[Hypercalcemic crisis and hypocalcemic tetany]. / Hyperkalzämische Krise und hypokalzämische Tetanie.

A serum calcium level >3.5 mmol/l together with clinical symptoms such as muscle weakness, fatigue, nausea, vomiting, pancreatitis or even coma are characteristic for a hypercalcemic crisis (HC). Primary hyperparathyroidism (1HPT) and malignancy-associated hypercalcemia are the most frequent causal diseases for a HC. The analysis of serum levels for calcium, phosphorous, intact parathyroid hormone, electrophoresis and renal function parameters indicate which further radiological, scintigraphic or serum diagnostic steps are adequate to identify the cause of the patient's acute situation (i. e. most frequently 1HPT or malignant disease with bone involvement, e. g. myeloma) and thus to initiate the required surgical or oncological intervention. However, the primary goals in the treatment of HC include correcting dehydration and improving kidney function, lowering calcium levels and decreasing osteoclastic bone resorption. The goals are accomplished by volume repletion, forced diuresis, antiresorptive agents and hemodialysis on an intensive care unit. Hypocalcemic tetany (HT) is the consequence of severely lowered calcium levels (<2.0 mmol/l), usually in patients with chronic hypocalcemia. The causal disease for hypocalcemic tetany is frequently a lack of parathyroid hormone (PTH), (e. g. as a complication of thyroid surgery) or, rarely, resistance to PTH. HT due to severe and painful clinical symptoms requires rapid i. v. calcium replacement by central venous catheter on an intensive care unit. For the treatment of chronic hypocalcemia oral calcium and 25OH-vitamin D or even 1,25(OH)2-vitamin D3 and magnesium supplements may be necessary to achieve the desired low normal calcium levels. Thiazides are useful to reduce renal calcium loss and to stabilize the calcium levels. Some patients continue to exhibit clinical symptoms despite adequate calcium levels; in these cases s. c. parathyroid hormone 1-84 should be considered to stabilize calcium levels and to lower the dosage of calcium and vitamin D supplements.

[Prevention of aortic erosion by a bone cement skid : Thoracic endovascular aortic repair following kyphoplasty]. / Pelottierung der A. thoracica descendens durch einen Zementsporn : Endovaskuläre Behandlung nach Kyphoplastie.

The underlying case report describes the successful endovascular prevention of an aortic injury by a bone cement skid after kyphoplasty. The intervention was performed in order to prohibit fatal aortic rupture or embolisation and underlines the role of vascular surgery techniques in interdisciplinary clinical networks.

[Kyphoplasty-Vertebroplasty. A critical assessment]. / Kyphoplastie-Vertebroplastie. Eine kritische Standortbestimmung.

CLINICAL ISSUE: Painful vertebral compression fractures. STANDARD TREATMENT: Analgesia. TREATMENT INNOVATIONS: Osteoplastic procedures, such as kyphoplasty and vertebroplasty. DIAGNOSTIC WORKUP: Anamnestic and radiological associations of clinical complaints with the radiomorphological findings of vertebral compression fractures are required for an adequate consideration to assess whether an osteoplastic procedure should be carried out. A computed tomography (CT) scan allows a reliable judgement whether an osteoplastic procedure is technically feasible and promising to improve the local vertebral fracture-associated pain. PERFORMANCE: Prospective controlled trials have demonstrated a satisfactory improvement of back pain associated with vertebral fractures and parameters of quality of life by osteoplastic interventions. ACHIEVEMENTS: No prospective, truly sham-controlled blind trials are currently available which demonstrate an advantage of osteoplastic interventions compared to standard pain treatment; however, the currently published prospective controlled trials show a satisfactory pain reduction by osteoplastic interventions, such as kyphoplasty and vertebroplasty. PRACTICAL RECOMMENDATIONS: Painful vertebral fractures and progressive loss of vertebral height of compression fractures should be evaluated in an interdisciplinary team consisting of radiologists, spinal surgeons and internists to assess whether an osteoplastic procedure is technically feasible and promising to improve local pain and immobility associated with vertebral fractures.

[Disorders of calcium metabolism]. / Störungen des Kalziumstoffwechsels.

