Vertebral Scheuermann's disease in Europe: prevalence, geographic variation and radiological correlates in men and women aged 50 and over.

UNLABELLED: In 27 centres across Europe, the prevalence of deforming spinal Scheuermann's disease in age-stratified population-based samples of over 10,000 men and women aged 50+ averaged 8% in each sex, but was highly variable between centres. Low DXA BMD was un-associated with Scheuermann's, helping the differential diagnosis from osteoporosis. INTRODUCTION: This study aims to assess the prevalence of Scheuermann's disease of the spine across Europe in men and women over 50 years of age, to quantitate its association with bone mineral density (BMD) and to assess its role as a confounder for the radiographic diagnosis of osteoporotic fracture. METHODS: In 27 centres participating in the population-based European Vertebral Osteoporosis Study (EVOS), standardised lateral radiographs of the lumbar and of the thoracic spine from T4 to L4 were assessed in all those of adequate quality. The presence of Scheuermann's disease, a confounder for prevalent fracture in later life, was defined by the presence of at least one Schmorl's node or irregular endplate together with kyphosis (sagittal Cobb angle >40° between T4 and T12) or a wedged-shaped vertebral body. Alternatively, the (rare) Edgren-Vaino sign was taken as diagnostic. The 6-point-per-vertebral-body (13 vertebrae) method was used to assess osteoporotic vertebral shape and fracture caseness. DXA BMD of the L2-L4 and femoral neck regions was measured in subsets. We also assessed the presence of Scheuermann's by alternative published algorithms when these used the radiographic signs we assessed. RESULTS: Vertebral radiographic images from 4486 men and 5655 women passed all quality checks. Prevalence of Scheuermann's varied considerably between centres, and based on random effect modelling, the overall European prevalence using our method was 8% with no significant difference between sexes. The highest prevalences were seen in Germany, Sweden, the UK and France and low prevalences were seen in Hungary, Poland and Slovakia. Centre-level prevalences in men and women were highly correlated. Scheuermann's was not associated with BMD of the spine or hip. CONCLUSIONS: Since most of the variation in population impact of Scheuermann's was unaccounted for by the radiological and anthropometric data, the search for new genetic and environmental determinants of this disease is encouraged.

[Indications and prerequisites for bone biopsy]. / Indikationen und Voraussetzungen zur Knochenbiopsie.

The iliac crest biopsy provides additional information for the therapeutic approach in selected questions if the indication is correct. Indications include osteoporosis with an atypical course with respect to age, fracture frequency or success of therapy. The aim of the iliac crest biopsy is to harvest an undestroyed and intact piece of bone, containing all compartments, including cancellous bone, cortical bone and bone marrow. Knowledge of clinical and paraclinical parameters is essential for diagnosis and assessment. A safe sampling technique under sterile conditions must be guaranteed. The biopsy itself takes place in the anterior superior iliac spine and posterior superior iliac spine, preferably by using a Burkhardt or a diamond burr. Hard cutting technique and knowledge or the histomorphometry are indispensable prerequisites.

Aluminum deposition in the bone of patients with chronic renal failure--detection of aluminum accumulation without signs of aluminum toxicity in bone using acid solochrome azurine.

In this study, the sensitivity of the aurine tricarboxylic acid (ATA) and acid solochrome azurine (ASA) stain for aluminum were compared under special consideration of the relationship to bone histology in renal osteodystrophy. Al deposition in iliac crest bone biopsies taken from 78 patients with chronic renal failure (CRF) was assessed histochemically using the ATA and ASA stain; the Al accumulation was correlated with bone histology and histomorphometry. Significantly more Al was detectable with the ASA method on trabecular bone surfaces and cement lines (18 +/- 20% vs 4 +/- 12% on surfaces; 13 +/- 18% vs 0.4 +/- 1.3% on cement lines). In 31 cases in which ATA yielded negative results, ASA in contrast indicated Al deposits on up to 20% of the trabecular bone surface. The specimens with more Al on the trabecular bone surface had a significantly higher osteoid volume and osteoid surface. With ATA, these differences were observed at a staining of > or = 10% of the trabecular surface, with ASA at a staining of > or = 40% of the trabecular surface. Therefore, it seems to be possible to detect a very low Al deposition, without any Al-induced changes in bone morphology or signs of Al toxicity in the bone using the ASA method. By contrast, a positive ATA stain is mainly found in biopsies with typical signs of Al-induced changes of histomorphometric bone parameters. We, therefore, recommend the routine use of the ASA stain to detect Al deposition in bone.

