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Local treatment of bone cancer produced survival rates on the order of 15 to 20 percent. Newer methods of aggressive chemotherapy have improved this outcome dramatically; rates of survival, free from metastasis, range from 60 to 70 percent. These rates are sufficiently good that it becomes important to consider the quality of life afforded by the treatment, which, in the case of bone cancer, usually refers to the preservation of a limb. There is some theoretical advantage to the use of an intraarterial injection for chemotherapy for bone cancer. If the cancer is in, for example, the leg, then an injection into the appropriate artery will carry the chemotherapeutic agent directly towards the tumor. On the other hand, an intravenous injection will carry the agent first to the heart, from which it will be spread equally throughout the body. The intraarterial injection may also have an advantage in that the venous return from the limb can be restricted by a tourniquet, thus giving tissue in the limb greater time to absorb the chemotherapeutic agent from the blood. However, while these conceptual notions may seem appealing, any true benefit must be demonstrated experimentally. While intraarterial injections have been reported to be effective, a previously published direct comparison of intraarterial and intravenous injection failed to demonstrate a beneficial effect for intraarterial injection. This study, however, involved several different drug regimens that were not directly comparable. In the current study patients were given high-dose methotrexate, doxorubicin, and ifosfamide intravenously; in addition, each patient also received cisplatin either intraarterially or intravenously. No significant differences in response were observed between the intravenous and the intraarterial groups, indicating that the intraarterial injection does not provide appreciable benefit in this aggressive chemotherapy scheme. (Consumer Summary produced by Reliance Medical Information, Inc.)

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.

Giant cell tumor (GCT) offers a unique model for the hematopoietic–stromal cell interaction in human bone marrow. Evidence has been presented that GCT stromal cells (GCTSCs) promote accumulation, size and activity of the giant cells. Although GCTSCs are considered the neoplastic component of GCT, little is known about their genetic basis and, to date, a tumor-specific gene expression pattern has not been characterized. Mesenchymal stem cells (MSCs) have been identified as the origin of the GCT neoplastic stromal cell. Using state of the art array technology, expression profiling was applied to enriched stromal cell populations from five different GCTs and two primary MSCs as controls. Of the 29 differentially expressed genes found, 25 showed an increased expression. Differential mRNA expression was verified by real-time polymerase chain reaction analysis of 10 selected genes, supporting the validity of cDNA arrays as a tool to identify tumor-related genes in GCTSCs. Increased expression of two oncogenes, JUN and NME2, was substantiated at the protein level, utilizing immunohistochemical evaluation of GCT sections and Western-blot analysis. Increased phosphorylation of JUN Ser-63 was also found.

Bei einer 66-jährigen Patientin war seit 1997 ein Sjögren-Syndrom mit systemischer Vaskulitis und begleitender Episkleris bekannt. Die Vorstellung in der orthopädischen Klinik erfolgte wegen einer spontan aufgetretenen Achillessehnenruptur auf der linken Seite. Die Patientin war wegen ihrer Grunderkrankung 2 Jahre lang hochdosiert mit Glukokortikoiden therapiert worden. Zeitnahe zur Ruptur war eine Umstellung auf Cyclophosphamid zur Reduktion der Kortikoiddosis vorgenommen worden, da eine ausgeprägte Osteoporose mit Sinterungsfrakturen der Wirbelkörper aufgetreten war. Intraoperativ konnte ein Granulom im Bereich der Rupturstelle festgestellt werden. Ursprünglich war die Glucokortikoidgabe als Ursache für die Ruptur vermutet worden, diese Auffassung musste jedoch aufgrund dieses Befundes revidiert werden. In einer MRT-Kontrolle 3 Monate postoperativ ergab sich eine Restitution der Kontinuität der Achillessehne. Die Spontanruptur der Achillessehne durch ein granulomatöses Infiltrat auf dem Boden einer Vaskulitis ist ein seltenes Ereignis. Sehnenrupturen im Rahmen eines systemischen Lupus erythematodes sind bekannt, wobei als Ursache teilweise eine langdauernde Glucokortikoidmedikation vermutet wird. Die spontane Achillessehnenruptur bei systemischer Glucokortikoidmedikation ist möglicherweise ein unterschätztes Problem. A 66-year old patient sustained a non-traumatic rupture of her left achilles tendon. She suffered from Sjögren’s syndrome which occurred in conjunction with a systemic vasculitis, and recurrent episcleritis. The combination of Sjögren’s syndrome and systemic vasculitis is well known. Subsequently, she was treated with high-dose systemic steroids over a period of 2 years. In order to reduce the amount of steroids due to preexisting severe osteoporosis and thoracic vertebral fractures, her medication was changed to cyclophosphamide shortly before her injury. Intraoperatively, a granuloma was discovered at the site of the rupture. This granuloma had infiltrated most of the achilles tendon at this site and virtually replaced viable tendon tissue. Originally, the rupture was supposedly due to the high dose steroids. This theory had to be revised according to the intraoperative findings. Following excision of the granuloma and operative treatment of the achilles tendon rupture, the continuity of the tendon could be completely restored. A MRI scan 3 months after the procedure demonstrated a completely healed Achilles tendon. Spontaneous achilles tendon rupture due to a granuloma in patients with vasculitis seems to be a rare event. However, tendon ruptures in combination with systemic lupus erythematodes have been described. Mostly, these events are attributed to long term application of steroids. Spontaneous rupture in combination with high dose treatment of steroids seems to be an underestimated problem.

