Incident Vertebral Fractures in Children With Leukemia During the Four Years Following Diagnosis

Cummings, Elizabeth A.; Ma, Jinhui; Fernandez, Conrad V.; Halton, Jacqueline; Alos, Nathalie; Miettunen, Paivi; Jaremko, Jacob L.; Ho, Josephine; Shenouda, Nazih; Matzinger, Mary Ann; Lentle, Brian C.; Stephure, David; Stein, Robert; Sbrocchi, Ann Marie; Rodd, Celia; Lang, Bianca; Israels, Sara J.; Grant, Ronald; Couch, Robert; Barr, Ronald D.; Hay, John; Rauch, Frank; Siminoski, Kerry; Ward, Leanne M.

doi:10.1210/jc.2015-2176

Cited by 94 publications

(96 citation statements)

References 34 publications

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“…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. The fact that vertebral fractures at any time point in a patient’s clinical course are predictive of future spine fractures even when the initial vertebral fractures are mild or asymptomatic 71 —a phenomenon known as the vertebral fracture cascade 86 — underscores the need for early identification.…”

Section: Bone Health and Osteoporosis Managementmentioning

confidence: 99%

“…The current call for routine spine radiographs for all patients with DMD will lead to diagnosis of symptomatic vertebral fractures (mild, moderate, and severe) and asymptomatic moderate and severe vertebral fractures, all of which should prompt referral to an osteoporosis expert for treatment. 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.…”

Section: Bone Health and Osteoporosis Managementmentioning

confidence: 99%

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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

724

886

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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.

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Section: Bone Health and Osteoporosis Managementmentioning

confidence: 99%

Section: Bone Health and Osteoporosis Managementmentioning

confidence: 99%

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

724

886

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“…The most common site of fractures in these children may not be the forearm; lower extremity fractures are common in immobilized children, 28,29 and spine fractures are more common in young patients with childhood leukemia, osteogenesis imperfecta, or exposure to glucocorticoids. 30,31 Clinical variables have been shown to influence the risk of fractures in older adults independent of their bone mass by densitometry. Age, weight, alcohol or smoking history, glucocorticoid use, and a history of previous fracture are used to calculate the absolute fracture risk.…”

Section: Ability Of Bone Densitometry To Predict Fracturesmentioning

confidence: 99%

Bone Densitometry in Children and Adolescents

Bachrach¹,

Gordon²,

Sills³

et al. 2016

Pediatrics

140

104

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Concerns about bone health and potential fragility in children and adolescents have led to a high interest in bone densitometry. Pediatric patients with genetic and acquired chronic diseases, immobility, and inadequate nutrition may fail to achieve expected gains in bone size, mass, and strength, leaving them vulnerable to fracture. In older adults, bone densitometry has been shown to predict fracture risk and reflect response to therapy. The role of densitometry in the management of children at risk of bone fragility is less clear. This clinical report summarizes current knowledge about bone densitometry in the pediatric population, including indications for its use, interpretation of results, and risks and costs. The report emphasizes updated consensus statements generated at the 2013 Pediatric Position Development Conference of the International Society of Clinical Densitometry by an international panel of bone experts. Some of these recommendations are evidence-based, whereas others reflect expert opinion, because data are sparse on many topics. The statements from this and other expert panels provide general guidance to the pediatrician, but decisions about ordering and interpreting bone densitometry still require clinical judgment. The interpretation of bone densitometry results in children differs from that in older adults. The terms “osteopenia” and “osteoporosis” based on bone densitometry findings alone should not be used in younger patients; instead, bone mineral content or density that falls >2 SDs below expected is labeled “low for age.” Pediatric osteoporosis is defined by the Pediatric Position Development Conference by using 1 of the following criteria: ≥1 vertebral fractures occurring in the absence of local disease or high-energy trauma (without or with densitometry measurements) or low bone density for age and a significant fracture history (defined as ≥2 long bone fractures before 10 years of age or ≥3 long bone fractures before 19 years of age). Ongoing research will help define the indications and best methods for assessing bone strength in children and the clinical factors that contribute to fracture risk. The Pediatric Endocrine Society affirms the educational value of this publication.

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“…Detailed fracture histories reported vertebral fracture in 1 patient in the HSCT-TBI group and 2 subjects from the chemotherapy group reported long bone fractures from trauma. Although individuals are likely to recall significant history of fractures, vertebral compression fractures are commonly asymptomatic and often under-recognised during or after treatment in leukaemia patients [33]. Disproportionate loss of spinal height in HSCT, especially in those on growth hormone replacement, is commonly assumed to result from poorer growth responses in the vertebral growth plates after irradiation [33].…”

Section: Discussionmentioning

confidence: 99%

“…Although individuals are likely to recall significant history of fractures, vertebral compression fractures are commonly asymptomatic and often under-recognised during or after treatment in leukaemia patients [33]. Disproportionate loss of spinal height in HSCT, especially in those on growth hormone replacement, is commonly assumed to result from poorer growth responses in the vertebral growth plates after irradiation [33]. Unrecognised vertebral compression fracture, which can lead to over 20% height loss, may also contribute to spinal height loss in some patients, but data in this aspect are lacking.…”

Section: Discussionmentioning

confidence: 99%

Bone Mineral Density Corrected for Size in Childhood Leukaemia Survivors Treated with Haematopoietic Stem Cell Transplantation and Total Body Irradiation

et al. 2018

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Background: Childhood leukaemia survivors treated with haematopoietic stem cell transplantation and total body irradiation (HSCT-TBI) have multiple risk factors for reduced bone mineral density (BMD) and growth failure; hence, BMD assessment must take body size into consideration. This study aimed to evaluate size-corrected BMD in leukaemia survivors treated with and without HSCT-TBI. Methods: Childhood leukaemia survivors treated with HSCT-TBI (n = 35), aged 17.3 (10.5–20.9) years, were compared with those treated with chemotherapy only, (n = 16) aged 18.5 (16.1–20.9) years, and population references. Outcome measures included anthropometric measurements and BMD by dual-energy X-ray absorptiometry. BMD was corrected for size as bone mineral apparent density (BMAD). Statistical analysis was performed by 1- and 2-sample t tests as well as regression analysis (5% significance). Results: HSCT-TBI survivors were lighter and shorter with reduced spinal heights compared with chemotherapy-only subjects and population references. Compared with population references, HSCT-TBI survivors showed lower BMD standard deviation scores (SDS) (p = 0.008), but no difference in BMAD-SDS, and chemotherapy-only survivors showed no differences in neither BMD-SDS nor BMAD-SDS. All HSCT-TBI participants with BMD-SDS <–2 had BMAD-SDS >–2. BMAD-SDS was negatively associated with age (r = –0.38, p = 0.029) in HSCT-TBI survivors. Conclusions: Size-corrected BMD are normal in HSCT-TBI survivors in young adulthood, but may reduce overtime. BMD measurements should be corrected for size in these patients to be clinically meaningful.

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Incident Vertebral Fractures in Children With Leukemia During the Four Years Following Diagnosis

Cited by 94 publications

References 34 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 Densitometry in Children and Adolescents

Bone Mineral Density Corrected for Size in Childhood Leukaemia Survivors Treated with Haematopoietic Stem Cell Transplantation and Total Body Irradiation

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