The impact of osteogenesis imperfecta severity on oral health-related quality of life in Spain: a cross-sectional study.

BACKGROUND: Osteogenesis imperfecta (OI) affects dental and craniofacial development; therefore, it can influence oral health-related quality of life (OHRQoL). The objective of this study was to explore the influence of the severity of OI on OHRQoL in adults older than eighteen years residing in Spain. METHOD: Adults with OI were recruited from the Spanish Association of Crystal Bone (AHUCE) foundation. OHRQoL was evaluated using the Spanish version of the Oral Health Impact Profile questionnaire (OHIP-14sp), oral hygiene habits, and a dental care survey. Clinical and radiological dental examinations were performed to evaluate the patients' oral conditions. RESULTS: A total of 65 adults (n = 46 females) aged between nineteen and sixty-two years who were diagnosed with OI and classified as type I, III, and IV (n = 20, 14, and 31, respectively) participated in this research. The total OHIP-14sp scores were significantly greater (worse) for type III (23 [SD = 10]) and type IV (21.4 [SD = 12]) than for type I (13.8 [SD = 6]) (P < 0.05). The negative impact of OHRQoL was due to the association of type III OI with all domains except for the handicap domain, while type IV OI was associated with the physical disability, social disability, and handicap domains (P < 0.05 for all). CONCLUSION: The severity of OI negatively impacted OHRQoL in adults. This association was statistically significant.

Influence of zoledronic acid and pamidronate on tooth eruption in children with osteogenesis imperfecta.

INTRODUCTION: Osteogenesis imperfecta (OI) is a congenital disease comprising a heterogeneous group of inherited connective tissue disorders. The main treatment in children is bisphosphonate therapy. Previous animal studies have shown that bisphosphonates delay tooth eruption. The aim of this study is to determine whether patients with OI treated with pamidronate and/or zoledronic acid have a delayed eruption age compared to a control group of healthy children. METHODS: An ambispective longitudinal cohort study evaluating the age of eruption of the first stage mixed dentition in a group of children with OI (n = 37) all treated with intravenous bisphosphonates compared with a group of healthy children (n = 89). Within the study group, the correlation (Pearson correlation test) between the type of medication administered (pamidronate and/or zoledronic acid) and the chronology of tooth eruption is established, as well as the relationship between the amount of cumulative dose received and tooth eruption. RESULTS: The age of eruption of the study group was significantly delayed compared to the age of eruption of the control group for molars and lateral incisors (p < 0.05). Patients who received higher cumulative doses had a delayed eruption age compared to those with lower cumulative doses (p < 0.05). There is a high positive correlation between age of delayed tooth eruption and Zoledronic acid administration. CONCLUSION: Patients with OI have a delayed eruption of the 1st stage mixed dentition compared to a control group of healthy children. This delayed eruption is directly related to the cumulative dose of bisphosphonates and the administration of zoledronic ac.

The IMPACT survey: a mixed methods study to understand the experience of children, adolescents and adults with osteogenesis imperfecta and their caregivers.

BACKGROUND: Osteogenesis imperfecta (OI) is a rare, heritable connective tissue disorder associated with a variety of symptoms, that affect individuals' quality of life (QoL) and can be associated with increased healthcare resource use. While some aspects of OI are well studied, others remain poorly understood. Therefore, the IMPACT survey aimed to elucidate the humanistic, clinical and economic burden of OI on individuals with OI, their families, caregivers and wider society. METHODS: We developed an international mixed methods online survey in eight languages (fielded July-September 2021), aimed at adults (aged ≥ 18 years) or adolescents (aged ≥ 12-17 years) with OI, caregivers (with or without OI) of individuals with OI and other close relatives. All respondents provided data on themselves; caregivers additionally provided data on individuals in their care by proxy. Data were cleaned, coded, and analysed using the pandas Python software package and Excel. RESULTS: IMPACT collected 2208 eligible questionnaires (covering 2988 individuals of whom 2312 had OI) including 1290 non-caregiver adults with OI, 92 adolescents with OI, 150 caregiver adults with OI, 560 caregivers for individuals with OI, 116 close relatives and 780 proxy care-recipients with OI. Most individuals with OI (direct or proxy) described their OI as moderate (41-52% across populations) and reported OI type 1 (33-38%). Pain (72-82%) was the most reported clinical condition experienced in the past 12 months and was also most frequently rated as severely or moderately impactful. Further, among adults, 67% reported fatigue, 47% scoliosis, and 46% sleep disturbance; in adolescents, fatigue affected 65%, scoliosis and other bone problems 60%, and mental health problems 46%; in children, fractures were common in 67%, fatigue in 47%, and dental problems in 46%. CONCLUSION: IMPACT has generated an extensive dataset on the experience of individuals with OI, their caregivers and relatives. We found that, irrespective of age, individuals with OI experience numerous and evolving symptoms that affect their QoL; however, pain and fatigue are consistently present. Upcoming analyses will provide further insights into the economic impact, healthcare journey and caregiver wellbeing, aiming to contribute to improved treatment and care for the OI community.

