The use of intravenous bisphosphonate therapy to treat vertebral fractures due to osteoporosis among boys with Duchenne muscular dystrophy

Summary

The impact of intravenous bisphosphonate treatment to treat painful vertebral fractures in boys with DMD has not been documented. In this retrospective observational study of seven boys, 2?years of intravenous bisphosphonate therapy was associated with back pain improvement and stabilization or increases in the height ratios of fractured vertebrae.

Introduction

Boys with Duchenne muscular dystrophy (DMD) are at risk for vertebral fractures. We studied the impact of intravenous bisphosphonate therapy for the treatment of painful vertebral fractures in DMD.

Methods

This was a retrospective observational study in seven boys with DMD (median 11.6?years, range 8.5 to 14.3) treated with intravenous pamidronate (9?mg/kg/year) or zoledronic acid (0.1?mg/kg/year) for painful vertebral fractures.

Results

At baseline, 27 vertebral fractures were evident in the seven boys. After 2?years of bisphosphonate therapy, 17 of the fractures had an increase in the most severely affected vertebral height ratio, 10 vertebrae stabilized, and none showed a decrease in height ratio. Back pain resolved completely (N?=?3) or improved (N?=?4). The median change in lumbar spine volumetric bone mineral density Z-score was 0.5 standard deviations (interquartile range, ?0.3 to 1.7). Two boys had three incident vertebral fractures in previously normal vertebral bodies that developed over the observation period. There was a decline in the trabecular bone formation rate on trans-iliac bone biopsy but no evidence of osteomalacia. First-dose side effects included fever and malaise (N?=?4), hypocalcemia (N?=?2), and vomiting (N?=?1); there were no side effects with subsequent infusions.

Conclusions

Intravenous bisphosphonate therapy was associated with improvements in back pain and stabilization to improvement in vertebral height ratios of previously fractured vertebral bodies. At the same time, such therapy does not appear to completely prevent the development of new vertebral fractures in this context.     

Non-fatal portal pyaemia complicating Crohn's disease of the terminal ileum.

A 40 year old woman with known Crohn's disease of the ileum but no abscess was found to have hepatic portal venous gas by computed tomography. Aggressive antibiotic treatment led to recovery and the ileum was resected two weeks later.     

Functional analysis in yeast of cDNA coding for the mitochondrial Rieske iron-sulfur protein of higher plants.

cDNA clones coding for the nuclear-encoded mitochondrial Rieske iron-sulfur protein (RISP) have been isolated from maize and tobacco. Complementation analysis of hybrid proteins consisting of different domains of plant and yeast RISPs showed that the carboxyl two-thirds of the plant protein is functionally equivalent to that of the yeast protein. The amino terminus of the RISP, however, seems to be species specific because this region is not interchangeable between plant and yeast proteins. Complementation analysis of hybrid proteins also identified a structurally conserved domain probably essential for the function of bc1 complex RISPs. A specific domain from the plant RISP was found to cause temperature-sensitive respiratory growth in yeast. We have demonstrated that yeast can serve as a model system to study the structural and functional relationships of plant gene products that are enzymatic components of the mitochondrial respiratory chain.     

Optimal treatment of descending necrotising mediastinitis

BACKGROUND: Descending necrotising mediastinitis is caused by downward spread of neck infection and has a high fatality rate of 31%. The seriousness of this infection is caused by the absence of barriers in the contiguous fascial planes of neck and mediastinum. METHODS: The recent successful treatment of seven adult patients with descending necrotising mediastinitis emphasises the importance of optimal early drainage of both neck and mediastinum and prolonged antibiotic therapy. The case is also presented of a child with descending necrotising mediastinitis, demonstrating the rapidity with which the infection can develop and lead to death. Twenty four case reports and 12 series of adult patients with descending necrotising mediastinitis published since 1970 were reviewed with meta-analysis. In each case of confirmed descending necrotising mediastinitis the method of surgical drainage (cervical, mediastinal, or none) and the survival outcome (discharge home or death) were noted. The chi 2 test of statistical significance was used to detect a difference between cases treated with cervical drainage alone and cases where mediastinal drainage was added. RESULTS: Cervical drainage alone was often insufficient to control the infection with a fatality rate of 47% compared with 19% when mediastinal drainage was added (p < 0.05). CONCLUSIONS: Early combined drainage with neck and chest incisions, together with broad spectrum intravenous antibiotics, should be considered standard care for this disease.


