Bone Disease, Metabolic Clinical Trial
Official title:
Molecular Genetic Study of Suspected Cases of Osteogenesis Imperfecta Attending Assiut University Children Hospital
The study will be conducted at Assiut university children hospital and it will include
patients with history of repeated fractures due to mild or irrelevant trauma.
Diagnosis will be established by biochemical tests, bone survey to exclude secondary causes
followed by Dual Energy absorbiometry scan to detect bone density of selected cases then
confirm our diagnosis by detection of gene mutations of Osteogenesis imperfecta during one
and half year duration with starting zoledronic acid therapy during this duration.
Osteogenesis imperfecta is a genetic disorder of the connective tissue matrix caused by
abnormal collagen microfibril assembly, .Several clinical subtypes of Osteogenesis imperfecta
have been described based on the clinical, biochemical, and molecular nature of the disorder
. New research is emphasizing the structural interaction within the microfibril and
identifying regions within the collagen, which play greater or lesser roles in the
structural properties of the triple helix, .In taking this information into account,
clinical phenotypes resulting from certain mutations can be predicted because of this
pathogenetic correlation.
The clinical manifestations vary considerably, ranging from a severe perinatal lethal form
to a mild disorder which only becomes evident in adulthood, manifesting as premature
osteoporosis, .Most commonly, however, Osteogenesis imperfecta presents in childhood with
multiple fractures and related complications, .The precise incidence of Osteogenesis
imperfecta is unknown and reports vary from approximately 1/100,000 to 1/25,000 dependent on
the criterion used to define Osteogenesis imperfecta.
Severe forms and milder disease occur with approximately similar incidence. Severe and mild
forms share the cardinal feature of bone fragility, which is characterized by bone fractures
often after little or no trauma, .Several findings in Osteogenesis imperfecta are common to
other disorders of connective tissues; hyper-mobile joints and a blue sclera are among these
features frequently described, The incorporation of abnormal type 1 collagen in teeth
results in brittle opalescent teeth, the hallmark of Dentinogenesis Imperfecta, often seen
in Osteogenesis imperfecta, .Progressive conductive hearing loss in early adulthood is the
result of damage to the ossicles in the middle ear; over time, hearing loss typically
progresses and combined conductive and sensorineural hearing loss may be seen in adults,
similar to that of otosclerosis. Short stature and bone deformity are common features of the
disorder The mainstay of treatment is orthopedic management along with physiotherapy,
Bisphosphonates are being evaluated for efficacy and clinical trials have shown improvement
at least in bone mineral density
Disorders associated with fragility fractures in children:
A) Primary conditions
1. Genetic disorders :- Osteogenesis imperfecta - Ehlers-Danlos syndrome - Marfan syndrome
Homocystinuria - Osteoporosis - Hypophosphatasia Polyostotic fibrous dysplasia -
Rickets (genetic forms)
2. Idiopathic juvenile osteoporosis B) Secondary conditions
1- Chronic inflammatory conditions Systemic lupus erythematosus - Inflammatory bowel disease
- Nephrotic syndrome 2- Reduced mobility Cerebral palsy - Duchenne muscular dystrophy -
Posttraumatic 3- Infiltrative Leukemia - Thalassemia
4- Endocrine Hypogonadism - Growth hormone deficiency - Cushing syndrome Hyperthyroidism -
Diabetes mellitus 5- Nutritional/malabsorptive Vitamin D deficiency - Celiac disease -
Biliary atresia Cystic fibrosis - Anorexia nervosa 6- Renal Chronic kidney disease -
Secondary hyperparathyroidism 7- Iatrogenic Glucocorticoids - Anticonvulsants - Methotrexate
- Radiation therapy
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