA levels and sarcopenia and assessed whether sarcopenia confounds associations between these low levels and mortality., Methods: We utilized data from the National Health and Nutrition Examination Survey (1999-2006). Participants with available whole-body dual x-ray absorptiometry body composition measurements and serum UA concentrations were included. Body composition assessments included body mass index (BMI), waist circumference, maximum lifetime BMI, and age-, sex-, and race-specific appendicular lean mass index (ALMI) and fat mass index (FMI) Z scores. We also calculated Z scores for ALMI relative to FMI (ALMI FMI ). We evaluated associations between serum UA levels and body composition using logistic regression and assessed associations between serum UA levels and mortality before and after adjusting for differences in body composition using Cox proportional hazards regression., Results: Among the 13,979 participants, low serum UA concentrations (<2.5 mg/dl in women, <3.5 mg/dl in men) were associated with low lean mass (ALMI and ALMI FMI Z scores), underweight BMI (<18.5 kg/m 2 ), and higher rates of weight loss. The proportion of patients with low ALMI Z scores was 29% in the low serum UA group and 16% in the normal serum UA group (P = 0.001). Low serum UA levels were associated with increased mortality before we adjusted for body composition (hazard ratio 1.61 [95% confidence interval 1.14-2.28]; P = 0.008) but was attenuated and not significant after adjustment for body composition and weight loss (hazard ratio 1.30 [95% confidence interval 0.92-1.85], P = 0.13)., Conclusion: Sarcopenia and weight loss are more common among patients with low serum UA concentrations. Differences in body composition may help to explain associations between low levels of serum UA and higher mortality., (© 2022 American College of Rheumatology. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

Introduction: Friedreich's Ataxia (FRDA) is a progressive neurological disorder caused by mutations in both alleles of the frataxin (FXN) gene. Impaired bone health is a complication of other disorders affecting mobility, but there is little information regarding bone health in FRDA., Methods: Dual energy X-ray absorptiometry (DXA) scan-based assessments of areal bone mineral density (aBMD) in individuals with FRDA were abstracted from four studies at the Children's Hospital of Philadelphia (CHOP). Disease outcomes, including the modified FRDA Rating Scale (mFARS), were abstracted from the FRDA Clinical Outcomes Measures Study (FACOMS), a longitudinal natural history study. A survey regarding bone health and fractures was sent to individuals in FACOMS-CHOP., Results: Adults with FRDA ( n = 24) have lower mean whole body (WB) (-0.45 vs. 0.33, p = 0.008) and femoral neck (FN) (-0.71 vs. 0.004, p = 0.02) aBMD Z-scores than healthy controls ( n = 24). Children with FRDA ( n = 10) have a lower WB-less-head (-2.2 vs. 0.19, p < 0.0001) and FN (-1.1 vs. 0.04, p = 0.01) aBMD than a reference population ( n = 30). In adults, lower FN aBMD correlated with functional disease severity, as reflected by mFARS ( R = -0.56, p = 0.04). Of 137 survey respondents (median age 27 y, 50% female), 70 (51%) reported using wheelchairs as their primary ambulatory device: of these, 20 (29%) reported a history of potentially pathologic fracture and 11 (16%) had undergone DXA scans., Conclusions: Low aBMD is prevalent in FRDA, but few of even the highest risk individuals are undergoing screening. Our findings highlight potential missed opportunities for the screening and treatment of low aBMD in FRDA., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Dunn, Tamaroff, DeDio, Nguyen, Wade, Cilenti, Weber, Lynch and McCormack.)