Comparison of peripheral bone and body axis skeleton in a rat model of mild-to-moderate renal failure in the presence of physiological serum levels of calcitropic hormones.

The skeleton is characterized by anatomic heterogeneity of metabolic turnover. Site-dependent differences in hormonal effects seem likely. Hyporesponsiveness of osteoclasts to parathyroid hormone (PTH) and probably calcitriol was recently demonstrated in the fifth lumbar vertebra of a rat model with moderate renal failure. We compared histomorphometric findings of the tibial head to these data. Histomorphometric measurements were carried out in sections of the right tibial head of pair-fed male Sprague-Dawley rats. Subtotally nephrectomized (SNx), parathyroidectomized (PTx), rats, which received either solvent or rat PTH(1-34) (100 ng/kg per hour) + calcitriol (5 pmol/kg per hour) via osmotic minipumps were compared with sham-operated controls. Results were compared with data from the fifth lumbar vertebra reported recently. Osteoclast numerical density and osteoclast surface density were lower in the tibial head and the lumbar vertebra of solvent-treated SNxPTx rats than in sham-operated controls (p < 0.05), and could not be returned to normal by the substitution of PTH + calcitriol (p < 0.05). On the other hand, there were differences between interventional effects on the tibial head and on the lumbar vertebra concerning parameters describing osteoblasts and trabecular bone volume. In the tibial head, osteoblast surface density was nearly unchanged in both interventions. Nevertheless, bone volume increased after SNxPTx without substitution of PTH + calcitriol (p < 0.05), and no further changes occurred after hormonal replacement. In contrast, osteoblast surface density in the lumbar vertebra was decreased slightly compared with values in sham-operated rats; a clear but nonsignificant increase occurred after the administration of calcitropic hormones. This was accompanied by unchanged trabecular bone volume after SNxPTx. Hormonal replacement, however, caused an increase in trabecular bone volume (p < 0.05), which represents an anabolic effect, which contrasts with findings from the tibial head. The different interventional effects on the lumbar spine and on peripheral bone, regarding the parameters reflecting the condition of osteoblasts, may be intrinsic to the uremic syndrome itself as well as to dissimilar growth manner, function, and mechanical requirements. The findings substantiate the site dependence of bone surface cell metabolism in renal failure and should be the subject of further study. Corresponding results with regard to bone resorption argue for a bone-site-independent, diminished response of osteoclasts to calcitropic hormones.

Enhanced chemosensitivity to CPT-11 with proteasome inhibitor PS-341: implications for systemic nuclear factor-kappaB inhibition.

Inducible activation of nuclear factor-kappaB (NF-kappaB) inhibits the apoptotic response to chemotherapy and irradiation. Activation of NF-kappaB via phosphorylation of an inhibitor protein IkappaB leads to degradation of IkappaB through the ubiquitin-proteasome pathway. We hypothesized that inactivation of proteasome function will inhibit inducible NF-kappaB activation, thereby increasing levels of apoptosis in response to chemotherapy and enhancing antitumor effects. To assess the effects of proteasome inhibition on chemotherapy response, human colorectal cancer cells were pretreated with the dipeptide boronic acid analogue PS-341 (1 microM) prior to exposure to SN-38, the active metabolite of the topoisomerase I inhibitor, CPT-11. Inducible activation of NF-kappaB and growth response were evaluated in vitro and in vivo. Effects on p53, p21, p27 and apoptosis were determined. Pretreatment with PS-341 inhibited activation of NF-kappaB induced by SN-38 and resulted in a significantly higher level of growth inhibition (64-75%) compared with treatment with PS-341 alone (20-30%) or SN-38 alone (24-47%; P < 0.002). Combination therapy resulted in a 94% decrease in tumor size compared with the control group and significantly improved tumoricidal response to treatment compared with all treatment groups (P = 0.02). The level of apoptosis was 80-90% in the treatment group that received combination treatment compared with treatment with single agent alone (10%). Proteasome inhibition blocks chemotherapy-induced NF-kappaB activation, leading to a dramatic augmentation of chemosensitivity and enhanced apoptosis. Combining proteasome inhibition with chemotherapy has significant potential to overcome the high incidence of chemotherapy resistance. Clinical studies are currently in development to evaluate the role of proteasome inhibition as an important adjuvant to systemic chemotherapy.