The majority of clinical complaints derive from disorders of calcium metabolism and are associated with a wide variety of clinical symptoms caused by numerous diseases with entirely different types of pathophysiology. The prognosis varies from favorable to fatal depending on the pathophysiology of the underlying disorder of calcium metabolism; therefore, the diagnostic work-up aims to quickly identify the underlying disease causing the disturbance in calcium homeostasis. Every clinical situation with a diminished state of calcium absorption is treated with calcium and vitamin D in varying doses whereas every disorder with an increased calcium absorptive or resorptive state is treated with improved diuresis in addition to antiresorptive drugs, such as bisphosphonates. In many situations the management of a disturbed calcium balance requires an interdisciplinary approach in order to treat the underlying disease in parallel with correction of the calcium homeostasis.

The effect of zoledronic acid on the fracture risk in men with osteoporosis.

BACKGROUND: Prospective, placebo-controlled, double-blind, randomized studies on osteoporosis treatment with bisphosphonates in men are rare. This review focuses on a recent trial and compares the results with other studies. METHODS: This review provides a summary of recent literature on fracture risk in men following treatment with zoledronic acid. According to a recent clinical study with 1,199 men, zoledronic acid was linked to a lower risk of vertebral fractures. In this manuscript, a re-analysis of the presented statistical data will be demonstrated by performing a Bonferroni-correction to adjust for type 1 error accumulation in multiple statistical tests. RESULTS: It will be shown that the provided evidence linking zoledronic acid to a lower fracture risk in male osteoporosis is true, but less pronounced than originally assumed. CONCLUSION: Comparative clinical studies are recommended, where the benefits of different bisphosphonates are compared to each other under the same experimental conditions.

[Fundus screening by medical technicians]. / Fundusscreening durch Assistenzpersonal.

Ocular fundus photography allows detection of both ocular and systemic diseases. This study investigated the efficacy of a broad screening in a department of internal medicine using nonmydriatic digital fundus photography. For 8 weeks a medical technician was trained in using the camera as well as interpreting the photographs. The medical technician and an ophthalmologist evaluated the fundus photographs separately by using a self-developed questionnaire. The fundus camera was user-friendly and after several weeks of adjustment and practical application the medical technician was able to detect the majority of pathological fundus photographs. Out of 218 patients examined 148 (68%) were identified as pathological by the medical technician and 163 (75%) by the ophthalmologist (p = 0.0003). The medical technician missed 15 (7%) patients. Furthermore the diagnoses made by the medical technician were faulty. In summary an ophthalmological screening by a medical technician is feasible but the diagnosis still remains the responsibility of ophthalmologists. Such a compromise could facilitate the examination of a large number of patients and disclose previously unrecognized diseases.

Dynamic contrast-enhanced MRI for monitoring bisphosphonate therapy in Paget's disease of bone.

PURPOSE: The purpose of this study was to evaluate changes in regional bone perfusion in Paget's disease (PD) following bisphosphonate therapy. We used dynamic contrast-enhanced MRI (DCE-MRI) for assessment of bone perfusion and compared MRI findings with alkaline phosphatase (AP) as a serum marker of bone turnover. MATERIALS AND METHODS: We examined 20 patients (8 women, 12 men, 66 ± 11 years) with symptomatic PD of the axial skeleton. Patients were selected for infusion therapy with the bisphosphonate pamidronate. The most affected bone of lumbar spine or pelvis was examined by DCE-MRI prior to therapy and after a 6-month follow-up. The contrast uptake was evaluated using a two-compartment model with the parameters amplitude A and exchange rate constant K(ep). Color-coded parametric images were generated to visualize bone vascularization. RESULTS: After a 6-month follow-up there was a significant decrease in alkaline phosphatase and in DCE-MRI parameters A and K(ep) (p < 0.0001). Patients without previous bisphosphonate treatment showed a significantly greater decrease in alkaline phosphatase and K(ep) (p < 0.001). CONCLUSION: DCE-MRI shows a significant reduction in regional bone perfusion in PD following parenteral bisphosphonate treatment. Reduction in bone perfusion is greater in bisphosphonate-naïve patients than in those who had been previously treated.

[Minimal-Invasive CT-guided spinal interventions--from pain therapy over biopsies to tumor therapy]. / Minimalinvasive CT-gesteuerte Wirbelsäuleninterventionen--von der Schmerztherapie über Gewebeentnahmen zur Tumortherapie.

CT-guided spinal interventions have undergone a remarkable evolution during the last view years, leading to a wider range of indications, as well as to the development of highly specialized new procedures. This review article deals with different aspects of spinal CT-guided pain management, biopsy and tumor therapies and emphasizes a selection of practical considerations of important interventions.