Bei der diffusen Form der pigmentierten villonodulären Synovialitis breitet sich die veränderte Synovialis infiltrierend aus und führt zu Knorpel- und Knochenerosionen. Die Folge ist die Zerstörung des Gelenkes. Eine maligne Entartung wird kontrovers diskutiert. Am häufigsten sind Kniegelenke betroffen. Ein Befall der Hüftgelenke ist eher selten, jedoch aus einigen Studien bekannt. Diese Übersicht soll einen Fall von diffuser pigmentierter villonodulärer Synovialitis (PVS) am Hüftgelenk vorstellen. Anhand dieses Falles wird zu dieser Erkrankung gehörige Diagnostik und Therapie vorgestellt und erörtert. Die Rolle der Endoprothetik bei der Behandlung der fortgeschrittenen PVS wird diskutiert. Auf die Bedeutung der frühzeitigen Diagnosestellung des tenosynovialen Riesenzelltumors auch an der Hüfte und den damit möglichen Gelenkerhalt wird verwiesen. In the diffuse form of pigmented villonodular synovitis, the transformed synovia invades local bone and cartilage, leading to destruction of the osseous and cartilage tissue. Secondary osteoarthritis and ultimately joint destruction is a result. Malignant development is under discussion. The knee is the most frequently involved joint, followed by involvement of the hip, which is well documented in several studies.    This paper introduces a case of pigmented villonodular synovitis involving the hip. Its general diagnostic features and treatment options are introduced and discussed, including the role of reconstructive joint surgery in advanced cases of PVS. The key function of early diagnosis and treatment resulting in joint-salvaging procedures is emphasized.

Abstract. Detection and dating of infants' fractures plays an important role in the diagnosis of the battered child syndrome. Under this aspect three cases of infants with multiple fractures of different ages due to child abuse were evaluated post-mortem. Radiological findings were compared with the autopsy results, followed by contact radiography and histopathological assessment. Out of a total of 44 osseous lesions, 27 fractures were diagnosed by post-mortem skeletal survey, additionally 5 recent rib fractures were suspected, 4 of which were confirmed histologically and all were located paravertebrally. The fractures not detected radiologically were mostly recent rib fractures diagnosed or suspected at autopsy or by contact radiography and confirmed histologically. The histological investigation allowed a more precise dating of the fractures, particularly with reference to the early stages of fracture healing. Microscopic signs of fracture healing processes, such as periosteal thickening, osteoid production and calcification of soft callus tissue, can be detected earlier and quantified more accurately. In advanced stages of healing the osseous apposition rate can be measured semiquantitatively up to a certain extent. A scheme involving a careful external investigation, skeletal survey, autopsy, contact radiography and histology has been proven useful for diagnosing and dating infants' fractures.

