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High bone turnover associated with an aluminum-induced impairment of bone mineralization.

A hemodialyzed patient showing x-ray and biochemical evidence of apparently pure severe hyperparathyroidism underwent a tetracycline-labeled transiliac bone biopsy. The bone biopsy not only confirmed the hyperparathyroid bone lesions but also revealed an impairment of bone mineralization induced by aluminum. This was demonstrated by a reduction of double-labeled osteoid surfaces, a significant increase in the osteoid seam thickness, and the presence of extensive aluminum deposits in bone. The planned parathyroidectomy was postponed, and deferoxamine (DFO) therapy, 2 g once a week, was initiated. A second bone biopsy, taken 6 months later, showed recovery of normal bone mineralization but the persistence of hyperparathyroid bone lesions. This was associated with a considerable reduction in the extent of aluminum deposits on trabecular bone surfaces. This observation shows that severe and apparently pure hyperparathyroidism can be associated with an impairment of bone mineralization induced by aluminum. This suggests that bone mineralization and aluminum overload should be evaluated in dialyzed patients who are being considered for parathyroidectomy.

Aluminum↗

Bone morphogenetic protein-2 but not bone morphogenetic protein-4 and -6 stimulates chemotactic migration of human osteoblasts, human marrow osteoblasts, and U2-OS cells.

Bone morphogenetic proteins (BMPs) have important functions for the differentiation of bone cells, but the exact role for bone remodeling and bone healing still needs to be defined. Migration of bone forming cells is an important physiological event both during bone healing and bone remodeling. The chemotatic properties of the bone morphogenetic protein family of growth factors have not been investigated. In this study the chemotactic effects of the bone morphogenetic proteins BMP-2, -4, and -6 have been quantitated toward human osteoblasts, human marrow stromal osteoblasts, and U2-OS human osteosarcoma cells. BMP-2 stimulated the migration of human stromal osteoblasts, human osteoblasts, and U2-OS cells with bell-shaped response curves in a dose-dependent manner with a 300% increase in cell migration at 1.0 ng/mL for human stromal osteoblasts and a 170-180% increase for human osteoblasts and U2-OS cells. At higher concentrations, migration decreased to background levels. BMP-4 and -6 did not show any effect on cellular migration. This study shows that BMP-2 can stimulate in vitro migration of human osteoblasts and human osteosarcoma cells. BMP-2 might play a role in the chemotactic recruitment of especially undifferentiated osteoblasts during bone remodeling and bone healing.

Bone Marrow↗

Relationship between gelatinases and bone turnover in the healing bone defect.

PURPOSE: The aim of this pilot study was to determine the relationship between gelatinase (MMP-9 and MMP-2) markers of soft tissue inflammation/turnover at the bone/soft tissue interface and bone turnover (osteocalcin [OC], pyridinoline cross-linked carboxyl-terminal telopeptide of type 1 collagen [ICTP], and bone fill) during healing of an alveolar bone defect. MATERIALS AND METHODS: Ten subjects undergoing oral surgery had a 5 x 5-mm trephine defect created on an edentulous ridge and were sampled at the bone/soft tissue interface at baseline (prior to flap reflection), 2 weeks and 12 weeks postsurgery, using a novel bone wash device. Recovered irrigants were analyzed for MMP-9 and MMP-2 by gelatin zymography, OC and ICTP with radioimmunoassays, and albumin (ALB; to normalize markers for blood content) with a sandwich enzyme-linked immunosorbent assay. Bone fill at 12 weeks was analyzed by radiographic absorptiometry. RESULTS: All markers of enzymatic activity and bone turnover varied significantly across time (P < or = .03), with bone turnover markers OC and ICTP decreasing between baseline and 2 weeks, and MMP-9 and MMP-2 increased. Measures generally returned to near baseline levels after 12 weeks. MMP-9 versus MMP-2 (r = 0.97, P < .0001) and OC versus ICTP (r = 0.38, P = .048) were correlated with each other, while MMP-9 and MMP-2 were negatively correlated with ICTP (r = -0.48, P = .011 and r = -0.62, P = .006, respectively). MMP-9 was negatively correlated with subsequent bone fill (r = -0.63, P = .07). CONCLUSIONS: Bone wash sampling showed that gelatinase activity at 2 weeks following creation of an alveolar defect appeared to decrease bone turnover and eventual bone fill, suggesting benefits for anti-MMP therapy during wound healing.

Alveolar Bone Loss↗

Open-label trial evaluating the safety and efficacy of zoledronic acid in preventing bone loss in patients with hormone-sensitive prostate cancer and bone metastases.