[Role and limitations of vertebroplasty and kyphoplasty in the management of spinal metastases]. / Rolle und Grenzen der Vertebro-/Kyphoplastie im Metastasenmanagement der Wirbelsäule.

The spine is the most common site for skeletal metastases. Tumor-induced osteolysis may lead to pain, dysfunction and ultimately vertebral fracture. In some patients conventional surgery is not suitable because of the palliative therapy approach. Just for this patient population it was shown that cement augmentation of the vertebra is an effective therapy option and plays an important role. Nevertheless, cement augmentation of the vertebra has its limitations and should only be applied by appropriate indications.

Prediction of immediate and long-term benefit after kyphoplasty of painful osteoporotic vertebral fractures by preoperative MRI.

BACKGROUND: It is unclear if an MR-detectable bone marrow edema is a prerequisite for pain reduction and morphological correction by kyphoplasty. This comparative trial evaluates clinical and radiomorphological outcomes after kyphoplasty of painful osteoporotic vertebral fractures with and without preoperative MR-detectable bone marrow edema for 1 year of follow-up. METHODS: Preoperative MR-images of 45 patients who received kyphoplasty for treatment of painful osteoporotic vertebral fractures were evaluated with regard to presence (n = 27) or absence (n = 18) of vertebral bone marrow edema. Pain scores (VAS 0-100) and radiomorphological measures (midline vertebral height, kyphosis angle) were analysed at baseline, postoperatively and after 12 months. RESULTS: In the "bone edema" group, pain scores improved from 72.7 to 46.8 (postoperative) and 48.0 (12 months, P < 0.001, both). In the group without preoperative bone edema, pain score improved from 70.7 to 60.3 (postoperative, P = 0.013) and to 50.1 (12 months, P = 0.001). Pain scores of both groups were significantly different directly postoperative (P = 0.026), but not after 12 months (P = 0.714). Vertebral height restoration was slightly greater in the "bone edema" group (10.2% vs. 7.8%, P = 0.289). Correction of the kyphosis angle was greater in the "bone edema" group (P = 0.014) compared to the "no bone edema" group (P = 0.838). CONCLUSION: A preoperative MR-detectable vertebral bone marrow edema predicts a better short-term outcome after kyphoplasty, but is not a prerequisite for long-term pain reduction in patients with old, chronically painful osteoporotic vertebral fractures.

Vertebroplasty and kyphoplasty - inefficient treatments for degenerative spine disease.

Osteoporotic vertebral fractures and pathological vertebral lesions are frequent clinical situations causing severe back pain. The pharmacological treatment of the underlying disease and the analgetic treatment of the associated back pain usually do not rid the patient's back pain completely and are insufficient to prevent the fracture-weakened vertebral body from further fracturing with long term consequences for the biomechanical competence of the entire spine. In the last 10 years the minimal invasive treatment options vertebroplasty (VP) and balloon kyphoplasty (BK) have spread quickly because these procedures appeared to be promising treatments to stop the fracture and vertebral lesion associated back pain and to internally stabilize a fractured vertebral body. Numerous published reports on VP and BK appeared to support the notion of an immediate and lasting pain reduction after VP and BK in additon to a prevention of further fracturing of the treated vertebrae. The first three randomized controlled and partly blinded trials have been published this year. Two of these trials demonstrate that VP does not result in a better pain control than a sham operation whereas BK was shown to reduce back pain due to verterbal fractures for at least 12 months. Considering that more than 1.5 million people world-wide have been treated with VP and BK until now this work discusses the recent trials and suggests clinical and academic consequences on the basis of the most recent evidence.

[Kyphoplasty : method for minimally invasive treatment of painful vertebral fractures]. / Kyphoplastie : Minimal-invasives Verfahren zur Versorgung schmerzhafter Wirbelkörperfrakturen.

Painful osteoporotic and malignant vertebral fractures are frequent causes of chronic back pain with negative consequences regarding immobility, quality of life, morbidity, mortality, and fracture incidence. The best currently available evidence-based treatment reduces vertebral fracture risk but does not totally prevent follow-up fractures. Kyphoplasty is a causal treatment of pain by internal stabilization that prevents the ongoing pain of constant vertebral (micro-)fracture. The indication for this minimally invasive procedure requires interdisciplinary discussion of the individual case to guarantee technical feasibility, increase the likelihood that kyphoplasty will indeed reduce pain, and embed this procedure in the individual patient's long-term therapeutic concept or treatment of painful vertebral metastases. In addition to internal stabilization of painful vertebral fractures, kyphoplasty seeks to restore lost vertebral height, which appears promising in acute and painful vertebral fractures. Available controlled prospective studies demonstrate long-term patient benefits in terms of pain reduction, mobility, and improved quality of life.

