Prognostic Factors in High-Grade Osteosarcoma of theExtremities or Trunk: An Analysis of 1,702 Patients Treatedon Neoadjuvant Cooperative Osteosarcoma Study GroupProtocols.

PURPOSE: To define prognostic factors for response and long-term outcome for a wide spectrum of osteosarcomas, extending well beyond those of the typical young patient with seemingly localized extremity disease. PATIENTS AND METHODS: A total of 1,702 consecutive newly diagnosed patients with high-grade osteosarcoma of the trunk or limbs registered into the neoadjuvant studies of the Cooperative Osteosarcoma Study Group before July 1998 were entered into an analysis of demographic, tumor-related, and treatment-related variables, response, and survival. The intended therapeutic strategy included preoperative and postoperative chemotherapy with multiple agents as well as surgery of all operable lesions. RESULTS: Axial tumor site, male sex, and a long history of symptoms were associated with poor response to chemotherapy in univariate and multivariate analysis. Actuarial 10-year overall and event-free survival rates were 59.8% and 48.9%. Among the variables assessable at diagnosis, patient age (actuarial 10-year survival ≥ 40, 41.6%; < 40, 60.2%; P = .012), tumor site (axial, 29.2%; limb, 61.7%; P < .0001), and primary metastases (yes, 26.7%; no, 64.4%; P < .0001), and for extremity osteosarcomas, also size (≥ one third, 52.5%; < one third, 66.7%; P < .0001) and location within the limb (proximal, 49.3%; other, 63.9%; P < .0001), had significant influence on outcome. Two additional important prognostic factors were treatment related: response to chemotherapy (poor, 47.2%; good, 73.4%; P < .0001) and the extent of surgery (incomplete, 14.6%; macroscopically complete, 64.8%; P < .0001). All factors except age maintained their significance in multivariate testing, with surgical remission and histologic response emerging as the key prognostic factors. CONCLUSION: Tumor site and size, primary metastases, response to chemotherapy, and surgical remission are of independent prognostic value in osteosarcoma.

Modulation of vitamin d status and dietary calcium affects bone mineral density and mineral metabolism in göttingen minipigs.

Calcium and vitamin D deficiency impairs bone health and may cause rickets in children and osteomalacia in adults. Large animal models are useful to study experimental osteopathies and associated metabolic changes. We intended to modulate vitamin D status and induce nutritional osteomalacia in minipigs. The control group (n = 9) was fed a semisynthetic reference diet with 6 g calcium and 6,500 IU vitamin D3/kg and the experimental group (n = 10) the same diet but with only 2 g calcium/kg and without vitamin D. After 15 months, the deficient animals were in negative calcium balance, having lost bone mineral density significantly (means ± SEM) with -51.2 ± 14.7 mg/cm(3) in contrast to controls (-2.3 ± 11.8 mg/cm(3)), whose calcium balance remained positive. Their osteoid surface was significantly higher, typical of osteomalacia. Their plasma 25(OH)D dropped significantly from 60.1 ± 11.4 nmol/L to 15.3 ± 3.4 nmol/L within 10 months, whereas that of the control group on the reference diet rose. Urinary phosphorus excretion and plasma 1,25-dihydroxyvitamin D concentrations were significantly higher and final plasma calcium significantly lower than in controls. We conclude that the minipig is a promising large animal model to induce nutritional osteomalacia and to study the time course of hypovitaminosis D and associated functional effects.

Improved osseointegration of PTFEP-coated titanium implants.

BACKGROUND: Clinical success of bone implants is critically related to the interaction between the implant surface and the surrounding tissue. The polymer poly(bis(trifluoroethoxy)phosphazene) (PTFEP) is a promising, highly biocompatible surface coating which also inhibits the adsorption of granulocytes, macrophages, inflammatory cells, bacteria, and platelets. However, there is limited clinical experience of PTFEP as a coating for bone implants. Therefore PTFEP-coated titanium implants in an animal model were examined. MATERIAL/METHODS: PTFEP-coated titanium cylinders were implanted into the lateral femoral condyles of rabbits. Osseointegration was examined six weeks and six months after implantation using a non-destructive mechanical pull-out measurement and a histological analysis. RESULTS: The results indicate improved osseointegration of PTFEP-coated implants. Six weeks after implantation, the PTFEP-coated implants showed a higher stiffness (pull-out length [pol]=7.1+/-2.0 microm) compared with uncoated cylinders (pol=10.2+/-3.4 microm, p<0.05). Six months after implantation, the mechanical properties of both implants had adjusted, and histological analysis revealed an increased bone-implant interface of PTFEP-coated cylinders compared with the first 6 weeks (17.5% vs. 8.2% in controls, p<0.05). CONCLUSIONS: Taken together, the results of this preliminary study indicate promising applications of PTFEP as a coating material for bone implants.

