Advances in Nanotechnology for the Treatment of Osteoporosis

Osteoporosis is a degenerative bone disease commonly related to aging. With an increase in life expectancies worldwide, the prevalence of the disease is expected to rise. Current clinical therapeutic treatments are not able to offer long-term solutions to counter the bone mass loss and the increased risk of fractures, which are the primary characteristics of the disease. However, the combination of bioactive nanomaterials within a biomaterial scaffold shows promise for the development of a localized, long-term treatment for those affected by osteoporosis. This review summarizes the unique characteristics of engineered nanoparticles that render them applicable for bone regeneration and recaps the current body of knowledge on nanomaterials with potential for osteoporosis treatment and bone regeneration. Specifically, we highlight new developments that are shaping this emerging field and evaluate applications of recently developed nanomaterials for osteoporosis treatment. Finally, we will identify promising new research directions in nanotechnology for bone regeneration.     

HIV Infection and Osteoporosis: Pathophysiology, Diagnosis, and Treatment Options

As the population with HIV continues to age, specialists in HIV care are increasingly encountering chronic health conditions, which now include osteoporosis, osteopenia, and fragility fractures. The pathophysiology of the bone effects of HIV infection is complex and includes traditional risk factors for bone loss as well as specific effects due to the virus itself, chronic inflammation, and HAART. Examining risk factors for low bone density and screening of certain patients is suggested, and consideration should be given to treatment for those considered high risk for fracture.     

Treatment Options for Tauopathies

To date, there are no approved and established pharmacologic treatment options for tauopathies, a very heterogenous group of neuropsychiatric diseases often leading to dementia and clinically diagnosed as atypical Parkinson syndromes. Among these so-called Parkinson plus syndromes are progressive supranuclear palsy (PSP), also referred to as Steele-Richardson-Olszewski syndrome; frontotemporal dementia (FTD); and corticobasal degeneration (CBD). Available treatment strategies are based mainly on small clinical trials, miscellaneous case reports, or small case-controlled studies. The results of these studies and conclusions about the efficacy of the medication used are often contradictory. Approved therapeutic agents for Alzheimer′s dementia, such as acetylcholinesterase inhibitors and memantine, have been used off-label to treat cognitive and behavioral symptoms in tauopathies, but the outcome has not been consistent. Therapeutic agents for the symptomatic treatment of Parkinson’s disease (levodopa or dopamine agonists) are used for motor symptoms in tauopathies. For behavioral or psychopathological symptoms, treatment with antidepressants—especially selective serotonin reuptake inhibitors—could be helpful. Antipsychotics are often not well tolerated because of their adverse effects, which are pronounced in tauopathies; these drugs should be given very carefully because of an increased risk of cerebrovascular events. In addition to pharmacologic options, physical, occupational, or speech therapy can be applied to improve functional abilities. Each pharmacologic or nonpharmacologic intervention should be fitted to the specific symptoms of the individual patient, and decisions about the type and duration of treatment should be based on its efficacy for the individual and the patient’s tolerance. Currently, no effective treatment is available that targets the cause of these diseases. Current research focuses on targeting tau protein pathology, including pathologic aggregation or phosphorylation; these approaches seem to be very promising.     

Healing,Inflammation, and Fibrosis: Radiation-Induced Tissue Damage: Clinical Consequences and Current Treatment Options

Radiation therapy is a valuable tool in the treatment of numerous malignancies but, in certain cases, can also causes significant acute and chronic damage to noncancerous neighboring tissues. This review focuses on the pathophysiology of radiation-induced damage and the clinical implications it has for plastic surgeons across breast reconstruction, osteoradionecrosis, radiation-induced skin cancers, and wound healing. The current understanding of treatment modalities presented here include hyperbaric oxygen therapy, autologous fat grafting and stem cells, and pharmaceutical agents.     