Short-term effects of Mediterranean diet on nutritional status in adults affected by Osteogenesis Imperfecta: a pilot study.

BACKGROUND: Osteogenesis Imperfecta (OI) is a heterogeneous group of connective tissue disorders, characterized by varying degrees of skeletal fragility. Patients experience a range of comorbidities, such as obesity, cardiovascular, and gastrointestinal complications, especially in adulthood. All aspects that could benefit from dietary intervention. The aim of this study was to evaluate the effects of a 6-months restricted Mediterranean Diet (rMD) on nutritional status in adult patients affected by OI. We carried out a 6-months longitudinal pilot study. 14 adults (median age: 35 years; 7 women; 7 OI type III) where recruited in 2019 among the members of As.It.O.I., the Italian Association of Osteogenesis Imperfecta. As.It.O.I. All the evaluations were performed at the University of Milan, Italy. The rMD provided a reduction of 30% from daily total energy expenditure. 45% of calories derived from carbohydrates, 35% from fat and 0.7-1.0 g/kg of body weight from proteins. Comparisons of continuous variables after 6 months of intervention were performed by the paired t-test. All P-values were two-tailed, and p < 0.05 was considered significant. RESULTS: Patients showed significant improvement in anthropometric measurements (BMI = 30.5 vs 28.1 kg/cm2, p < 0.001; Body Fat % = 32.9 vs 29.9, p = 0.006; Waist circumferences = 83.6 vs 79.6 cm; p < 0.001; Arm Fat Area = 29.8 vs 23.07 cm2; p < 0.011) and energy expenditure (REE/kg = 27.2 vs 29.2 kcal/kg, p < 0.001). Glucose and lipid profiles improved (Δglycemia = - 8.6 ± 7.3 mg/dL, p = 0.003; ΔTC = - 14.6 ± 20.1 mg/dL, p = 0.036; ΔLDL = - 12.0 ± 12.1 mg/dL, p = 0.009). Adherence to the MD significantly increased, moving from a moderate to a strong adherence and reporting an increased consumption of white meat, legumes, fish, nuts, fruits and vegetables. CONCLUSION: A rMD was effective in improving nutritional status and dietary quality in adults with OI. These results underscores the need to raise awareness of nutrition as part of the multidisciplinary treatment of this disease.

The impact of craniofacial and dental osteogenesis imperfecta manifestations on oral health-related quality of life of children and adolescents.

OBJECTIVE: Craniofacial and oral manifestations of Osteogenesis Imperfecta (OI) can affect the functioning of the stomatognathic system and impact the patient's quality of life. The objective of the study was to evaluate the relationship between craniofacial and oral manifestations and the Oral Health-related Quality of Life (OHRQoL) of OI children and adolescents. MATERIAL AND METHODS: A total of 30 OI patients aged eight to fourteen years old followed up at the Oral Care Center for Inherited Diseases were enrolled in the research. OHRQoL was assessed using the short form of the Child Perceptions Questionnaire (CPQ) for eight to ten-year-olds (CPQ8-10) and 11 to 14-year-olds (CPQ11-14). The relationship between the OHRQoL index and its assessment domains, OI types, and the presence of dentinogenesis imperfecta (DI), class III malocclusion, and dental agenesis were evaluated. RESULTS: The median CPQ score of patients was 5, and there was no significant difference in OHRQoL between children and adolescents, nor associated with the disease severity or the presence of DI. The oral manifestations evaluated did not directly impact the patients' OHRQoL. CONCLUSIONS: The study demonstrated that the perception of OHRQoL is similar for both adolescents and children. The oral symptom was the most relevant domain for the index among patients aged eight to fourteen years while the emotional well-being was the most impacted. CLINICAL RELEVANCE: this study makes contributions by indicating that addressing dental care for children and adolescents with OI is important in clinical management and better OHRQoL for this population.

