The time to and determinants of first fractures in boys with Duchenne muscular dystrophy

Ma, Jinhui; McMillan, Hugh J.; Karagüzel, Gülay; Goodin, C.; Wasson, John H.; Matzinger, Mary Ann; DesClouds, P.; Cram, David S.; Page, Marika; Konji, Victor N.; Lentle, Brian C.; Ward, Leanne M.

doi:10.1007/s00198-016-3774-5

Cited by 72 publications

(76 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…First, vertebral fractures—defined according to the Genant method 83 as mild (grade 1), moderate (grade 2), or severe (grade 3)—are now understood to be a frequent manifestation of osteoporosis in children with chronic illness, including those with glucocorticoid-treated DMD. 73,84 As noted, some individuals with vertebral fractures are relatively asymptomatic, even in more advanced stages of collapse. 71 Therefore, to detect vertebral fractures, spine imaging should not be prompted solely by back pain or deformity; rather, people with known risk factors for vertebral fractures, including motor disorders 85 or glucocorticoid therapy, 72,84 should receive regular spine imaging.…”

Section: Bone Health and Osteoporosis Managementmentioning

confidence: 95%

“…97-99 These data are particularly relevant to patients with glucocorticoid-treated DMD, who have a high frequency of vertebral fractures. 73 Recent reviews on the management of children with fractures due to osteoporosis concur with the view that intravenous rather than oral bisphosphonates should be used as first-line therapy. 81,82 Because bisphosphonates remain off label for children in most countries and they require judicious prescription, patients with a low-trauma fracture should be referred to an expert in osteoporosis management to ensure proper bisphosphonate dosing, dose titration on longer-term therapy, timing of treatment cessation, and monitoring of treatment safety and efficacy.…”

Section: Bone Health and Osteoporosis Managementmentioning

confidence: 96%

“…20–60% of boys with DMD have low-trauma extremity fractures (usually the distal femur, tibia, or fibula), while up to 30% develop symptomatic vertebral fractures. 66–68 Vertebral fractures are frequently asymptomatic when identified in children with glucocorticoid-treated illnesses through a monitoring programme that includes a lateral spine radiograph, 69-73 so the true prevalence is probably higher than existing reports suggest. Left untreated, vertebral fractures can lead to chronic back pain and spine deformity, while leg fractures can cause premature, permanent loss of ambulation.…”

Section: Bone Health and Osteoporosis Managementmentioning

confidence: 99%

“…By contrast, recent publications cast doubt on the bone-sparing properties of deflazacort, showing that bone fragility (including vertebral fractures) is frequent in deflazacort-treated boys with DMD, probably related partly to the large doses that are used in this condition. 73,79 Comparative studies of different steroid regimens in DMD are underway, assessing the effect on final adult height, body composition, and fractures. 80 …”

Section: Bone Health and Osteoporosis Managementmentioning

confidence: 99%

“…Because even mild and asymptomatic vertebral fractures are predictive of future fractures in both children 71 and adults, 91 treatment of asymptomatic moderate (Genant grade 2) and severe (Genant grade 3) vertebral fractures is now recommended. Treatment with intravenous bisphosphonate therapy had a protective effect on spine BMD and vertebral morphology in controlled trials of osteogenesis imperfecta 92-94 and in uncontrolled studies of osteogenesis imperfecta 95 and DM D. 84,96 Additional support for treatment of asymptomatic but nevertheless advanced (ie, moderate and severe) vertebral fractures stems from the fact that no cases of spontaneous (ie, medication unassisted) reshaping of previously fractured vertebral bodies have been reported in boys with DMD; 73 however, reshaping has been observed after intravenous bisphosphonate therapy in this population. 84 For children with glucocorticoid-treated diseases, such as DMD, including those with minimally symptomatic or asymptomatic mild (grade 1) vertebral fractures, controlled trials are underway to investigate the efficacy of antiresorptive therapy (ClinicalTrials.gov identifiers NCT00799266 and NCT02632916); for now, mild asymptomatic fractures should be closely monitored for symptomatology or progressive height loss that would prompt treatment.…”

Section: Bone Health and Osteoporosis Managementmentioning

confidence: 99%

See 4 more Smart Citations

Diagnosis and management of Duchenne muscular dystrophy, part 2: respiratory, cardiac, bone health, and orthopaedic management

Birnkrant

Bushby

Bann

et al. 2018

The Lancet Neurology

796

886

View full text Add to dashboard Cite

A coordinated, multidisciplinary approach to care is essential for optimum management of the primary manifestations and secondary complications of Duchenne muscular dystrophy (DMD). Contemporary care has been shaped by the availability of more sensitive diagnostic techniques and the earlier use of therapeutic interventions, which have the potential to improve patients’ duration and quality of life. In part 2 of this update of the DMD care considerations, we present the latest recommendations for respiratory, cardiac, bone health and osteoporosis, and orthopaedic and surgical management for boys and men with DMD. Additionally, we provide guidance on cardiac management for female carriers of a disease-causing mutation. The new care considerations acknowledge the effects of long-term glucocorticoid use on the natural history of DMD, and the need for care guidance across the lifespan as patients live longer. The management of DMD looks set to change substantially as new genetic and molecular therapies become available.

