scholarly journals Glucocorticoid-Induced Osteoporosis: Why Kids Are Different

2020 ◽  
Vol 11 ◽  
Author(s):  
Leanne M. Ward
Keyword(s):  
Vertebral Body ◽  
Vertebral Fractures ◽  
Early Identification ◽  
Treatment Strategies ◽  
Bone Fragility ◽  
Bisphosphonate Therapy ◽  
Growth Potential ◽  
Long Bone ◽  
Osteoporosis Therapy ◽  
Poor Growth

Glucocorticoids (GC) are an important risk factor for bone fragility in children with serious illnesses, largely due to their direct adverse effects on skeletal metabolism. To better appreciate the natural history of fractures in this setting, over a decade ago the Canadian STeroid-associated Osteoporosis in the Pediatric Population (“STOPP”) Consortium launched a 6 year, multi-center observational cohort study in GC-treated children. This study unveiled numerous key clinical-biological principles about GC-induced osteoporosis (GIO), many of which are unique to the growing skeleton. This was important, because most GIO recommendations to date have been guided by adult studies, and therefore do not acknowledge the pediatric-specific principles that inform monitoring, diagnosis and treatment strategies in the young. Some of the most informative observations from the STOPP study were that vertebral fractures are the hallmark of pediatric GIO, they occur early in the GC treatment course, and they are frequently asymptomatic (thereby undetected in the absence of routine monitoring). At the same time, some children have the unique, growth-mediated ability to restore normal vertebral body dimensions following vertebral fractures. This is an important index of recovery, since spontaneous vertebral body reshaping may preclude the need for osteoporosis therapy. Furthermore, we now better understand that children with poor growth, older children with less residual growth potential, and children with ongoing bone health threats have less potential for vertebral body reshaping following spine fractures, which can result in permanent vertebral deformity if treatment is not initiated in a timely fashion. Therefore, pediatric GIO management is now predicated upon early identification of vertebral fractures in those at risk, and timely intervention when there is limited potential for spontaneous recovery. A single, low-trauma long bone fracture can also signal an osteoporotic event, and a need for treatment. Intravenous bisphosphonates are currently the recommended therapy for pediatric GC-induced bone fragility, typically prescribed to children with limited potential for medication-unassisted recovery. It is recognized, however, that even early identification of bone fragility, combined with timely introduction of intravenous bisphosphonate therapy, may not completely rescue the osteoporosis in those with the most aggressive forms, opening the door to novel strategies.

Long bone fragility in NF1 is due to deficiency of architecture, micro-structure and matrix mineralization

2013 ◽  
Author(s):  
Jirko Kuhnisch ◽  
Jong Seto ◽  
Claudia Lange ◽  
Susanne Schrof ◽  
Sabine Stumpp ◽  
...  
Keyword(s):  
Bone Fragility ◽  
Long Bone ◽  
Micro Structure ◽  
Matrix Mineralization

scholarly journals Type 2 Diabetes Mellitus and Vertebral Fracture Risk

2021 ◽  
Author(s):  
Fjorda Koromani ◽  
Samuel Ghatan ◽  
Mandy van Hoek ◽  
M. Carola Zillikens ◽  
Edwin H. G. Oei ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Vertebral Fracture ◽  
Fracture Risk ◽  
Vertebral Fractures ◽  
Bone Fragility ◽  
Marrow Fat ◽  
Systematic Screening ◽  
Published Evidence ◽  
Vertebral Fracture Risk

Abstract Purpose of Review The purpose of this review is to summarize the recently published evidence concerning vertebral fracture risk in individuals with diabetes mellitus. Recent Findings Vertebral fracture risk is increased in individuals with T2DM. The presence of vertebral fractures in T2DM is associated with increased non-vertebral fracture risk and mortality. TBS could be helpful to estimate vertebral fracture risk in individuals with T2DM. An increased amount of bone marrow fat has been implicated in bone fragility in T2DM. Results from two recent studies show that both teriparatide and denosumab are effective in reducing vertebral fracture risk also in individuals with T2DM. Summary Individuals with T2DM could benefit from systematic screening in the clinic for presence of vertebral fractures.

