Osteogenesis imperfecta: towards an individualised interdisciplinary care strategy to improve physical activity and quality of life.

BACKGROUND: This report describes a new strategy for the care of patients with osteogenesis imperfecta, based on an interdisciplinary team working. Thereby, we aim at fulfilling three main goals: offering thorough coordinated management for all, and improving physical activity and quality of life of the patients. AIM: With rare diseases such as osteogenesis imperfecta (OI), patients and their family often suffer from inadequate recognition of their disease, poor care coordination and incomplete information. A coordinated interdisciplinary approach is one possible solution for providing both comprehensive and cost-effective care, with benefits for patient satisfaction. Poor physical activity and impaired quality of life represent a considerable burden for these patients. To better address these issues, in 2012 we created an interdisciplinary team for the management of OI patients in our University Hospital Centre (CHUV, Lausanne University Hospital,). In this article we describe the implementation of this interdisciplinary care strategy for patients suffering from OI, and its impact on their physical activity and quality of life. METHODS: All patients from the French part of Switzerland were invited to join us. We proposed two complementary evaluations: the initial interdisciplinary evaluation and a yearly follow-up during a special day – the “OI day”. This day features specialised medical appointments adapted to each patient’s needs, as well as lectures and/or workshops dedicated to patients’ and families’ education. Our first aim was to propose for each patient the same management, from diagnosis to the bone health evaluation and physical therapy advice. Our second aim was to evaluate the evolution of physical activity, quality of life (measured by EQ-5D, SF-36 and a dedicated questionnaire) and satisfaction of patients and their families. Here we report both the initial and the long-term results. RESULTS: Since 2012, 50 patients from the French part of Switzerland received the personalised medical evaluation. All of the patients included in this study had the same initial evaluation and at least one participation in an OI Day. All patients had an adaptation of their bone acting drugs. Over a 7-year period, 62% of inactive patients started some physical activity, and 44% of patients who were not involved in any athletic activity started participating in sports. The mean EQ-5D increased from 0.73 to 0.75 (p = 0.59). The mean physical SF36 (musculoskeletal function) score was 59.09 ± 22.72 and improved to 65.79 ± 21.51 (p = 0.08), whereas it was 68.06 ± 20.05 for the mental SF36 without alteration during follow-up. The OI day was revealed to be useful, it contributed to improvement in continuity of care and helped families to better understand the OI patients’ health. CONCLUSIONS: Our interdisciplinary approach aimed at offering the same thorough management for all patients from the French part of Switzerland, and at improving both the physical activity and the satisfaction of the patients and their family. This report is a basis for future work focusing on the effect of bone fragility and the impact of OI on patients’ social relations.

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. METHODS: We collected mobility data at five clinical sites to analyze the largest cohort of individuals with OI (n = 491) to date. Linear mixed models were developed to explore relationships among subject demographics and mobility metrics. RESULTS: Results showed minor limitations in the mild group while the more severe types showed more significant limitations in all mobility metrics analyzed. Height and weight were shown to be the most significant predictors of mobility. Relationships with mobility and bisphosphonates varied with OI type and type used (oral/IV). CONCLUSION: These results are significant to understanding mobility limitations of specific types of OI and beneficial when developing rehabilitation protocols for this population. It is important for physicians, patients, and caregivers to gain insight into severity and classification of the disease and the influence of disease-related characteristics on prognosis for mobility.

Incorporating the patient perspective in the study of rare bone disease: insights from the osteogenesis imperfecta community.

