Risedronate in the treatment of children with osteogenesis imperfecta: retrospective review of practice and outcomes at a large paediatric metabolic bone unit

Summary A 19-year-old woman was diagnosed with osteogenesis imperfecta (OI). She had sustained numerous low-trauma fractures throughout her childhood, including a recent pelvic fracture (superior and inferior ramus) following a low-impact fall. She had the classical blue sclerae, and dual energy X-ray absorptiometry (DEXA) bone scanning confirmed low bone mass for her age in the lumbar spine (Z-score was −2.6). However, despite these classical clinical features, the diagnosis of OI had not been entertained throughout the whole of her childhood. Sequencing of her genomic DNA revealed that she was heterozygous for the c.3880_3883dup mutation in exon 50 of the COL1A1 gene. This mutation is predicted to result in a frameshift at p.Thr1295, and truncating stop codon 3 amino acids downstream. To our knowledge, this mutation has not previously been reported in OI. Learning points OI is a rare but important genetic metabolic bone and connective tissue disorder that manifests a diverse clinical phenotype that includes recurrent low-impact fractures. Most mutations that underlie OI occur within exon 50 of the COL1A1 gene (coding for protein constituents of type 1 pro-collagen). The diagnosis of OI is easily missed in its mild form. Early diagnosis is important, and there is a need for improved awareness of OI among health care professionals. OI is a diagnosis of exclusion, although the key diagnostic criterion is through genetic testing for mutations within the COL1A1 gene. Effective management of OI should be instituted through a multidisciplinary team approach that includes a bone specialist (usually an endocrinologist or rheumatologist), a geneticist, an audiometrist and a genetic counsellor. Physiotherapy and orthopaedic surgery may also be required.

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Prolyl 3-hydroxylase 1 deficiency causes a recessive metabolic bone disorder resembling lethal/severe osteogenesis imperfecta

Nature Genetics ◽

10.1038/ng1968 ◽

2007 ◽

Vol 39 (3) ◽

pp. 359-365 ◽

Cited By ~ 309

Author(s):

Wayne A Cabral ◽

Weizhong Chang ◽

Aileen M Barnes ◽

MaryAnn Weis ◽

Melissa A Scott ◽

...

Keyword(s):

Osteogenesis Imperfecta ◽

Metabolic Bone Disorder ◽

Metabolic Bone ◽

Bone Disorder

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Erratum: Corrigendum: Prolyl 3-hydroxylase 1 deficiency causes a recessive metabolic bone disorder resembling lethal/severe osteogenesis imperfecta

Nature Genetics ◽

10.1038/ng0708-927a ◽

2008 ◽

Vol 40 (7) ◽

pp. 927-927 ◽

Cited By ~ 2

Author(s):

Wayne A Cabral ◽

Weizhong Chang ◽

Aileen M Barnes ◽

MaryAnn Weis ◽

Melissa A Scott ◽

...

Keyword(s):

Osteogenesis Imperfecta ◽

Metabolic Bone Disorder ◽

Metabolic Bone ◽

Bone Disorder

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Bone diseases, skeletal dysplasias, and collagen disorders

10.1093/med/9780198738756.003.0005 ◽

2018 ◽

Author(s):

Brogan Foster ◽

Paul A. Brogan

Keyword(s):

Connective Tissue ◽

Osteogenesis Imperfecta ◽

Avascular Necrosis ◽

Marfan Syndrome ◽

Bone Densitometry ◽

Bone Diseases ◽

Radiological Findings ◽

Metabolic Bone Diseases ◽

Skeletal Dysplasias ◽

Metabolic Bone

This chapter provides detailed clinical descriptions and treatment guidance for metabolic bone diseases, skeletal dysplasias, the osteochondroses, and heritable disorders of connective tissue. It provides updated descriptions of osteoporosis (both primary and secondary), rickets, osteopetrosis, avascular necrosis, and guidance on the use of bone densitometry in children. An extensive description of the skeletal dysplasias is provided, including a table for easy reference summarising the principal clinical features, radiological findings, and genetics of more commonly encountered conditions. Comprehensive clinical descriptions of the osteochondroses, including features found on imaging, differential diagnoses, important clinical pitfalls to be wary of, and treatment recommendations are provided. The heritable disorders of connective tissue are described in detail, and fully updated with current nosology, including Ehlers–Danlos syndromes, Marfan syndrome, and osteogenesis imperfecta.

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Basilar impression and osteogenesis imperfecta: a 21-year retrospective review of outcomes in 20 patients

Journal of Neurosurgery Spine ◽

10.3171/spi-07/12/594 ◽

2007 ◽

Vol 7 (6) ◽

pp. 594-600 ◽

Cited By ~ 34

Author(s):

Ahmed G. Ibrahim ◽

H. Alan Crockard

Keyword(s):

Osteogenesis Imperfecta ◽

Retrospective Review ◽

Senior Author ◽

Karnofsky Performance Scale ◽

Decompression Surgery ◽

Basilar Impression ◽

Occipitocervical Fixation ◽

Dorsal Stabilization ◽

Patient Series

Object Basilar impression (BI) secondary to osteogenesis imperfecta (OI) is a rare but debilitating condition that is often progressive unless it is halted. More recently, ventral decompression surgery has been advocated for this condition. This study is a retrospective review of the 21-year experience of ventral decompression surgery and dorsal occipitocervical fixation in patients with BI secondary to OI and is the largest patient series reported to date. Methods Twenty patients treated between 1982 and 2003 by the senior author at the authors' institution were included in this study. All patients underwent ventral decompression surgery followed by dorsal craniocervical stabilization. Patients were followed up for a median of 10 years. Results There were no intraoperative or perioperative deaths. Postoperatively, 16 of 20 (80%) patients showed objective improvement or maintained their good preoperative level of function. After surgery, of the 15 patients admitted with Karnofsky Performance Scale (KPS) scores of 70% or less, 11 improved, two remained unchanged, one patient's condition deteriorated, and one patient died of an unrelated cause. Of five patients admitted with a KPS score of 80% or greater, no patient's condition deteriorated in the short- and midterm period, but one patient had recurrence 15 years after surgery. At the end of follow-up, 25% of the patients had recurrence of brainstem compression symptoms or had died, and 15% showed no improvement after surgery. All of the remaining patients (60%) had sustained a long-term benefit from surgery. Conclusions Aggressive ventral decompression surgery and dorsal stabilization for patients with BI secondary to OI can not only halt disease progression but can also produce a good and sustainable long-term functional outcome, even in those patients who present as severely symptomatic. Patients who presented early with minor symptoms had good long-term outcomes.

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