The Clinical Use of Denosumab for the Management of Low Bone Mineral Density in Postmenopausal Women

2012 ◽  
Vol 25 (3) ◽  
pp. 310-318 ◽  
Author(s):  
Kira B. Harris ◽  
Kimberly L. Nealy ◽  
Delilah J. Jackson ◽  
Phillip L. Thornton
Keyword(s):  
Bone Mineral Density ◽  
Postmenopausal Women ◽  
Bone Mineral ◽  
Hip Fractures ◽  
Nuclear Factor Κb ◽  
Bisphosphonate Therapy ◽  
Mineral Density ◽  
Osteoporosis Therapy ◽  
Cost Of Health Care ◽  
Therapy Studies

Osteoporosis is a leading cause of debility and declining quality of life in postmenopausal women worldwide. Treatment of osteoporosis has been ubiquitous throughout the developed world since the mid-1990s, most notably with the introduction of bisphosphonates in 1995. Nonetheless, the incidence of hip fractures increased by 25% between 1990 and 2000, despite advances in osteoporosis therapy. Studies indicate that bone density increases over the first 3 years of bisphosphonate therapy and then plateaus or perhaps even declines, placing these patients at greater risk of fracture. Since hip fractures are associated with increased morbidity, mortality, and increased cost of health care, improvements in treating osteoporosis are critical. Denosumab is a novel monoclonal antibody targeted against the receptor activator of nuclear factor-κB ligand (RANKL) that inhibits osteoclast activity. Initial data suggest that denosumab increases bone mineral density for greater than 3 years. Of greater importance, denosumab has been shown to decrease vertebral fractures by 68%, nonvertebral fractures by 19%, and hip fractures by 42% for at least 36 months. Data also indicate that the safety profile of denosumab is equivalent to other drugs used in osteoporosis management, but potential risks of immunosuppression and cancer have been hypothesized.

scholarly journals Biomarkers for sepsis: past, present and future

2016 ◽  
Vol 10 (4) ◽  
pp. 301 ◽  
Author(s):  
Giuseppe Chesi ◽  
Natale Vazzana ◽  
Claudio Giumelli
Keyword(s):  
Clinical Practice ◽  
Risk Stratification ◽  
Supportive Care ◽  
Early Identification ◽  
Antibiotic Stewardship ◽  
Treatment Strategies ◽  
Severe Infection ◽  
Antibiotic Use ◽  
Evidence Based ◽  
Drug Resistant

Sepsis is a complication of severe infection associated with high mortality and open diagnostic issues. Treatment strategies are currently limited and essentially based on prompt recognition, aggressive supportive care and early antibiotic treatment. In the last years, extensive antibiotic use has led to selection, propagation and maintenance of drug-resistant microorganisms. In this context, several biomarkers have been proposed for early identification, etiological definition, risk stratification and improving antibiotic stewardship in septic patient care. Among these molecules, only a few have been translated into clinical practice. In this review, we provided an updated overview of established and developing biomarkers for sepsis, focusing our attention on their pathophysiological profile, advantages, limitations, and appropriate evidence-based use in the management of septic patients.

A new predictive index for vertebral fractures: The sum of the anterior vertebral body heights

Bone ◽  
2010 ◽  
Vol 46 (3) ◽  
pp. 768-773 ◽  
Author(s):  
D. Diacinti ◽  
D. Pisani ◽  
F. Barone-Adesi ◽  
R. Del Fiacco ◽  
S. Minisola ◽  
...  
Keyword(s):  
Vertebral Body ◽  
Vertebral Fractures ◽  
Predictive Index

scholarly journals Outcome after Implantation of a Hydraulic Vertebral Body Replacement in Traumatic Vertebral Fractures

2016 ◽  
Vol 6 (1_suppl) ◽  
pp. s-0036-1582693-s-0036-1582693
Author(s):  
Michael Kreinest ◽  
Dorothee Schmahl ◽  
Paul A. Grützner ◽  
Stefan Matschke
Keyword(s):  
Vertebral Body ◽  
Vertebral Fractures ◽  
Vertebral Body Replacement

Risedronate for the Prevention of Fractures in Postmenopausal Osteoporosis

2002 ◽  
Vol 36 (4) ◽  
pp. 664-670 ◽  
Author(s):  
Jennifer M Sickels ◽  
Chi-Sing Nip
Keyword(s):  
Postmenopausal Osteoporosis ◽  
Bone Fragility ◽  
Mineral Density ◽  
Osteoporosis Therapy ◽  
Treatment Of Osteoporosis ◽  
Medline Search ◽  
Secondary Sources ◽  
Nonvertebral Fractures ◽  
Search Terms ◽  
Increased Risk

OBJECTIVE: To evaluate current scientific literature regarding the efficacy of risedronate in the prevention of vertebral and nonvertebral fractures in women with postmenopausal osteoporosis. DATA SOURCES: Primary research articles were identified by MEDLINE search (1966–May 2001) and through secondary sources. Key search terms were risedronate, postmenopausal osteoporosis, and fractures. DATA SYNTHESIS: Osteoporosis results in a reduction of bone mineral density, increased bone fragility, and increased risk of fractures. The goal of osteoporosis therapy is not only to increase bone mass, but also to reduce the rate of fractures. Risedronate is the newest bisphosphonate to be approved for the prevention and treatment of osteoporosis. An evaluation of clinical trials using risedronate in the treatment of postmenopausal osteoporosis was performed to determine its efficacy at decreasing fracture rates. CONCLUSIONS: Risedronate is an effective and safe option for the treatment of postmenopausal osteoporosis. Risedronate significantly decreases the risk of vertebral and nonvertebral fractures in women who have had ≥1 fractures in the past. More studies are warranted to evaluate the efficacy of risedronate in women without preexisting vertebral fractures.

