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.

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.

Quantitative study of articular cartilage and subchondral bone remodeling in the knee joint of dogs after strenuous running training.

All tissues of the joint are affected in some way in osteoarthritis because the joint is an interactively functioning unit. Our goal was to investigate the combined responses of articular cartilage and subchondral bone to altered loading conditions to improve our understanding of the physiology of these two components and, ultimately, the pathophysiology of osteoarthritis. A group of 20 female beagle dogs were divided pairwise into runners (n = 10) and controls (n = 10). The running training on a treadmill started at the age of 15 weeks, and during the following 40 weeks the running distance was gradually increased to 40 km/day with a 15 degree uphill inclination. With this daily running distance the beagles ran another 15 weeks. The samples for histology were taken from 11 different locations of the knee joint. Subchondral bone and articular cartilage histomorphometry was carried out in three different regions of the specimens (central, middle, and peripheral regions) using an image-analyzing system and an eyepiece graticule. In all regions of the articular cartilage, both the uncalcified and calcified cartilage showed slightly increased thickness in the runner dogs. The change was more evident in the peripheral and the central areas. The thickness of the subchondral bone plate tended to be higher in runners, too. Bone histomorphometric parameters showed significant signs of increased remodeling. The most notable change was the enlargement of the bone formation surface. The most intense remodeling was usually observed either centrally or peripherally in the articular surface. The strongest increase in trabecular bone volume and thickness of the cartilage was recorded in the femoropatellar area.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

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.

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.

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.

No tissue level abnormality of vitamin A concentration despite elevated serum vitamin A of uremic patients.

In 57 patients with chronic renal failure (CRF) [44 patients on regular dialysis treatment (RDT), 33 renal transplant patients (RT) and 26 normal patients (NP)] and in a further 11 patients with CRF (8 patients on RDT and 17 patients without any renal disease in the post mortem) the vitamin A content of the serum obtained from the tissue of the liver, the stomach, the subcutaneous adipose tissue and the bone were analyzed. The vitamin A content of the serum was increased significantly for all groups of patients in comparison with the control group, but hypervitaminotic ranges were not reached in any case. The vitamin A content decreased depending on the time of dialysis treatment and the period after kidney transplantation. The retinol-binding protein accumulated even more than vitamin A in CRF and RDT. This statement is not in conformity with that of a hypervitaminosis A, of which normal respectively decreased RBP levels are characteristic. The serum prealbumin concentration was near the upper limit of the normal range in all groups of patients. The serum content of beta-carotene in patients with CRF and RDT was raised in comparison with NP and RT patients. As to the vitamin A content of the organs, a distinctive decrease appeared in the liver, so that a marginal supply must be assumed. In the stomach and the subcutaneous adipose tissue no changes, in comparison with the control patients, resulted. Due to renal insufficiency the results indicated an unphysiological situation in the vitamin A metabolism. Connections with disturbances of the fat-household could not be set up.(ABSTRACT TRUNCATED AT 250 WORDS)

Studies on psoriatic osteopathy.

To demonstrate an as yet merely postulated generalized osteopathy in psoriatics, the serum calcium level, the alkaline phosphatase in the serum and the urinary excretion of hydroxyproline were evaluated in 24 patients with Ps and 24 patients with PA. Moreover, the bone bioptates from 25 patients with PA and 10 patients with Ps were examined histologically and measured morphometrically. The investigations provide evidence for the existence of a generalized "latent" osteopathy in terms of an elevated bone turnover rate without loss of bone volume (high turnover remodelling) in both patients with PA as well as those with Ps without arthritis. As a pathogenetically essential factor shared by dermatosis and "osteopathy", latent vitamin D deficiency and/or D hormone resistance is discussed.

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.

[Current musculoskeletal symptoms in peri and postmenopausal women: results of a multicenter population epidemiological study. The EVOS Study Group]. / Aktuelle muskuloskeletale Beschwerden bei peri- und postmenopausalen Frauen: Ergebnisse einer multizentrischen bevölkerungsepidemiologischen Studie. EVOS-Studiengruppe.

