[Solitary bone cysts of the pelvis. A frequently misinterpreted entity]. / Solitäre Knochenzysten des Beckens. Eine häufig verkannte Entität.

Solitary bone cyst of the pelvis is a rare lesion. The diagnosis is relatively simple providing sufficient material is accumulated during biopsy or surgery. Calcifying forms often cause difficulties in terms of differential diagnosis. Radiographic imaging can be complex when examining large lesions of the pelvis. Biopsy is the method of choice for definitive diagnosis, which should be verified against material gathered surgically or during curettage. Bone tumors of the pelvis have to be considered in the differential diagnosis of the lesion. Large cystic lesions of the pelvis in particular are to be reviewed pathohistologically to avoid false diagnosis. The consequences for the patient in terms of quality of life and life expectancy can be serious. The need for interdisciplinary cooperation is greater than ever to ensure correct diagnosis and therapy of bone lesions.

Ibandronate treatment reverses glucocorticoid-induced loss of bone mineral density and strength in minipigs.

The Göttingen minipig is one of the few large animal models that show glucocorticoid (GC)-induced bone loss. We investigated whether GC-induced loss of bone mineral density (BMD) and bone strength in minipigs can be recovered by treatment with the bisphosphonate ibandronate (IBN). 40 primiparous sows were allocated to 4 groups when they were 30 months old: GC treatment for 8 months (GC8), for 15 months (GC15), GC treatment for 15 months plus IBN treatment for months 8-15 (GC&IBN), and a control group without GC treatment. Prednisolone was given at a daily oral dose of 1 mg/kg body weight for 8 weeks and thereafter 0.5 mg/kg body weight. IBN was administered intramuscularly and intermittently with an integral dose of 2.0 mg/kg body weight. BMD of the lumbar spine (L1-3) was assessed in vivo by Quantitative Computed Tomography (QCT) at months 0, 8, and 15. Blood and urine samples were obtained every 2-3 months. After sacrificing the animals lumbar vertebrae L4 were tested mechanically (Young's modulus and ultimate stress). Histomorphometry was performed on L2 and mineral content determined in ashed specimens of T12 and L4. In the GC&IBN group, the GC associated losses in BMD of -10.5%+/-1.9% (mean+/-standard error of the mean, p<0.001) during the first 8 months were more than recovered during the following 7 months of IBN treatment (+14.8%+/-1.2%, p<0.0001). This increase was significantly larger (p<0.0001) than the insignificant +2.1%+/-1.2% change in group GC15. At month 15, the difference between groups GC&IBN and GC15 was 22% (p<0.01) for BMD, 48% (p<0.05) for Young's modulus, and 31% (p<0.14) for ultimate stress; bone-specific alkaline phosphatase showed trends to lower values (p<0.2) while deoxypyridinoline was comparable. This minipig study demonstrates that GC-induced impairment of bone strength can be effectively and consistently treated by IBN. GC&IBN associated alterations in BMD and bone turnover markers can be monitored in vivo using QCT of the spine and by biochemical analyses, reflecting the changes in bone strength.

Cementless fixation of megaprostheses using a conical fluted stem in the treatment of bone tumours.

We reviewed 25 patients in whom a MUTARS megaprosthesis with a conical fluted stem had been implanted. There were three types of stem: a standard stem was used in 17 cases (three in the proximal femur, nine in the distal femur and five proximal tibia), a custom-made proximal femoral stem in four cases and a custom-made distal femoral stem in four cases. The mean age of the patients was 40.1 years (17 to 70) and the mean follow-up was for 2.5 years (0.9 to 7.4). At follow-up two patients had died from their disease: one was alive with disease and 22 were disease-free. One of 23 prostheses had been removed for infection and another revised to a cemented stem. The mean Musculoskeletal Tumor Society score was 24.9 (12 to 30) and the mean Karnofsky index was 82% (60% to 100%). There was no radiological evidence of loosening or subsidence. Stem stress shielding was seen in 11 patients and was marked in five of these. There were five complications, rupture of the extensor mechanism of the knee after extra-articular resection in two patients, deep venous thrombosis in one, septic loosening in one, and dislocation of the hip in one. The survival rate after seven years was 87% (95% confidence interval (CI) 83 to 91) for the patients and 95% (95% CI 91 to 99) for the megaprosthesis. A longer follow-up is needed to confirm these encouraging results.