The advent of highly effective CFTR modulator therapies has slowed the progression of pulmonary complications in people with cystic fibrosis. There is increased interest in cystic fibrosis bone disease (CFBD) due to the increasing longevity of people with cystic fibrosis. CFBD is a complex and multifactorial disease. CFBD is a result of hypomineralized bone leading to poor strength, structure and quality leading to susceptibility to fractures. The development of CFBD spans different age groups. The management must be tailored to each group with nuance and based on available guidelines while balancing therapeutic benefits to risks of long-term use of bone-active medication. For now, the mainstay of treatment includes bisphosphonates. However, the long-term effects of bisphosphonate treatment in people with CF are not fully understood. We describe newer agents available for osteoporosis treatment. Still, the lack of data behooves trials of monoclonal antibodies treatments such as Denosumab and Romozosumab and anabolic bone therapy such as teriparatide and Abaloparatide. In this review, we also summarize screening and non-pharmacologic treatment of CFBD and describe the various options available for the pharmacotherapy of CFBD. We address the prospect of CFTR modulators on bone health while awaiting long-term trials to describe the effects of these medications on bone health., Competing Interests: Conflict of Interest or Competing Interest: My coauthors and I do not have any conflict of interest other than the fact that 3 of us were funded by the Cystic Fibrosis Foundation. A Declaration of Interest: there is no financial/personal interest or belief that could affect our objectivity, and there is no potential competing interests., (© 2021 The Authors.)

People with type 1 diabetes (T1D) are at increased risk of developing low bone mineral density and fractures. Optimization of calcium intake is a key component of pediatric bone health care. Despite the known risk factors for impaired bone health in T1D and the known benefits of calcium on bone accrual, there are limited data describing calcium intake in youth with T1D. In this cross-sectional study, calcium intake was assessed in 238 youth with T1D. One third of study participants were found to have inadequate calcium intake. Female sex, especially during adolescence, and obesity were identified as specific risk factors for inadequate calcium intake. Given the known adverse effects of T1D on bone health, efforts to promote calcium intake in youth with T1D should be considered., Competing Interests: Conflict of Interest: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Background: This study aims to assess the construct validity of a body composition-defined definition of sarcopenic obesity based on low appendicular lean mass relative to fat mass (ALMI FMI ) and high fat mass index (FMI) and to compare with an alternative definition using appendicular lean mass index (ALMI) and percent body fat (%BF)., Methods: This is a secondary analysis of two cohort studies: the National Health and Examination Survey (NHANES) and the Health, Aging, and Body Composition study (Health ABC). Sarcopenic obesity was defined as low ALMI FMI combined with high FMI and was compared with a widely used definition based on ALMI and %BF cut-points. Body composition Z-scores, self-reported disability, physical functioning, and incident disability were compared across body composition categories using linear and logistic regression and Cox proportional hazards models., Results: Among 14, 850 participants from NHANES, patients with sarcopenic obesity defined by low ALMI FMI and high FMI (ALMI FMI -FMI) had above-average FMI Z-scores [mean (standard deviation): 1.00 (0.72)]. In contrast, those with sarcopenic obesity based on low ALMI and high %BF (ALMI-%BF) had below-average FMI Z-scores. A similar pattern was observed for 2846 participants from Health ABC. Participants with sarcopenic obesity based on ALMI FMI -FMI had a greater number of disabilities, worse physical function, and a greater risk of incident disability compared with those defined based on ALMI-%BF., Conclusions: Body composition-defined measures of sarcopenic obesity defined as excess adiposity and lower-than-expected ALMI relative to FMI are associated with functional deficits and incident disability and overcome the limitations of using %BF in estimating obesity in this context., (© 2020 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of Society on Sarcopenia, Cachexia and Wasting Disorders.)

Background: Osteogenesis imperfecta (OI) is a rare group of disorders characterized by increased susceptibility to fractures due to genetically determined bone fragility. About 90% of cases are due to mutations in COL1A1 (17q21.33) or COL1A2 (7q21.3) resulting in quantitative or qualitative defects in type I collagen, a key structural constituent of bone. OI due to complete COL1A1 deletion is rare., Methods: We present a case of OI type I in a Caucasian female referred at 10 months of age for investigation of multiple fractures associated with minimal or no known trauma, small stature, and blue sclera. Her father has four to five lifetime fractures, blue sclera, normal stature, and a 14.5 kilobase (kb) deletion of COL1A1 detected by targeted array performed at an outside institution. Microarray comparative genomic hybridization was performed on the proband and all members of the family., Results: A previously unreported 235 kb deletion at 17q21.33 encompassing COL1A1, ITGA3, PDK2, SGCA, and HILS1 was detected in the proband. Also identified in both the proband and sibling is a maternally inherited 283 kb gain at 8p21.3 encompassing CSGALNACT1 and a 163 kb loss at 10q21.3 encompassing CTNNA3. Analysis in the father revealed the same size deletion at 17q21.33 as in the proband., Conclusion: Together with previously reported cases of COL1A1 deletions, this case report emphasizes the importance of a whole-genome DNA copy number assessment in patients suspected for OI, which will elucidate the presence of precise COL1A1 deletions and any pathogenic secondary copy number variations., (© 2020 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.)

