[Paget's disease of bone-a current review of clinical aspects, diagnostics and treatment]. / Morbus Paget des Knochens ­ eine aktuelle Übersicht zu Klinik, Diagnostik und Therapie.

Paget's disease is a monostotic or polyostotic progressive skeletal disease with a genetic predisposition. The affected bone areas show osseous swelling and often grotesque deformation, chronic pain and fractures. Many cases are asymptomatic for a long time resulting in a late diagnosis. The pathogenesis is still unknown. In addition to a genetic predisposition, viral factors are also discussed. Laboratory tests and imaging are used for diagnosis. The effective principle of medicinal bisphosphonate treatment is to inhibit osteoclastic bone resorption and should be initiated early to prevent secondary complications. This article presents the current knowledge about this rare osteological disease.

[Rheumatism and bone metabolism]. / Rheuma und Knochenstoffwechsel.

Inflammatory rheumatic diseases are often associated with secondary osteoporosis, as many inflammatory messengers can interfere with bone metabolism and adversely affect it. In addition to a decrease in densitometric bone density, remodeling occurs in the trabecular bone, which can lead to a disturbed microarchitecture and increase the risk of fracture.Central to this is the close integration of bone metabolism and the immune system. Proinflammatory cytokines play an important role not only in the inflammatory process, but also as mediators of bone resorption because they stimulate osteoclastogenesis and induce further signal transduction cascades with negative influence on the bone. The understanding gained in recent years of the underlying immunological processes has led to the development of new and targeted treatment approaches.

[Effects of serial mud baths on inflammatory rheumatic and degenerative diseases]. / Wirkeffekte serieller Heiltorfbäder bei entzündlich-rheumatischen und degenerativen Erkrankungen.

BACKGROUND: Mud baths have been used for a long time for the treatment of musculoskeletal diseases. In addition to a reduction of pain and improved function, serially applied mud baths lead to a reduction in the inflammatory processes, which often underlie degenerative and inflammatory rheumatic diseases. OBJECTIVE: This study investigated the effects of serial mud baths on parameters of functional health, on pain perception and at the molecular level in patients with inflammatory rheumatic diseases, e.g. rheumatoid arthritis (RA) and ankylosing spondylitis (AS), and degenerative alterations, e.g. gonarthritis and/or coxarthritis. MATERIAL AND METHODS: A total of 41 patients with inflammatory rheumatic (33 RA and 8 AS) and 40 patients with degenerative diseases were subdived into 2 groups by computer-assisted randomization. In each group a subgroup received 9 serial mud baths within 21 days in addition to a multimodal physical rehabilitative complex treatment (intervention groups). In the other subgroups only the physical rehabilitative treatment was carried out and no mud baths were administered (control group). The outcome parameters were assessment of the functional capacity and pain perception (HAQ, FFbH, VAS and WOMAC), diesease activity (DAS28 and BASDAI) as well as laboratory markers of inflammatory activity (CRP, BSG, IL-1 beta and IL-10) and the patient assessment. RESULTS: In the intervention groups after serial mud baths there was a significant improvement in the functional parameters (HAQ and FFbH, both p < 0.01) and a significant reduction in pain strength (VAS, p < 0.01) persisting for 3 months after the end of treatment. A significant reduction in disease activity (RA in DAS28 and AS in BASDAI) could be shown for the intervention groups as well as the control groups, whereby the effect strength was more pronounced in the intervention groups. In patients with gonarthritis and/or coxarthritis a significant improvement in functional limitations (WOMAC, p < 0.01) was only found in the intervention groups. A significant improvement in the proinflammatory cytokine IL-1 beta (p < 0.01) was only found in the intervention groups with a simultaneous increase in the anti-inflammatory cytokine IL-10 (p < 0.01). The CRP and BSG remained within the normal range and showed no significant changes even after serial mud baths. CONCLUSION: Mud baths applied within the framework of a physical rehabilitative complex treatment brought about an improvement of parameters of functional health for both inflammatory rheumatic and degenerative diseases. Effects at the molecular level were induced, which are possibly accompanied by osteoprotective and chondroprotective effects.

Time course of cigarette smoke-induced changes of systemic inflammation and muscle structure.

It has become more evident that long-term cigarette smoking (LTCS) has an important extrapulmonary toxicity. The aim of the study was to investigate the time-dependent effects of cigarette smoke exposure on exercise capacity, markers of systemic inflammation, and skeletal muscle structure. c57bl/6j-mice were either exposed to mainstream cigarette smoke for 6 h/day, 5 days/wk [smoke-exposed (SE) group] or assigned to the control, unexposed group (Con group). SE group mice were exposed for 8, 16, 24, and 32 wk to smoke and unexposed Con mice were used as age-matched controls. Exercise capacity was investigated by spiroergometry. Systemic inflammatory status was analyzed by flow cytometry and multiplexed fluorescent immunoassay. For analysis of muscle tissue, histological techniques and microarray analysis were used. Mice of the SE group exhibited a lower increase of body mass and a decrease of V̇o2 max (P < 0.05). An increase of lymphocyte CD62, ICAM, and VCAM expression was found in SE mice (P < 0.05). A biphasic trend of protein up- and downregulation was observed in markers of systemic inflammation, tissue deterioration, and allergic reactions such as C-reactive protein (CRP), eotaxin, haptoglobin, macrophage colony-stimulating factor-1 (M-CSF-1), and macrophage inflammatory protein-1γ (MIP-1γ). Thereby, the expression of several chemotactic proteins in plasma correlated with their expression in muscle. A time-dependent decrease of muscle mass, oxidative type-I fibers, and muscle cross-sectional area was found (P < 0.05). Microarray analysis revealed a SE-induced upregulation of several pathways of metabolic processes and tissue degradation. Taken together it was found that the loss of exercise capacity and systemic inflammation are early events of SE, which might induce muscular atrophy and loss of oxidative muscle capacity.