There is limited research which examines health concerns of individuals with osteogenesis imperfecta (OI). Discussion groups with leaders of the adult OI community identified a broad range of medical priorities beyond fractures and brittle bones. Our work underscores the need to include patient-reported outcomes in rare bone disease research. INTRODUCTION: Osteogenesis imperfecta (OI) is a rare genetic disorder affecting collagen protein leading to brittle bones and a number of other medical complications. To date, there is limited research which examines the life-long process of aging with this rare disease, much less the perspective of individuals with OI. METHODS: In order to explore and prioritize health concerns that adults with OI feel have been inadequately addressed in health care and research, investigators held discussions with leaders from the global adult OI community. The meetings were held in August 2017 at the 13th International Conference on OI in Oslo, Norway as part of the preconference seminar "Patient Participation in OI Research". Investigators were part of the Brittle Bone Disease Consortium (BBDC), a multicenter research program devoted to the study of OI, and their focus was on patient-reported outcomes (PRO). RESULTS: Participants noted that while fractures and brittle bones are the most common feature of OI, a number of body systems are under-studied in this disorder. They particularly emphasized breathing, hearing, and the effects of aging as primary concerns that researchers and physicians may not fully understand or address. Other areas included pain, gastrointestinal problems, mental health, nutrition, menopause/pregnancy, and basilar invagination. Participants also emphasized that they must be informed of study results. They underscored that outcome measures incorporated into future drug trials must look beyond fractures and consider the whole patient. CONCLUSIONS: This work will help guide the incorporation of PROs into the next phase of the BBDC Natural History Study of OI and underscores the importance of including PROs in the study of rare diseases.

Health-related quality of life in children with osteogenesis imperfecta: a large-sample study.

In this large-sample study, we demonstrated that osteogenesis imperfecta (OI) significantly impaired the quality of life (QoL) in children. Moderate/severe OI patients had worse QoL scores than patients with mild OI. Furthermore, the QoL for OI patients was correlated with the presence of pathogenic gene mutations. INTRODUCTION: Osteogenesis imperfecta (OI) is a hereditary disease characterized by multiple fragility fractures and progressive skeletal deformities. No detailed investigations about the quality of life (QoL) have been carried out in a large sample of patients with OI. We evaluated the QoL and its influencing factors in a large and well-characterized OI cohort. METHODS: We used a validated questionnaire of PedsQL 4.0 to evaluate the health-related quality of life (HRQoL) of children and adolescents with OI. We compared HRQoL among patients with OI types I, III, and IV. The relationship between HRQoL and pathogenic mutations in candidate OI genes was investigated. We also evaluated the influencing factors of HRQoL in OI patients. RESULTS: A total of 138 children with OI and 138 healthy controls were enrolled in this study. The HRQoL scores of OI patients were 64.4 ± 30.0, 71.9 ± 22.2, 75.7 ± 24.8, 63.7 ± 24.5, and 68.9 ± 22.0 in physical, emotional, social, school functioning, and total score, respectively, which were significantly lower than those of healthy children (86.5 ± 12.7, 83.3 ± 16.0, 92.1 ± 11.8, 87.5 ± 11.8, and 87.3 ± 10.7, all p < 0.01). Moderate and severe OI (type III/IV) patients had poorer HRQoL scores than patients with mild OI (type I). Gene mutations inducing qualitative defects in type I collagen led to worse HRQoL scores than those with quantitative defects in type I collagen, except in emotional functioning. The total HRQoL score was positively correlated with family income, lumbar, and femoral bone mineral density (BMD) Z-scores and negatively correlated with disease severity and fracture frequency. CONCLUSION: HRQoL was significantly impaired in OI patients, and patients with more severe OI had poorer HRQoL scores. For the first time, we found that children with qualitative defects in type I collagen had poorer HRQoL scores than those with quantitative defects in type I collagen.

Consensus statement on physical rehabilitation in children and adolescents with osteogenesis imperfecta.

On the occasion of the 13th International Conference on Osteogenesis imperfecta in August 2017 an expert panel was convened to develop an international consensus paper regarding physical rehabilitation in children and adolescents with Osteogenesis imperfecta. The experts were chosen based on their clinical experience with children with osteogenesis imperfecta and were identified by sending out questionnaires to specialized centers and patient organizations in 26 different countries. The final expert-group included 16 representatives (12 physiotherapists, two occupational therapists and two medical doctors) from 14 countries. Within the framework of a collation of personal experiences and the results of a literature search, the participating physiotherapists, occupational therapists and medical doctors formulated 17 expert-statements on physical rehabilitation in patients aged 0-18 years with osteogenesis imperfecta.