The last 2 decades have seen growing recognition of the need to appropriately identify and treat children with osteoporotic fractures. This focus stems from important advances in our understanding of the genetic basis of bone fragility, the natural history and predictors of fractures in chronic conditions, the use of bone-active medications in children, and the inclusion of bone health screening into clinical guidelines for high-risk populations. Given the historic focus on bone densitometry in this setting, the International Society for Clinical Densitometry published revised criteria in 2013 to define osteoporosis in the young, oriented towards prevention of overdiagnosis given the high frequency of extremity fractures during the growing years. This definition has been successful in avoiding an inappropriate diagnosis of osteoporosis in healthy children who sustain long bone fractures during play. However, its emphasis on the number of long bone fractures plus a concomitant bone mineral density (BMD) threshold ≤ -2.0, without consideration for long bone fracture characteristics (eg, skeletal site, radiographic features) or the clinical context (eg, known fracture risk in serious illnesses or physical-radiographic stigmata of osteoporosis), inappropriately misses clinically relevant bone fragility in some children. In this perspective, we propose a new approach to the definition and diagnosis of osteoporosis in children, one that balances the role of BMD in the pediatric fracture assessment with other important clinical features, including fracture characteristics, the clinical context and, where appropriate, the need to define the underlying genetic etiology as far as possible., (© Endocrine Society 2019. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Context: Type 1 diabetes (T1D) is associated with an increased fracture risk across the life course. The effects on bone accrual early in the disease are unknown., Objective: To characterize changes in bone density and structure over the year following diagnosis of T1D and to identify contributors to impaired bone accrual., Design: Prospective cohort study., Setting: Academic children's hospital., Participants: Thirty-six children, ages 7 to 17 years, enrolled at diagnosis of T1D., Outcomes: Whole body and regional dual-energy X-ray absorptiometry and tibia peripheral quantitative computed tomography obtained at baseline and 12 months. The primary outcome was bone accrual assessed by bone mineral content (BMC) and areal bone mineral density (aBMD) velocity z score., Results: Participants had low total body less head (TBLH) BMC (z = -0.46 ± 0.76), femoral neck aBMD (z = -0.57 ± 0.99), and tibia cortical volumetric BMD (z = -0.44 ± 1.11) at diagnosis, compared with reference data, P < 0.05. TBLH BMC velocity in the year following diagnosis was lower in participants with poor (hemoglobin A1c ≥7.5%) vs good (hemoglobin A1c <7.5%) glycemic control at 12 months, z = -0.36 ± 0.84 vs 0.58 ± 0.71, P = 0.003. TBLH BMC velocity was correlated with gains in tibia cortical area (R = 0.71, P = 0.003) and periosteal circumference (R = 0.67, P = 0.007) z scores in participants with good, but not poor control., Conclusions: Our results suggest that the adverse effects of T1D on BMD develop early in the disease. Bone accrual following diagnosis was impaired in participants with poor glycemic control and appeared to be mediated by diminished bone formation on the periosteal surface., (Copyright © 2019 Endocrine Society.)