Biopsy of tumors of the musculoskeletal system.

INTRODUCTION: Malignant tumors of the musculoskeletal system are rare, and their symptoms are non-specific. The diagnosis of primary malignant tumors of bone or soft tissue by tissue biopsy is necessary before multimodal treatment with chemo- and/or radiotherapy and resection can be provided. These biopsies are straightforward surgical procedures; they must, however, be performed according to the guidelines if high rates of error and complications are to be avoided. METHODS: Selective literature review. RESULTS: Biopsies are either incisional or excisional. There are guidelines for the performance of both kinds. The biopsy channel is inevitably contaminated with tumor cells and thus must be completely removed together with the tumor. Excisional biopsies are indicated only for the histopathological diagnosis of small (< 5 cm), epifascial soft-tissue tumors and small, slowly growing bony tumors that are considered most likely to be benign. If in doubt, an incision biopsy should be performed. DISCUSSION: The complication rate of tumor biopsies is known to be higher when they are performed in an institution without extensive experience in the treatment of sarcoma. Thus, patients with musculoskeletal tumors that are suspected of being malignant should be referred to a suitable tumor center for biopsy.

The influence of callus distraction on the growth plate.

OBJECTIVES: This study was designed to investigate the morphology, thickness and cellularity of the growth plate during callus distraction performed in the immediate vicinity of the growth plate. METHODS: Lengthening of the right tibia by 25% was carried out on 24 beagle dogs by callus distraction. Distraction was started at the fifth postoperative day with a distraction rate of 0.5 mm twice a day. A control group of six dogs underwent tibial osteotomy and external fixation without distraction. Half of the dogs of both groups were sacrificed at the end of the distraction phase of 25 days (Group A) and the remaining 15 dogs after an additional consolidation period of 25 days (Group B). The tibia and femur was removed from the distracted right leg and from the left control side of each animal and longitudinal sections were cut and stained with Pentachrome. The thickness and cellularity of the regeneration zone, the proliferation zone and the hypertrophic zone were determined for the proximal tibial and the distal femoral epiphysis. RESULTS: During the distraction phase the thickness of the proximal tibial growth plate and its cellularity were reduced on the distraction side. During the consolidation phase there was a slight recovery in the proximal tibial growth plate. CONCLUSIONS: Callus distraction leads to a temporary reduction in growth of the affected physis.

Ultrasound in the diagnosis of craniosynostosis.

Diagnosis of craniosynostosis is based on clinical aspects but may be difficult in some cases where characteristic features are missing and radiographic imaging is necessary. In this context near-field high-frequency ultrasound has been used to evaluate the sonographic characteristics of synostotic sutures and its potential confirming the correct diagnosis. Sutures of 26 infants, aged 2-7 months, were investigated by ultrasound (Siemens Elegra, 7.5 MHz linear scanner). Sonographic features of synostotic sutures were correlated to CT imaging and compared to the sonographic and histopathological findings of normal cranial sutures. Hyperechogenic bridging of sutures with or without ridging were the characteristic aspects of synostotic sutures. All 26 patients could be reliable diagnosed showing partial (n = 21) or total fusion (n = 5) of one or more sutures consisting with craniosynostosis. Length of synostosis was identified exactly by sonography and imaging found to enable a classification of ultrastructural details of bony and soft tissue next to the synostotic suture. Ultrasound is a less expensive, nonradiating and easy-to-handle tool ensuring the diagnosis of craniosynostosis. Sonography offers the potential to be a standard investigation for infants with head deformities suspecting a suture pathology and has been therefore integrated in our craniofacial outpatient clinic as a daily routine method.