[Molecular effects of physical therapy. What's new?]. / Molekulare Wirkungen physikalischer Therapiemaßnahmen. Was gibt es Neues?

Modern molecular medicine offers the possibility to investigate the potential influences of different methods of physical therapy on pivotal mechanisms and mediators of the inflammatory processes of rheumatic diseases and interactions between cells of the immune system and bone. Based on recent studies, it could be shown that modulation of these regulatory systems can be achieved by various physiotherapeutics.

[Severe osteoarthritic manifestations of ochronosis]. / Schwerste arthrotische Veränderungen durch eine Ochronose.

The congenital form of ochronosis is a result of the rare autosomal recessive inherited metabolic disease alkaptonuria. The disruption of tyrosine metabolism based on a genetic defect in the enzyme homogentisate dioxygenase results in accumulation of homogentisic acid (HA) which is excreted in the urine and leads to a dark discoloration after a certain incubation time at room temperature. Furthermore, HA polymerizes forming a pigment that is deposited in connective tissues such as tendons, cartilage, bones, intervertebral discs, sclerae, ossicles, cardiac valves and coronary arteries and leads to dark brown discoloration and degeneration. The case of a 74-year-old female patient with ochronosis and classical manifestations is described and in addition a current overview of this rare disease is provided.

[Molecular genetic analysis and clinical aspects of patients with hereditary hemochromatosis]. / Molekulargenetische Analyse und klinische Aspekte bei Patienten mit hereditärer Hämochromatose.

BACKGROUND: The purpose of the study was to perform a molecular genetic analysis and to document clinical aspects in patients with hereditary hemochromatosis. PATIENTS AND METHODS: The study included 33 outpatients (23 males average age 50.6 years and 10 females average age 60.6 years) with a disorder of iron metabolism (transferrin saturation > 75 %) as confirmation of hemochromatosis who were subjected to molecular genetic and clinical analyses. RESULTS: A homozygous mutation of the hemochromatosis (HFE) gene (C282YY) was detected in 63.6 %, a compound heterozygous mutation (C282Y/H63D) in 30.3% and no mutation of the HFE gene was detected in 6.1 %. The following organ manifestations could be objectified: arthralgia (78.8 %), liver disease (39.9 %), skin hyperpigmentation (30.3 %), osteoporosis (24.2 %), diabetes mellitus (24.2 %) and cardiomyopathy (12.1 %). Comparison between patients with heterozygous and homozygous hemochromatosis revealed the following differences: compound heterozygote patients presented less frequently with osteoarthritis of the metacarpophalangeal (MCP) joints and hands (85.7 %/71.4 % homozygotes vs. 60 %/60 % heterozygotes). Osteoarthritis of the shoulder joints and osteoporosis as well as hypothyroidism were more frequent in compound heterozygote patients, whereas osteoarthritis of the knee and hip joints as well as liver disease were more common in homozygote patients. No differences between both groups were seen with respect to the clinical manifestations of cardiomyopathy and diabetes mellitus. CONCLUSION: Prevalent causes of death in hereditary hemochromatosis are heart failure, liver disease (cirrhosis and hepatocellular carcinoma) and portal hypertension. Therefore, an early diagnosis, adequate therapy and genetic screening of family members are of great importance. Medicinal treatment will only effectively prevent deleterious organ involvement and subsequent complications if initiated at an early stage. Furthermore, an overview of the current data is given.

[Osteoporosis - inflammatory effects on bone metabolism and fracture risk]. / Osteoporose - inflammatorische Effekte auf den Knochenstoffwechsel und das Frakturrisiko.

There is a large body of evidence that proinflammatory cytokines, particularly interleukin-1, interleukin-6, and tumour necrosis factor-α, play an important role in bone metabolism. Moreover, it is suspected that proinflammatory cytokines are also important in the pathogenesis of age- and estrogen deficiency-related bone loss. Although an accelerated decrease in bone mass is observed in patients with chronic inflammatory disorders, the definite meaning of proinflammatory cytokines in the aetiology of osteoporosis is still unclear. Some studies suggest a relationship between increased concentrations of proinflammatory cytokines and a decrease in bone mineral density, as well as an increased risk of fracture. In sum, the evidence is rather scarce and does not permit any clear conclusions about the effects of single cytokines in bone metabolism. To be able to define more exactly at which stage of the pathogenesis of osteoporosis parameters of a systemic inflammation take effect, further studies will be necessary, particularly for developing suitable diagnostic markers for clinicians. These diagnostic markers may be able to identify patients at risk for osteoporosis and therefore predict fracture risks. Thus, early interventions to preserve bone health, for example, by anti-cytokine therapy, could be more effective and efficient.

[Septic monarthritis caused by Sphingomonas paucimobilis]. / Septische monoartikuläre Arthritis durch Sphingomonas paucimobilis.

Sphingomonas paucimobilis, formerly known as Pseudomonas paucimobilis, is a rare cause of septic arthritis and is therefore regarded as being of minor clinical interest in rheumatological diagnostics. In this connection the yellow pigmented, aerobic, glucose non-fermenting, Gram negative bacillus is usually associated with immunocompromised patients. A case of septic arthritis in a 70-year-old man with chronic obstructive pulmonary disease (COPD) initially presenting with right knee pain, swelling and redness is reported. After diagnosis of septic gonarthritis due to Sphingomonas paucimobilis, the infection was successfully treated by oral antibiotic therapy with ofloxacine based on the patient's antibiotic susceptibility profile, combined with analgesic and anti-inflammatory local physical therapy several times a day leading to a considerable improvement in the symptoms so that operative interventions could therefore be avoided.