Rationale for Treatment of Involutional Osteoporosis in Women and for Prevention and Treatment of Corticosteroid-Induced Osteoporosis with Alfacalcidol

Increased cytokine release and increased activity of osteoclasts (reduced osteoclast apoptosis) due to a fall in estrogen is of causal significance in postmenopausal bone loss as well as malfunction of the vitamin D activation and concomitant calcium (Ca) malabsorption. Alfacalcidol prevents rapid postmenopausal bone loss by elimination of Ca malabsorption and by blocking resorbing cytokines. Established osteoporosis in older patients of both sexes is characterized by decoupled bone remodeling induced by sex hormone deficits and by a so-called somatopause (insulin-like growth factor [IGF]-deficit), but also by lack of vitamin D and, very importantly, by reduced synthesis of D-hormone (Calcitriol) in kidneys and bone as well as by a lack of receptors or receptor affinity for D-hormone in the target organs. As a consequence of these facts, a rise in parathormone (PTH) frequently occurs. The lack of D-hormone and IGF-1 evidently causes a reduction in muscle strength as well and reinforces the risk of falling and, thus, the risk of a fracture. Alfacalcidol, a prodrug of D-hormone, is a specific antiosteoporotic therapy. In alfacalcidol therapy, D-hormone is provided to the body in circumvention of its own regulation, by means of which much higher hormone concentrations can be achieved in the target tissues than by administration of plain vitamin D. Chances have been significantly improved of reducing and frequently preventing the real osteoporosis complication for older male and female patients, i.e., bone fractures, by alfacalcidol. A clear distinction should be made between supplementation with low-dosed plain vitamin D and calcium as base supply in elderly housebound subjects or as adjuvant to antiosteoporotic drugs and the specific antiosteoporotic therapy with alfacalcidol in patients with osteoporosis. The expanded understanding of the pathogenesis of corticosteroid-induced osteoporosis with its disturbed Ca homeostasis and the pharmacological effects of alfacalcidol, counteracting such iatrogenic bone loss, explain the particularly good clinical efficacy in this most frequent form of secondary osteoporosis. Normalizing de-coupled bone remodeling due to cytokine modulation and the potential influence on deteriorated bone quality in patients with rheumatoid arthritis and Crohn's disease predestine this form of therapy for prevention and treatment of osteoporosis as a result of chronic inflammatory diseases as well as of transplantation osteoporosis cases in particular.     

Current Treatment Strategies and Future Treatment Options for Dravet Syndrome

Purpose of review

Dravet syndrome is a rare but severe genetic epilepsy that has unique treatment challenges. This is a review of current and future potential treatment options.

Recent findings

Treatment for Dravet syndrome should encompass many aspects of the syndrome such as gait, behavior, and nutrition, as well as focus on seizure control. Many sodium channel blockers should be avoided as they are likely to exacerbate seizures. Current options for treatment include valproic acid, clobazam, stiripentol, and ketogenic diet. Testing is underway for several new treatment options with unique mechanisms of action and therapeutic targets, including the serotonin system and genetic modulation.

Summary

Accurate and early diagnosis of Dravet syndrome will lead to avoidance of medications that may exacerbate seizures. Additionally, a multi-disciplinary approach and careful planning for management of episodes of status epilepticus may lead to improved outcomes. Ongoing research for novel approaches to treatment creates optimism for future improvement in outcomes.

     

Denosumab for the Treatment of Osteoporosis

Being a connective tissue, bone can increase or decrease its mass through the process of remodeling. Using a discovery in the mid-1980s—that tumor necrosis factor (TNF) could dramatically increase formation of osteoclasts (the cells that break down bone)—researchers at Amgen (Thousand Oaks, CA) discovered a TNF-like molecule that regulated bone resorption. Elevations in the expression of this molecule, receptor activator of nuclear factor-κB ligand (RANKL), can cause excessive bone destruction. A blocking antibody to RANKL named denosumab inhibits osteoclast formation and bone degradation. In a large multicenter clinical trial, known as the FREEDOM trial (Fracture Reduction Evaluation of Denosumab in Osteoporosis Every 6 Months), the effects of denosumab were tested in 60- to 90-year-old women over 3 years. Statistically significant reductions in fracture risk at the vertebral column, hip, and nonvertebral sites were associated with increases in bone mineral density (BMD) and reciprocal decreases in markers of bone resorption. However, the FREEDOM trial did not test the most beneficial use of a resorption blocking drug—to target the rapid bone loss that occurs in late perimenopause and early postmenopause. One adverse effect from denosumab is cellulitis, and research in animals suggests that RANKL/RANK interaction is needed for Langerhans cell (LC) survival in the skin. Further mechanistic and clinical studies on the role of RANKL in the skin are needed.     