Prosthodontic Treatment of a Patient with Gnathodiaphyseal Dysplasia: 30-Year Follow-up.

This case history report describes the long-term prosthodontic treatment of a patient with gnathodiaphyseal dysplasia (GDD). The patient was initially diagnosed with osteomyelitis in the maxilla in 1986, followed by osteonecrosis spread throughout the mandible. GDD was genetically diagnosed in 2006. Despite the severe alveolar bone resorption, prosthodontic treatment improved the patient's satisfaction and ability to perform essential functions. Regular prosthesis adjustments and periodic follow-up should continue to avoid future complications.

The Effect of Whole Body Vibration Training on Bone and Muscle Function in Children With Osteogenesis Imperfecta.

Context: Osteogenesis imperfecta (OI) is associated with reduced muscle size, dynamic muscle function, and mobility. Objective: To assess the effect of whole body vibration (WBV) on bone density and geometry, muscle size and function, mobility, and balance in children with OI. Design: Randomized controlled pilot trial. Setting: Tertiary pediatric research center. Participants: Twenty-four children (5 to 16 years) with OI types 1, 4, and limited mobility [Child Health Assessment Questionnaire (CHAQ) score ≥ 0.13] recruited in sex- and pubertal stage-matched pairs. Incident fractures in two boys (WBV arm) led to exclusion of two prepubertal pairs. Intervention: Five months of WBV training (3 × 3 minutes twice daily) or regular care. Main Outcome Measures: Bone and muscle variables measured by dual-energy X-ray absorptiometry (spine, hip, total body) and peripheral quantitative computed tomography (tibia). Mobility assessed by 6-minute walk tests and CHAQ; dynamic muscle function by mechanography. Results: All participants had reduced walking distances and muscle function (P < 0.001). Body mass index z score was associated with higher CHAQ scores (ρ + 0.552; P = 0.005) and lower walking and two-leg jumping performance (ρ - 0.405 to -0.654, P < 0.05). The WBV and control groups did not differ in the 5-month changes in bone. Total lean mass increased more in the WBV group [+1119 g (+224 to +1744)] compared with controls [+635 g (-951 to +1006)], P = 0.01, without improving mobility, muscle function, or balance. Conclusions: The increase in lean mass without changes in muscle function or bone mass suggests reduced biomechanical responsiveness of the muscle-bone unit in children with OI.

Gnathodiaphyseal Dysplasia: Surgical Treatment and Prosthetic Rehabilitation of 2 Members of the Same Family.

Gnathodiaphyseal dysplasia (GDD) is a rare hereditary syndrome characterized by cemento-ossifying fibromas of the maxillary bones, fragile bones, curvature and cortical thinning of the tubular bones, and diaphyseal sclerosis of the long bones. In this study, 2 complex clinical cases of 2 members of the same family had GDD and were treated in the authors' odonto-stomatology department. The first was treated with a block bone graft and implant-prosthetic therapy; the other, who had extensive osteomyelitis of the second quadrant, was managed with extraction of the involved teeth, surgical revision of the site, and a graft of autologous platelet concentrate.

A specialized rehabilitation approach improves mobility in children with osteogenesis imperfecta.

OBJECTIVE: Osteogenesis imperfecta (OI) is a rare disease leading to recurrent fractures, hyperlaxicity of ligaments, short stature and muscular weakness. Physiotherapy is one important treatment approach. The objective of our analysis was to evaluate the effect of a new physiotherapy approach including side alternating whole body vibration on motor function in children with OI. METHODS: In a retrospective analysis data of 53 children were analyzed. The 12 months approach included 6 months of side alternating whole body vibration training, concomitant physiotherapy, resistance training, treadmill training and 6 months follow up. Primary outcome parameter was the Gross Motor Function Measure after 12 months (M12). RESULTS: 53 children (male: 32; age (mean±SEM): 9.1±0.61, range 2.54-24.81 years) participated in the treatment approach. A significant increase of motor function (GMFM-66 score 55.47±2.45 to 58.67±2.83; p=0.001) and walking distance (47.04 m±6.52 to 63.36±8.25 m (p<0.01) between M0 and M12 was seen. Total body without head bone mineral density increased significantly at M12 (p=0.0189). CONCLUSIONS: In the cohort of OI children which participated in the specialized treatment approach improvements of motor function were observed. Therefore this program should be considered as additional therapeutic approach for children with severe OI.