Sitting still for extended periods of time can lead to physical discomfort and even serious health risks. Due to safety regulations, reducing passenger' sitting time in aircrafts is not feasible. This paper presents the results of a laboratory study, in where an interactive airplane seat was compared with a current economy class seat. Participants used both seats for 3.5 h, and performed significantly more in-seat movements when using the interactive seating system. Furthermore, this interactive seat predominantly lead to significantly better comfort experiences and reduced discomfort experiences, however no significant differences have been found in self-reported localized musculoskeletal discomfort. Passengers indicated that they would prefer this interactive seat over a standard aircraft seat., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Humans are one of the few species undergoing an adolescent growth spurt. Because children enter the spurt at different ages making age a poor maturity measure, longitudinal studies are necessary to identify the growth patterns and identify commonalities in adolescent growth. The standard maturity determinant, peak height velocity (PHV) timing, is difficult to estimate in individuals due to diurnal, postural, and measurement variation. Using prospective longitudinal populations of healthy children from two North American populations, we compared the timing of the adolescent growth spurt's peak height velocity to normalized heights and hand skeletal maturity radiographs. We found that in healthy children, the adolescent growth spurt is standardized at 90% of final height with similar patterns for children of both sexes beginning at the initiation of the growth spurt. Once children enter the growth spurt, their growth pattern is consistent between children with peak growth at 90% of final height and skeletal maturity closely reflecting growth remaining. This ability to use 90% of final height as easily identified important maturity standard with its close relationship to skeletal maturity represents a significant advance allowing accurate prediction of future growth for individual children and accurate maturity comparisons for future studies of children's growth.

Background/objectives: Many children do not consume the recommended daily allowance of calcium. Inadequate calcium intake in childhood may limit bone accrual. The objective of this study was to determine if a behavioral modification and nutritional education (BM-NE) intervention improved dietary calcium intake and bone accrual in children., Subjects/methods: 139 (86 female) healthy children, 7-10 years of age, were enrolled in this randomized controlled trial conducted over 36 months. Participants randomized to the BM-NE intervention attended five sessions over a 6-week period designed to increase calcium intake to 1500 mg/day. Participants randomized to the usual care (UC) group received a single nutritional counseling session. The Calcium Counts Food Frequency Questionnaire was used to assess calcium intake; dual energy X-ray absorptiometry was used to assess areal bone mineral density (aBMD) and bone mineral content (BMC). Longitudinal mixed effects models were used to assess for an effect of the intervention on calcium intake, BMC and aBMD., Results: BM-NE participants had greater increases in calcium intake that persisted for 12 months following the intervention compared with UC. The intervention had no effect on BMC or aBMD accrual. Secondary analyses found a negative association between calcium intake and adiposity such that greater calcium intake was associated with lesser gains in body mass index and fat mass index., Conclusions: A family-centered BM-NE intervention program in healthy children was successful in increasing calcium intake for up to 12 months but had no effect on bone accrual. A beneficial relationship between calcium intake and adiposity was observed and warrants future study.

Context: Zoledronic acid (ZA) is increasingly used in young patients with bone disorders. However, data related to the safety of ZA administration in this population are limited., Objective: The study aimed to characterize the short-term safety profile of ZA and identify risk factors for ZA-related adverse events (AEs) in young patients., Design, Setting, and Participants: This was a retrospective chart review of inpatients and outpatients less than 21 years old who received at least one ZA infusion between July 2010 and January 2014 at The Children's Hospital of Philadelphia., Results: Eighty-one patients (56% male; median age, 12 y; age at first infusion, 0.5 to 20 y) with diverse skeletal disorders received a total of 204 infusions. The most common indications were osteoporosis (33% of cohort) and osteogenesis imperfecta (27.2%). The median ZA dose was 0.025 mg/kg (interquartile range, 0.025-0.05); the median dosing interval was 6 months (range, 1 to 25.6 mo). AEs were mild and more common after the first ZA infusion in patients with no previous bisphosphonate exposure: hypophosphatemia (25.2% of infusions), acute phase reactions (19.1%), and hypocalcemia (16.4%). Symptomatic hypocalcemia requiring iv calcium occurred after two infusions. ZA dose was significantly associated with hypophosphatemia, but not other AEs. Hypocalcemia was more common in patients with high bone turnover as assessed by preinfusion alkaline phosphatase levels. AEs were not associated with diagnosis, baseline serum calcium, or calcium/calcitriol supplementation., Conclusion: Acute AEs related to ZA infusion in youths are common, occur principally after the first ZA infusion in bisphosphonate-naive patients, and are typically mild and easily managed. Future prospective studies are needed to determine the potential long-term risks, as well as benefits, of ZA therapy in the pediatric population.