Characteristics of femoral neck fractures in osteogenesis imperfecta: Series of four-teen consecutive hips in twelve patients.

INTRODUCTION: While long bone fractures are commonly seen in individuals with Osteogenesis Imperfecta (OI), femoral neck fractures (FNF) are exceedingly rare. There is a lack of comprehensive data regarding the etiology of FNFs, their characteristics, and the treatment protocols. Our aim was to determine the characteristics of femoral neck fractures in children with OI. MATERIALS AND METHODS: This study was conducted as retrospective series covering period of January 2011-December 2022. Total of 14 femoral neck fractures in 12 patients were included into final analysis. Age, gender, fracture location, ambulation level, injury mechanism, Sillence type, pre-fracture collo-diaphyseal angle, presence of previous implants and applied treatments were noted. RESULTS: The mean age was 9.3 (range: 3-16), 8 out of 12 patients were males. Sillence type 3 OI was most common (50 %) type. Among 12 patients, 2 (16.6 %) were restricted ambulatory while 5 (41.6 %) were non-ambulatory. Seven patients had prior femoral implants. Six fractures were managed non-operatively, while others underwent surgery, with cannulated screws (42.8 %) or plate osteosynthesis (7.1 %). All eight cases (100 %) with minor trauma or unknown origin were Sillence type 3-4, displaying varus deformity. FNFs that occured in mobile patients required higher-energy traumas. CONCLUSION: Femoral neck fractures in OI showed differing trauma mechanisms in ambulatory vs. non-ambulatory patients. Non-surgical treatment may be considered with in patients with high-risk anesthesia concerns, requiring higher level clinical studies.

Bleeding assessment in a large cohort of patients with Osteogenesis Imperfecta.

BACKGROUND: Osteogenesis Imperfecta (OI) is characterised by bone fragility. Among several features, easy bruising and multiple case reports on haemorrhagic events have been reported. This paper describes the diverse manifestations of bleeding and bruising in a large cohort of 328 OI patients. The aim of this study is to provide insight in the diverse aspects and therapeutic considerations of bleedings in OI. METHODS: This descriptive cohort study was conducted at the National Expert Center for adults with OI in the Netherlands. Bleeding was assessed by the validated self-bleeding assessment tool (Self-BAT) The tool was distributed among 328 adults with different clinically confirmed types of OI. RESULTS: 195 of 328 invited patients (completion rate 60%) with OI type 1 (n = 144), OI type 3 (n = 17) and OI type 4 (n = 34), aged between 18 and 82 years, completed the tool. Self-BAT scores were above the normal range in 42% of all patients. For males Self-BAT scores were increased in 37% with a mean score of 3.7, ranged between 0 and 18. For females the Self-BAT scores were increased in 44% with a mean of 5.4 and a range of 0-24. No statistical differences in OI subtypes were found. CONCLUSIONS: Bleeding tendency appears to be a relevant complication in OI patients as this study confirms the presumption of bleeding tendency. There are specific recommendations to clinicians who treat OI patients to consider an assessment of bleeding tendency and use potential interventions to reduce haemorrhagic complications and improve quality of life.

Efficacy of Bisphosphonate for Urolithiasis Complicated by Osteogenesis Imperfecta.

A 44-year-old man with osteogenesis imperfecta presented with left renal colic. Non-contrast computed tomography revealed a stone (10×9 mm) in the left upper ureter. Ureteroscopic lithotripsy was performed twice and stone-free status was achieved. An analysis of the stone revealed a mixed composition including calcium oxalate and calcium phosphate. Postoperatively, we administered bisphosphonates to prevent recurrence of urolithiasis, as 24-hour urine collection revealed marked hypercalciuria. Eighteen months after surgery, the urinary calcium levels had normalized, and there was no recurrence of urolithiasis. Osteogenesis imperfecta can be complicated by urolithiasis, but bisphosphonates may be useful in preventing recurrence of this disease.