Implantes dentales en osteogénesis imperfecta. Niños con huesos de cristal: algo más que un caso clínico / Dental implants in osteogenesis imperfecta. Children with crystal bones: more than a clinical case

La osteogénesis imperfecta, también llamada enfermedad de los niños con huesos de cirstal, es una enfermedad genética. La misma se caracteriza porque los huesos se rompen tras un mínimo traumatismo e incluso sin causa. Su incidencia es alta. Puede no sercongénita. Se debe a la insuficiente y/o defectuosa formación del colágeno tipo I, que constituye el 85 a 90 por ciento del hueso. En tipos severos causa la muerte al nacer. Ha sido contraindicada la colocación de implantes. Este caso clínico de implantes fue exitoso en un Tipo moderado (IV) y se realizó a pedido del paciente, luego de explicársele la falta de antecedentesen la bibliografía y la contraindicación teórica.

Determinantes da marcha independente na osteogênese imperfeita / Independent walk in osteogenesis imperfect

OBJETIVOS: Investigar o processo de locomoção em pacientes com osteogênese imperfeita (OI) e os fatores que o influenciam, sublinhando pontos clínicos relevantes à reabilitação motora. MÉTODOS: Estudo transversal, retrospectivo, realizado no ambulatório de fisioterapia motora do Instituto Fernandes Figueira. Foram incluídos todos os pacientes com diagnóstico clínico de OI. Foram excluídos os que apresentavam comorbidades e idade inferior a dois anos. Utilizou-se o Epi-Info versão 3.4 para construção do banco de dados e o SPSS versão 15 para análise estatística. Foi calculado risco relativo para mensurar associação de características clínicas com a marcha independente, adotando-se nível de significância de 5 por cento para as análises. RESULTADOS: Foram incluídos 69 pacientes. Dentre eles, 43,5 por cento tinham OI tipo I; 37,7 por cento tipo III e 18,8 por cento tipo IV. 76,8 por cento apresentavam deformidades em ossos longos. Observou-se associação negativa entre hipotonia, número de fraturas e marcha independente e positiva entre marcha independente e OI tipo I. CONCLUSÕES: A clínica fisioterápica, como complementar à ortopédica e à administração de fármacos da família dos bifosfonatos, é de fundamental importância para a reabilitação da capacidade motora dos indivíduos com OI. Nivel de Evidência, estudos transversais.

OBJECTIVES: Investigation of the locomotion process in patients with osteogenesis imperfecta (OI), and the factors that influence it, with special attention to clinical aspects relating to motor rehabilitation. METHODS: a retrospective, cross-sectional study was carried out at the physical therapy outpatient clinic of the Instituto Fernandes Figueira. All patients with a clinical diagnosis of OI were included. Patients with other diseases, and those aged under two years, old were excluded. Epi-Info version 3.4 was used to construct the database, and SPSS version 15 for the statistical analysis. RESULTS: The odds-ratio was used to measure the association between independent walking and clinical characteristics, adopting a level of significance of 5 percent for the analysis. Results: 69 patients were included. Of these, 43.5 percent were classified as OI type I; 37.7 percent as type III and 18.8 percent as type IV. 76.8 percent presented long bone deformities. A negative association was observed between hypotonia, number of fractures, and independent walking. A positive association was observed between independent walking and OI type I. CONCLUSIONS: physical therapy, as a complementary approach to orthopedics, and the administration of medications of the biophosphonates class, are of fundamental importance for the rehabilitation of motor capacity of individuals with OI. Level of Evidence, cross sectional.

Ankle strength and functional limitations in children and adolescents with type I osteogenesis imperfecta.