Transiliac bone biopsy in osteoporosis: frequency, indications, consequences and complications. An evaluation of 99 consecutive cases over a period of 14 years.

Bone biopsy is a diagnostic procedure restricted to untypical, unclear and complicated cases in evidence-based guidelines on diagnosis and treatment of osteoporosis. Its relevance has been a topic of recent controversial discussion. This study was performed to evaluate its role and relevance in routine use. A total of 99 horizontal transiliac bone biopsies performed over a time period of 14 years because of an osteological indication in one single centre were analysed, which reflects that bone biopsy followed about 0.003% of patients' consultations. Bone biopsies were indicated for osteoporotic males (n = 63) and premenopausal osteoporotic females (n = 18) without endocrine abnormality and normal immunofixation (serum and urine), suspected systemic/malignant disease such as mastocytosis, osteogenesis imperfecta, non-secreting plasmocytoma, metastatic infiltration (n = 16) and decreasing bone mineral density under anti-osteoporotic treatment (n = 2). The most frequent diagnoses besides osteoporosis were normal histology, borderline finding towards mild osteoporosis, and osteoporomalacia with relevant osteoidosis. In some cases, pathological findings in bone marrow were detected. In most cases (82/99), bone biopsy led to consequences in medical treatment. Following histopathological diagnosis, 16 patients did not receive any anti-osteoporotic treatment. In six patients, further diagnostic procedures were initiated because of bone histology. Bone biopsy was well tolerated and complications were rare and mild. In conclusion, despite all progress in non-invasive diagnostic procedures for metabolic bone diseases such as osteoporosis, there remains a small but significant subset of patients who may benefit from inclusion of bone biopsy into the diagnostic procedure.

Biomechanical, morphological, and histological analysis of early failures in hip resurfacing arthroplasty.

The present revival of hip resurfacing arthroplasty may be related to an increase in early failures owing to the challenging technique of the procedure. Fifty-five retrieved implants were analysed with respect to wear, cement mantle and cement penetration, fracture and head morphology, as well as standard histology. Femoral neck fractures occurred in median after 102 days. The time to failure was shorter for older women. Major deviations from the suggested cement mantle thickness and cement penetration were found. Indications for high trauma during implantation leading to early failure due to weakening of the femoral neck were also observed. Some failures had signs of pseudarthrosis beneath the implant. Four different fracture patterns with different mean survival times were identified. Observed wear was minor with the exception of that due to alignment mistakes (rim loading). The cups were not damaged by the failures. Histological results indicate that avascular necrosis is not necessarily connected with this kind of endoprosthetic surgery. Most of the failures analysed can probably be attributed to the 'learning curve' effect, which is an unsatisfactory situation.

Neoadjuvant chemotherapy of osteosarcoma: results of a randomized cooperative trial (COSS-82) with salvage chemotherapy based on histological tumor response.

Following observation of the predictive value of the histologic extent of tumor cell destruction after preoperative chemotherapy for metastasis-free survival (MFS) in osteosarcoma, a randomized study was undertaken with the aim of (1) sparing some patients the unpleasant side effects of highly toxic drugs like doxorubicin (DOX) and cisplatin (CPDD) by administering these drugs postoperatively only after poor response with a milder preoperative regimen, and (2) improving the prognosis of patients responding poorly to the initial treatment by use of a salvage chemotherapy postoperatively. The available patients were divided into two groups. Those in the study arm received a preoperative chemotherapy consisting of high-dose methotrexate (HDMTX) and the triple drug combination of bleomycin, cyclophosphamide, and dactinomycin (BCD) and were switched to DOX/CPDD postoperatively in case of poor response. DOX/CPDD was used besides HDMTX for initial treatment in the control arm, and BCD alternatively with CPDD/ifosfamide (IFO) for postoperative salvage treatment. The response rate of the study arm was significantly inferior to the control arm (26% v 60%; P less than .001). The actuarial 4-year MFS rate of poor responders after salvage chemotherapy also was poorest in the study arm (41%); it was unchanged in the control arm (53%) as compared with that of poor responders from the COSS-80 study without salvage chemotherapy (52%). The actuarial 4-year MFS rate of good responders was 73% in the study arm, 79% in the control arm, and not significantly different from that of the COSS-80 study (84%), although postoperative chemotherapy of good responders had been markedly shortened as compared with the COSS-80 study. The actuarial 4-year MFS rate of the study arm as a whole was inferior to that of the control arm (49% v 68%; P less than .1) and also inferior to the COSS-80 study (68%; P less than .01), indicating a failure of the employed salvage strategy in general and especially of the effort to restrict the use of the very effective but highly toxic drugs DOX and CPDD to patients resistant to a less toxic initial treatment.