Alpha CTX as a biomarker of skeletal invasion of breast cancer: immunolocalization and the load dependency of urinary excretion.

We recently showed that increased urinary excretion of the cross-linked, nonisomerized form of the C-telopeptide of collagen type I (alphaalphaCTX) could be a sensitive indicator of the presence of bone metastases in breast cancer patients. The present study was sought to investigate (a) the localization of alphaCTX epitopes in the proximity of a bone metastasis and (b) the relationship between number of metastases and the urinary excretion of alphaalphaCTX. Adjacent bone sections from breast cancer patients were stained for the presence of tumor cells (anti-cytokeratin antibody), osteoclasts (TRAcP activity), and alphaCTX (anti-alphaCTX antibody). The association between the extent of metastatic bone disease and urinary excretion of alphaalphaCTX measured with ELISA was assessed in 90 breast cancer patients (45 with bone metastasis and 45 without bone metastasis). Immunohistochemistry revealed accumulation of TRAcP-positive osteoclasts and intense staining for alphaCTX epitopes in the proximity of cytokeratin-positive bone metastasis. Areas of alphaCTX staining showed unstructured bone tissue under polarized light. In addition, there was a significant linear association between the number of bone metastases and the urinary levels of alphaalphaCTX in breast cancer patients with metastatic bone disease, independent of age and body mass index (r = 0.56, P < 0.001). The estimated relative increases in alphaalphaCTX associated with the presence of one, two, or three metastases are 38%, 57%, and 81%, respectively. Taken into account the 17% intraindividual variation of the assay, alphaalphaCTX could be a sensitive biochemical marker for the close monitoring of cancer patients aiming the facilitation of early metastasis detection.

Classical and atypical location of adamantinomas--presentation of two cases.

BACKGROUND: Adamantinomas are rare low-grade primary bone tumors of unknown histological origin. They typically develop in the diaphyses and metaphyses of long bones, prevalently the tibia. CASE REPORTS: The cases of 2 female patients, one with localized swelling of the lateral metatarsals and one with pain of the tibia are being reported. The diagnostic work-up including biopsy verified an adamantinoma in both cases. In the younger patient, the tumor was located in the metatarsals 4 and 5, in the older patient in the left tibial diaphyses. In both patients, an en-bloc resection of the tumor with wide surgical margins was performed. Further follow-ups 73 and 36 months after surgery showed no local recurrence or metastatic spread. CONCLUSION: Adamantinomas of the short bones are rarely reported. In accordance to the literature, an en-bloc resection with wide surgical margins seems to reduce the risk of local recurrence and metastatic spread.

High-frequency ultrasound confirmation of positional plagiocephaly.

OBJECT: Positional plagiocephaly has become an increasing problem for pediatricians and craniofacial specialists. Diagnosis is commonly based on history and clinical features, but may be difficult in some cases when characteristic features are missing and radiographic studies seem to be necessary. Near-field high-frequency ultrasound has been used to evaluate the sonographic findings of suture anatomy and confirm the diagnosis of positional plagiocephaly as well as provide information of prognostic value. METHODS: The authors report on 100 pediatric patients between the ages of 2 and 13 months, who were admitted to their department since 2004 with an abnormal head shape suggesting nonsynostotic plagiocephaly (NSP). Suture anatomy was examined using a 7.5-MHz linear transducer and a Siemens Elegra ultrasound scanner by two independent investigators. Measurements of suture width and bone thickness were obtained, and the findings were correlated with clinical data as well as sonographic and histopathological findings in both normal and fused cranial sutures. Interobserver variability was assessed by means of paired t-tests. Linear regression analyses were used for correlating patient age with suture width and bone thickness. Patency of lambdoid sutures was confirmed in 99 cases in which the clinical findings suggested NSP. Morphological characteristics of the sutures--interosseous hypoechoic areas between hyperechoic bone plates--were comparable to those of normal cranial sutures. In one patient, partial synostosis was diagnosed. Overlapping hyperechoic bone plates were found in 51 patients on the affected side of the skull and in 36 patients on the unaffected side. Suture width decreased over time from 6.5 to 2 mm, and thickness of bone in the affected area increased from 0.6 to 1.2 mm until the age of 13 months. The method was found to be limited by age (upper limit 13 months) and anatomical variations but did not show any interobserver variability (p < 0.05). CONCLUSIONS: High-frequency ultrasound is a relatively inexpensive, safe, and easy-to-use tool for confirming the diagnosis of positional plagiocephaly and excluding true synostosis. Overlapping bone plates may be seen on the affected side of the skull in a majority of plagiocephalic patients, but this finding seems to have no prognostic value regarding early fusion of sutures and therefore should not affect treatment decisions. With its lack of interobserver variability and the advantage of not involving ionizing radiation, sonography has the potential to be a standard modality for investigating plagiocephaly in infants and should be offered in craniofacial outpatient clinics.