[Indications and results of kypho- and vertebroplasty]. / Indikationen und Ergebnisse der Kypho- und Vertebroplastie.

The best currently available evidence based treatment reduces vertebral fracture risk but does not totally prevent osteoporotic and malignant follow-up fractures. Kyphoplasty and vertebroplasty are options of a causal treatment to reduce pain by internal stabilization of fractured vertebrae. The indication for these minimal invasive procedures requires an interdisciplinary discussion of the individual case to guarantee technical feasibility, to increase the likelihood that these procedures will indeed reduce pain and to embed these procedures into the long term therapeutic concept of every single patient. In addition to internal stabilization of a painfully fractured vertebra kyphoplasty also seeks to restore lost vertebral height which appears promising in acute vertebral fractures. Due to the procedure there are more cement leakages after vertebroplasty. Available controlled prospective studies demonstrate only for kyphoplasty a long-term benefit for the patient in terms of pain reduction, increased mobility and improved quality of life.

Metastases and multiple myeloma generate distinct transcriptional footprints in osteocytes in vivo.

Osteocytes are the most abundant bone cells, playing important roles in tissue maintenance. Little is known of how they react in vivo to cancer stress. Here we present a comparative study of the effect of a bone-residing tumour (myeloma) and metastases of bone-remote cancers on osteocytes. While no differences in morphology of the bone are seen, the changes in the transcriptome of osteocytes are specifically related to the tumour stress present. Screening approximately 22 000 genes in osteocytes prepared from cryosections of native bone using laser-supported microdissection, we observed approximately 1400 and approximately 1800 gene expression differences between osteocytes dissected from normal bone compared with those associated with metastases and multiple myeloma, respectively. The genes up-regulated due to the stress exerted by metastases were repressed by multiple myeloma and vice versa, indicating stress-specific footprints in the transcriptome of osteocytes. Functionally, the stressors seem to impose selective pressures on signalling pathways such as that of TGFbeta, a major player in bone biology. Our data show for the first time that the transcriptome of osteocytes in vivo becomes strongly affected by cancer stress, generating gene expression footprints which, in contrast to comparable morphological changes, appear to relate to the nature of cancer and might thus become helpful in distinguishing different bone diseases.

Dynamic contrast-enhanced MRI in Paget's disease of bone--correlation of regional microcirculation and bone turnover.

The purpose of this study was to evaluate regional microcirculation in Paget's disease of bone (PD) with dynamic contrast-enhanced MR imaging (DCE-MRI). Additionally, we correlated regional bone perfusion with alkaline phosphatase as serum marker of bone turnover. We examined 71 patients with PD (27 men, 44 women, 67+/-10 years) localized at the axial and appendicular skeleton. Contrast uptake was analyzed using a two-compartment model with the output variables amplitude A and exchange rate constant k(ep). Color-coded parametric images were generated to visualize microcirculation. Serum levels of alkaline phosphatase (AP) were compared with DCE-MRI parameters. Amplitude A and exchange rate constant k(ep) were significantly increased in PD compared to unaffected bone (A(PD) 0.81+/-0.24 vs. A(control) 0.34+/-0.1 and k(ep PD) 4.0+/-2.86 vs. k(ep control) 1.73+/-0.88, p<0.001). There was a significant correlation (r(s)=0.5-0.7) of DCE-MRI parameters and AP at the axial (pelvis, spine) and appendicular skeleton (femur, tibia). The long bones showed increased circulation of the advancing peripheral zones and no vascularization of the central part, which had been replaced by fatty tissue. Regional microcirculation in PD is inhomogeneous with focal areas of excessive hypervascularity, especially in the advancing peripheral zone. There is a significant correlation of bone circulation and bone turnover in PD. DCE-MRI might therefore be a diagnostic tool for monitoring therapeutic effects of bisphosphonates in Paget's disease of bone.

Relevance of laser irradiance threshold in the induction of alkaline phosphatase in human osteoblast cultures.