Dedifferentiated chondrosarcoma--a fatal disease.

BACKGROUND: We report on 13 patients with dedifferentiated chondrosarcomas. The mean age of the patients at diagnosis was 59.8 years. Nine patients were classified as stage IIB and four as stage III. METHODS: In 11/13 cases surgery was performed. Mostly, limb salvage with tumour resection and implantation of a megaprosthesis was done; three patients needed amputation or disarticulation. In one out of three patients with a pelvic tumour resection was followed by implantation of a pelvic replacement; the other two patients received tumour resection with autologous stabilisation of the pelvis. Surgical margins were wide in six patients, marginal in two and intralesional in three. Adjuvant chemotherapy was given to five patients. RESULTS: Recurrence was detected in 5/11 of the patients operated on: in two with wide, in one with marginal, and in two with intralesional resection. No recurrence was seen in 5/11 patients: in four after wide and in one after marginal resection. In one patient the stage was unknown. At follow-up 11 patients were dead of disease (DOD), one dead of unknown reason (DOU) and one alive with disease (AWD). The mean survival time was 9.7 months. Metastasis to different anatomical sites was evident after a period of 10 months. CONCLUSIONS: Our results resemble those reported in the literature. DDCS is rare and is the primary malignant bone tumour with the worst prognosis. Surgery is the most important procedure, although it is unclear whether a radical resection improves the long-term results. Information regarding neoadjuvant and/or adjuvant therapy with chemotherapy is very limited.

Microcallus formations of the cancellous bone: a quantitative analysis of the human spine.

Microcallus formations are demonstrable in nearly all spongy bone by means of suitable preparation techniques. Histologically, these structures are immature fibrous bone. Their genesis, frequency, and importance are largely unknown. To address these issues, 26 normal human spines, 11 osteoporotic spines, and different parts of the skeleton (femur head, iliac crest) were investigated for microcallus using a new preparation technique--allowing a combined 2- and 3-dimensional analysis. According to our analysis, microcallus formation occurs frequently in persons older than 45 years of age. These formations are mainly localized in the lower thoracic and lumbar spine and are obviously more frequent in females than in males. In individuals with a trabecular bone volume (BV/TV) in the spine below 11%, microcallus formations occur regularly. But the number of microcallus formations depends more on the microarchitecture of the cancellous bone (trabecular bone pattern factor, TBPf), than on individual trabecular parameters (trabecular number, TbN; trabecular bone volume, BV/TV; and trabecular thickness, TbTh). In about 33% of cases microfractures are demonstrable in the center of the microcallus formation. It is unclear whether microcallus may be the result of a nontraumatic process. In therapy studies the bone mass could be misrepresented due to the amount of microcallus. Although it indicates instability of the bone structure, microcallus formation is not only a negative mechanism, but stabilizes and regenerates the bone tissue. Furthermore, complete new trabeculae can be formed due to bridges of microcallus between the remnant trabeculae. Osteoporosis is not the result of an inability to form microcallus formations.

The thickness of human vertebral cortical bone and its changes in aging and osteoporosis: a histomorphometric analysis of the complete spinal column from thirty-seven autopsy specimens.