Extraskeletal osteosarcoma has a favourable prognosis when treated like conventional osteosarcoma.

PURPOSE: The aims of this analysis were to investigate the clinical features of extraskeletal osteosarcoma (ESOS) and examine the outcome after multi-modal therapy. METHODS: The co-operative osteosarcoma study-group database was searched for patients with extraskeletal osteosarcoma. Eligible patients were included in a retrospective analysis of patient, tumour and treatment related variables and outcome. As for conventional osteosarcoma, scheduled treatment included surgery and multi-agent chemotherapy. RESULTS: Seventeen eligible patients were identified with a median age of 44 years (range, 3-65 years). The thigh was the commonest tumour site. Two patients had a history of previous malignancies and two had primary metastases. Median follow-up was 3.2 years (range: 0.6-7.4 years) and at last follow-up, 11 patients were alive in complete remission, 3 patients were alive with disease and 3 patients had died of their disease. Three-year overall actuarial and event-free survival rates were 77% and 56%, respectively. Patients with macroscopically complete surgical remission had an improved overall survival (P = 0.0004). CONCLUSIONS: The patients in this retrospective study had a surprisingly good survival rate. This may be due to the combination of multi-agent chemotherapy with surgery, and we recommend this approach in the treatment of ESOS.

Gorham-Stout disease--stabilization during bisphosphonate treatment.

A 45-year-old woman presented with recent onset of left-sided chest pain. On clinical examination, these symptoms seemed to be strictly localized to a region that was marked by a long-standing cutaneous erythematous lesion. Laboratory results showed no gross abnormalities. Radiological imaging including conventional X-ray, MRI scans, and 3D CT reconstruction of the rib cage revealed circumscript destruction of the left lateral ribs 9-11. Histological analysis of a rib biopsy showed angiomatous hypervascularization and intracortical fibrosis. In keeping with these findings, the patient's condition was diagnosed as Gorham-Stout disease, a rare condition with localized, often unilateral, bone destruction. Monotherapy with bisphosphonates (pamidronate 30 mg i.v. every 3 months) was initiated, leading to rapid disappearance of local pain. Follow-up over 24 months documented a stable clinical and radiological picture without evidence of progressive bone destruction.

Methylation status of the retinoblastoma gene (RB1) in osteosarcoma: no evidence for hypermethylation.

Alterations of the retinoblastoma (RB1) tumor suppressor gene are not only associated with retinoblastoma but also with several other malignancies including osteosarcoma. Besides direct sequence alterations, hypermethylation of a CpG island in the promoter region can cause inactivation of the RB1 gene as it has been shown in retinoblastomas. We examined the methylation status of the RB1 gene in 25 osteosarcoma specimens by using the methylation-sensitive restriction enzymes SacII and SmaI. The restriction fragments were hybridized with clone p123, which is a 1.8-kb genomic subclone that spans the RB1 CpG island including the promoter region and exon 1. Whereas we reconfirmed hypermethylation of the RB1 gene in a sporadic retinoblastoma, no hypermethylation could be detected in the 25 osteosarcoma specimens, suggesting that hypermethylation of the RB1 promoter is not of major importance during osteosarcoma genesis.

A reproducible and simple grading system for classical chondrosarcomas. Analysis of 35 chondrosarcomas and 16 enchondromas with emphasis on recurrence rate and radiological and clinical data.