Abstract: Giant cell tumor of bone (GCT) is a locally osteolytic tumor with variable aggressiveness. In rare cases, pulmonary metastasis can be observed. The lesion most frequently occurs in the epiphysis of long tubular bones of the knee region, predominantly affecting young adults after closure of the growth plate. The characteristic histological appearance of GCT displays a high number of osteoclast-like multinucleated giant cells, which resulted in the classification “osteoclastoma” or “giant cell tumor”. Apart from the multinucleated giant cells, there are two mononuclear cell types in GCT. The first one has a round morphology and resembles monocytes. The second cell type is the spindle-shaped, fibroblast-like stromal cell. Cell culture experiments with GCT cells revealed the stromal cell to be the proliferating component of the GCT. The other two cell types, the monocyte and the multinucleated giant cell, were lost after a few cell culture passages. Furthermore, latest results from GCT reveal that the stromal cells secrete a variety of cytokines and differentiation factors, including MCP1, ODF, and M-CSF. These molecules are monocyte chemoattractants and are essential for osteoclast differentiation, suggesting that the stromal cell stimulates blood monocyte immigration into tumor tissue and enhances their fusion into osteoclast-like, multinucleated giant cells. The multinucleated giant cell itself resembles a normal osteoclast that is able to resorb bone leading to extended osteolysis. This new model of GCT genesis supports the hypothesis that the stromal cell is the neoplastic component whilst the monocytes and the multinucleated giant cells are just reactive components of this tumor. Taking this into consideration, the nomenclature of the “giant cell tumor” needs to be reconsidered.

A series of nine cases with monostotic fibrous dysplasia (FD) and five cases of fibrous dysplasia-like low-grade central osteosarcoma (fd-like lgcOSA) were applied in a mutational analysis. Restriction digestion analysis, single-stranded conformational polymorphism (SSCP) analysis, and repeated sequencing demonstrated a R201H mutation in six cases and a R201C mutation in three cases of patients with monostotic FD. These results demonstrate that the presence of Gsα gene mutations is a constant finding in monostotic FD. To our knowledge, this is the first report in the literature investigating Gsα gene mutations in lgcOSA, which is one of the most important differential diagnoses of FD because of its low-grade malignant behavior. In four of five cases of fd-like lgcOSA, no mutation has been detected. In one case of this tumor, a R201C mutation could be demonstrated. Because our results demonstrate a low prevalence of Gsα gene mutations in this tumor in contrast to monostotic FD, mutational analysis may be an additional helpful parameter in individual cases for the differential diagnosis of FD and fd-like lgcOSA.

Glass ionomer cement (Ionocem) was developed for use in bone surgery and is reported to be notably biocompatible. Between 1991 and 1994 we performed revision operations for aseptic loosening of arthroplasties of the hip on 45 patients using this material in its granulate form (Ionogran) mixed with homologous bone as a bone substitute. Of these 45 patients, 42 were followed up for a mean of 42 months. Early reloosening of the acetabular component has occurred in ten after a mean of 30 months. Histological examination showed large deposits of aluminium in the adjacent connective tissue and bone. Osteoblastic function and bone mineralisation were clearly inhibited. The serum levels of aluminium were also increased. The toxic damage at the bone interface caused by high local levels of aluminium must be seen as an important factor in the high rate of early reloosening. Our findings cast doubt on the biocompatibility of this material and we do not recommend continuation of its further use in orthopaedic surgery.

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.

The Gorham-Stout Syndrome (Gorham’s massive osteolysis) is a rare condition in which spontaneous, progressive resorption of bone occurs. The aetiology is poorly understood. We report six cases of the condition and present evidence that osteolysis is due to an increased number of stimulated osteoclasts. This suggests that early potent antiresorptive therapy such as with calcitonin or bisphosphonates may prevent local progressive osteolysis.