Cranio-cervical abnormalities in moderate-to-severe osteogenesis imperfecta - Genotypic and phenotypic determinants.

INTRODUCTION: Cranio-cervical anomalies are significant complications of osteogenesis imperfecta (OI), a rare bone fragility disorder that is usually caused by mutations in collagen type I encoding genes. OBJECTIVE: To assess cranio-cervical anomalies and associated clinical findings in patients with moderate-to-severe OI using 3D cone beam computed tomography (CBCT) scans. METHODS: Cross-sectional analysis of CBCT scans in 52 individuals with OI (age 10-37 years; 32 females) and 40 healthy controls (age 10-32 years; 26 females). Individuals with a diagnosis of OI type III (severe, n = 11), type IV (moderate, n = 33) and non-collagen OI (n = 8) were recruited through the Brittle Bone Disorders Consortium. Controls were recruited through the orthodontic clinic of the University of Missouri-Kansas City (UMKC). RESULTS: OI and control groups were similar in mean age (OI: 18.4 [SD: 7.2] years, controls: 18.1 [SD: 6.3] years). The cranial base angle was increased in the OI group (OI: mean 148.6° [SD: 19.3], controls: mean 130.4° [SD: 5.7], P = .001), indicating a flatter cranial base. Protrusion of the odontoid process into the foramen magnum (n = 7, 14%) and abnormally located odontoid process (n = 19, 37%) were observed in the OI group but not in controls. Low stature, expressed as height z-score (P = .01), presence of DI (P = .04) and being male (P = .04) were strong predictors of platybasia, whereas height z-score (P = .049) alone was found as positive predictor for basilar impression as per the Chamberlain measurement. CONCLUSION: The severity of the phenotype in OI, as expressed by the height z-score, correlates with the severity of cranial base anomalies such as platybasia and basilar impression in moderate-to-severe OI. Screening for cranial base anomalies is advisable in individuals with moderate-to-severe OI, with special regards to the individuals with a shorter stature and DI.

[Features and results of surgical rehabilitation of hearing loss in osteogenesis imperfecta]. / Osobennosti i rezul'taty khirurgicheskogo lecheniya tugoukhosti pri nesovershennom osteogeneze.

Osteogenesis imperfecta (OI) is a form of congenital osteoporosis. Depending on the type of OI, patients experience various types of hearing loss. Depending on the type and degree of hearing loss, various methods of hearing rehabilitation are used in this category of patients. OBJECTIVE: To evaluate the features and results of surgical rehabilitation of hearing loss in patients with osteogenesis imperfecta. MATERIAL AND METHODS: During the period from 2009 to 2022, 2221 primary stapedoplasty was performed in the department, of which 23 (1.04%) in 21 patients were performed in patients with OI. There were 14 women and 7 men. According to TPA, bilateral hearing loss was detected in 19 patients and unilateral in 2. Conductive hearing loss was observed in 9 cases and mixed - in 14. The average thresholds for bone conduction (BC) were 22.7±8.04 dB, and the bone-air interval (ABG) - 36.1±5.3 dB. According to CT of the temporal bones, all patients showed a bilateral and symmetrical decrease in the density of the auditory ossicles, and in 7 patients there were extensive areas of non-uniform decrease in the density of the bone labyrinth up to +500 - +1000 HU.21 patients underwent 23 operations: in 21 cases stapedoplasty with laser assistance and in 2 cases ossiculoplasty. RESULTS: BC thresholds 6 months after surgery averaged 24.6±8.2 dB, and ABG - 12.1±2.9 dB. Closing of ABG ≤10 dB at spoken frequencies was detected in 30.5%, ABG ≤20 dB - in 95%. After 12 months or more after the operation, no change in the audiological parameters was noted. CONCLUSIONS: Stapes surgery for conductive and mixed hearing loss in OI patients is functionally effective. The best results are achieved after therapy with bisphosphonates with preparations of sodium fluoride, calcium and vitamin D, performing the operation when the density of demineralization zones reaches 1000 HU and using laser assistance. Taking into account the demineralization of the bone structures of the temporal bone, it is recommended to use autocartilaginous stirrup prostheses to restore sound conduction or to cover the attachment area of other prostheses with autologous tissues to prevent necrosis of the long stalk of the incus and stabilize long-term functional results.