In the past, six histological grading systems for classical chondrosarcoma have been published. Due to the inhomogeneity and complexity of these classifications, the comparison of clinical data, survival rates and local failures has to be considered critically. In 1996, the author published a grading system that was simple to use and easily reproduced. This system was based on a few nuclear features. The main intention of the current study was to verify whether the histological grade, which was defined by the author's classification, correlates with the recurrence rate. In a retrospective study, clinical data, X-rays and histological material from 35 patients with classical chondrosarcoma and 16 patients with enchondroma were analysed. Statistical analysis was done using the chi-squared test and the Fisher exact test. Local recurrence occurred in 25.7% of all patients. The difference in recurrence rate among grades 1-3 was statistically significant ( P=0.002). The frequency of grades 1-3 varied up to 54%, when published grading systems were compared. No significant difference between the histological grade and features such as double nuclei and mitosis were observed. The frequency of cellularity, double nuclei and mitoses was similar between enchondromas and low-grade chondrosarcomas. Of chondrosarcoma patients, 90.6% of total patients and 87.5% of those with grade-1 lesions reported pain, whereas only 43.8% of the enchondroma patients did. Even in patients with grade-1 chondrosarcomas, radiological findings were much more aggressive in comparison with enchondromas. The histological grade, defined on the basis of the author's simple and reproducible grading system, indicates the risk of local recurrence, especially in cases that are inadequately treated. Grade-3 chondrosarcomas and lesions located in regions where the removal of the tumour would be difficult have to be given special attention.

Zoledronic acid to prevent bone loss in the first 6 months after renal transplantation.

BACKGROUND: Bisphosphonates can prevent bone mineral density loss after renal transplantation, but their effect on trabecular mineralization and bone morphology, two key factors of bone stability, remains unknown. METHODS: In a 6-month, randomized, placebo-controlled study, 20 kidney transplant recipients received either 4 mg zoledronic acid or placebo twice within 3 months after engraftment. At transplantation and after 6 months, mean trabecular calcium concentration and trabecular morphometry were measured in bone biopsies. Bone mineral density (BMD) of the femoral neck and the lumbar spine were evaluated by dual-energy x-ray absorptiometry, and serum biochemical markers of bone metabolism were determined monthly. RESULTS: Trabecular calcium content increased significantly in the zoledronic acid group, but remained unchanged in the placebo group. BMD at femoral neck showed no change in the zoledronic acid group, but decreased in the placebo group. BMD of the lumbar spine was increased in the zoledronic acid group without change in the placebo group. High-turnover bone disease resolved similarly in both groups, as evidenced by a significant decrease of eroded bone surface, osteoclast and osteoblast surface. Serologic markers of bone formation and resorption were significantly lower in zoledronic acid-treated patients throughout the study. Kidney transplant function was stable after zoledronic acid therapy. CONCLUSIONS: Our results show that administration of zoledronic acid improves the calcium content of cancellous bone after kidney transplantation. The beneficial effect of bisphosphonate therapy is further evidenced by an increase of lumbar spine BMD, and stabilization of femur BMD.

Pathological alterations in the archaic Homo sapiens cranium from Eliye Springs, Kenya.

This paper reports on the results of a first computerized tomography (CT)-based study of the Middle Pleistocene matrix-filled skull KNM-ES 11693 from Eliye Springs at Lake Turkana. Ectocranially, the hominid cranium exhibits a remarkable enlargement of the vault symmetrical to the sagittal suture and a porotic surface covering most of the vault. CT analysis further revealed a strong thickening of the cranial vault as well as other relevant aspects. Differential diagnosis suggests that the changes of the Eliye Springs cranium were probably caused by chronic anemia in the childhood or youth of this individual.

Osteosarcoma of the pelvis: experience of the Cooperative Osteosarcoma Study Group.