Prevalent vertebral deformity predicts incident hip though not distal forearm fracture: results from the European Prospective Osteoporosis Study.

The presence of a vertebral deformity increases the risk of subsequent spinal deformities. The aim of this analysis was to determine whether the presence of vertebral deformity predicts incident hip and other limb fractures. Six thousand three hundred and forty-four men and 6788 women aged 50 years and over were recruited from population registers in 31 European centers and followed prospectively for a median of 3 years. All subjects had radiographs performed at baseline and the presence of vertebral deformity was assessed using established morphometric methods. Incident limb fractures which occurred during the follow- up period were ascertained by annual postal questionnaire and confirmed by radiographs, review of medical records and personal interview. During a total of 40348 person-years of follow-up, 138 men and 391 women sustained a limb fracture. Amongst the women, after adjustment for age, prevalent vertebral deformity was a strong predictor of incident hip fracture, (rate ratio (RR) = 4.5; 95% CI 2.1-9.4) and a weak predictor of 'other' limb fractures (RR = 1.6; 95% CI 1.1-2.4), though not distal forearm fracture (RR = 1.0; 95% CI 0.6-1.6). The predictive risk increased with increasing number of prevalent deformities, particularly for subsequent hip fracture: for two or more deformities, RR = 7.2 (95% CI 3.0-17.3). Amongst men, vertebral deformity was not associated with an increased risk of incident limb fracture though there was a nonsignificant trend toward an increased risk of hip fracture with increasing number of deformities. In summary, prevalent radiographic vertebral deformities in women are a strong predictor of hip fracture, and to a lesser extent humerus and 'other' limb fractures; however, they do not predict distal forearm fractures.

Sex steroid receptors in Hodgkin's disease.

A case report of a dramatic therapeutic response of Hodgkin's disease (HD) to diethylstilbestrol (DES) in a man who was being treated for concurrent prostate cancer suggested that there also may be a role for sex steroids in the pathogenesis of HD (1). High levels of estrogen receptors (ER) comparable to those seen in breast carcinoma cells were detected in that patient's Hodgkin's biopsy specimen. In order to determine whether this patient was unique or whether sex steroid receptors commonly are present in HD specimens, we examined expression of ER and progesterone receptors (PR) in diagnostic tissue from pediatric (n = 14) and adult (n = 41) patients with HD using immunohistochemistry. None of the 55 samples expressed PR. 16/55 (29%) demonstrated weak nuclear ER positivity, which was confined to germinal center and occasional mantle zone lymphocytes and was comparable to that seen in non-malignant control lymph nodes. (4/5)5 (7.3%) samples exhibited moderate positivity in Reed Sternberg cells, which in one case was nuclear. ER commonly are expressed weakly in some HD tumors unrelated to clinical stage or patient sex but are generally limited to germinal center and mantle zone lymphocytes. A rare patient displays moderate cytoplasmic or nuclear ER in Reed-Sternberg cells.

Ultrasound bone densitometry of the os calcis in children and adolescents.