The object of this study was to analyze the cortical thickness (Ct.Th) of the ventral and dorsal shell of the vertebral bodies throughout the human spine in aging and in osteoporosis. Therefore, the complete front column of the spine of 26 autopsy cases (aged 17-90, mean 42 years) without diseases affecting the skeleton and of 11 cases (aged 58-92, mean 77 years) with proven osteoporosis were removed. A sagittal segment prepared through the center of all vertebral bodies was undecalcified, embedded in plastic, ground to a 1 mm thick block, and stained using a modification of the von Kossa method. The analysis included the measurement of the mean cortical thickness of both the ventral and dorsal shell, respectively (from the third cervical to the fifth lumbar vertebral body). The qualitative investigation of the structure of the cortical ring completed the analysis. The presented data revealed a biphasic curve for both the ventral and dorsal shell, skeletally intact with high values of the cortical thickness in the cervical spine (285 microm), and a decrease in the thoracic (244 microm) and an increase in the lumbar spine (290 microm). The mean thickness of the ventral shell is in general greater than the thickness of the dorsal shell in both skeletally normal and osteoporotic cases. The cortical thickness of the spine showed no gender-specific differences (p = NS). There was a slight decrease of the cortical thickness with aging; however, this decrease and the correlation of cortical thickness to age was only significant below vertebral body T8 (r = 0.225-0.574; p(r) < 0.05-0.005). Most interestingly, however, osteoporosis presents itself with a highly significant loss of cortical thickness throughout the whole spine. This decrease of cortical thickness was more marked in the dorsal shell (p < 0.05) than in the ventral shell (ventral from C3 to T6 [p < 0.05] below T6 [p = NS]). We therefore conclude that in osteoporosis the loss of spinal bone mass is not only a loss of trabecular structure but also a loss of cortical thickness. Furthermore, these results may explain the development of regions of least resistance within the spine in aging and the clustering of osteoporotic fractures in the lower thoracic and lumbar spine.

Heterogeneity of the skeleton: comparison of the trabecular microarchitecture of the spine, the iliac crest, the femur, and the calcaneus.

The objective of this study was to elucidate the structure of cancellous bone and its age-related changes at different skeletal sites. Therefore, the lumbar spine, iliac crest, femur, and calcaneus of 12 age- and sex-matched skeletal healthy autopsy cases (6 females, 6 males, aged 28-84 years, mean 54 years) were removed. The following analysis includes an evaluation of the trabecular bone volume (BV/TV, %) and the trabecular interconnection (TBPf, mm-1) as well as a qualitative investigation of the structure of trabecular bone. BV/TV shows the following mean values: lumbar spine, 8.3% (+/- 0.8%); iliac crest, 11.5% (+/- 1.6%); intertrochanteric, 10.2% (+/- 1.2%); femoral neck, 15.8% (+/- 1.6%); and calcaneus, 15.4% (+/- 2.0%). There are significant differences between the BV/TV of the femoral neck and that of the lumbar spine as well as between that of the calcaneus and the lumbar spine (p < 0.01). However, a positive correlation can be seen between the bone mass of the spine and that of all other investigated sites (r = 0.67 to r = 0.80; pr < 0.1). The trabecular interconnection of the lumbar spine (2.7 mm-1, SEM +/- 0.2 mm-1) and the femoral neck (0.3 mm-1, SEM +/- 0.3 mm-1) differs significantly. Only these two sites show a significant positive correlation of TBPf (r = 0.60; pr < 0.1). Age-dependent alteration of the spine and the femoral neck in bone mass and bone structure is nearly the same. The trabecular microarchitecture of the iliac crest varies systematically. A region 4-10 cm behind and 1-3 cm below the anterior superior iliac spine turns out to be the most suitable biopsy site because of its closest relation to the lumbar bone mass. However, drawing information about the trabecular interconnection within the lumbar spine by measurement of the iliac crest at any site seems to be impossible. The horizontal specimens reveal a vertical running tubular spongiosa pattern that is arranged in concentric rings starting from the dorsal shell like a honeycomb. The comparison of TBPf in horizontal and vertical planes and its age-related changes indicates the age-related bone loss to be predominantly a loss of horizontal trabeculae. Thus, the presented data provide further information about the skeletal distribution and heterogeneity of the trabecular microarchitecture.

Severe osteoporosis in familial Hajdu-Cheney syndrome: progression of acro-osteolysis and osteoporosis during long-term follow-up.

Hajdu-Cheney syndrome is an autosomal dominant inherited osteodysplastic bone disease with the hallmarks of acro-osteolysis, skull deformations, and generalized osteoporosis. Very few patients have been followed long-term with respect to the prognosis of acro-osteolysis and osteoporosis. Here we describe a 39-year-old woman and her 19-year-old daughter who are both affected with the Hajdu-Cheney syndrome. Skeletal lesions were followed in the mother between the ages of 22 and 39 years. The acro-osteolytic lesions progressed markedly and caused shortening of several fingers; some end phalanges had completely disappeared. Severe spinal osteoporosis with serial vertebral fractures was found at the age of 22 years. New vertebral fractures developed until the age of 33 years, but did not progress afterward. High turnover osteoporosis was found in the bone histology of iliac crest biopsies performed at the ages of 22 and 34 years. Bone mineral content (BMC) was strikingly decreased at the age of 34 years (T score -5.1 SD) and did not significantly change during further follow-up. In the daughter, BMC failed to increase between the ages of 12 and 19 years and was also markedly decreased (T score -4.4 SD). This suggests that osteoporosis in Hajdu-Cheney syndrome is related to a low peak bone mass and a high bone turnover, leading to insufficient bone formation compared with the increased bone resorption.