PURPOSE: To determine whether children with type I osteogenesis imperfecta (OI) exhibit ankle plantar flexor weakness and whether this correlates with physical function. METHODS: Twenty children and adolescents with type I OI and 20 age-matched controls (age 6-18 years) participated in a single evaluation session. Data included strength assessment, Gillette Functional Assessment Questionnaire, Pediatric Outcome Data Collection Instrument (PODCI), and Faces Pain Scale-Revised. RESULTS: Ankle plantar flexor weakness was evident in the OI group compared with the control group. Heel-rise strength correlated with ankle isometric plantar flexion strength. Limitations in PODCI subscales-sports and physical function and pain/comfort-are present in the OI group. CONCLUSION: Ankle plantar flexor weakness is present in children and adolescents with type I OI and correlates with function. Gillette Functional Assessment Questionnaire, PODCI, and strength assessment are valuable evaluation tools for children and adolescents with type I OI and can aid therapists in goal setting.

[Nursing care of osteogenesis imperfecta child: implications for nursing practice. A review of the literature]. / Nursing del bambino affetto da osteogenesi imperfetta:implicazioni per la pratica infermieristica. Una revisione della letteratura.

This work provides a systematic review of literature, a careful analysis, synthesis and critical review, gathering the relevant findings and results of 20 clinical studies on Osteogenesis Imperfecta all with the ultimate goal of generating an overview of nursing assistance addressed to the child with this rare chronic disease. The works come from texts considered scientifically validated. The review will serve as a stimulus to improve nursing care and lead nurses to care conscious choices based on scientific evidence, as it is only by an experienced and experimental evidence that can rise to the optimal treatment for each patient (R. Iovine, 2000).

Sobrevida de uma haste intramedular extensível (HIMEX) no tratamento de crianças com ostegênese imperfeita / Survival rates of the HIMEX extensible nail in the treatment of children with osteogenesis imperfecta

OBJETIVO: avaliar o desempenho da haste extensível ancorada por ganchos (HIMEX) em deformidades da osteogênese imperfeita (OI). MÉTODOS: Todas as crianças operadas com HIMEX entre 1990 - 2004. Foi comparado o número de fraturas, reaparecimento de deformidades e capacidade de deambulação antes e após a HIMEX; incidência de migração e sobrevida da haste por curvas de sobrevivência. RESULTADOS: 14 pacientes (2 a 18 anos), oito do sexo feminino, incluindo 46 procedimentos, 39 primários e sete re-operações. Idade média na primeira fratura de 148,21 dias e média de 42,6 fraturas/paciente pré colocação da HIMEX. Dos 46 procedimentos, 28 no fêmur e 18 na tíbia. Tempo médio de seguimento de 80,21 ± 36,71 meses. Houve diminuição significativa de fraturas/paciente (0,78) e melhora na deambulação em sete dos 14 pacientes. Porcentagem de re-operação de 18 por cento e migração do implante em 12 por cento (05/39). 80 por cento dos implantes in situ até 108 meses. Implantes na tíbia tiveram sobrevida significativamente menor que os do fêmur. O tipo da OI e a idade na época da cirurgia não influenciaram significativamente a incidência de re-operação. CONCLUSÃO: A HIMEX levou à redução significativa no número de fraturas, incidência menor de migração e sobrevida maior da haste do que a referida na literatura.

OBJECTIVE: To evaluate the performance of an extensible nail with hooks, named HIMEX, in osteogenesis imperfecta (OI) deformities. METHODS: All child patients were operated on with HIMEX from 1990 to 2004. The number of fractures, reappearance of deformities, improvement of motor development before and after the use of HIMEX, and the incidence of the migration and nail survival were compared. RESULTS: Fourteen patients, with ages from 2 to 18 years, including 8 females, underwent 46 procedures, 39 primary and 7 re-operations. The average age at the first fracture was 148.21 days, and there was an average of 42.6 fractures per patient prior to HIMEX placement. Of the forty-six bones affected, 28 were femurs and 18 were tibias. Average follow-up care lasted 80.21±36.71 months. There was a statistically significant decrease (0.78) in the number of fractures per patient and an improvement in walking in seven of the fourteen patients. Revision occurred in 18 percent of patients and migration of the nail occurred in 12 percent (5/39). Eighty percent of the nails remained in situ until 108 months, with femoral procedures lasting significantly longer than tibial procedures. The type of OI and the age at the procedure did not significantly affect the incidence of revision. CONCLUSION: HIMEX significantly reduced the number of fractures, presenting lower incidence of migration and higher survival rates than those described in literature.