Summary In contrast to prevention, the therapy of manifest osteoporosis remains a clinically significant problem. So far all therapeutic attempts have yielded unsatisfying results. For this reason we have tried to achieve a positive bone balance by sequential stimulation and inhibition of the osseous metabolism. The therapy consisted of six 14-day courses with 400 units (1–38)hPTH per day and, in addition, starting with the 2nd week of PTH therapy, EHDP 5 mg per kg body weight per day for a total of 2 weeks. Already the initial therapeutic course resulted in a stimulation of decreased bone metabolism which could be documented by an increase in the calcium-47 accretion rate (six patients). An increase of the alkaline phosphatase could be noted (four patients); this, however, did not correlate with the calcium accretion. A positive calcium balance could, nonetheless, only be attained in four of eight patients within this period, while neither the alkaline phosphatase nor the kinetics would allow a prediction of this effect. Changes of the balance coincided with equal changes in the net calcium absorption. The urinary calcium excretion increased temporarily during the therapeutic phase. We were not able to detect an influence on the vitamin D metabolites. Histomorphometric studies did not demonstrate an increase in bone mass in the iliac creast after six therapeutic courses. Nevertheless, progressive deformations of vertebral bodies did not occur. We conclude that already after 2 weeks this therapeutic concept can lead to a stimulation of bone metabolism.

Summary Growth arrest and renal osteodystrophy is a major problem in renal insufficiency of children. The present report describes our experiences in managing renal osteodystrophy by using vitamin D3 for 24 months. Values in plasma of Ca, Mg, alkaline phosphatase, iPTH, 25-OH-D were determined regularly. Skeletal X-rays and analysis of iliac crest bone biopsies were obtained in each child.

Until now numerous studies on central giant cell granuloma of jawbones have not been able to reveal the histogenesis of this tumourlike lesion. The aim of the present investigation in two surgically proven cases was to study this question by means of histochemical and electron-microscopic methods.

The cytogenesis of giant osteoclasts in Paget's disease of bone was studied by means of electron microscopy. 26 iliac crest biopsies were made and divided for light and electron microscopic investigation. A special procedure was used for electron microscopic preparation of bone without previous decalcification.

Osteocytic development was studied in cortical bone of the tibial metaphysis in the rat, with respect to the relationship between age and localization of the cells. The different development stages through which the osteocytes pass during their life cycle are characterized by functional alterations of the osteocyte itself, as well as pericellular structures of bone substance.

Fourteen solitary bone cysts (SBC) with large areas of calcification (7 in the femur, 4 in the humerus, and 1 each in the pelvis, the tibia and the scapula) and 402 SBC from the Hamburg Bone Tumour Registry were reviewed in a retrospective study. The analysis was done with emphasis on the clinical, radiological and histological appearances. SBC are well known lesions, but calcifying SBC (CSBC) or extensive extragnathic cement-like bone productions are rare. The clinical and radiological differential diagnosis includes fibrous dysplasia, chondroma, low-grade chondrosarcoma and osteosarcoma. Bits of this cement-like matrix are detectable within the wall of approximately 70% (278 of 402) of SBC from the registry. CSBC are changed SBC. The intraoperative confirmation of the diagnosis on a frozen section by the bone pathologist leads to curettage which is currently the most common therapy in this benign lesion.

Radiological examination of 31 patients with established ankylosing spondylitis revealed 58 disco-vertebral destructive lesions. Careful assessment of their radiological features permitted differentiation into two main types, (1) inflammatory and (2) non-inflammatory. The ‘inflammatory’ type may represent either an active inflammatory process or a late sequel to such a lesion. In this series 44 lesions were included in this category, with a marked predilection for the lumbar spine. Moreover, all were observed within the first decade following the onset of the disease.

The clinical and morphological characteristics of Shwachman's syndrome (exocrine pancreatic insufficiency, pancytopenia, skeletal changes) were observed in a boy who, at the age of 8 years, developed a juvenile form of chronic myeloic leukemia which did not respond to cytostatic treatment. Autopsy revealed a striking lipomatous atrophy of the pancreas, defects in the ossification zones of the bones and marked dwarfism. In addition there was leukaemic infiltration of the pancreas, the spleen, the liver and the lymph nodes. The association of Shwachman's syndrome with leukaemia is a rare, but remarkable complication of this entity because of its relationship to the preceeding pancytopenia. Thorough follow-up of the haematological status of patients with Shwachman's syndrome is recommended.