scholarly journals Gentamicin induces LAMB3 nonsense mutation readthrough and restores functional laminin 332 in junctional epidermolysis bullosa

2018 ◽  
Vol 115 (28) ◽  
pp. E6536-E6545 ◽  
Author(s):  
Vadim Lincoln ◽  
Jon Cogan ◽  
Yingping Hou ◽  
Michaela Hirsch ◽  
Michelle Hao ◽  
...  
Keyword(s):  
Epidermolysis Bullosa ◽  
Skin Diseases ◽  
Growth Potential ◽  
Equivalent Model ◽  
Expression Vectors ◽  
Loss Of Function ◽  
Nonsense Mutations ◽  
Poor Growth ◽  
Junctional Epidermolysis Bullosa ◽  
Laminin 332

Herlitz junctional epidermolysis bullosa (H-JEB) is an incurable, devastating, and mostly fatal inherited skin disease for which there is only supportive care. H-JEB is caused by loss-of-function mutations in LAMA3, LAMB3, or LAMC2, leading to complete loss of laminin 332, the major component of anchoring filaments, which mediate epidermal-dermal adherence. LAMB3 (laminin β3) mutations account for 80% of patients with H-JEB, and ∼95% of H-JEB–associated LAMB3 mutations are nonsense mutations leading to premature termination codons (PTCs). In this study, we evaluated the ability of gentamicin to induce PTC readthrough in H-JEB laminin β3-null keratinocytes transfected with expression vectors encoding eight different LAMB3 nonsense mutations. We found that gentamicin induced PTC readthrough in all eight nonsense mutations tested. We next used lentiviral vectors to generate stably transduced H-JEB cells with the R635X and C290X nonsense mutations. Incubation of these cell lines with various concentrations of gentamicin resulted in the synthesis and secretion of full-length laminin β3 in a dose-dependent and sustained manner. Importantly, the gentamicin-induced laminin β3 led to the restoration of laminin 332 assembly, secretion, and deposition within the dermal/epidermal junction, as well as proper polarization of α6β4 integrin in basal keratinocytes, as assessed by immunoblot analysis, immunofluorescent microscopy, and an in vitro 3D skin equivalent model. Finally, newly restored laminin 332 corrected the abnormal cellular phenotype of H-JEB cells by reversing abnormal cell morphology, poor growth potential, poor cell-substratum adhesion, and hypermotility. Therefore, gentamicin may offer a therapy for H-JEB and other inherited skin diseases caused by PTC mutations.

Management of limb and pelvic injuries

2016 ◽  
Author(s):  
Omar Sabri ◽  
Martin Bircher
Keyword(s):  
Early Identification ◽  
Bone Fractures ◽  
Pelvic Ring ◽  
Prehospital Care ◽  
Physiological State ◽  
Long Bone ◽  
Mechanism Of Injury ◽  
Early Management ◽  
Pelvic Ring Injuries ◽  
Lethal Triad

Pelvic ring injuries can be life and limb threatening. The mechanism of injury can often be a good indicator of the type of injury; the Young & Burgess classification deploys that concept to full effect. Early identification based on mechanism of injury and improved prehospital care can play a major role in the outcome following such injuries. Pelvic ring injuries can lead to significant haemorrhage. Mechanical measures to stabilize the pelvis, in addition to modern concepts of damage control resuscitation (DCR), have been shown to be effective in early management of potentially life-threatening haemorrhage. Emphasis is now entirely on protecting the primary clot following a pelvic ring injury. Mechanical disturbance by log rolling the patient or springing of the pelvis are strongly discouraged. Early radiological clearance of the pelvis is encouraged. The lethal triad of coagulopathy, acidosis, and hypothermia should be corrected simultaneously to improve outcome. A traffic light system for monitoring venous lactate as an indicator of the patients’ physiological state can help the intensive care practitioner and the surgeon identify optimum timing for surgery. Pelvic ring injuries are associated with significant concomitant injuries. Limb trauma can also be life or limb threatening. Early identification, splinting, and resuscitation follow the same guidelines as pelvic ring injuries. Open long bone fractures should be managed by senior orthopaedic and plastic surgeons.

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