Context: Rapid bone accrual and calcium demands during puberty may result in compensatory increases in PTH and 1,25-dihydroxyvitamin D [1,25(OH)2D] levels; however, these relations have not been established in longitudinal studies., Objective: To determine whether greater bone accrual velocity is associated with greater PTH and 1,25(OH)2D levels in healthy children and adolescents., Design: Prospective cohort study with baseline PTH, 25-hydroxyvitamin D [25(OH)D], and 1,25(OH)2D levels and dual-energy x-ray absorptiometry whole-body bone mineral content (BMC) accrual over 12 months. Secondary analyses examined bone biomarkers and tibia quantitative computed tomography midshaft cortical-BMC., Participants: A total of 594 healthy participants, ages 5-21 years, with longitudinal measures in a subset of 145 participants., Main Outcome Measures: PTH and 1,25(OH)2D levels., Results: PTH levels were higher during Tanner stages 3 and 4 compared to Tanner 1 (P < .05) in males and females and were inversely and significantly associated with 25(OH)D levels and dietary calcium intake. In multivariable analyses, greater bone accrual [measured directly as change in dual-energy x-ray absorptiometry-BMC (P < .001) or quantitative computed tomography-BMC (P < .05), or indirectly as growth velocity (P < .05) or greater bone-formation biomarker level (P < .01)] was associated with higher PTH levels, independent of 25(OH)D level and dietary calcium intake. Similar associations were observed between these direct and indirect indices of bone accrual and 1,25(OH)2D levels., Conclusions: PTH levels rise in midpuberty, in association with multiple measures of bone accrual. This is consistent with compensatory increases in PTH to drive 1,25(OH)2D production and calcium absorption during periods of increased calcium demands. Additional studies are needed to address PTH effects on bone modeling and remodeling during growth and development.

Objective: This study was conducted to determine if type 1 diabetes is associated with an increased risk of fracture across the life span., Research Design and Methods: This population-based cohort study used data from The Health Improvement Network (THIN) in the U.K. (data from 1994 to 2012), in which 30,394 participants aged 0-89 years with type 1 diabetes were compared with 303,872 randomly selected age-, sex-, and practice-matched participants without diabetes. Cox regression analysis was used to determine hazard ratios (HRs) for incident fracture in participants with type 1 diabetes., Results: A total of 334,266 participants, median age 34 years, were monitored for 1.9 million person-years. HR were lowest in males and females age <20 years, with HR 1.14 (95% CI 1.01-1.29) and 1.35 (95% CI 1.12-1.63), respectively. Risk was highest in men 60-69 years (HR 2.18 [95% CI 1.79-2.65]), and in women 40-49 years (HR 2.03 [95% CI 1.73-2.39]). Lower extremity fractures comprised a higher proportion of incident fractures in participants with versus those without type 1 diabetes (31.1% vs. 25.1% in males, 39.3% vs. 32% in females; P < 0.001). Secondary analyses for incident hip fractures identified the highest HR of 5.64 (95% CI 3.55-8.97) in men 60-69 years and the highest HR of 5.63 (95% CI 2.25-14.11) in women 30-39 years., Conclusions: Type 1 diabetes was associated with increased risk of incident fracture that began in childhood and extended across the life span. Participants with type 1 diabetes sustained a disproportionately greater number of lower extremity fractures. These findings have important public health implications, given the increasing prevalence of type 1 diabetes and the morbidity and mortality associated with hip fractures., (© 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.)

Metaphyseal anadysplasia (MANDP) is an uncommon chondrodysplasia characterized by early-onset metaphyseal dysplasia and short stature that improves with age. MANDP is caused by mutations in the matrix metalloproteinase (MMP) 9 and 13 genes. Autosomal dominant (AD) MANDP has been described as more severe, and has been associated with dominant-negative MMP13 mutations that suppress activity of both MMP9 and MMP13; autosomal recessive (AR) MANDP has been described as a milder form associated with AR missense mutations in MMP9 or MMP13. Here we describe the molecular characterization of skeletal dysplasia in two brothers who presented with short stature and mixed epiphyseal and metaphyseal dysplasia. Whole-exome sequencing (WES) identified a homozygous C>T transition mutation in exon 2 of MMP13 (c.325C>T) on chromosome 11q22.2 resulting in a premature stop codon p.(R109*) that is predicted to abolish MMP13 activity. This report extends the MANDP phenotype by illustrating that AR nonsense mutations in MMP13 can lead to short stature that persists beyond childhood.