show abstract

Section: Bone Health and Osteoporosis Managementmentioning

confidence: 95%

Section: Bone Health and Osteoporosis Managementmentioning

confidence: 96%

Section: Bone Health and Osteoporosis Managementmentioning

confidence: 99%

Section: Bone Health and Osteoporosis Managementmentioning

confidence: 99%

Section: Bone Health and Osteoporosis Managementmentioning

confidence: 99%

See 3 more Smart Citations

Diagnosis and management of Duchenne muscular dystrophy, part 2: respiratory, cardiac, bone health, and orthopaedic management

Birnkrant

Bushby

Bann

et al. 2018

The Lancet Neurology

796

886

View full text Add to dashboard Cite

show abstract

Bone Morbidity and Recovery in Children With Acute Lymphoblastic Leukemia: Results of a Six-Year Prospective Cohort Study

Ward¹,

Lang³

et al. 2018

Journal of Bone and Mineral Research

118

View full text Add to dashboard Cite

Osteoporotic fractures are a significant cause of morbidity in acute lymphoblastic leukemia (ALL). Our objective was to determine the incidence and predictors of fractures and recovery from osteoporosis in pediatric ALL over 6 years following glucocorticoid initiation. Vertebral fractures (VF) and vertebral body reshaping were assessed on annual spine radiographs, low-trauma non-VF were recorded at regular intervals and spine bone mineral density (BMD) was captured every 6 months for 4 years and then annually. A total of 186 children with ALL were enrolled (median age 5.3 years; range, 1.3 to 17.0 years). The cumulative fracture incidence was 32.5% for VF and 23.0% for non-VF; 39.0% of children with VF were asymptomatic. No fractures occurred in the sixth year and 71.3% of incident fractures occurred in the first 2 years. Baseline VF, cumulative glucocorticoid dose, and baseline lumbar spine (LS) BMD Z-score predicted both VF and non-VF. Vertebral body reshaping following VF was incomplete or absent in 22.7% of children. Those with residual vertebral deformity following VF were older compared to those without (median age 8.0 years at baseline [interquartile range {IQR}, 5.5 to 9.4] versus 4.8 years [IQR, 3.6 to 6.2], p = 0.04) and had more severe vertebral collapse (median maximum spinal deformity index 3.5 [IQR, 1.0 to 8.0] versus 0.5 [IQR, 0.0 to 1.0], p = 0.01). VF and low LS BMD Z-score at baseline as well as glucocorticoid exposure predicted incident VF and non-VF. Nearly 25% of children had persistent vertebral deformity following VF, more frequent in older children, and in those with more severe collapse. These results suggest the need for trials addressing interventions in the first 2 years of chemotherapy, targeting older children and children with more severe vertebral collapse, because these children are at greatest risk for incident VF and subsequent residual vertebral deformity. © 2018 American Society for Bone and Mineral Research.

show abstract

The Radiology of Osteoporotic Vertebral Fractures Revisited

Lentle¹,

Koromani

Brown³

et al. 2019

Journal of Bone and Mineral Research

View full text Add to dashboard Cite

Until recently there has been little evidence available to validate any method by which to make an accurate diagnosis of an osteoporotic vertebral fractures (OVFs) from plain radiographs. In part this reflects a lack of a completely satisfactory “gold standard,” but primarily it relates to the absence of well‐designed prospective studies in this context. Historically, OVFs were recognized by evidence of macroscopic structural failure in vertebrae using the criteria applied elsewhere in the skeleton. This comprised altered alignment, fragmentation, cortical disruptions, and breaks, among other changes. However, these morphological criteria were replaced by vertebral morphometry, referring to the use of quantitative or quasi‐quantitative measurement tools for fracture diagnosis. Vertebral morphometry emerged as an understanding of and treatment for osteoporosis evolved, mainly in response to the need for expeditious assessments of large numbers of spine images for epidemiological and pharmaceutical purposes. Although most of the descriptions of such morphometric tools have stressed that they were not to be applied to clinical diagnosis with respect to individual patients, this constraint has been widely disregarded. Here we review the major attempts to develop a diagnostic strategy for OVF and describe their characteristics in adults and children. Recent evidence suggests that morphometric (quantitative; ie, based on measurement of dimensions and shape description) criteria are inferior to morphologic (qualitative; ie, based on structural integrity) vertebral damage assessment in identifying people with low bone density and at an increased risk of future fracture. Thus there is now an evidentiary basis for suggesting that morphological assessment is the preferred strategy for use in diagnosing OVF from radiographs. © 2019 American Society for Bone and Mineral Research.

show abstract

The time to and determinants of first fractures in boys with Duchenne muscular dystrophy

Cited by 72 publications

References 40 publications

Diagnosis and management of Duchenne muscular dystrophy, part 2: respiratory, cardiac, bone health, and orthopaedic management

Diagnosis and management of Duchenne muscular dystrophy, part 2: respiratory, cardiac, bone health, and orthopaedic management

Bone Morbidity and Recovery in Children With Acute Lymphoblastic Leukemia: Results of a Six-Year Prospective Cohort Study

The Radiology of Osteoporotic Vertebral Fractures Revisited

Contact Info

Product

Resources

About