The aim of the present investigation was to evaluate reference data and to examine whether there were weight-, height-, age-, and sex-related differences of the quantitative ultrasound bone parameters for healthy children and adolescents. A total of 3299 healthy Caucasian children and teenagers (1623 girls and 1676 boys), age range from 6-18 years (mean age 11.4 +/- 3.4 years for boys and mean age 11.5 +/- 3.3 years for girls) were examined by quantitative ultrasound densitometry (QUS) using the bone sonometer SAHARA (Hologic Inc., Waltham, MA, USA), a waterless, dry system. The parameters broadband ultrasound attenuation (BUA) [dB/MHz] and speed of sound (SOS) [m/second] were evaluated on the right heel in relation to age, sex, weight, and height. There is no correlation between the ultrasound bone parameter SOS and age, height, and weight. BUA increases with age, height, and weight. Significant differences in SOS and BUA between girls and boys were found to probably be caused by the different onset of growth phases and the onset of puberty. SOS and BUA are influenced by changes of bone mineral density. But BUA is dependent on bone size, too. In conclusion, ultrasound bone densitometry is a useful measuring method showing the physiological bone development in childhood and adolescence. The presented results can be used as reference data. Further studies in children with disorders influencing bone metabolism will show in what way various patterns of osteopenia in childhood can be detected.

[Interdisciplinary quality circle for osteoporosis. First results from the Regional Advisory Board for Osteoporosis for Saxony-Thuringia]. / Interdisziplinäre Qualitätszirkel für Osteoporose. Erste Erfahrungen aus dem Regionalen Expertenkreis Osteoporose von Sachsen-Thüringen.

The Regional Advisory Board Osteoporosis (REKO) for Saxony-Thuringia has established interdisciplinary quality circles in different districts with the goal to standardize the diagnosis of osteoporosis. Therefore, they developed a standardized program for general practitioners, gynecologists, internists and orthopedics. The documentation sheet covers 5 areas: Identification of the anamnestic osteoporosis risk with 7 standardized questions: If the patient reaches 3 or more out of 13 possible points, we assume he is at risk. 3 out of 5 clinical symptoms, 3 out of 6 x-ray symptoms and osteoporosis typical results of the bone density measurement in combination with the anamnesis give us a scale which allows us to classify each symptom for diagnostic purpose. The differential diagnostic laboratory program includes: Blood sedimentation rate, calcium, alkaline phosphatase, creatine, TSH basal and 25 OH vitamin D3 in the serum. To check effectiveness of the antiresorptive therapy, bone specific resorption markers are sometimes usable. The program will be implemented this year in all quality circles, evaluated and then defined in its final form. Among the participants of the quality circles, the program is already usable and offers a reliable basis for the therapy.

Physiological doses of calcium regulatory hormones do not normalize bone cells in uraemic rats.

BACKGROUND: Low bone turnover despite normal parathyroid hormone (PTH) concentrations has been found in many patients with end-stage renal failure. Hyporesponsiveness to the calcaemic action is also a known feature of uraemia. Hyporesponsiveness of bone surface cells involved in bone modelling has not been demonstrated to date. It was the purpose of this study using a rat model of moderate renal failure to investigate whether doses of PTH and calcitriol that reverse the effect of parathyroidectomy on calcaemia also normalize bone surface cell activity. MATERIALS AND METHODS: Sham-operated pair-fed male Spraque-Dawley rats were compared with subtotally nephrectomized (SNX), parathyroidectomized (PTX) rats that received either solvent or calcitriol (5 pmol kg -1 h-1) + 1,34 rat PTH (100 ng kg -1 h-1) by osmotic mini-pump. Histomorphometric measurements were carried out in the vertebral body (L5). RESULTS: In SNX/PTX animals, calcitriol + 1,34 rat PTH caused a modest increase in serum calcium (S-Ca) within the normal range. Osteoclast surface per cent was significantly lower in solvent-treated SNX/PTX rats than in sham-operated controls [3.7 +/- 2.8 osteoclast surface/bone surface (OcS/BS%) vs. 6.3 +/- 3.9], and this was not normalized by PTH + calcitriol (3.3 +/- 3). In contrast, osteoblast surface per cent and osteoid surface per cent were increased over values in sham-operated rats; as a result, co-administration of calcitriol and 1,34 rat PTH caused a highly significant increase in fractional bone volume (BV/TV). CONCLUSIONS: The results show that administration of PTH and calcitriol in doses that raise serum calcium fails to normalize the percentage of osteoclast surface, but was effective in raising osteoblast number and osteoblast volume in experimental renal failure. The results argue for abnormal response of bone cells to calcium-regulating hormones and/or the action of factors other than calcium regulatory hormones in the genesis of skeletal abnormalities of renal failure.