PURPOSE: To define patients and tumor characteristics as well as therapy results, patients with pelvic osteosarcoma who were registered in the Cooperative Osteosarcoma Study Group (COSS) were analyzed. PATIENTS AND METHODS: Sixty-seven patients with a high-grade pelvic osteosarcoma were eligible for this analysis. Fifteen patients had primary metastases. All patients received chemotherapy according to COSS protocols. Thirty-eight patients underwent limb-sparing surgery, 12 patients underwent hemipelvectomy, and 17 patients did not undergo definitive surgery. Eleven patients received irradiation to the primary tumor site: four postoperatively and seven as the only form of local therapy. RESULTS: Local failure occurred in 47 of all 67 patients (70%) and in 31 of 50 patients (62%) who underwent definitive surgery. Five-year overall survival (OS) and progression-free survival rates were 27% and 19%, respectively. Large tumor size (P =.0137), primary metastases (P =.0001), and no or intralesional surgery (P <.0001) were poor prognostic factors. In 30 patients with no or intralesional surgery, 11 patients with radiotherapy had better OS than 19 patients without radiotherapy (P =.0033). Among the variables, primary metastasis, large tumor, no or intralesional surgery, no radiotherapy, existence of primary metastasis (relative risk [RR] = 3.456; P =.0009), surgical margin (intralesional or no surgical excision; RR = 5.619; P <.0001), and no radiotherapy (RR = 4.196; P =.0059) were independent poor prognostic factors. CONCLUSION: An operative approach with wide or marginal margins improves local control and OS. If the surgical margin is intralesional or excision is impossible, additional radiotherapy has a positive influence on prognosis.

Successful transpedicular lumbar interbody fusion by means of a composite of osteogenic protein-1 (rhBMP-7) and hydroxyapatite carrier: a comparison with autograft and hydroxyapatite in the sheep spine.

STUDY DESIGN: Transpedicular lumbar interbody fusion (TLIF) was performed in a sheep model comparing three treatment groups: a composite of osteogenic protein (OP)-1 and hydroxyapatite carrier (HA), HA without OP-1, and autograft. OBJECTIVE: To evaluate the efficacy of the composite of OP-1 and HA (HA-OP-1) in achieving reliable TLIF. SUMMARY OF BACKGROUND DATA: Anterior fusion techniques directly address disc-related problems and achieve primary axial stability. However, they are characterized by high morbidity. Alternatively, the theoretically advantageous posterior TLIF technique using autograft fails clinically because it lacks compressive stability. METHODS: In 36 sheep, lumbar vertebrae L4 to L6 were instrumented posteriorly. Endoscopically assisted TLIF of L4 to L5 was performed. In 12 sheep, the defect was filled with injectable HA-OP-1. Another 12 sheep were treated with HA and another 12 with autograft. Animals were killed at 8 weeks and evaluated by radiologic, histologic, and histomorphometric analysis and by fluorochrome labeling. RESULTS: Only 10 autograft sheep were available for evaluation. Radiologically and histologically, TLIF with HA-OP-1 led to a fusion rate of 10 in 12 compared with autograft (one in 10 fused) and HA (two in 12 fused) ( = 0.0016). Semiquantitative radiologic and histologic scoring also revealed significant differences with superiority of HA-OP-1 ( = 0.0011). Compared with HA, HA-OP-1 presented significantly more ossification at the bone-cement interface ( = 0.0003) and less cement resorption ( = 0.0209). In four of 12 HA sheep, excessive resorption was responsible for local aseptic inflammation. CONCLUSIONS: Biointegration of the osteoconductive HA does not occur, because shear forces cause early HA fracture, subsequent fragmentation, and gross resorption (initiating severe inflammation in four of 12 sheep). In contrast, osteoinductive effects of HA-OP-1 enable bio-integration, resulting in full osseous composite sheathing and solid fusion. By use of this composite, TLIF is successfully applied in sheep. Harvesting autograft and the anterior approach are avoided.

[Do markers of bone metabolism reflect the presence of a high- or low-turnover state of bone metabolism?]. / Korrelieren biochemische Knochenstoffwechselmarker mit einer histologisch gesicherten High- bzw. Low-Turnover-Osteoporose?