Monochorionic twin pregnancy in a patient with type III osteogenesis imperfecta: a multidisciplinary challenge.

A woman with severe type III osteogenesis imperfecta spontaneously conceived a monochorionic, diamniotic twin pregnancy. Due to the severity of her condition, her pregnancy required close follow-up involving a multidisciplinary team, including high-risk obstetricians, anaesthetists, pulmonologists and respiratory therapists. Eventually, the twins were delivered via caesarean section at 26 weeks' gestation.We discuss the challenges and considerations in managing her high-risk pregnancy, highlighting the importance of multidisciplinary care in achieving a safe outcome for mother and babies.

Protocol of a randomised trial of teriparatide followed by zoledronic acid to reduce fracture risk in adults with osteogenesis imperfecta.

INTRODUCTION: Osteogenesis imperfecta (OI) is a rare genetic disease associated with multiple fractures throughout life. It is often treated with osteoporosis medications but their effectiveness at preventing fractures is unknown. The Treatment of Osteogenesis Imperfecta with Parathyroid Hormone and Zoledronic Acid trial will determine if therapy with teriparatide (TPTD) followed by zoledronic acid (ZA) can reduce the risk of clinical fractures in OI. METHODS AND ANALYSIS: Individuals aged ≥18 years with a clinical diagnosis of OI are eligible to take part. At baseline, participants will undergo a spine X-ray, and have bone mineral density (BMD) measured by dual-energy X-ray absorptiometry (DXA) at the spine and hip. Information on previous fractures and previous bone targeted treatments will be collected. Questionnaires will be completed to assess pain and other aspects of health-related quality of life (HRQoL). Participants will be randomised to receive a 2-year course of TPTD injections 20 µg daily followed by a single intravenous infusion of 5 mg ZA, or to receive standard care, which will exclude the use of bone anabolic drugs. Participants will be followed up annually, have a repeat DXA at 2 years and at the end of study. Spine X-rays will be repeated at the end of study. The duration of follow-up will range between 2 and 8 years. The primary endpoint will be new clinical fractures confirmed by X-ray or other imaging. Secondary endpoints will include participant reported fractures, BMD and changes in pain and HRQoL. ETHICS AND DISSEMINATION: The study received ethical approval in December 2016. Following completion of the trial, a manuscript will be submitted to a peer-reviewed journal. The results will inform clinical practice by determining if TPTD/ZA can reduce the risk of fractures in OI compared with standard care. TRIAL REGISTRATION NUMBER: ISRCTN15313991.

A case-control study of early-stage radiological markers of endothelial dysfunction and cardiovascular findings in patients with osteogenesis imperfecta: genotype-phenotype correlations.

OBJECTIVES: Osteogenesis imperfecta (OI) is a disease caused by defective collagen synthesis. Collagen type 1 is found in many structures in the cardiovascular system. Endothelial dysfunction, which develops prior to the emergence of structural and clinical signs of atherosclerosis, is believed to play a key role in atherogenesis. Endothelial dysfunction may be detected presymptomatically by non-invasive radiologic methods, such as flow-mediated dilatation (FMD) and carotid intima-media thickness (CIMT). These modalities may provide early indicators of endothelial dysfunction. This cross-sectional comparative study aimed to investigate early-stage radiological markers of endothelial dysfunction and cardiovascular diseases in OI patients and healthy controls and to investigate the correlation of findings with OI genotype. METHODS: Thirty patients diagnosed with OI were paired with thirty healthy age- and gender-matched controls and echocardiogram findings were compared. RESULTS: None of the patients had known underlying cardiovascular disease. The mean age was 13.18 ± 2.91 years. According to Sillence classification, 15 patients had type 1 OI, 10 had type III, and 5 had type IV. Mean CIMT in the OI group was higher in the control group (OI group: 0.42 ± 0.06 vs. healthy controls: 0.34 ± 0.04 mm, p<0.01), and mean FMD percent was lower in the patient group (p<0.01). Left ventricular ejection fraction was 78.97 ± 10.32 vs. 77.56 ± 8.50 %, (OI group: 7.00 ± 3.06 vs. healthy controls: 12.14 ± 1.99, p=0.56), and fractional shortening was 42.68 ± 11.94 vs. 40.23 ± 7.99 %, (p=0.35), in OI patients and controls, respectively. CONCLUSIONS: Pediatric patients with OI without clinical signs of cardiovascular abnormality had significantly worse CIMT and FMD findings than healthy controls. However, no difference was determined when comparing left ventricular ejection fraction or fractional shortening. OI patients may need to be screened for cardiovascular system complications starting from an early age.