Periarticular bone alterations in chronic antigen-induced arthritis: free and liposome-encapsulated clodronate prevent loss of bone mass in the secondary spongiosa.

The long-term effects of acutely administered clodronate (free or liposome-encapsulated) on periarticular bone mass and bone turnover were investigated in chronic antigen-induced arthritis (AIA; day 28). Wistar rats were treated intraperitoneally at 3 h and on days 1, 2, and 7 of AIA, with phosphate-buffered saline (PBS; sham), PBS-containing liposomes, free clodronate, or liposome-encapsulated clodronate (cumulative dose, 3.64 mg/animal). In the primary spongiosa (1.25 mm from the growth plate), sham-treated AIA was associated with: (a) a marked significant decrease in trabecular bone volume (-56%); (b) a significant increase of osteoid-covered surface (+135%); and (c) a numerical increase of resorption surface with osteoclasts (+96%). In the secondary spongiosa, free clodronate completely prevented the loss of periarticular bone mass and selectively normalized the parameters of bone formation (i.e., osteoid-covered surface and osteoid-covered surface with osteoblasts). Clodronate liposomes, in addition to these effects, also significantly suppressed bone resorption (i.e., resorption surface covered with osteoclasts). The effects of clodronate liposomes coincided with in vivo targeting of osteoclasts in primary and secondary spongiosa. Thus, low-dose, acutely administered clodronate, both in free and encapsulated forms, exerts an excellent preventive effect on bone loss in the secondary spongiosa of chronic AIA.

Dysregulation of insulin-like growth factors in a case of generalized acquired lipoatrophic diabetes mellitus (Lawrence Syndrome) connected with autoantibodies against adipocyte membranes.

We report on a 33-year-old male patient with generalized acquired lipodystrophy, insulin resistant diabetes mellitus and acanthosis nigricans (Lawrence Syndrome). First probable symptoms of lipodystrophy (weight loss, shrinkage of subcutaneous fatty tissue, and loss of muscular strength) became evident three years ago, with the onset of diabetes mellitus occurring about six months later. The patient suffered from the following clinical symptoms: IDDM with increasing insulin-requirement, extreme reduction of fatty tissue, fatty liver hepatitis with elevated liver enzymes, glomerulopathy, muscular and neuropathic pains, as well as hypertriglyceridaemia. A basal C-peptide concentration is rather high. Definitely, the endogenous insulin secretion is increased. In other words, insulin resistance is documented. In an effort to identify the pathogenetic mechanisms of lipoatrophic diabetes mellitus in this patient and to develop a therapeutic strategy, antibodies against different tissues and endocrinologic regulation were investigated. It was possible to demonstrate the presence of serum autoantibodies against lipocytes of the subcutis and other tissues, against hepatic stellate cells, together with autoantibodies against different endocrine organs. By studying the basis of diabetic abnormalities relating to the growth hormone (GH), the insulin-like growth factor (IGF) dynamics in this patient, i.e. reductions of GH, IGF-I, IGF-II, IGF-Binding protein (IGF-BP) 2 and IGF-BP 3, were detected. An immunosuppressive treatment strategy was not beneficial.

Relationship between disease activity and serum levels of vitamin D metabolites and PTH in rheumatoid arthritis.