Normalization of mineral ion homeostasis by dietary means prevents hyperparathyroidism, rickets, and osteomalacia, but not alopecia in vitamin D receptor-ablated mice.

1,25-Dihydroxyvitamin D3 plays a major role in intestinal calcium transport. To determine what phenotypic abnormalities observed in vitamin D receptor (VDR)-ablated mice are secondary to impaired intestinal calcium absorption rather than receptor deficiency, mineral ion levels were normalized by dietary means. VDR-ablated mice and control littermates were fed a diet that has been shown to prevent secondary hyperparathyroidism in vitamin D-deficient rats. This diet normalized growth and random serum ionized calcium levels in the VDR-ablated mice. The correction of ionized calcium levels prevented the development of parathyroid hyperplasia and the increases in PTH messenger RNA synthesis and in serum PTH levels. VDR-ablated animals fed this diet did not develop rickets or osteomalacia. However, alopecia was still observed in the VDR-ablated mice with normal mineral ions, suggesting that the VDR is required for normal hair growth. This study demonstrates that normalization of mineral ion homeostasis can prevent the development of hyperparathyroidism, osteomalacia, and rickets in the absence of the genomic actions of 1,25-dihydroxyvitamin D3.

Relation between 2- and 3-dimensional architecture of trabecular bone in the human spine.

By means of a new preparation technique which allows the combined 2- and 3-dimensional analysis of trabecular bone we analyzed the vertebral bodies of 22 autopsy cases. None of these cases had any skeletal disease. With increasing age bone volume was decreased in all vertebral bodies (2nd cervical to 5th lumbar body) but this decrease was more pronounced in the lower vertebrae. In the upper cervical spine there was nearly no age-related loss of trabecular bone volume. 3-D analysis demonstrated that the loss of bone tissue is due to a loss of trabecular plates which are transformed to trabecular rods by perforations. The number of plates and rods could be measured directly. In the 2nd lumbar vertebra at the age of 20 years the density of plates was 0.61 mm, the density of rods was 0.2/mm. At the age of 80 years the density of plates was 0.2/mm. The density of rods remained constant at all ages. Perforations could be seen directly. They were located mainly in trabecular plates. At higher ages they occurred in rods either. The number of vertically oriented trabeculae was about twice the number of horizontal ones. The rate of age-dependent reduction of trabeculae was the same in horizontal and vertical trabeculae. It was possible to do real 3-dimensional measurements of the diameter of trabecular rods. These values were compared to the calculated values of trabecular plates. In mean trabecular plates are thinner than rods. It could be demonstrated that microcallus formation is a common feature in the human spine.(ABSTRACT TRUNCATED AT 250 WORDS)

Trabecular bone pattern factor--a new parameter for simple quantification of bone microarchitecture.

The stability of trabecular bone depends not only on the amount of bone tissue, but also on the three-dimensional orientation and connectedness of trabeculae, which is summarized as trabecular microarchitecture. In previous studies we could demonstrate that in three-dimensional bone tissue the relation of trabecular plates to rods is reflected in the ratio of concave to convex surfaces of the bone pattern in two-dimensional bone sections. For the quantification of the connectedness of these bone patterns we developed a new histomorphometric parameter called Trabecular Bone Pattern factor (TBPf). The basic idea is that the connectedness of structures can be described by the relation of convex to concave surfaces. A lot of concave surfaces represent a well connected spongy lattice, whereas a lot of convex surfaces indicate a badly connected trabecular lattice in two-dimensional sections. By means of an automatic image analysis system we measure trabecular bone area (A1) and perimeter (P1). A second measurement of these two parameters (now A2 and P2) is done after a simulated dilatation of trabeculae on the screen. This dilatation results in a characteristic change of bone area and perimeter depending on the relation of convex to concave surfaces. TBPf is defined as a quotient of the difference of the first and the second measurement: TBPf = (P1 - P2)/(A1 - A2). First measurements of TBPf in 192 iliac crest bone biopsies of autopsy cases show that there is not only age-related loss of bone volume, but also a decrease of trabecular connectedness. By means of TBPf we can demonstrate a significant difference in the age-related loss of trabecular connectivity between male and female individuals.