BACKGROUND: A pathophysiological concept of osteoporosis therapy - antiresorptive treatment of high-turnover osteoporosis (e. g. bisphosphonates, raloxifen) and osteoanabolic treatment of low-turnover osteoporosis (e. g. parathyroid hormone) - is clinically and economically reasonable to enable physicians to decide who will benefit most from which drug. Biochemical bone markers in serum and urine are frequently used for the diagnosis of high- or low-turnover osteoporosis. We investigated whether bone marker levels reflect the histologically diagnosed high- or low-turnover state of osteoporosis. MATERIALS AND METHODS: 175 bone biopsies of male and female osteoporotic patients (WHO criteria) were histologically classified in high- and low-turnover osteoporosis and associated with bone marker levels in serum and urine. Patients with any osteotropic therapy and with fractures were excluded. RESULTS: There were no significant differences between patients with high- and low-turnover osteoporosis with regards to osteocalcin, DPD crosslinks, alkaline phosphatase, 25-OH vitamin D(3), parathyroid hormone and bone mass (spine and hip). CONCLUSIONS: Single measurements of biochemical bone markers in serum and urine do not allow a valid differentiation between histologically diagnosed high- and low-turnover states of osteoporosis. The therapeutic concept of treating with osteoanabolic drugs requires valid diagnostic criteria for the differentiation between high- and low-turnover state of bone metabolism which can be provided by a bone biopsy but not by single measurements of bone markers.

The influence of material and design features on the mechanical properties of transpedicular spinal fixation implants.

This study describes the finding and performance of mechanical strength and corrosion testing procedures for comparative examination of multiple internal transpedicular spine fixators. Seven different implant models from five different manufacturers were compared regarding their bending strength and fatigue resistance. Because of the unacceptably high levels of time and material that they require, ISO and ASTM testing standards are not applicable to comparative testing. In addition, there is a lack of knowledge about clinically defined and proven strength-limit values. Therefore, actual standard testing procedures have been modified and extended to corrosion testing. Overall, the effort necessary to obtain reproducible comparative data has been reduced significantly. Although a reduced number of implants of each type were available for destructive testing, the results revealed fundamental differences in the tested implants between different materials and design features. During fatigue testing some of the implants showed poor corrosion properties. Because spinal fixation implants tend to be used as long-duration implants, corrosion testing as well as comparative strength testing with clinically successful implant models should be performed as preclinical evaluations.

Osteoprotegerin and parathyroid hormone as markers of high-turnover osteodystrophy and decreased bone mineralization in hemodialysis patients.

Osteoprotegerin (OPG) has a profound inhibitory effect on osteoclast differentiation and bone resorption. Because high-turnover renal osteodystrophy (ROD) is characterized by increased osteoclast activity, serum OPG concentrations might be used to distinguish between forms of ROD. Twenty-six patients on maintenance hemodialysis therapy underwent a transiliac crest biopsy for evaluation of histopathologic characteristics and histomorphometric studies. ROD was diagnosed as type II (normal or low turnover) or type III (high turnover plus osteoidosis) disease. Bone mineralization density distribution (BMDD) was characterized by measuring the mean trabecular calcium concentration in the biopsy specimen with quantitative backscattered electron imaging. Patients underwent additional dual-energy x-ray absorptiometry (DEXA) of the spine and hip and measurement of such biochemical markers of bone turnover as OPG, intact parathyroid hormone (iPTH), osteocalcin, calcitonin, bone alkaline phosphatase, and cross-laps. OPG levels were significantly reduced in patients with ROD III compared with ROD II (118 +/- 38 versus 204 +/- 130 pg/mL; P < 0.05) and correlated with BMDD (r = 0.43; P < 0.05). Patients with ROD III showed significantly lower BMDD compared with healthy controls (21.42% +/- 0.12% versus 22.17% +/- 0.81% weight; P < 0.01). Besides iPTH, which showed significantly greater levels in patients with ROD III than ROD II (382 +/- 322 versus 136 +/- 156 pg/mL; P < 0.05), none of the serological markers or DEXA was useful in separation of the groups. Discriminant function analysis showed that a combination of OPG and iPTH correctly classifies ROD II in 72% and ROD III in 88% of patients. We conclude that OPG in combination with iPTH can be used as a marker for noninvasive diagnosis of ROD in hemodialysis patients. Furthermore, OPG serum levels might be used to estimate trabecular bone mineralization in these subjects.