Growth Arrest in Type IV Osteogenesis Imperfecta After Fassier-Duval Rod Insertion Treated by a Lengthening Magnetic Intramedullary Nail: A Case Report.

CASE: A child with Type IV Osteogenesis Imperfecta (OI) sustained a growth arrest of the distal femur after fixation of a left femur fracture with a Fassier-Duval expanding rod at 3 years old. Despite bar resection with fat interposition, the discrepancy progressed to 7.5 cm at maturity. Because the femur had grown to a sufficient diameter, he underwent successful lengthening with a magnetic intramedullary rod. CONCLUSION: Although it is a potential complication, growth arrest has not been reported in association with placement of an expanding nail in a child with osteogenesis imperfecta. This case illustrates this rare complication and treatment using a magnetic intramedullary rod.

Dental anomalies in individuals with osteogenesis imperfecta: a systematic review and meta-analysis of prevalence and comparative studies.

BACKGROUND: Osteogenesis imperfecta (OI) is a rare genetic disorder primarily caused by mutations in the genes involved in the production of type 1 collagen. OI is also known as brittle bone disease. OBJECTIVE: This study aims to describe the prevalence of dental anomalies (except dentinogenesis imperfecta) in individuals with OI, and compare the prevalence of dental anomalies between individuals with and without OI and between individuals with different types of OI. SEARCH METHODS: Searches in PubMed, Web of Science, Scopus, Ovid, and gray literature were performed in October 2022. SELECTION CRITERIA: Observational studies (with or without a comparison group) that evaluated the prevalence of dental anomalies in individuals with OI. Data collection and analysis: Data items were extracted by two authors. Quality assessment employing the Joanna Briggs Institute checklists and meta-analyses was conducted. Results were provided in prevalence values and odds ratio (OR) / 95% confidence interval (CI). Strength of evidence was determined. RESULTS: Eighteen studies were included. Most prevalent dental anomalies in individuals with OI included pulp obliteration (46.4%), dental impaction (33.5%), dental impaction of second molars (27%), and tooth agenesis (23.9%). Individuals with OI type III/IV had 20.16-fold greater chance of exhibiting tooth discoloration in comparison with individuals with OI type I (CI: 1.10-370.98). In comparison with the group without OI, the individuals with OI had 6.90-fold greater chance of exhibiting dental impaction (CI: 1.54-31.00). High methodological quality was found in 47% of the studies. Strength of evidence was low or very low. CONCLUSIONS: Pulp obliteration, dental impaction, and tooth agenesis were the most prevalent dental anomalies in the OI group. Individuals with OI were more likely to have dental impaction than individuals without OI. Individuals with OI type III/IV (severe-moderate) are more likely to have tooth discoloration than individuals with OI type I (mild).

A novel mutation in COL1A1 causing osteogenesis imperfecta/hearing loss.

OBJECTIVES: To screen the COL1A1 and COL1A2 gene mutation sites in a family with type I osteogenesis imperfecta (OI)/hearing loss and analyze the characteristics and recovery of hearing loss in patients with osteogenesis imperfecta. METHODS: The basic clinical data of OI proband and her parents were collected, and the COL1A1 and COL1A2 genes were detected in peripheral blood by PCR amplification and generation Sanger sequencing. Literature of stapedial surgery in patients with osteogenesis imperfecta was collected. RESULTS: The heterozygous mutation of the 26 exon c.1922_1923 ins C in the OI progenitor COL1A1 gene led to the amino acid frameshift mutation of p.Pro 601FS, which was not detected in the phenotypic parents. The homozygous of exon 28 c.1782>G in COL1A2 was detected in the proband and her parents, resulting in changes in the protein p.Pro 549Ala. CONCLUSION: The clinical symptoms of the OI proband is caused by heterozygous mutation of the 26 exon c.1922_1923 ins C in COL1A1 gene. Stapedial surgery can provide short-term and long-term hearing benefits for OI patients with hearing loss. LEVEL OF EVIDENCE: Level 4.