Fractures following pregnancy in Osteogenesis imperfecta – A self-controlled case series using Danish Health Registers

Context: Hyperthyroidism is associated with severe comorbidity, such as stroke, and seems to confer increased mortality. However, it is unknown whether this increased mortality is explained by hyperthyroidism per se, comorbidity, and/or genetic confounding. Objective: The objective of the study was to investigate whether hyperthyroidism is associated with an increased mortality and, if so, whether the association is influenced by comorbidity and/or genetic confounding. Methods: This was an observational cohort study using record-linkage data from nationwide Danish health registers. We identified 4850 singletons and 926 twins from same-sex pairs diagnosed with hyperthyroidism. Each case was matched with four controls for age and gender. The Charlson score was calculated from discharge diagnoses on an individual level to measure comorbidity. Cases and controls were followed up for a mean of 10 yr (range 0–31 yr), and the hazard ratio (HR) for mortality was calculated using Cox regression analyses. Results: In singletons there was a significantly higher mortality in individuals diagnosed with hyperthyroidism than in controls [HR 1.37; 95% confidence interval (CI) 1.30–1.46]. This persisted after adjustment for preexisting comorbidity (HR 1,28; 95% CI 1.21–1.36). In twin pairs discordant for hyperthyroidism (625 pairs), the twin with hyperthyroidism had an increased mortality compared with the corresponding cotwin (HR 1.43; 95% CI 1.09–1.88). However, this was found only in dizygotic pairs (HR 1.80; 95% CI 1.27–2.55) but not in monozygotic pairs (HR 0.95; 95% CI 0.60–1.50). Conclusions: Hyperthyroidism is associated with an increased mortality independent of preexisting comorbidity. The study of twin pairs discordant for hyperthyroidism suggests that genetic confounding influences the association between hyperthyroidism and mortality.

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Interpreting Osteogenesis Imperfecta Variants of Uncertain Significance in the Context of Physical Abuse: A Case Series

Journal of Pediatric Genetics ◽

10.1055/s-0038-1672135 ◽

2018 ◽

Vol 08 (02) ◽

pp. 063-068

Author(s):

Jennifer Canter ◽

Vinod Rao ◽

Vincent Palusci ◽

David Kronn ◽

Michal Manaster ◽

...

Keyword(s):

Child Abuse ◽

Osteogenesis Imperfecta ◽

Physical Abuse ◽

Clinical Significance ◽

Case Series ◽

Variants Of Unknown Significance ◽

Unknown Significance ◽

Potential Abuse ◽

Uncertain Significance

AbstractUnexplained childhood fracture(s) warrant consideration of physical abuse and osteogenesis imperfecta (OI). Genetic OI testing may identify “variants of unknown significance (VUS).” Interpretation of VUS in context of potential abuse may have protective, criminal, and medical impacts. This case series explores practices regarding clinicians' interpretation of VUS during child abuse evaluations. Variability was noted regarding factors considered for interpreting clinical significance. Based on these cases, recommendations for careful and thorough evaluation are detailed, including proposed use of a limited follow-up skeletal survey in 3 months, as a consideration to assess healing of prior fractures and to look for any additional injuries.

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Abnormal corneal properties in osteogenesis imperfecta and glaucoma: a case series

BMJ Open Ophthalmology ◽

10.1136/bmjophth-2020-000684 ◽

2021 ◽

Vol 6 (1) ◽

pp. e000684

Author(s):

Emer Doolan ◽

Colm O’Brien

Keyword(s):