Context: The use of body mass index (BMI) to assess risk for cardiometabolic disease in the pediatric population may be limited by a failure to differentiate between fat and lean body mass., Objectives: The objectives of the study were to identify biologically based criteria for the definition of obesity using fat (FMI) and lean body mass index (LBMI) and to compare the ability of FMI and LBMI to BMI to identify the presence of metabolic syndrome (MetSyn)., Design: This was a cross-sectional study using National Health and Nutrition Examination Survey 1999-2006 data., Participants: A total of 3004 participants aged 12-20 years with dual-energy X-ray absorptiometry body composition and fasting laboratory data participated in the study., Main Outcome Measures: Adjusted odds ratios for MetSyn according to FMI and LBMI status and area under the curve for the identification of MetSyn were measured., Results: Receiver-operating characteristic curve analyses identified the 80th percentile for FMI and the 74th percentile for LBMI as the optimal cut points for the identification of MetSyn. There was no difference in the area under the curve for FMI [0.867; 95% confidence interval (CI) 0.838-0.891] vs BMI (0.868; 95% CI 0.837-0.894) Z-scores for MetSyn discrimination. Separate multivariate regression models identified odds ratios for the identification of MetSyn of 6.2 (95% CI 3.3-11.5) for BMI-Z, 6.4 (95% CI 3.7-11.1) for FMI-Z, and 4.6 (95% CI 3.0-7.1) for LBMI-Z. Models containing both FMI-Z and LBMI-Z revealed that greater LBMI-Z was associated with greater odds of low high-density lipoprotein (1.5; 95% CI 1.2-1.9), high blood pressure (1.8; 95% CI 1.1-2.9), and insulin resistance (1.8; 95% CI 1.4-2.5), independent of FMI-Z., Conclusions: The use of FMI and LBMI does not improve upon BMI for the identification of MetSyn in the pediatric population. Unexpectedly, higher LBMI was associated with greater odds of multiple cardiometabolic risk factors independent of FMI. The use of FMI and LBMI allow for the independent evaluation of relationships between body compartments and disease and warrants future research.

Background: Anomalous aortic origin of a coronary artery with an interarterial and intramural course (AAOCA) is a rare anomaly with increased risk of sudden cardiac death during or just after exercise among otherwise healthy youth. Risk stratification and management remain controversial, especially for the asymptomatic child with an anomalous right coronary artery from the left coronary sinus (ARCA). Medium-term surgical and quality-of-life (QOL) outcome data are lacking in this population., Methods: We performed medical record review on 24 subjects who underwent AAOCA repair between 2001 and 2007 at The Children's Hospital of Philadelphia. QOL was prospectively assessed with age-appropriate questionnaires., Results: Median age at follow-up was 18 (range, 11-25) years, median follow-up from surgery was 63 (range, 12-110) months, and 16 (67%) had ARCA. All were alive without exercise restriction. Thirteen (54%) complained of cardiac-type symptoms postoperatively, most commonly chest pain, none correlating with evidence of ischemia on testing. Of the 13 patients, 7 (54%) reported the same symptoms preoperatively; and of these, 5 had ARCA. Postoperative morbidity occurred in 16 (67%), including pericardial effusion (n = 11), wound infection (n = 2), and development of mild aortic insufficiency (n = 4). QOL questionnaires were sent to 21 subjects; 12 (57%) were returned. Average QOL was normal for all subjects., Conclusions: In the medium-term after AAOCA repair, cardiac-type symptoms frequently persist and morbidity is common, but these do not impair QOL. The significance of these findings in the long-term is unknown and warrants continued follow-up., (Copyright © 2014 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.)