Hangman骨折治疗方法的选择

目的探讨Hangman骨折治疗方法的选择及疗效。方法回顾性研究47例Hangman骨折，分别采用非手术治疗或后路手术、前路手术和前后路联合手术。采用ASIA评分标准分级评定神经功能恢复情况，影像学评定植骨融合情况。结果47例均获得6～36个月的随访。21例不全瘫患者均有不同程度恢复，ASIA评分提高1～2级。46例术后X线示椎间高度、生理曲度以及颈椎稳定性均得到满意的重建，未发生钢板螺钉断裂或退出。结论Hangman骨折的治疗方案的选择取决于颈椎稳定性，应根据颈椎的稳定性合理选择治疗方案。     

Novel Assessment Tools for Osteoporosis Diagnosis and Treatment

This review describes new technologies for the diagnosis and treatment, including fracture risk prediction, of postmenopausal osteoporosis. Four promising technologies and their potential for clinical translation and basic science studies are discussed. These include reference point indentation (RPI), Fourier transform infrared spectroscopy (FTIR), Raman spectroscopy, and magnetic resonance imaging (MRI). While each modality exploits different physical principles, the commonality is that none of them require use of ionizing radiation. To provide context for the new developments, brief summaries are provided for the current state of biomarker assays, fracture risk assessment (FRAX), and other fracture risk prediction algorithms and quantitative ultrasound (QUS) measurements.     

A Review of Osteoporosis Diagnosis and Treatment Options in New and Recently Updated Guidelines on Case Finding Around the World

Fracture rates are known to vary by more than an order of magnitude worldwide; therefore, a single approach cannot be universally applied to all countries. National considerations must reflect the burden of osteoporosis, available resources, the disease costs to the individual and society, and how these relate to competing health and other societal priorities. Recent developments in terms of diagnosis, fracture risk prediction, and therapeutic options have prompted many countries to review and update their clinical practice guidelines (CPGs) for the prevention and management of osteoporosis intended for use in primary care in the general adult population. This paper reviews recently updated CPGs from the following countries: Australia, Belgium, Canada, Germany, the United Kingdom, and the United States.     

Acute Treatment Options for Spinal Cord Injury

Most treatment options for acute traumatic spinal cord injury (SCI) are directed at minimizing progression of the initial injury and preventing secondary injury. Failure to adhere to certain guiding principles can be detrimental to the long-term neurologic and functional outcome of these patients. Therapy for the hyperacute phase of traumatic SCI focuses on stabilizing vital signs and follows the Advanced Trauma Life Support (ATLS) algorithm for ensuring stability of airway, breathing and circulation, and disability (neurologic evaluation)—with spinal stabilization—and exposure. Spinal stabilization, with cervical collars and long backboards, is used to prevent movement of a potentially unstable spinal column injury to prevent further injury to the spinal cord and nerve roots, especially during prehospital transport. Surgery to stabilize the spine is undertaken after life-threatening injuries (hemorrhage, evacuation of intracranial hemorrhage, acute vascular compromise) are addressed. Intensive care unit (ICU) admission is to be considered for all patients with high SCI or hemodynamic instability, as well as those with other injuries that independently warrant ICU admission. Avoidance of hypotension and hypoxia may minimize secondary neurologic injury. Elevating the mean arterial pressure above 85 mmHg for 7 days should be considered, to allow for spinal cord perfusion. The use of intravenous steroids (methylprednisolone) is controversial. Early tracheostomy in patients with lesions above C5 may reduce the number of ventilator days and the incidence of ventilator-associated pneumonia. Select patients may benefit from the placement of a diaphragmatic pacer. Aggressive measures, including CoughAssist and Intermittent Positive Pressure Breaths (IPPB), should be used to maintain lung recruitment and aid in the mobilization of secretions. Some patients with high SCI who are dependent on mechanical ventilation can eventually be liberated from the ventilator with consistent efforts from both the patient and the caregiver, along with some patience. Intermittent catheterization by the patient or a caregiver may be associated with a lower incidence of urinary tract infections, compared with an in-dwelling urinary catheter. Early mobilization of patients and a multidisciplinary approach (including respiratory therapists, nutritional experts, physical therapists, and occupational therapists) can streamline care and may improve long-term outcomes. A number of investigational drugs and therapies offer hope of neurologic recovery for some patients.