At Risk ◽

Osteogenesis Imperfecta ◽

Open Angle Glaucoma ◽

Topical Therapy ◽

Corneal Thickness ◽

Family Members ◽

Significant Risk ◽

Case Series ◽

Splice Site Mutation ◽

Site Mutation

ObjectiveWe aimed to carry out ocular examination and genetic studies in a family in which some members are affected with osteogenesis imperfecta (OI) and primary open-angle glaucoma (POAG). We compared the corneal properties of affected and unaffected members (ie, cases and controls).MethodsEight family members from two generations, both affected and unaffected, were examined. Corneal hysteresis (CH), intraocular pressure (IOP) measured with Goldmann applanation tonometer, central corneal thickness (CCT) and cornea-corrected IOP (IOPcc) were recorded. Blood samples were obtained from seven family members, both affected and unaffected, and tested for a panel of genes associated with OI.ResultsFamily members affected with OI (n=6) had a heterozygous splice site mutation in intron 26 of the COL1A1 gene. The family members affected with OI had reduced CCT (476.5±24.6 µm) and CH (7.9 ±1.4 mmHg) compared with the unaffected controls (CCT, 575.8±10.8 µm; CH, 12.3±0.8 mmHg). Two of the six patients affected with OI had a glaucoma diagnosis and were on topical therapy and under regular clinical review.ConclusionsPatients affected with OI have a significant risk of developing POAG due to the effects of abnormal collagen on various ocular structures. Two of these effects which place them at risk are reduced CCT and CH. They should be screened and monitored for glaucoma from a young age, and the examination should include corneal biomechanical measurements and CCT to identify those most at risk. IOPcc may be a more accurate way to monitor IOP in the presence of abnormal corneal properties.

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Cochlear implantation in patients with osteogenesis imperfecta

Otolaryngology ◽

10.1016/j.otohns.2004.12.012 ◽

2005 ◽

Vol 132 (5) ◽

pp. 735-740 ◽

Cited By ~ 19

Author(s):

Sven-Olrik Streubel ◽

L. R. Lustig

Keyword(s):

Hearing Loss ◽

Osteogenesis Imperfecta ◽

Sensorineural Hearing Loss ◽

Cochlear Implantation ◽

Single Case ◽

Case Reports ◽

Test Word ◽

Case Series ◽

Sensorineural Hearing ◽

Type I

OBJECTIVE: Hearing loss has been shown to occur in 42% to 58% of patients with osteogenesis imperfecta (OI), with deafness arising in 25% to 60% of the patients. Implantation in patients with OI is relatively rare, with only 4 prior single case reports published in the English-language literature. The goal of this study was to evaluate the feasibility and functional outcome of cochlear implantation in 2 patients with OI tarda type I with profound sensorineural hearing loss. STUDY DESIGN: Case series. SETTING:. The implantations were performed in a tertiary academic referral center (Johns Hopkins University). RESULTS: Though promontory vascularity was encountered, full insertion of a normal cochlear implant array could be achieved in both cases. One-year postimplant scores demonstrated 20 to 40 dB hearing thresholds, Consonant-Nucleus-Consonant Test word scores of 54% and 70%, Consonant-Nucleus-Consonant Test phoneme scores of 75% and 83%, Hearing in Noise Test scores of 76% and 99%, and Central Institute of the Deaf Sentence Score sentence scores of 99% and 100%, for patients 1 and 2, respectively. CONCLUSIONS: Cochlear implantation in patients with OI is not only technically possible but the results are similar to implant outcomes for patients with sensorineural hearing loss from a variety of other causes. EBM rating: C (Otolaryngol Head Neck Surg 2005;132:735-40.)

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G68 Case series: RIB fractures in infants with osteogenesis imperfecta

10.1136/archdischild-2017-313087.67 ◽

2017 ◽

Author(s):

C Avann ◽

S Chapman ◽

N Shaw

Keyword(s):

Osteogenesis Imperfecta ◽

Case Series ◽

Rib Fractures

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Femoral neck fractures in osteogenesis imperfecta patients: A retrospective case series and novel surgical technique

Case Studies in Surgery ◽

10.5430/css.v3n3p14 ◽

2017 ◽

Vol 3 (3) ◽

pp. 14

Author(s):

Mark T. Gorsche ◽

Michelle S. Caird ◽

Frances A. Farley ◽

G. Ying Li ◽

Matthew D. Abbott

Keyword(s):

Femoral Neck ◽

Osteogenesis Imperfecta ◽

Proximal Femur ◽

Screw Fixation ◽

Case Series ◽

Femoral Neck Fractures ◽

Cannulated Screw ◽

Coxa Vara ◽

Retrospective Case ◽

Revision Procedure

Case: We conducted a retrospective review of three cases of femoral neck fractures treated operatively in patients with osteogenesis imperfecta (OI). All of our patients had acetabular protrusio as well as coxa vara deformity. All patients successfully underwent cannulated screw fixation without avascular necrosis (AVN). One patient required a sub-adductor hip arthrogram during a revision procedure to assist with visualization of the proximal femur which resulted in improved screw purchase.Conclusions: We report on three cases of femoral neck fractures in OI patients and a previously undescribed technique; using a hip arthrogram to assist in fluoroscopic evaluation of the proximal femur in these osteopenic patients.