A current strategy for osteosarcoma treatment is neo-adjuvant chemotherapy prior to the resection of the tumour. It appears that some tumours respond very well to the cytostatic therapy, while others show little or no effect. It is desirable to be able predict the response of the tumour before starting chemotherapy.

Primary malignant bone tumors, osteosarcomas (9 cases), and Ewing's sarcomas (10 cases) were examined for their reactivities with monoclonal and polyclonal antibodies against filamentous proteins and cell membrane determinants of the lymphoid and macrophage marker series. The reactivity of antibodies was studied on snap-frozen tissue probes by using a triple layer immunoperoxidase method.

To investigate the suitability of the pig as animal model for postmenopausal osteoprosis, effects of ovariectomy (OVX) on bone metabolism and histology were studied in two groups of sows (9 months, nulliparous or 35 months, multiparous). A standard diet of about 1.5 % calcium (Ca) was fed till sacrifice at either 12 or 20 months post OVX when mineral content and histology were studied in representative bone specimens of proximal tibia, iliac crest and lumbar vertebrae. At 4, 8, 12, and 18 months post OVX, total and bone-specific alkaline phosphatase (APt, APb) calcidiol, calcitriol and parathyroid hormone (PTH) were measured in plasma. In young sows OVX did not significantly affect plasma variables except for calcitriol, which was higher at 4 months post OVX. No significant differences between OVX or control animals were observed in the variables of bone chemical and histological analyses, neither 12 nor 20 months post OVX. In multiparous sows OVX significantly increased PTH plasma concentrations at 8 months post OVX and plasma calcitriol, APtand APbat 12 months post OVX. All effects were moderate and transient. OVX did not significantly affect the variables of bone chemical and histological analyses neither 12 nor 20 months post OVX. Although undoubtedly the clinical-chemical changes observed were not accompanied by any histomorphometric signs of osteopenia/osteoporosis, it must be left to future experiments as to whether this resulted from the ample calcium supply provided. This possibility is supported by recent observations showing that porcine osteopenia could be induced by OVX in animals maintained on only 0.75 % dietary calcium but not on higher (0.9 %) Ca regimens (33). In der vorliegenden Untersuchung sollte die Eignung des ovariektomierten Schweins als Modell für die postmenopausale Osteoporose beschrieben werden. Hierzu wurde der Einfluß der Ovariektomie (OVX) auf Plasmaparameter des Knochenstoffwechsels und auf knochenhistologische Parameter bei zwei Gruppen von Sauen (9 Monate alt, Nullipara oder 35 Monate alt, Multipara) untersucht. Eine Standarddiät für Schweine mit einem Calciumgehalt von 1,5 % wurde verabreicht. Gesamt-und knochenspezifische alkalische Phosphatase (APt, APb) Calcidiol, Calcitriol und Parathormon (PTH) wurden im Plasma 4, 8, 12 und 18 Monate nach OVX bestimmt. Der Mineralgehalt sowie histologische Parameter wurden in repräsentativen Knochenproben 12 Monate nach OVX und am Ende des Versuchs 18 Monate nach OVX gemessen. Bei jungen Sauen führte die Ovariektomie zu keinen signifikanten Veränderungen der Plasmaparameter mit Ausnahme höherer Konzentrationen des Calcitriols 4 Monate nach OVX. Es wurden weder 12 noch 20 Monate nach OVX signifikante Unterschiede zwischen OVX- und Kontrolltieren in den Parametern der chemischen oder histologischen Knochenanalyse beobachtet. Bei multiparen Sauen waren die Plasmakonzentrationen des PTH gegenüber den Kontrolltieren 8 Monate nach OVX signifikant erhöht. Die Konzentrationen des Calcitriols sowie die Aktivität der APtund APblagen 12 Monate nach OVX signifikant über den Werten der intakten Tiere. Alle Effekte waren moderat. Weder 12 Monate noch 20 Monate nach OVX kam es zu signifikanten Veränderungen in den Parametern der chemischen oder histologischen Knochenanalyse. Obwohl die beobachteten Veränderungen in den klinisch-chemischen Plasmaparametern zweifellos keine histomorphometrischen Anzeichen einer Osteopenie/Osteoporose zur Folge hatten, bleibt es zukünftigen Untersuchungen überlassen nachzuprüfen, ob das Ausbleiben des Osteopenie ein Ergebnis der in diesem Experiment hohen Calciumzufuhr war. Eine solche Möglichkeit sollte aufgrund der Beobachtung in Betracht gezogen werden, daß Osteopenie beim Schwein nach OVX eintritt, wenn eine Diät mit geringerer Calciumzufuhr (0,75 % im Vergleich zu 0,9 %) verabreicht wurde (33).