Morphometric analysis of noninvasively assessed bone biopsies: comparison of high-resolution computed tomography and histologic sections.

This article describes a new method to analyze the structural behavior of trabecular bone structure by means of noninvasive measurements of the three-dimensional cancellous bone architecture. For the noninvasive data acquisition, a high-resolution quantitative computed tomography system for peripheral measuring sites (pQCT) was used. With this system and the help of a multiple thin-slice measuring technique, it became possible to examine three-dimensional bone structure with a resolution of 0.25 mm. Using a special three-dimensional segmentation algorithm, mineralized bone was separated from bone marrow and muscle tissue within the three-dimensional stack of CT slices. These segmented data sets can then be processed nondestructively and, even more important, repetitively in either two or three dimensions. In order to validate this noninvasive procedure, a two-dimensional comparative morphometric study was performed including CT slices and corresponding histologic sections prepared after CT measurement. Three representative sections from the three-dimensional stack of CT slices were selected and the morphometric indices of the segmented CT slices were compared with the indices stemming from the corresponding histologic sections prepared after CT measurement. Although the presented approach can only give an example of the method, the results from the morphometric analysis support the assumption that cancellous bone structures based on noninvasive high-resolution CT measurements are representative for trabecular microstructures assessed from histologic bone sections. The study demonstrates the potential of high-resolution CT imaging for in vivo applications of quantitative bone morphometry. This is especially true for repetitive follow-up measurements, which cannot be performed using histologic sections. Additionally, the method offers an easy access to the three-dimensional structure of trabecular bone, which is mandatory for the analyses of the anisotropic mechanical behavior of cancellous bone.

Intervertebral variation in trabecular microarchitecture throughout the normal spine in relation to age.

The vertebral bodies of the complete spine (C-3-L-5) were removed in 26 autopsy cases without evidence for primary or secondary bone disease (13 males aged 19-79 years and 13 females aged 17-90 years). A sagittal segment through the center of all vertebral bodies was embedded undecalcified in hydroxyethylmethacrylate and processed to so-called surface stained block grindings. Histomorphometric analysis of the complete segment was performed using a computer-assisted image analysis system (IBAS 2000). The structural parameters investigated were bone volume (BV/TV) and trabecular interconnection quantificated by trabecular bone pattern factor (TBPf). A close correlation of BV/TV and TBPf was found in all vertebral bodies irrespective of vertebral region (r = 0.8, p < 0.001). This indicates that the age-related decrease of trabecular bone mass is primarily the consequence of the transformation from plates to rods and the loss of whole trabecular structures. This basic principle is valid throughout the complete spine. However, the systematic analysis of vertebral trabecular bone from C-3 to L-5 revealed a significant intervertebral variation of trabecular microarchitecture. The density of trabecular structure of cervical vertebrae is much higher than that of thoracic and lumbar vertebrae (p < 0.001). The extent of age-related loss of trabecular bone mass and structure showed a decrease within the spine from the caudal to the cranial region (p < 0.05). The loss of bone volume in individuals between the ages of 30 and 80 years in the lumbar spine was 53%, whereas in the thoracic spine the decrease was 41%, and in the cervical spine only 24%.(ABSTRACT TRUNCATED AT 250 WORDS)

Evaluation of neoadjuvant therapy response of osteogenic sarcoma using FDG PET.

UNLABELLED: According to the current treatment protocol of the Cooperative Osteosarcoma Study (COSS), monitoring preoperative chemotherapy response and estimating grade of tumor regression in patients with osteosarcoma is mandatory before surgical removal of the tumor, particularly if a limb salvage procedure is intended. In addition, response to neoadjuvant chemotherapy is considered as an important prognostic indicator. The aim of this prospective study was to assess the usefulness of 2-(18F) fluoro-2-deoxy-D-glucose (FDG) PET in the noninvasive evaluation of neoadjuvant chemotherapy response in osteosarcoma. METHODS: In 27 patients with osteosarcoma, we determined tumor-to-background ratios (TBRs) of FDG uptake with PET, before and after neoadjuvant chemotherapy according to COSS 86c or COSS 96 protocols, respectively. We compared changes in glucose metabolism of osteosarcomas with the histologic grade of regression in the resected specimen, according to Salzer-Kuntschik, discriminating responders (grades I-III; n = 17) and nonresponders (grades IV-VI; n = 10). RESULTS: The decrease of FDG uptake in osteosarcomas expressed as a ratio of posttherapeutic and pretherapeutic TBRs showed a close correlation to the amount of tumor necrosis induced by polychemotherapy (P < 0.001; Spearman). With a TBR ratio cutoff level of 0.6, all responders and 8 of 10 nonresponders could be identified by PET. In addition, lung metastases of osteosarcoma were detected with FDG PET in 4 patients. CONCLUSION: FDG PET provides a promising tool for noninvasive evaluation of neoadjuvant chemotherapy response in osteosarcoma. This could imply consequences for the choice of surgical strategy, because a limb salvage procedure cannot be recommended in patients nonresponsive to preoperative chemotherapy unless wide surgical margins can safely be achieved.