Background: Body mass index (BMI) and percentage body fat (%BF) are widely used to assess adiposity. These indexes fail to account for independent contributions of fat mass (FM) and lean body mass (LBM) to body weight, which vary according to age, sex, pubertal status, and population ancestry in the pediatric population., Objective: The objective was to develop pediatric reference curves for fat mass index (FMI) and lean body mass index (LBMI) and evaluate the effects of population ancestry and LBM on measures of excess adiposity (BMI, %BF, and FMI)., Design: Sex-specific FMI and LBMI reference curves relative to age for children and adolescents aged 8-20 y were generated from cross-sectional body-composition data measured by dual-energy X-ray absorptiometry from NHANES., Results: The mean LBMI z score was higher in blacks (males: 0.26; females: 0.45) than in whites (males: -0.07; females: -0.09) and Mexican Americans (males: 0.05; females: -0.09). The positive predictive value of overweight by BMI to identify excess adiposity defined by FMI was lower in blacks (males: 35.9%; females: 30.3%) than in whites (males: 65.4%; females: 52.2%) and Mexican Americans (males: 73.3%; females: 68.3%). Participants classified as having excess adiposity by FMI but normal adiposity by %BF had significantly higher BMI, LBMI, and height z scores than did those classified as having excess adiposity by %BF but normal adiposity by FMI., Conclusions: Relative to FMI, the prevalence of excess adiposity is overestimated by BMI in blacks and underestimated by %BF in individuals with high LBM. The use of FMI and LBMI improves on the use of %BF and BMI by allowing for the independent assessment of FM and LBM.

In a previous study, a 24-kilodalton (kDa) protein surface antigen of Legionella pneumophila was cloned into Escherichia coli and found to be expressed on the host cell surface. Subsequently, a site-directed mutation in this gene (designated mip) in L. pneumophila was found to impair the capacity of this bacterium to initiate intracellular infection in human macrophages. The work presented here indicates that the antigenic gene product is distinct from the 24- to 29-kDa major outer membrane protein of L. pneumophila. In addition, the antigen was identified as a highly basic protein on two-dimensional nonequilibrium polyacrylamide gels and on two-dimensional monoclonal antibody immunoblots. When the DNA fragment encoding this protein was sequenced, a long open reading frame of 699 base pairs was identified within a region to which antigen expression was previously mapped. mip mRNA isolated from both L. pneumophila and transformed E. coli had the same 5' end, as determined by primer extension analysis, indicating that the same promoter sequences are used in both species. A likely factor-independent transcriptional terminator was found 20 residues downstream of the stop codon, suggesting that mip is encoded on a monocistronic message. The inferred polypeptide began with a possible 20- to 24-residue signal sequence, and, as predicted by two-dimensional electrophoresis, had a molecular weight of 24,868 and was a potent polycation with an estimated pI of 9.8.

Metabolites of arachidonic acid (eicosanoids) may have an important role in the healing process after myocardial infarction. We examined the ability of cardiac fibroblasts from normal and from healing infarcted ventricle to metabolize arachidonate. We induced myocardial infarction in dogs and then allowed them to recover for 1 week, at which time they were killed, and the heart was removed. Fibroblasts were harvested from normal and from the healing, infarcted areas of the left ventricle. The cells from each source were morphologically indistinguishable. There were 347 +/- 102-fold more fibroblasts cultured from the infarcted area than from the normal area. Interestingly, the infarct-derived cells had a slower doubling time (37.4 +/- 3.7 hours) than the normal cells (22.0 +/- 3.6 hours). The uptake of exogenous arachidonate and its distribution in complex lipids was the same in the cells from each area. When stimulated with the calcium ionophore, free exogenous arachidonate, bradykinin, or histamine the cells produced prostaglandin E2 and prostaglandin I2. In each case the infarct-derived cells produced from twofold to fivefold more prostaglandin than the normal cells. We also found that prostaglandin synthesis was highly dependent on the growth state of the cells with a marked decrease a confluence. Finally, in experiments designed to mimic the early state of infarction, we confirmed that isolated cardiac myocytes release arachidonate and showed that normal fibroblasts can incorporate it. The production of eicosanoids by cardiac fibroblasts may be substantial during the healing of myocardial infarction due to their dramatic proliferation and the increased prostaglandin production per cell.