Summary Radical surgery in malignant bone tumors can either be limited by anatomical structures or seems inadequate in the palliative stabilization of bone metastases. Incomplete removal of the tumor and stabilization by compound osteosynthesis or endoprosthesis contains two problems: 1) the wide spread of malignant cells by manipulation in the tumor bearing area; 2) progressive destruction of bone due to remaining tumor. To overcome these problems we developed methotrexate bone cement (MTX-Palacos) with the aim to obtain high local concentrations of methotrexate in order to destroy remaining tumor cells and avoid systemic side effects. In vitro studies showed that methotrexate is released continuously from this cement without relevant changes of its biomechanical properties. Animal studies with transplanted osteosarcomas and mamma carcinomas in mice showed a considerable decrease of tumor growth when a plug of MTX-Palacos was inserted in the center of the tumor. Histological findings showed that in the surroundings of the plug the tumor was destroyed considerably contrary to normal bone cement which had no effect on the tumor at all. The results are discussed with regard to clinical application of MTX-Palacos.

Zusammenfassung: Geschildert wird der seltene Fall einer pathologischen Oberarmfraktur bei histologisch gesichertem Paget-Sarkom. Mit Rcksicht auf den Wunsch der Patientin, das fortgeschrittene Lebensalter und die Begleiterkrankungen wurde ein primr palliativer Therapieansatz gewhlt. Die berlebenszeit nach Erstdiagnose betrug neun Monate, wobei die Patientin an einer nicht tumorassoziierten Erkrankung verstorben ist. In Anbetracht der auerordentlich schlechten Prognose des Paget-Sarkoms und des eingeschrnkten therapeutischen Spektrums sollten Art und Umfang der Behandlung bewut von der persnlichen Situation des Patienten abhngig gemacht werden.

The effects of exogenous 1,25-dihydroxycholecalciferol (1,25(OH)2D3) in two adults with late-onset hypophosphataemic osteomalacia were studied. In the presence of elevated 25-hydroxyvitamin D levels 1,25(OH)2D3improved intestinal 17Ca absorption and increased urinary calcium, phosphate and hydroxyproline excretion. Hypophosphataemia, parathyroid hormone and bone mineralization were not significantly affected. The rise of the 1,25-dihydroxyvitamin D concentrations was dose dependent. The results indicate that the impaired renal phosphate conservation - the primary defect in this disorder - is not corrected by exogenous 1,25-dihydroxycholecalciferol.

The application of various high-resolution (<100 µm) imaging techniques for in vitro bone mineral analysis is explored.

The effect of preoperative chemotherapy (PCT) on the uptake of 99mTc-labeled diphosphonates into tumor bone was quantitatively assessed from serial scan studies of 30 osteosarcomas and correlated with the histomorphological changes determined from the surgical specimens. The parametric images of the tumor blood pool and labeled methylene diphosphonate (99mTc-MDP) plasma clearance by the tumor bone enabled a sensitive distinction to be made preoperatively between a good (>90% tumor cell destruction) and a poor (<90% tumor cell destruction) tumor response. Overall accuracy in presurgical prediction of tumor regression was found to be 88% and 96% for the blood pool and 99mTc-MDP clearance measurements, respectively (P≤0.0004). In addition, it proved possible to localize resisting areas of viable tumor up to 1.0 cm in diameter. Even at the half-way stage of PCT, a poor response could be reliably predicted (overall accuracy 91% and 100%, respectively; p≤0.011). Therefore, 99mTc-MDP parametric imaging is a highly sensitive and specific modality for an objective and accurate assessment of tumor regression during PCT of osteosarcoma.

