Therapy of aseptic nonunions with parathyroid hormone.

The absence of osseous consolidation of a fracture for 9 or more months with no potential to heal is defined as nonunion. Both for the patient and from a socioeconomic point of view, nonunions represent a major problem. Hypertrophic, vital nonunions are distinguished from atrophic avital ones. Risk factors for a delayed fracture healing are insufficient immobilisation, poor adaptation of the fracture surfaces or residual instability, interposition of soft tissue within the fracture gap, as well as circulation disturbances and infections. The incidence of nonunions after fractures of the long bones lies between 2.6 and 16% depending on the surgical technique used. In human and animal studies, a positive effect of parathyroid hormone (PTH) on fracture healing has been shown. PTH has a direct stimulatory effect on osteoblasts and osteoclasts. In addition, it appears to influence the effect of osseous growth factors. In this prospective study, 32 patients with nonunions were treated with teriparatide to investigate the effects of PTH on fracture healing. Definitive healing of the nonunions following PTH treatment could be observed in 95% of the cases.

Balloon sacroplasty as a palliative pain treatment in patients with metastasis-induced bone destruction and pathological fractures.

PURPOSE: In the case of metastatic involvement of the sacrum with destruction and consecutive pathological fracture, intense disabling pain is one of the defining factors. The feasibility, safety and pain development with cement augmentation were to be investigated. MATERIALS AND METHODS: CT-guided balloon sacroplasty was conducted in 10 patients with metastasis-induced bone destruction of the sacrum. After establishment of the entry point, a K-wire was first introduced as far as the central tumor lesion via the short, or transiliac axis. A cannula was then positioned over the wire. Under CT guidance, a balloon catheter was introduced through the cannula and inflated and deflated several times. The PMMA cement was then injected into the preformed cavity. The procedure was completed by a spiral CT control using the thin-slice technique. Pain intensity was determined using a visual analog scale (VAS) before the procedure, on the 2nd postoperative day and 6 months after the intervention. Finally, the patients were asked to state how satisfied they were. RESULTS: Balloon sacroplasty was technically feasible in all patients. The control CT scan showed central distribution of the cement in the tumor lesion. On average 6 +/- 1.78 (4 - 10) ml of PMMA cement were introduced per treated lesion. A significant (p < 0.001) reduction in pain according to the VAS occurred in all patients from 9.3 +/- 0.67 (8 - 10) pre-operatively to 2.7 +/- 1.28 (1 - 5) on the 2nd postoperative day and 2.9 +/- 0.81 (2 - 5) 6 months after the intervention. All of the patients were re-mobilized after the procedure and underwent the further therapeutic measures as planned. CONCLUSION: Balloon sacroplasty is a helpful therapeutic option in the overall palliative treatment of patients with tumor-induced destruction. It is a safe and practicable procedure that markedly reduces disabling pain.

[TSH secreting adenoma of pituitary gland (TSHom) - rare cause of hyperthyroidism in pregnancy]. / TSH-sezernierendes Hypophysenadenom (TSHom) - seltene Ursache einer Hyperthyreose in der Schwangerschaft.

HISTORY AND ADMISSION FINDINGS: A 28 year-old woman in her first pregnancy was referred to the department of obstetrics and gynecology at 24 weeks of gestation because of pregnancy-induced hypertension. INVESTIGATIONS: Thyroid stimulating hormone (TSH), free T3 and free T4 were elevated. Antibody screening did not show antithyroid peroxidase (anti-TPO) antibodies and TSH receptor antibodies. Clinical findings were suspicious of TSH secreting pituitary tumour (TSH-om) or thyroid hormone resistance (RTH). In absence of clinical sings of elevated intracranial pressure magnetic resonance imaging (MR) was discussed but not carried out and planned after delivery. A visual-field defect was ruled out by orbital field evaluation. TREATMENT AND COURSE: Treatment with 3 × 50 mg propylthiouracil daily was initiated. However, normal fT3/fT4 titers could not be achieved. Serum levels were in the high normal ranges and TSH remained increased. The clinical situation of the patient improved resulting in a normal delivery at term. The healthy newborn was breast feed and MR imaging of the mother revealed a 5×8 mm tumor of the pituitary gland. CONCLUSION: In pregnant women with pregnancy-induced hypertension thyroid diseases have to be ruled out. Rare causes of hyperthyreoidism are TSH secreting pituitary tumors or thyroid hormone resistance (RTH). Treatment of choice for hyperthyreoidism in pregnancy is propylthiouracil. Normal vaginal delivery and breast feeding are possible. Following delivery it is mandatory to determine an individual treatment strategy.