Within the European vertebral osteoporosis study four stratified systematic samples of German residents aged 50-79 in Lübeck, Heidelberg, Jena and East Berlin have been drawn. Overall 4628 subjects were included, of whom 4385 were contactable and 3106 (71%) responded to the postal questionnaire enquiring about rheumatic complaints "today". 2348 (54%) followed an invitation to a medical examination in which a specific gynaecological history was taken. The prevalence of current back-, neck- and joint-pain is consistently higher in females than in males in all age groups. Females show a peak prevalence in the age group 55-64. 104/1134 women were pre- or perimenopausal. 1030 women had not had their period for at least 13 months and were classified as "postmenopausal". Neither the menopausal status nor the duration of the postmenopause were statistically significantly associated with the frequency of the three rheumatic complaints.

[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.

[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.

[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.

[Current aspects of fluoride therapy of osteoporosis]. / Moderne Aspekte zur Fluortherapie der Osteoporose.

Fluorine has an effect on the bone, it increases both the number and the activity of osteoblasts and, thus, at first leads to an osteoidosis. The mineralization is somewhat lagging behind. This mode of action is best suited for low-turnover osteoporosis. For all other forms of osteoporosis, such as high-turnover osteoporosis, osteoporomalacia and mixed osteopathies, fluorine therapy as the sole treatment is not optimal. In our opinion, it is not the action principle "fluorine" that is insufficient or dangerous, but the indication for this therapy was not given in case of treatment failures or certain side effects. The decisive progress in the treatment of osteoporosis is to be expected from an essentially improved and pathophysiologically oriented differential diagnosis and the resulting differential therapy.

[Acute leukemia and pregnancy]. / Akute Leukose und Schwangerschaft.

It is reported on an undifferentiated cell leukosis of the type PAS in the 2nd trimenon of a pregnancy. The paralymphoblastosis could well be influenced by a prednisolone monotherapy so that a healthy baby was born. After birth very quickly developed a severe recidivation of leucosis which no more could be influenced therapeutically so that the patient dies on the 10th day after birth. The problems of the therapy of undifferentiated cell leucosis during pregnancy are discussed and possible hormonal protective mechanisms are taken into consideration.

[Osteopenia--comments on the concept of osteoporosis]. / Die Osteopenie--zur Diskussion um den Osteoporosebegriff.

On the basis of instances the problems of the simultaneous use of the notion of osteoporosis for a clinical picture of a disease and a roentgen-morphological symptom is discussed. The described errors of diagnostics avail themselves of the introduction of the notion of osteopenia as initial findings which then further must be differentiated into the defined clinical pictures of osteomalacia, fibroosteoclasia and into the so-called syndrome of osteoporosis. In the nomenclature proposed the radiologists have the main responsibility, since instead of osteoporosis as X-ray-morphological symptom they must propose the clinician the osteopenia with sings for an adequate clinical picture and so compel the clinician to perform the differential diagnosis of demineralisation of the bone as far as possible.

[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.

[Principles of differential pathogenesis-oriented therapy of various forms of osteopenia]. / Prinzipien der pathogeneseorientierten Differentialtherapie der verschiedenen Formen der Osteopenie.

From the demonstration of etiopathogenetic mechanisms of osteopenia 7 different histologically and histomorphometrically defined pictures of the state (diseases) of the skeleton are derived. From this 4 different possibilities of the influence on the permanent transformation of the skeleton--the remodeling are the result. The medicamentous support of the blockade or stimulation of osteoclasts and the optimization of the mineralization are the basis of therapeutic considerations. In the light of these pathogenetically orientated treatment strategies the real and at present practicable therapy regimes of the various clinical manifestations of the osteopenia and new beginnings especially also of the therapy of osteoporosis are discussed.