Widespread disturbance in extracellular matrix collagen biomarker responses to teriparatide therapy in osteogenesis imperfecta.

Osteogenesis imperfecta (OI), a heritable disorder caused by abnormalities in synthesis or processing of type I collagen, is characterized by skeletal fragility. Type I collagen interacts with multiple components of the extracellular matrix (ECM) including other collagens types. Thus, alterations in structure or quantity may broadly affect ECM homeostasis.

ADULT OSTEOPOROSIS WITH A HISTORY OF CHILDHOOD-ONSET FRACTURE DUE TO AN LRP5 RECEPTOR VARIANT MUTATION.

Objective: This case highlights the value of genetic screening for idiopathic osteoporosis with recurrent fractures.

Methods: Case report and review of the literature.

Results: A 52-year-old Caucasian female with idiopathic osteoporosis with recurrent fractures was identified with a heterozygous low-density lipoprotein receptor related protein 5 (LRP5) mutation.

Hearing loss in individuals with osteogenesis imperfecta in North America: Results from a multicenter study.

Hearing loss (HL) is an extra-skeletal manifestation of the connective tissue disorder osteogenesis imperfecta (OI). Systematic evaluation of the prevalence and characteristics of HL in COL1A1/COL1A2-related OI will contribute to a better clinical management of individuals with OI. We collected and analyzed pure-tone audiometry data from 312 individuals with OI who were enrolled in the Linked Clinical Research Centers and the Brittle Bone Disorders Consortium.

HR-pQCT Measures of Bone Microarchitecture Predict Fracture: Systematic Review and Meta-Analysis.

High-resolution peripheral quantitative computed tomography (HR-pQCT) is a noninvasive imaging modality for assessing volumetric bone mineral density (vBMD) and microarchitecture of cancellous and cortical bone. The objective was to (1) assess fracture-associated differences in HR-pQCT bone parameters; and (2) to determine if HR-pQCT is sufficiently precise to reliably detect these differences in individuals. We systematically identified 40 studies that used HR-pQCT (39/40 used XtremeCT scanners) to assess 1291 to 3253 and 3389 to 10,687 individuals with and without fractures, respectively, ranging in age from 10.

A Multicenter Observational Cohort Study to Evaluate the Effects of Bisphosphonate Exposure on Bone Mineral Density and Other Health Outcomes in Osteogenesis Imperfecta.

Osteogenesis imperfecta (OI) is characterized by low bone mass and bone fragility. Using data from a large cohort of individuals with OI from the Osteogenesis Imperfecta Foundation's linked clinical research centers, we examined the association between exposure to bisphosphonate (BPN) treatment (past or present) and lumbar spine (LS) areal bone mineral density (aBMD), fractures, scoliosis, and mobility. From 466 individuals, we obtained 1394 participant-age LS aBMD data points.

Mobility in osteogenesis imperfecta: a multicenter North American study.

Purpose: Osteogenesis imperfecta (OI) is a genetic connective tissue disorder that causes bone fragility. Phenotypic severity influences ability to walk, however, little is known about ambulatory characteristics of individuals with OI, especially in more severe forms. The purpose of this work was to characterize mobility in OI using standard clinical assessment tools and determine if patient characteristics could be used to predict mobility outcomes.

Alterations in non-type I collagen biomarkers in osteogenesis imperfecta.

Osteogenesis imperfecta [1] is a rare disorder of connective tissue caused by abnormalities in the synthesis or processing of type I collagen. Type I collagen is the most abundant type of collagen and is expressed in almost all connective tissues. Given that type I collagen interacts with other collagens based in the extracellular matrix (ECM), we hypothesized changes in type I collagen in OI would result in perturbations in the homeostasis of other collagen types.

A multicenter study to evaluate pulmonary function in osteogenesis imperfecta.

Pulmonary complications are a significant cause for morbidity and mortality in osteogenesis imperfecta (OI). However, to date, there have been few studies that have systematically evaluated pulmonary function in individuals with OI. We analyzed spirometry measurements, including forced vital capacity (FVC) and forced expiratory volume in the first second (FEV ), in a large cohort of individuals with OI (n = 217) enrolled in a multicenter, observational study.

Growth characteristics in individuals with osteogenesis imperfecta in North America: results from a multicenter study.

Purpose: Osteogenesis imperfecta (OI) predisposes people to recurrent fractures, bone deformities, and short stature. There is a lack of large-scale systematic studies that have investigated growth parameters in OI.

Methods: Using data from the Linked Clinical Research Centers, we compared height, growth velocity, weight, and body mass index (BMI) in 552 individuals with OI.

Serum Sclerostin Levels in Adults With Osteogenesis Imperfecta: Comparison With Normal Individuals and Response to Teriparatide Therapy.

Sclerostin (SOST), a glycoprotein primarily derived from osteocytes, is an important regulator of bone remodeling. Osteogenesis imperfecta (OI) is a heritable disorder of bone characterized by low bone mass, bone fragility, recurrent fractures, and bone deformities. Altered SOST-mediated signaling may have a role in pathogenesis of type I collagen-related OI; however, this has not been evaluated in humans.

Revised consensus statement on the preventive and symptomatic care of patients with leukodystrophies.

Leukodystrophies are a broad class of genetic disorders that result in disruption or destruction of central myelination. Although the mechanisms underlying these disorders are heterogeneous, there are many common symptoms that affect patients irrespective of the genetic diagnosis. The comfort and quality of life of these children is a primary goal that can complement efforts directed at curative therapies.