Ciprofloxacin reduces the risk of hemolytic uremic syndrome in patients with Escherichia coli O104:H4-associated diarrhea.

BACKGROUND: Whether antibiotic treatment in patients with enterohemorrhagic Escherichia coli (EHEC)-associated diarrhea influences the risk of hemolytic uremic syndrome (HUS) has still to be elucidated. PATIENTS AND METHODS: During the EHEC epidemic which occurred in northern Germany in spring 2011, 24 patients with E. coli O104:H4 infection were treated at our hospitals, 19 of whom developed HUS. The use of antibiotics before and after the onset of HUS was documented, and the outcome in patients with and without antibiotic treatment was evaluated. RESULTS: Of the 24 patients with EHEC-associated diarrhea, seven received antibiotics before any signs of HUS were present (ciprofloxacin, cefotaxime, amoxicillin and/or metronidazole). Four of these seven patients (57 %) and 15 of the 17 patients (88 %) who were treated without antibiotics developed HUS (p = 0.12). Microbiological testing showed all E. coli O104:H4 to be extended-spectrum beta lactamase producers and thus susceptible only to fluoroquinolones, aminoglycosides and carbapenems. Two of the five patients (40 %) treated with ciprofloxacin and 17 of the 19 patients (89 %) treated without ciprofloxacin developed HUS (p = 0.043). CONCLUSION: In our E. coli O104:H4-infected patients, treatment of diarrhea with antibiotics did not increase the risk of HUS. Significantly fewer patients treated with ciprofloxacin developed HUS than patients who did not receive ciprofloxacin.

Radiograph-based study of gender-specific vertebral area gain in healthy children and adolescents as a function of age, height, and weight.

This study reports gender-specific vertebral area gain data from children and adolescents. Vertebral area was measured on lateral and anteroposterior thoracic and lumbar spine radiographs from 100 female and 100 male subjects aged 7-28 yr. T9, T11, T12, L1, and L2 X-ray area calculation was based on calculation of the area of the geometric figure of a trapezoid whose 2 nonparallel sides were equal in length, taking account of the waisted shape of the vertebrae. Both the boys and girls of our study population showed statistically significant dependence (p<0.001) of vertebral area gain on chronologic age, height, and weight right through the end of puberty, and especially so up to age 15 yr. However, height and weight were clearly better predictors of lateral and anteroposterior vertebral area gain than was chronologic age. Once vertebral growth is complete by age 18 yr or so, the lateral vertebral areas of the male subjects-regardless of body weight and height-are, on average, 25% larger, and the anteroposterior areas up to 30% larger than those of their female counterparts. After adjusting for chronologic age, height, and weight however we did not find significant differences, between gender, in vertebral area of male and female subjects, neither among children younger than 11 yr nor adolescents ages of 12-14 yr and young adults older than 18 yr.

[Interventional pain relief using balloon-kyphoplasty in patients with osteoporotic-based fatigue fractures of the os sacrum]. / Interventionelle Schmerztherapie mittels Ballon-Kyphoplastie bei Patienten mit osteoporosebedingten Insuffizienzfrakturen des Os sacrum.

PURPOSE: In older patients with reduced bone quality, fatigue fractures of the os sacrum are relatively common and are typically accompanied by strong, disabling pain. The aim of our study was to verify the feasibility and safety of sacroplasty using a balloon catheter as well as the reduction of pain. MATERIALS AND METHODS: 25 patients were diagnosed with an os sacrum fracture in MRI. As a manifestation of an extant bone reconstruction process, all patients were diagnosed with distinctive edema on the basis of MRI strong T 2-weighted images. CT-controlled balloon sacroplasty was performed in all patients. To allow the cement to be dispensed at a longitudinal angle to the fracture, the balloon catheter is directed through a hollow needle in the os sacrum either from the caudal to the cranial direction or from the craniodorsal to the caudoventral direction. The thus created cavity was then filled with PMMA cement. A control CT and a conventional X-ray in two planes were then carried out. The pain intensity was defined by means of VAS before the intervention, on the second day, and 6 and 12 months after the intervention. RESULTS: The balloon sacroplasty yielded good technical performance in every patient. The control CT and the X-ray control of the os sacrum showed adequate distribution of the cement, and cement leakage was not detected. Before the operation, the average pain encountered was in accordance with VAS 8.3. On the second postoperative day, a considerable reduction with an average of 2.7 was reported, and this remained stable with an average of 2.5 after 6 and 12 months. CONCLUSION: Balloon sacroplasty is an effective treatment method for fast pain relief in patients with fatigue fractures of the os sacrum.