The concept and treatment of osteoporosis.

Osteoporosis is a dynamic process, thought to be caused by an uncoupling between osteoblast and osteoclast activity. Altered pulsatile secretion of growth hormone and parathyroid hormone (PTH) have been proposed as pathogenetic factors for this unbalanced coupling. The anatomical lesions are believed to be reversible until trabecular perforations develop, if fractures already occurred the anatomical defect is permanent. It is helpful to classify osteoporosis in stages of increasing severity depending on bone density and the presence of fractures. Theoretically, if the bone density is above the fracture threshold, then the only therapeutic goal is to maintain the bone mass. If instead the mineral density is below the threshold, an active therapy is needed with drugs that can possibly increase the skeletal mass. Osteoporosis with multiple fractures cannot be reversed. The authors propose a promising pharmacologic treatment for osteoporosis, based on the combination of human PTH-(1-38) and intranasal salmon calcitonin. If started in the early stages of the osteoporotic process, this regimen may restore the initial bone mass. In more advanced stages, only a correction of the metabolic defect is possible, but the irreversible vertebral deformities are not affected. On the basis of the results, cyclic therapy with human PTH-(1-38) and salmon calcitonin represents a good treatment choice for osteoporosis.

High spatial resolution imaging of bone mineral using computed microtomography. Comparison with microradiography and undecalcified histologic sections.

RATIONALE AND OBJECTIVES: The application of various high-resolution (< 100 microns) imaging techniques for in vitro bone mineral analysis is explored. METHODS: The techniques of contact microradiography and microtomography, using the x-ray spectrum filtered out of synchrotron radiation (SR) and conventional staining techniques, are compared to each other by presenting a variety of different samples. The relationship between radiation exposure and spatial resolution micro-computed tomography (CT) images of a finger bone is explored. The relevant properties of SR are explained. RESULTS: In CT images, a spatial resolution of 100 microns was obtained. New bone mineral induced by mechanical periosteal irritation in a rabbit tibia was quantified. In one case a microradiogram and a microtomogram of the same slice were taken for comparison. Histologic sections and microradiograms taken from a specimen of a human femur for comparison are presented. CONCLUSIONS: Microradiography and staining techniques require rather sophisticated sample preparation; quantitative image analysis is more difficult as the resulting image must be digitized. The CT technique requires almost no sample preparation and allows for accurate bone mineral quantification. However, CT images with a resolution of several microns limit the sample size to a few mm. Micro-CT and microradiography can be performed with conventional x-ray sources, but the use of SR is of particular interest in high resolution imaging, because its white spectrum allows for optimum x-ray energy selection and its high intensity for short scan times.

Morphological changes in osteosarcoma after chemotherapy--COSS 80.

Forty-five osteosarcomas were investigated by special methods such as preparation of undecalcified bone tumor tissue, imprint cytology, histochemistry, and quantitative analysis. The morphological regression grades and their relation to chemotherapy are reported by Salzer-Kuntschik et al. (1983). The results presented demonstrate that smaller osteosarcomas respond more favorably than larger tumors. The function of bone-tumor cells, e.g., osteoid production, trabecular tumor bone formation, and mineralization, seems to be more important for the sensitivity to chemotherapy than the cell polymorphism. The estimation of bone-tumor morphology in at least two total areas of the bone tumor is essential in borderline cases (grade III/grade IV). Imprint cytology is very helpful for rapid estimation of the effect of therapy and the demonstration of cellular polymorphism. At the moment, we are not able to determine the effect of chemotherapy from the first biopsy before starting chemotherapy.