Recent Advances in Osteogenesis Imperfecta

Cundy, Tim

doi:10.1007/s00223-012-9588-3

Cited by 85 publications

(69 citation statements)

References 47 publications

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“…Clinical manifestations include osteopenia/osteoporosis, fractures, skeletal deformities, short stature, and skeletal muscle weakness. Current therapies entail use of antiresorptive drugs and surgical interventions but have limited success (1). New approaches that decrease fracture risk while minimizing long-term damage to bone integrity are greatly needed.…”

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confidence: 99%

Decreasing maternal myostatin programs adult offspring bone strength in a mouse model of osteogenesis imperfecta

Oestreich

Kamp

McCray

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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During fetal development, the uterine environment can have effects on offspring bone architecture and integrity that persist into adulthood; however, the biochemical and molecular mechanisms remain unknown. Myostatin is a negative regulator of muscle mass. Parental myostatin deficiency (Mstn tm1Sjl/+ ) increases muscle mass in wild-type offspring, suggesting an intrauterine programming effect. Here, we hypothesized that Mstn tm1Sjl/+ dams would also confer increased bone strength. In wild-type offspring, maternal myostatin deficiency altered fetal growth and calvarial collagen content of newborn mice and conferred a lasting impact on bone geometry and biomechanical integrity of offspring at 4 mo of age, the age of peak bone mass. Second, we sought to apply maternal myostatin deficiency to a mouse model with osteogenesis imperfecta (Col1a2 oim ), a heritable connective tissue disorder caused by abnormalities in the structure and/or synthesis of type I collagen. Femora of male Col1a2 oim/+ offspring from natural mating of Mstn tm1Sjl/+ dams to Col1a2 oim/+ sires had a 15% increase in torsional ultimate strength, a 29% increase in tensile strength, and a 24% increase in energy to failure compared with age, sex, and genotype-matched offspring from natural mating of Col1a2 oim/+ dams to Col1a2 oim/+ sires. Finally, increased bone biomechanical strength of Col1a2 oim/+ offspring that had been transferred into Mstn tm1Sjl/+ dams as blastocysts demonstrated that the effects of maternal myostatin deficiency were conferred by the postimplantation environment. Thus, targeting the gestational environment, and specifically prenatal myostatin pathways, provides a potential therapeutic window and an approach for treating osteogenesis imperfecta.osteogenesis imperfecta | developmental origins of health and disease | fetal programming | myostatin | bone health O steogenesis imperfecta (OI) is a genetically and clinically heterogeneous heritable connective tissue disorder characterized by anomalies in type I collagen-containing tissues, particularly bone. Clinical manifestations include osteopenia/osteoporosis, fractures, skeletal deformities, short stature, and skeletal muscle weakness. Current therapies entail use of antiresorptive drugs and surgical interventions but have limited success (1). New approaches that decrease fracture risk while minimizing long-term damage to bone integrity are greatly needed. Myostatin, or growth and differentiation factor 8 (GDF8), is a TGF-β family member and negative regulator of muscle growth and development. It is highly conserved across species, primarily expressed in muscle cells, and participates in paracrine and endocrine signaling (2). Recently, we and others have shown that inhibiting myostatin, either genetically or pharmacologically, increases muscle mass and improves bone microarchitecture (3) and mechanical strength (4) in the OI murine (Col1a2 oim ) model. In addition to regulating muscle growth postnatally, myostatin deficiency in the maternal environment increases muscle mass in ...