In several studies on patients with rheumatoid arthritis, an association of bone loss with a persistently high disease activity has been found. The aim of our study was to investigate the relation between disease activity and serum levels of vitamin D metabolites, parathyroid hormone (PTH), and parameters of bone turnover in patients with rheumatoid arthritis. A total of 96 patients (83 women and 13 men) were divided into three groups according to disease activity measured by serum levels of C-reactive protein (CRP). In the whole group, serum levels of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) (P < 0.001) and PTH (P < 0.05) were negatively correlated to disease activity. The urinary excretion of collagen crosslinks--pyridinoline (Pyd) (P < 0.001) and deoxypyridinoline (Dpd) (P < 0.05)--showed a positive correlation with disease activity. The inverse correlation between serum 1,25(OH)2D3 and disease activity was separately evident in patients with (P < 0.001) and without (P < 0.01) glucocorticoid treatment, in pre- (P < 0.01) and postmenopausal (P < 0.001) women, and in men (P < 0.01). 1,25(OH)2D3 and PTH serum levels were positively correlated to serum bone alkaline phosphatase (ALP) (P < 0.01). The results indicate that high disease activity in patients with rheumatoid arthritis is associated with an alteration in vitamin D metabolism and increased bone resorption. The decrease of 1,25(OH)2D3 levels in these patients may contribute to a negative calcium balance and inhibition of bone formation. Furthermore, low levels of 1,25(OH)2D3 as an endogenous immunomodulator suppressing activated T cells and the proliferation of cells may accelerate the arthritic process in rheumatoid arthritis.

PICP as bone formation and NTx as bone resorption marker in patients with chronic renal failure.

UNLABELLED: Renal bone disease which develops in patients with chronic renal failure (CRF) is not a uniform metabolic disorder. Although bone histomorphometry is accepted to be the gold standard for characterizing the state of disease progression, the techniques involved are cumbersome and expensive so that it cannot be used routinely. As a result, numerous biochemical markes have been developed to measure bone formation and resorption. The purpose of this study was to evaluate the suitability of procollagen type-I C-terminal peptide (PICP) in serum as an indicator of bone formation and cross-linked amino-terminal telopeptide of type I collagen (NTx) in urine as an indicator of bone degradation processes, and to investigate their relation to histomorphometric and other biochemical parameters. 77 patients with CRF and 49 patients on intermittent hemodialysis treatment (DT) were investigated. PICP was measured in serum and NTx in urine. In addition, iPTH, phosphate, calcium, alkaline phosphatase (APH), osteocalcin and creatinine in serum were determined. Bone biopsies were obtained from the anterior, superior iliac crest, and the histomorphometric parameters were measured and expressed according to the standardized nomenclature. Patients with CRF and DT had significantly higher PICP and NTx levels as compared to controls. In the CRF group significant correlations could be obtained between PICP and histomorphometric parameters of bone formation as well as between NTx and histomorphometric indices of bone resorption. In this group, PICP levels were positively correlated to iPTH, phosphate and creatinine levels and negatively to calcium concentrations. Furthermore, there were significant correlations between NTx values and those of both iPTH and APH. In the group of dialysis patients, levels of PICP and NTx did not correlate with any of the histomorphometric parameters or the classical humoral markers. CONCLUSIONS: The results suggest that PICP as bone formation and NTx as bone resorption markers are of potential use for screening bone turnover in predialysis chronic renal failure patients. But in patients undergoing dialysis, neither PICP nor NTx yielded any substantial information as noninvasive markers of bone histology.

[Oral calcitriol pulse therapy in hemodialysis patients. Effects on histomorphometry of bone in renal hyperparathyroidism]. / Orale Calcitriolstosstherapie bei Hämodialysepatienten. Auswirkungen auf die Histomorphometrie des Knochens bei renalem Hyperparathyreoidismus.