Upper extremity biomechanical model of crutch-assisted gait in children.

A 3D biomechanical model with a novel instrumented Lofstrand crutch system is presented. The novel Lofstrand crutch system consists of two six-axis load cells incorporated in the crutch to study the reaction forces occurring at the crutch handle and the cuff. The goal of this study is to quantify the effect of the cuff forces with the help of this improved crutch system. The kinematic model developed is verified based on previous studies. The kinetic model, consisting of the forces, is derived using the kinematic data, anthropometric data and the reaction forces generated from the load cells. The kinetic data is also in accordance with previous studies. Thus, the novel crutch system has been verified for evaluating the force loading on shoulder, elbow and wrist. This model would be further implemented on children suffering from Osteogenesis Imperfecta (OI), which would help in evaluating injury prevention criteria for long-term crutch users.

Augmentation of the mandible via a "tent-pole" procedure and implant treatment in a patient with type III osteogenesis imperfecta: clinical and histologic considerations.

The present report describes the oral rehabilitation of a female patient suffering from type III osteogenesis imperfecta. Agenesis of the mandibular anterior teeth and malocclusion caused partly by heavily worn teeth made dental rehabilitation necessary. Before a decision to use implants following a grafting procedure, the osseointegration of microimplants was tested. After 4 and 12 months, bone plugs containing two microimplants were retrieved from the patient. Histologic evaluation showed very sparse/poor osseointegration, and the healing time seemed to be much longer than normal. A decision was made to use the "tent-pole" procedure described by Marx et al, followed by prolonged healing. Surgery was uneventful, and the patient was provided with four implants that were partly covered with bone obtained from the iliac crest. Platelet-rich plasma was used to accelerate bone healing. After 9 months, the implants were uncovered and the prosthetic construction was completed. The implant-supported metal-ceramic restoration was serving well at the 1-year and 3-year follow-ups. Minimal resorption of marginal bone was detected during the first year.

New trends in the treatment of osteogenesis imperfecta type III - own experience.

INTRODUCTION: Osteogenesis imperfecta (OI) is a genetic disorder caused by a mutation in the genes that encode the chains of type I collagen. Clinical manifestations include increased bone fragility and blue sclerae. OI type III is the most severe form with fractures occurring already in utero. Fracture immobilisation and orthopaedic surgery are the mainstay of treatment for patients with OI, and are combined with rehabilitation and bisphosphonate therapy. PATIENTS AND METHODS: The study involved 8 children with osteogenesis imperfecta type III, aged 1 month to 6 years. All of them were treated with cyclic intravenous infusions of pamidronate. Laboratory studies conducted before and after each 3-day cycle of pamidronate therapy included complete blood count, serum calcium, phosphorus, magnesium, osteocalcin, and calcium/creatinine index in morning urine and collagen type I cross-linked N-telopeptide (NTx). Infant total body densitometric scans were obtained in 5/8 patients. RESULTS: Patients were treated for periods of 3-58 months. Fracture rates decreased with treatment in all patients compared to the prenatal period. Pamidronate also slowed down bone turnover, and particularly the resorption rate. The most common side effects during treatment included hypocalcaemia (7/8 patients) and fever (up to 39 degrees C) after the first cycle of treatment. CONCLUSION: Symptomatic bisphosphonate therapy in children with osteogenesis imperfecta ameliorated the clinical course (decreased bone pain and reduced incidence of fractures). Pamidronate therapy had a positive impact on functional parameters such as independence in everyday activities and better mobility. The treatment was safe.