[Quantitative analysis of corneal subbasal nerve plexus with in vivo confocal laser scanning microscopy]. / Quantitative Analyse des subbasalen Nervenplexus der Kornea mittels in vivo konfokaler Laser-Scanning-Mikroskopie.

BACKGROUND: An analysis of the corneal subbasal nerve plexus (SNP) allows an evaluation of the peripheral neuropathy in cases of degenerative diseases. In order to study the SNP structures quantitatively the automatically calculated morphological and topological parameters are required. METHODS: In vivo confocal laser scanning microscopy (Heidelberg Retina Tomograph II/Rostock Cornea Module) was performed in healthy volunteers as well as patients with severe diabetic neuropathy. An adapted image processing algorithm was used to preprocess, segment and evaluate quantitatively the nerve fibers of the SNP. Data sets were analysed statistically. RESULTS: The developed algorithm allows an automated detection of SNP structures. Furthermore, it allows the collection of data based on morphological and topological parameters. The main parameters that show significant differences between healthy cornea and cases of diabetic neuropathy are nerve fibre density and length, number of branching, tortuosity and number of terminal and crossing points. All parameters of the measurements can be used isolated, combined or weighted for quantification of the SNP networks. CONCLUSION: The presented fully automated preprocessing eliminates a large number of motion-induced artefacts. The quality of the resulting pictures allows an automated quantification using characteristic measurements. This represents an in vivo, non-invasive technology analysing degenerative changes of SNP especially in the course of diabetes mellitus.

[Value of fall-risk tests for patients with rheumatoid arthritis]. / Wertigkeit von Sturzrisikotests bei Patienten mit rheumatoider Arthritis.

The aim of the study was to quickly and efficiently determine the risk of falling in patients with rheumatoid arthritis over the age of 46 with established methods, to discover parameters which influence the risk of falling and fractures. The study group consisted of 67 patients (median age 69±7.4 years, duration of disease <10 years 71%).With the help of the present data on fractures the performance of the chair-rising (CR) test, the timed up-and-go (TUG) test and the tandem stand (TS) test plus determination of the average daily and cumulative glucocorticoid (GC) dosage, it was possible to detect parameters which influence the risk of falling and fractures.Higher age (>60 years), overweight, deficits in muscle strength in the lower extremities and very low GC dosage (≤5 mg) were found to be associated with an increased risk of falling, which is accompanied by an increased risk of fractures.

[Parathyroid hormone injection to counteract delayed bone fractures]. / Parathormon bei verzögerter Frakturheilung.

CASE HISTORY AND CLINICAL FINDINGS: Two women, aged 71 and 53 years with periprosthetic fractures of the left femur and an 18 year old man with a non-union of fracture of the left radius presented for assessment and treatment. INVESTIGATIONS: Serial radiographs showed that osteosynthesis and/or autogenous bone-grafting and multiple revisions had not resulted in healing of the fractures. TREATMENT AND CLINICAL COURSE: In all three patients parathyroid hormone (teriparatide), 20 to 60 microg, was injected subcutaneously once daily for 6 - 10 weeks. Subsequently a stable consolidation of the bone occurred in all of them. CONCLUSION: Administration of parathyroid hormone can induce stable consolidation of the bone in non-unions and delayed healing of bone fractures.

Effects of different regimens of sodium fluoride treatment for osteoporosis on the structure, remodeling and mineralization of bone.

We compared initial and final bone histomorphometric findings in 66 osteoporotic patients treated with sodium fluoride (NaF) according to three regimens, and in 7 osteoporotic patients who did not receive NaF. Fourteen patients received continuous NaF 75 mg/day (high-dose) with calcium 1500 mg/day for a mean of 41 months. Twenty-six patients received continuous NaF 50 mg/day (low-dose) with calcium 2000 mg/day for a mean of 15 months, either with (10 patients) or without (16 patients) vitamin D. Twenty-six patients received cyclical low-dose NaF, alternating with vitamin D, for a mean of 15 months and a total treatment duration of 28 months, of whom 14 were and 12 were not on NaF at the time of the second biopsy. Disregarding differences between regimens, there were significant increases in total and mineralized bone volume and trabecular thickness and nonsignificant decreases in these measurements in the control group. Fluoride-induced bone formation was exclusively appositional with no evidence for the creation of new trabeculae. The effect of low-dose NaF on bone structure was the same when the same total dose was given continuously or intermittently, and when the patient was or was not taking vitamin D. The increases in total and mineralized bone volume but not trabecular thickness were greater with high-dose than with low-dose NaF. Low-dose NaF caused modest but significant increases in all osteoid indices, and modest but significant declines in adjusted apposition rate and osteoid maturation rate and no change in bone formation rate. With high-dose NaF, the increase in BV/TV was greater but all indices of osteoid accumulation were much higher and all indices of impaired osteoblast function and mineralization were much lower, and 12 of 14 patients had some form of osteomalacia. This occurred also in 3 of 30 patients treated with low-dose NaF who were not taking vitamin D; the mean increase in osteoid thickness was significantly greater in these patients than in 22 low-dose patients who were taking vitamin D. We conclude: (1) The inconsistent effect of NaF in increasing bone strength is partly due to failure to restore connectivity in patients with severe bone loss and partly due to substantial osteoid accumulation. (2) Even low-dose NaF causes impaired osteoblast function, but this is much greater with high-dose prolonged therapy. (3) There is an unexplained discrepancy between the increase in bone formation implied by increases in spinal bone mineral and the lack of increase in bone formation measured histomorphometrically. (4) Defective mineralization is more closely related to the total cumulative dose of NaF than to the duration of treatment, and with low-dose treatment may be preventable by vitamin D. (5) Future clinical trials should be carried out with smaller doses of NaF and before there has been substantial loss of horizontal trabeculae in the spine.