BACKGROUND: Hemodialysis patients with symptomatic renal hyperparathyroidism should only get a surgical parathyroidectomy if the oral calcitriol pulse therapy fails. Unfortunately there is no general accepted recommendation for the dosage and intervals of the oral calcitriol pulse therapy. PATIENTS AND METHODS: In 34 hemodialysis patients (9 women, 25 men, mean age: 50 +/- 13 years, mean duration time of dialysis: 20 +/- 30 months) with renal hyperparathyroidism (intact parathormon = iPTH > 20 pmol/l) an oral calcitriol pulse therapy was performed over a period of one year. The initial dosage of calcitriol was 0.1 microgram/kg bwt a week, splitted into two equal dosages given at night. After 3 months the calcitriol dosage was changed according to the iPTH, calcium and phosphate levels. The dialysate calcium concentration was kept constant with 1.5 mmol/l. Before and after one year a bone biopsy was performed. The target level for a successful treatment was < or = 20 pmol/l. RESULTS: In the group of responders (n = 24) the iPTH level decreased significantly (p < 0.01) from 37.5 +/- 3.2 to 14.3 +/- 1.9 pmol/l after a period of 12 months. There was no significant change of the iPTH levels in the 10 non-responders (55.5 +/- 6.5 vs 57.2 +/- 9.7 pmol/l). The incidence of hypercalcemia was higher in the non-responder group (19.2%) as compared to the responder group (13.4%). In the group of responders the bone resorption decreased, whereas the bone formation increased under an oral calcitriol pulse therapy. CONCLUSION: A decrease in iPTH level in hemodialysis patients undergoing an oral calcitriol pulse therapy with an initial dosage of 0.1 microgram/kg bwt. was found in 71% of the patients after one year. Calcitriol improves the histomorphometrical parameters in responders.

Management of primary idiopathic hyperphosphatasemia with calcitonin: a case report.

We describe a patient with primary idiopathic hyperphosphatasemia, a rare hereditary disease caused by a primary enzymatic disorder. The clinical, radiological, histological and biochemical features of the disease and their response to treatment with Calcitonin are described. We recommend Calcitonin for this rare disease in specialist units. It leads to improvement in many markers and better function.

Predictors of flares and long-term outcome of systemic lupus erythematosus during combined treatment with azathioprine and low-dose prednisolone.

Many patients with systemic lupus erythematosus (SLE) receive long-term treatment with azathioprine and prednisolone to control disease activity. In a retrospective study we evaluated the efficacy of combined treatment with azathioprine (2 mg/kg body weight/d) and low-dose prednisolone (7-12 mg/d) and the predictors of disease flares during this therapy regimen in 61 patients with SLE. We found three predictors of flares: renal disease, persistence of dsDNA antibodies for at least 1 year after the beginning of treatment and reduction in azathioprine dosage to below 2 mg/kg/d. The occurrence of flares was significantly associated with a higher rate of disease-related death. Furthermore, the persistence of dsDNA antibodies for at least 2 years was associated with progression of renal disease. We concluded that suppression of production of dsDNA antibodies with high avidity is a suitable parameter to determine efficacy of treatment and long-term outcome during combined therapy with azathioprine and low-dose prednisolone in SLE.

[Pathophysiology and epidemiology of osteoporosis]. / Pathophysiologie und Epidemiologie der Osteoporose.

The international consensus definition characterizes the osteoporosis by low bone mass and microarchitectural deterioration. New genetic aspects of the pathogenesis of osteoporosis underline these characteristics. In the younger age, a reduced bone mineral density and a reduction of the bone structure are predictors of a genetically caused osteoporosis. The short-term maximal mechanical load of the bone structure by Frost (4) was pointed out to be an important pathophysiological element for the balance of the bone metabolism. Sex hormones and other calcium regulating hormones determine the effect of this biomechanical signal. The deficiency of the osteoblast's activity in the older age is caused by a reduced proliferating cell pool of bone tissue. The epidemiologic data of the osteoporosis were derived from incidence of the hip fractures. A densitometrical osteoporosis screening test analyzes only the bone density but not the organisation of the bone structure. There is too little informations about the disease of osteoporosis. It is to hope that, in the future, the European-Vertebral-Osteoporosis-Study will give additional knowledge about osteoporosis.