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confidence: 99%

Decreasing maternal myostatin programs adult offspring bone strength in a mouse model of osteogenesis imperfecta

Oestreich

Kamp

McCray

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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“…The vast majority of OI cases (~90%) are the result of dominant mutations in either of the two type I collagen genes, COL1A1 or COL1A2 (1). A rapidly growing list of recessive gene mutations has emerged, which account for the remaining 5-10% of OI cases although, with a few exceptions (e.g., SERPINF1, IFITM5, WNT1, SP7), most of these genes are involved in the trafficking or complex post-translational processing of type I collagen (2).…”

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confidence: 99%

“…In order of increasing severity, the five phenotypic classifications of OI are type I (classic, nondeforming OI with blue sclerae), type IV (common variable OI with normal or blue sclerae), type V (OI with ossification in interosseous membranes), type III (progressively deforming OI with normal or blue sclerae), and type II (perinatally lethal OI). The majority of the rare, recessive types of OI and newly discovered noncollagen molecular defects, which had previously been assigned their own OI types, have clinically similar phenotypes to OI types II and III (1)(2)(3)(4).…”

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confidence: 99%

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

et al. 2015

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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). Longitudinal height data for 36 children (18 girls, 18 boys) with OI type I and 10 children (8 girls, 2 boys) with OI type III were obtained. results: In all cases, the height Z-scores were negatively impacted, and final height Z-scores were impacted the most. In type I, the growth velocities taper near puberty, and there is a blunted pubertal growth spurt. The growth velocities of children with type III decelerate before age 5 y; poor growth continues without an obvious pubertal growth spurt. Obesity is a concern for all patients with OI, with type III patients being the most affected. conclusion: The linear growth patterns, in addition to the marked increase in weight over time, indicate a need for lifestyle modifications early in childhood, especially a need for weight control. Further definition of the anthropometric measures in OI enables patients to begin modifications as early as possible.o steogenesis imperfecta (OI) comprises a group of heri-

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“…In addition, while this happens at a younger age, the behavior of patient is worse, as well as patient's cooperation (19). On the other hand, since OI type I has an autosomal dominant inheritance, with a good family medical record, diagnostic suspicion may be reached before recurrent fractures 3,10 . However, in our cohort, this referral cause belongs only to 6% of the cases, although there was one case of a parent affected by this disease among the 35% of patients, unlike the one described in one of the previously mentioned studies, in which the presence of family medical record reached 46% of the cases, which makes the diagnosis easier to perform 17 .…”

Section: Discussionmentioning

confidence: 99%

“…They have been shown to be effective in increasing the density and size of vertebral bodies, thickening the cortical bone, increasing the trabecular and improving patient's height [9][10][11] . However, those mild forms of OI are debatable, since they remain for a long time at the bone level (about 10 years) and its long-term effects are still unknown 6,8,10,12,13 .…”

Section: Introductionmentioning

confidence: 99%

Fracturas vertebrales en niños con osteogénesis imperfecta tipo I

Sepúlveda

Terrazas

Sáez

et al. 2017

Rev. chil. pediatr.

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Background: Osteogenesis imperfecta (OI) is an hereditary disease affecting conective tissue, mainly associated to growth retardation and pathological fractures. OI type I (OI type I), is the mildest, most often, and homogeneous in its fenotype. Vertebral fractures are the most significant complications, associated to skeletical and cardiopulmonary morbidity. Objectives: To characterize clinically a cohort of children with OI type I. Patients and Methods: A cohort of OI type I children younger than 20 year old was evaluated. Demographic, clinical, biochemical and radiological data were registered. Results: Sixty seven patients were included, 55% male, 69% resident in the Metropolitan Region. The mean age of diagnose was 2.9 years, 70% presented vertebral fractures on follow-up, mostly thoracic, and 50% before the age of 5 years. Fifty percentage presented vertebral fractures at diagnose, which was about the age of 5 years. Bone metabolic parameters were in the normal range, without significant change at the moment of vertebral fractures. Calcium intake was found to be below American Academy of Pediatrics recommendations at the time of the first fracture. Conclusions: In this study OI type I has an early diagnose, and vertebral fractures show a high incidence, mostly in toddlers. Calcium intake was found to be below reccomended values, and should be closely supervised in these patients.

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Recent Advances in Osteogenesis Imperfecta

Cited by 85 publications

References 47 publications

Decreasing maternal myostatin programs adult offspring bone strength in a mouse model of osteogenesis imperfecta

Decreasing maternal myostatin programs adult offspring bone strength in a mouse model of osteogenesis imperfecta

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

Fracturas vertebrales en niños con osteogénesis imperfecta tipo I

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