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Outcomes of Operative Treatment of Forearm Deformity in Children with Osteogenesis Imperfecta: 18 Cases

Osteology ◽

10.3390/osteology2010003 ◽

2022 ◽

Vol 2 (1) ◽

pp. 21-30

Author(s):

Maegen Wallace ◽

Paul Esposito

Keyword(s):

Osteogenesis Imperfecta ◽

Medical Center ◽

Case Series ◽

Deformity Correction ◽

Retrospective Case ◽

Surgical Interventions ◽

Patient Demographics ◽

Impact Function ◽

Institutional Review ◽

The University

Osteogenesis imperfecta (OI) often results in recurrent fractures and/or progressive bowing of the long bones, including the arms. Upper extremity deformity has been shown to negatively impact function. The objective of this retrospective case series is to assess the ability to correct deformity, improve function and evaluate the complications and revision rates in our patients with OI who have undergone forearm deformity correction. A retrospective study, approved by The University of Nebraska Medical Center Institutional Review Board, was conducted with OI patients who underwent forearm osteotomy and fixation of one or both forearm bones between December 2011 and August 2018. There were no exclusion criteria. The electronic medical records were reviewed for patient demographics, surgical details, revisions and complications. A total of 48 procedures on 27 forearms in 18 patients were performed during the study. Surgery was performed in children with forearm deformity and recurrent fractures that were interfering with function. Half of the patients had surgery on one forearm and half had surgery on both forearms. The majority of the patients have Type III OI. There were multiple complications, the most common being wire migration which required either replacement or advancement of the wire. In conclusion, forearm deformity in OI is possible, with good healing of osteotomies and fractures, although many patients may require multiple surgical interventions.

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Efficacy and Safety of Denosumab Therapy for Osteogenesis Imperfecta Patients with Osteoporosis—Case Series

Journal of Clinical Medicine ◽

10.3390/jcm7120479 ◽

2018 ◽

Vol 7 (12) ◽

pp. 479 ◽

Cited By ~ 5

Author(s):

Tsukasa Kobayashi ◽

Yukio Nakamura ◽

Takako Suzuki ◽

Tomomi Yamaguchi ◽

Ryojun Takeda ◽

...

Keyword(s):

Osteogenesis Imperfecta ◽

Type I Collagen ◽

Therapeutic Option ◽

Case Series ◽

Connective Tissue Disorder ◽

Tartrate Resistant Acid Phosphatase ◽

Type I ◽

Mineral Density ◽

Bone Specific Alkaline Phosphatase ◽

Amino Terminal

Osteogenesis imperfecta (OI) is a connective tissue disorder that is characterized by low bone density leading to recurrent fractures. The efficacy of the anti-resorption drug denosumab for OI with osteoporosis is still largely unknown. We herein describe the clinical outcomes of eight osteoporotic cases of OI to examine the effects and safety of denosumab. This retrospective, consecutive case series included eight patients respectively aged 42, 40, 14, 22, 3, 51, 37, and 9 years. We measured the bone mineral density (BMD) of the lumbar 1–4 spine (L-BMD) and bilateral hips (H-BMD), bone-specific alkaline phosphatase, urinary type I collagen amino-terminal telopeptide, and tartrate-resistant acid phosphatase 5b before and during denosumab therapy. Despite multiple pretreatment fractures in the cohort, no fractures or severe side effects, such as hypocalcemia, were observed during the observational period apart from a fracture in a young pediatric girl. Both L-BMD and H-BMD were increased by denosumab in seven of eight cases. Bone turnover markers were inhibited in most cases by denosumab therapy. Denosumab treatment could generally raise BMD without any adverse effects. The agent therefore represents a good therapeutic option for OI with osteoporosis.

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