Contribution of the cortical shell of vertebrae to mechanical behaviour of the lumbar vertebrae with implications for predicting fracture risk.

In the diagnosis of osteoporosis using single energy quantitative CT (SE-QCT) on the axial skeleton, only spongy bone mineral density (BMD) is used at present. Although the density of cortical bone is also determined by most QCT methods, it is not used for evaluation. The objective of this study was to determine the extent to which the cortical bone of the lumbar vertebral bodies accounts for their load-bearing capacity and failure behaviour, and to use this information to suggest improvements in the differential diagnosis of osteoporosis. Investigations were conducted in a clinical, theoretical-numerical and biomechanical-experimental context. Cortical (BMDC) and spongy (BMDS) bone mineral density was measured by SE-QCT/85 kV on 179 patients (68 males, 111 females). These bone densities were matched with the vertebral body fractures previously determined from conventional X-rays. A finite element model was used to study the variation in structural and material parameters of the vertebral body. 19 vertebral bodies that had been removed post-mortem were available for the biomechanical-experimental investigations. Spongy and cortical bone densities were also determined by SE-QCT on these vertebral bodies. Their failure load was then measured in the axial compression test. These investigations show that, in addition to the spongiosa, the cortical shell plays an important role in the load-bearing capacity of the vertebral body. If the spongiosa is weakened due to a loss of BMD, the residual load-bearing capacity of the vertebral bodies is increasingly shouldered by the cortical bone. The lower susceptibility to fracture in men compared with women when spongy bone mineral density is reduced can thus be attributed to the lack of a reduction in cortical bone mineral density. It is recommended that the BMDC also be evaluated in future, especially in the diagnosis of bone mass losses in women, to improve the estimation of the individual fracture risk.

Noninvasive assessment of stiffness and failure load of human vertebrae from CT-data.

A calculational method based on noninvasively derived data for the assessment of the mechanical quality of individual vertebrae is presented. Dimensional data obtained from serial, segmented CT scans were used as the geometric input for a newly developed finite element model designed to calculate stiffness and failure load of these complex bone structures. Mechanical, structural data for cancellous bone was obtained by measurements of the compressive strength and failure load of actual vertebral specimens obtained at autopsy. The stiffness and failure load calculated by the newly developed finite element model were compared with the data obtained from mechanical measurements of vertebral specimens. A high correlation between measured and calculated failure load was found (r = 0.89, p < 0.001, n = 16). The correlation between the failure load and bone mineral density (BMD) was significant (r = 0.82, p < 0.001, n = 16). A similar correlation between calculated and measured stiffness (r = 0.81, p < 0.001, n = 15) was also found using the finite element model described herein. Thus the newly developed calculation methodology has been verified and can be used to predict the failure load and stiffness of osteoporotic vertebrae using data obtained non-invasively from CT scans.

Mineralized bone loss at different sites in dialysis patients: implications for prevention.