     

Pancreatic pseudocysts drained through a percutaneous transgastric approach: further experience

Percutaneous transgastric placement of a drainage catheter under ultrasonographic and fluoroscopic guidance was performed in 12 patients with pancreatic pseudocysts. Complete resolution of the pseudocysts was obtained in eight patients, and the result was indeterminate in one patient due to early death from unrelated causes. Surgical intervention followed in two patients, one with a multiloculated pseudocyst that was incompletely drained and another with a pseudocyst that became infected following drainage. In one patient with metastatic tumor to the head of the pancreas the pseudocyst resolved initially, but a pseudocyst later recurred. There were no pancreaticocutaneous fistulas or other major complications. The transgastric route of pseudocyst drainage is safe and effective, and it offers a low risk of recurrence and fistula formation.     

The Spectrum of Recovery From Fracture‐Induced Vertebral Deformity in Pediatric Leukemia

Vertebral fractures (VF) are a frequent complication of acute lymphoblastic leukemia. Some children with VF undergo vertebral body reshaping to the point of complete restoration of normal vertebral dimensions. Others are left with permanent vertebral deformity if the degree of reshaping has been incomplete by the time of final adult height attainment. In this report, we describe three children with painful VF at leukemia diagnosis or during chemotherapy. Each patient highlights different clinical trajectories in their recovery from VF and underscores the need for osteoporosis intervention trials with the goal to prevent permanent vertebral deformity in selected patients.     

The Accuracy of Prevalent Vertebral Fracture Detection in Children Using Targeted Case-Finding Approaches

Due to concerns about cumulative radiation exposure in the pediatric population, it is not standard practice to perform spine radiographs in most conditions that predispose to vertebral fracture (VF). In this study we examined the accuracy of two clinical predictors, back pain and lumbar spine bone mineral density (LS BMD), to derive four case-finding paradigms for detection of prevalent VF (PVF). Subjects were 400 children at risk for PVF (leukemia 186, rheumatic disorders 135, nephrotic syndrome 79). Back pain was assessed by patient report, LS BMD was measured by dual-energy X-ray absorptiometry, and PVF were quantified on spine radiographs using the modified Genant semiquantitative method. Forty-four patients (11.0%) had PVF. Logistic regression analysis between LS BMD and PVF produced an odds ratio (OR) of 1.9 (95% confidence interval [CI], 1.5 to 2.5) per reduction in Z-score unit, an area under the receiver operating characteristic curve of 0.70 (95% CI, 0.60 to 0.79), and an optimal BMD Z-score cutoff of −1.6. Case identification using either low BMD alone (Z-score < −1.6) or back pain alone gave similar results for sensitivity (55%, 52%, respectively), specificity (78%, 81%, respectively), positive predictive value (PPV; 24%, 25%, respectively), and negative predictive value (NPV; 93%, 93%, respectively). The paradigm using low BMD plus back pain produced lower sensitivity (32%), higher specificity (96%), higher PPV (47%), and similar NPV (92%). The approach using low BMD or back pain had the highest sensitivity (75%), lowest specificity (64%), lowest PPV (20%), and highest NPV (95%). All paradigms had increased sensitivities for higher fracture grades. Our results show that BMD and back pain history can be used to identify children with the highest risk of PVF so that radiography can be used judiciously. The specific paradigm to be applied will depend on the expected PVF rate and the clinical approach to the use of radiography. © 2019 American Society for Bone and Mineral Research.     

Lack of photoprotection against UVB-induced erythema by immediate pigmentation induced by 382 nm radiation

Immediate pigment darkening (IPD) was induced on the backs of 11 human volunteers of skin types III and IV by exposing the skin to UVA radiation (382 nm). The minimum erythema dose (MED) of UVB radiation was also determined by exposing sites to graduated doses of 304 nm radiation. The order of exposure of distinct anatomic areas was as follow: UVB followed by IPD induction; IPD induction followed by UVB; IPD induction followed 3 h later by UVB; and UVB only. Erythema responses induced by UVB were graded by inspection 24 h later and the MEDs in the 4 areas were compared. The induction of IPD before UVB exposure caused no significant change in the MED compared to sites receiving UVB only, or receiving UVA radiation after UVB, confirming that the IPD reaction does not protect against UVB-induced erythema. There was also no evidence of photorecovery, i.e., an increase in the MED of UVB resulting from exposure to longer wavelength, UV or visible radiation following UVB exposure.