Induction of matrix synthesis by low-level laser has been demonstrated extensively. However, the question of dose- or power intensity-dependency is under-investigated. To address this issue we chose human osteoblast cell cultures and measured their alkaline phosphatase (ALP) activity after laser irradiation. The cell cultures were irradiated periodically by 690 nm radiation via optical transmission fiber-based laser needles, reaching into the culture dishes. The osteoblasts showed no induction of ALP activity when we used a single laser needle stimulation with a laser irradiance of 51 mW/cm(2), an increase of approximately 43% at 102 mW/cm(2) irradiance (two needles per well) and a ninefold increase at 204 mW/cm(2) irradiance (four needles per well), leaving the temperature of the culture medium unaffected. We concluded that the osteoblastic response in ALP activity to a laser stimulus shows a logarithmic relationship, with a distinct threshold, rather than a linear dose-dependency. Secondly, the laser irradiance, rather than the dose, is relevant for the impact of the laser.

[Screening for osteoporosis]. / Osteoporosescreening.

Osteoporosis affects approximately 7 million patients in Germany and severely impairs quality of life. The clinical picture, subjective complaints as well as the presence or absence of risk factors are essential to determine the individual risk profile and to decide on possible serum blood tests, osteodensitometry, and X-ray examinations. Back pain or other clinical evidence of impaired bone stability should be evaluated with X-ray studies of the spine. If osteoporosis and an increased risk of fracture are present, treatment is indicated which includes an evidence-based pharmaceutical regimen in order to increase bone stability and to lower the risk of fractures. Drug treatment with adequate calcium and vitamin D supplementation and antiresorptive or osteoanabolic substances, usually for 3-5 years, should be accompanied by pain medication and neuromuscular rehabilitation to help prevent falls and maintain independence of the elderly.

Long-term treatment of central Cushing's syndrome with rosiglitazone.

CONTEXT: Central Cushing's syndrome is not always curable by surgery or radiation of the pituitary. Medical treatment is often not possible or effective. Some studies revealed beneficial effects of the PPARgamma (Peroxisome-Proliferator-Activator- Receptor-gamma)-agonist rosiglitazone (RG) in in vitro studies, animal models and short term clinical studies. OBJECTIVE: of this study was to observe the long-term effects of RG-treatment on cortisol- and ACTH -secretion, clinical outcomes and morphological changes of the pituitary in patients with persistent ACTH-overproduction despite previous operation and radiation. DESIGN, SETTING AND PATIENTS: 14 patients with persistent central ACTH -production were included and monitored over a period up to 12 months. RG was administered daily and increased to a maximum dosage of 24 mg daily, according to the response of ACTH and cortisol secretion. ACTH and cortisol were measured at least every 4 weeks during RG treatment. RESULTS: Patients were treated between 4 and 12 months with RG (mean 6.8 months). Compared to baseline, ACTH- and cortisol levels dropped significantly (p<0.01) after 12, 16, 20, 24 and 28 weeks but thereafter rose again during the study period, despite continuous RG- treatment and dose increase up to the maximum dosage. This was paralleled by reocurrence of clinical symptoms. MRI-scans were performed in 6 patients because of persisting visible adenoma, but showed no morphological changes. CONCLUSION: RG seems not to be a long-term treatment option for patients with persistent central ACTH-evcess. Though, in order to reduce perioperative complications, short term treatment of patients could be an alternative.

[Balloon kyphoplasty in the therapy of vertebral fractures]. / Ballonkyphoplastie in der Therapie von Wirbelkörperfrakturen.

Approximately 500,000 vertebral fractures occur as a result of osteoporosis every year in Europe. One third of the patients thus affected complain of severe back pain and seek treatment. In the past, the treatment of such fractures was limited to conservative methods, such as the use of braces and analgesics and long-term immobilisation followed by physiotherapy. Since 1998 balloon kyphoplasty, a minimally invasive procedure, has also been available for their treatment. During balloon kyphoplasty a balloon system is introduced into a fractured vertebral body to achieve bitranspedicular augmentation, after which low-viscosity bone cement is injected into the vertebral body, where it sets very quickly. In general the patient can be fully mobilized 24-48 h after the procedure and in most cases the symptoms are then considerably attenuated; many patients are actually free of pain. Published studies and our own experience indicate that balloon kyphoplasty is a safe method of treating painful vertebral compression fractures sustained in various ways and that complications are rare with this procedure.