The prognosis of osteosarcoma has improved significantly with recent advances in chemotherapy. Evaluation of the effect of chemotherapy is important for optimal timing of surgery, for selecting an alternative drug regimen in instances of poor response to chemotherapy and for testing combinations of new drugs. The purpose of this paper is to define the value of plain radiographs and angiography in assessing tumor response to chemotherapy. Studies were obtained before and after chemotherapy. The radiographic results were correlated with histologic evaluation of the resected specimen. Patients with less than 10% residual viable tumor in the resected bone were designated “responders” and patients with more than 10% of remaining viable tumor were “nonresponders”. Angiographic appearances correctly separated 15 patients with good response to chemotherapy from seven patients who were not responsive. Conversely, comparison of plain radiographs obtained before and after chemotherapy did not allow a reliable differentiation between patients with good, poor, or no response to chemotherapy. The current role of angiography in the management of patients with osteosarcoma is discussed. It is concluded that — in contrast to plain film radiography — angiography is an accurate method for assessing the response of osteosarcoma to chemotherapy.

Summary: Elongation of fetal chick long bone rudiments is formed by a mitogenic activity from porcine bonein vitro. Fractions of mitogenic activity from a heat- and acid-treated extract and from sequential chromatography on hydroxyapatite and from gelfiltration in 4 M guanidine-HCl increase diaphyseal elongation of metatarsals. The bone elongation-forming activity is associated with the mitogenic activity estimated by the incorporation of [3H]-methyl thymidine into the DNA of cells from embryonic chick periosteum. Histological examination of the mitogen-treated embryonic chick long bone shows that the partially purified fractions with a preferential effect on osteogenic cells increase diaphyseal elongation via cartilage cell proliferation. DNA of primary cells [15, 17] or cell lines of mesodermal origin in monolayer culture [14, 16]. Another approach to studying the effect of growth promotion is the use of ektopic bone formation. Bone morphogenetic protein BMP [18], osteogenin [19], and other distinct bone-inducing factors [20] induce bone formation locally in subcutaneouous sitesin vivo. The purification and characterization, however, have been hampered by the cumbersomein vivo assay. In view of this we used a mitogenic assay on primary embryonic cells to accompany purification, and further analyzed mitogenic fractions for their ability to induce elongation of long bones in culture.

Abstract.: The purpose of this study was to quantify the heterogeneity in the trabecular bone structure in the calcaneus. Magnetic resonance (MR) images of the calcaneus were obtained in the sagittal plane at an inplane resolution of 195 μm and a slice thickness of 1000 μm in 12 young normal subjects. Regions of interest (ROI) were selected to cover the calcaneus using a grid of square boxes (10 mm per side). A thresholding technique based on the regional intensity histogram was used to segment the images into trabecular bone and marrow phases and to calculate measures such as apparent trabecular bone area fraction, apparent trabecular spacing, apparent trabecular thickness and apparent trabecular number. Bone mineral density (BMD) of the calcaneus was assessed using dual-energy X-ray absorptiometry (DXA). Histological sections of three calcanei were also analyzed using transmission light illumination, and the results used to calibrate our computational software. For a relatively narrow inter-subject variation in posterior BMD, a significant inter-subject variation was seen in MRI-derived structural parameters. Furthermore, the spatial heterogeneity of the structural parameters in the posterior region was as high as 40%. Thus, the posterior tuberosity of the calcaneus, a typical site for BMD and single-point ultrasound assessments, can demonstrate significant regional variation in trabecular bone structure.

Summary Growth arrest and renal osteodystrophy are major problems in renal insufficiency of children. The present report describes our experiences in managing renal osteodystrophy in 14 dialyzed children using 1,25-DHCC for 12 months. Values in plasma of Ca, P, Mg, alkaline phosphatase, iPTH, 25-OH-D, and 1,25-DHCC were determined regulary. Skeletal X-rays and analysis of iliac crest biopsies were obtained in each child.

Summary 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.