To characterize the magnitude and location of mineralized bone loss, 40 patients (20 men, 20 women, 29 white, 11 black) with clinically significant renal osteodystrophy who could be unambiguously classified based on histologic criteria as having osteitis fibrosa (OF; 20 cases) or osteomalacia (OM; 20 cases) were studied; they had been on maintenance hemodialysis for 4.6 +/- 3.0 yr. One hundred forty-two healthy women of similar age and ethnic composition served as control subjects. In all subjects, the proportions of mineralized bone, osteoid, and porosity (nonbone soft tissue) were measured separately in cortical and cancellous bone tissue, from intact full-thickness biopsies of the ilium, representative of the axial skeleton. The results were related to the volumes of cortical and cancellous bone tissue separately and to the volume of the entire biopsy core. Approximately three-quarters of the patients had measurements in the appendicular skeleton by single photon absorptiometry of the radius and morphometry of the metacarpal. Disease effects did not differ significantly between ethnic groups. Mineralized cortical bone volume (per unit of core volume) was reduced by approximately 45% in both patient groups. Mineralized cancellous bone volume was significantly increased by 36% in the patients with OF and nonsignificantly reduced by 9% in the patients with OM; however, the reduction in the latter patients was significant in relation to tissue volume. The combined total deficit for both types of iliac bone was approximately 20% in the patients with OF and approximately 40% in the patients with OM. Significant reductions in appendicular cortical bone were demonstrated in both patient groups at both measurement sites. Regardless of the current histologic classification, the major structural abnormality in the skeleton is generalized thinning of cortical bone due to increased net endocortical resorption, the most characteristic effect on bone of hyperparathyroidism. Protection of the skeleton from the adverse consequences of renal failure will require therapeutic intervention in patients with no symptoms of either renal or bone disease.

The loss of stiffness as osteoporosis progresses.

The routine diagnosis of osteoporosis is based on radiological measurements of bone mineral content. An osteoporotic failure is influenced both by a loss of mineralized bone and internal bone structure. The structure cannot be estimated by bone reconstruction based on standard radiological equipment. To investigate the influence of structure on cancellous bone stiffness, a new finite element model of cancellous bone is developed. The model describes a cancellous bone unit as an open-celled structure. Trabecular length, trabecular thickness, diameter of trabecular connections, relative lattice disorder and relative bone loss determine the real architecture. Using this model, the loss of stiffness as a result of trabecular thinning and loss of trabecular connections is estimated. The volume fraction as a scalar value for a volume can not be a marker for orthotropic stiffness changes. A formula in the form Y = e(a *1 n(X) + b) can describe the correlation between cancellous bone stiffness and volume fraction. These formulas are appropriate for those cases, when the loss of bone mineral (decrease in trabecular thickness) is closely connected to a loss of structure (increasingly perforated trabecular network).

[Loss of bone substance in long-term dialysis--the value of serochemical parameters]. / Knochensubstanzverlust bei Langzeitdialyse--Wertigkeit serochemischer Parameter.

During long-term hemodialysis therapy a loss of bone substance--an osteopenia--may occur. The diagnosis is possible by bone biopsy. We have analyzed the bone metabolism-associated serochemical parameters in patients suffering from osteopenia in comparison with patients with normal bone volume. 21 patients were analyzed: 14 females, 7 males, duration of dialysis 44 +/- 29.9 months, age 47.3 +/- 12.5 years. The serum values of calcium, anorganic phosphate, alkaline phosphatase, pH and c-terminal parathormone are determined. The histological bone examination according to the Delling classification did show following distribution: Type I--0, type II--10, type III--10 (without renal osteopenia--1). A quarter of the patients did show a reduction of the bone mass. The parathormone value was significantly reduced in these patients in comparison with patients without osteopenia. No significant changes could observed in the comparison of alkaline phosphatase, serum calcium, anorganic phosphate and pH value. Our results show that in patients with osteopenia the serum parathormone level is reduced relatively.

[A decrease in height as an expression of disordered bone metabolism in hyperthyroidism]. / Grössenabnahme als Ausdruck der Knochenstoffwechselstörung bei Hyperthyreose.

Disturbances of the bone metabolism are only rarely observed in hyperthyroidism. The description of the case demonstrates clinical signs of osteopathy, connections with the duration of the disease and the possibility to be able to treat on the basis of a fundamental diagnosis.

[Peptide hormones and the "new endocrinology"]. / Peptidhormone und "Neue Endokrinologie".

On the basis of the results found in literature a survey is given of the state of the peptide-chemical research from the point of view of the clinic. The functional mechanisms of the peptide hormones are explained, their effect as hormone and neurotransmitter is demonstrated. Particularly emphasized are the integrative tasks of the peptide hormones, which thus as another regulation principle of the organism are to be put by the side of the nervous and hormonal regulation. By the demonstration of the most frequent endocrine tumour syndromes with formation of adequate hormones the clinical importance of these substances is dealt with. The infrequency of these diseases is emphasized by the small number of own observations. It is referred to the growing importance of the peptide hormones in the diagnostics and therapy of internal and surgical diseases.