Hypophosphatasia in Adults: Clinical Assessment and Treatment Considerations.

Hypophosphatasia (HPP) is a rare inherited disorder of bone affecting approximately 500 to 600 known individuals in the United States. HPP is the result of mutations involving the gene for tissue nonspecific alkaline phosphatase. Five clinical types of HPP are recognized.

Zoledronic acid improves bone histomorphometry in a murine model of Rett syndrome.

Rett syndrome (RTT) is a neurodevelopmental disorder predominately affecting young females, caused by deficiency of the global transcriptional protein methyl CpG binding protein 2 (MeCP2). Osteoblasts express MeCP2 and girls with RTT experience early onset osteoporosis, decreased bone mass and an increased fracture risk. There is no defined treatment for osteoporosis associated with RTT.

Bone health in facioscapulohumeral muscular dystrophy: A cross-sectional study.

Introduction: Herein we provide a comprehensive overview of bone health in facioscapulohumeral muscular dystrophy (FSHD).

Methods: Ninety-four adult individuals with FSHD type 1 from 2 sites were included in this cross-sectional study. Clinical characteristics and determinants of bone health were examined.

Health outcomes of neonates with osteogenesis imperfecta: a cross-sectional study.

Objective: To assess at-birth health outcomes of neonates with osteogenesis imperfecta (OI).

Study Design: A total of 53 women who self-reported having had at least one child with OI completed the survey. We evaluated pregnancy length, neonatal intensive care unit (NICU) usage, at-birth complications, and the child's clinical information including OI type, height and weight.

Clinical Guidelines for Management of Bone Health in Rett Syndrome Based on Expert Consensus and Available Evidence.

Objectives: We developed clinical guidelines for the management of bone health in Rett syndrome through evidence review and the consensus of an expert panel of clinicians.

Methods: An initial guidelines draft was created which included statements based upon literature review and 11 open-ended questions where literature was lacking. The international expert panel reviewed the draft online using a 2-stage Delphi process to reach consensus agreement.

Bulbous epiphysis and popcorn calcification as related to growth plate differentiation in osteogenesis imperfecta.

Background: Osteogenesis Imperfecta (OI) is an heritable systemic disorder of connective tissue due to different sequence variants in genes affecting both the synthesis of type I collagen and osteoblast function. Dominant and recessive inheritance is recognized. Approximately 90% of the OI cases are due to mutations in COL1A1/A2 genes.

Cross-sectional and longitudinal growth patterns in osteogenesis imperfecta: implications for clinical care.

Background: There is strikingly limited information on linear growth and weight in the different types of osteogenesis imperfecta (OI). Here, we define growth patterns further with the intent of implementing appropriate adaptations proactively.

Methods: We report cross-sectional anthropometric data for 343 subjects with different OI types (144 children, 199 adults).

Pregnancy outcomes in women with osteogenesis imperfecta.

Objective: To assess the relationship between osteogenesis imperfecta (OI) type, mode of delivery and outcomes as self-reported by women in the International Osteogenesis Imperfecta (OI) Registry.

Methods: A cross-sectional study using data from 274 women with OI who reported their experience with pregnancy practices, including mode of delivery, number of children, genetic counseling, assisted conception techniques, mean ages at menarche and at menopause, and pregnancy complications. Chi-square analyses were performed to compare pregnancy outcomes, number of children and OI type.

Bisphosphonate treatment of children and adults with osteogenesis imperfecta: unanswered questions.

Bisphosphonates are extensively used for treatment of children and adults with osteogenesis imperfecta. Over years, studies have reported the response of BP treatment in individuals with OI but some questions remain still unanswered.

Osteoblast function and bone histomorphometry in a murine model of Rett syndrome.

Rett syndrome (RTT) is an X-linked neurodevelopmental disorder due to mutations affecting the neural transcription factor MeCP2. Approximately 50% of affected females have decreased bone mass. We studied osteoblast function using a murine model of RTT.

Sandwich allografts for long-bone nonunions in patients with osteogenesis imperfecta: a retrospective study.

Background: Patients with osteogenesis imperfecta often develop nonunions, as internal fixation has limited applicability in this condition. We report the outcomes of a modified "sandwich technique" in the treatment of long-bone nonunions in patients with osteogenesis imperfecta; this technique brings circumferential stabilization and normal collagen to the nonunion site.

Methods: From May 2003 through February 2012, twelve patients (eight females, four males; median age, 39.

Evaluation of teriparatide treatment in adults with osteogenesis imperfecta.

Background: Adults with osteogenesis imperfecta (OI) have a high risk of fracture. Currently, few treatment options are available, and bone anabolic therapies have not been tested in clinical trials for OI treatment.

Methods: 79 adults with OI were randomized to receive 20 μg recombinant human parathyroid hormone (teriparatide) or placebo for 18 months in a double-blind, placebo-controlled trial.

Somatic and germline CACNA1D calcium channel mutations in aldosterone-producing adenomas and primary aldosteronism.

Adrenal aldosterone-producing adenomas (APAs) constitutively produce the salt-retaining hormone aldosterone and are a common cause of severe hypertension. Recurrent mutations in the potassium channel gene KCNJ5 that result in cell depolarization and Ca(2+) influx cause ∼40% of these tumors. We identified 5 somatic mutations (4 altering Gly403 and 1 altering Ile770) in CACNA1D, encoding a voltage-gated calcium channel, among 43 APAs without mutated KCNJ5.