OBJECTIVES: To evaluate the efficacy and safety of zoledronic acid in preventing bone loss in patients with hormone-sensitive prostate cancer and bone metastases who were receiving androgen deprivation therapy. METHODS: Patients received zoledronic acid 4 mg as a 15-minute infusion every 3 weeks for 1 year. Bone mineral density of the lumbar spine (L2 to L4) and total hip was measured by dual-energy x-ray absorptiometry at baseline and 12 months. Biochemical markers of bone turnover (N-telopeptide and bone alkaline phosphatase) and serum creatinine levels were evaluated at baseline and during the study. Skeletal-related events were assessed at each study visit. RESULTS: Of the 221 enrolled patients, 202 and 221 patients were included in the efficacy and safety analyses, respectively. The mean increase in bone mineral density of the lumbar spine and total hip was 7.7% (P <0.001) and 3.6% (P <0.001), respectively. Decreases in N-telopeptide and bone alkaline phosphatase levels were significant and sustained. The median time to the first skeletal-related event was not reached; 11.9% of patients had a skeletal-related event. Arthralgia (20.4%), nausea (14%), fatigue (14%), and back pain (12.2%) were the most common adverse events. Adverse events due to renal function deterioration were infrequent. The mean maximal change in serum creatinine level from baseline was 0.3 mg/dL. CONCLUSIONS: Zoledronic acid administration for 1 year to patients with hormone-sensitive prostate cancer and bone metastases who were receiving androgen deprivation therapy was safe and prevented bone loss, as demonstrated by significant increases in bone mineral density and sustained suppression of biochemical markers of bone turnover.

Aged↗

Role of microenvironmental deterioration of the bone marrow in the development of bone atrophy in magnesium silicate-treated rats.

The role of microenvironmental deterioration of the bone marrow in the development of bone atrophy was examined in rats with bone atrophy induced by magnesium silicate. In the tibial metaphyses, proliferation of myelocytic elements of haematopoietic tissue was prominent and caused narrowing of sinusoids, increased distance between sinusoids and trabecular bone and atrophy of trabecular bone. There was a significant correlation in volume percentage between haematopoietic cells and trabecular bone, between haematopoietic cells and sinusoids and between sinusoids and trabecular bone. These results imply that atrophy of trabecular bone is related to microenvironmental deterioration of the bone marrow, that is, a decrease in efficiency of exchange of nutrients and waste products between sinusoids and trabecular bone due to the proliferation of haematopoietic cells and a deficiency of nutrient supply to the bone marrow due to the narrowing of sinusoids.

Animals↗

The influence of bone volume fraction and ash fraction on bone strength and modulus.

Although bone strength and modulus are known to be influenced by both volume fraction and mineral content (ash fraction), the relative influence of these two parameters remains unknown. Single-parameter power law functions are used widely to relate bone volume or ash fraction to bone strength and elastic modulus. In this study we evaluate the potential for predicting bone mechanical properties with two-parameter power law functions of bone volume fraction (BV/TV) and ash fraction (alpha) of the form y = a(BV/TV)(b) alpha(c) (where y is either ultimate strength or elastic modulus). We derived an expression for bone volume fraction as a function of apparent density and ash fraction to perform a new analysis of data presented by Keller in 1994. Exponents b and c for the prediction of bone strength were found to be 1.92 +/- 0.02 and 2.79 +/- 0.09 (mean +/- SE), respectively, with r(2) = 0.97. The value of b was found to be consistent with that found previously, whereas the value of c was lower than values previously reported. For the prediction of elastic modulus we found b and c to be 2.58 +/- 0.02 and 2.74 +/- 0.13, respectively, with r(2) = 0.97. The exponent related to ash fraction was typically larger than that associated with bone volume fraction, suggesting that a change in mineral content will, in general, generate a larger change in bone strength and stiffness than a similar change in bone volume fraction. These findings are important for interpreting the results of antiresorptive drug treatments that can cause changes in both ash and bone volume fraction.

Biomechanical Phenomena↗

The effect of hyperbaric oxygen treatment on bone tissue reactions to c.p. titanium implants placed in free autogenous bone grafts. A histomorphometric study in the rabbit mandible.

This study aimed to investigate the effect of hyperbaric oxygen (HBO) therapy on the tissue reactions to commercially pure (c.p.) titanium implants placed in free autogenous bone graft by a 1-stage procedure. Eighty c.p. titanium implants were placed in the bone grafted from iliac crest to bilateral mandible of 40 Japanese white rabbits without tapping. Twenty rabbits underwent daily a HBO treatment for 60 min under 2.4 ATA during 20 consecutive days and the other untreated 20 rabbits served as controls. The implants with surrounding bone tissue were retrieved 20, 30, 60, 90 and 120 days after surgery, fixated, dehydrated and embedded in resin. About 20 microns thick ground sections were prepared prior to microscopical observations. The bone area and the bone-to-implant contact inside the threads were calculated separately in the grafted bone and in the host bone for each implant. After 30 and up to 120 days, the HBO treated group showed more bone-to-implant contacts in the grafted bone as compared to the non-HBO treated group. In the host bone there were no differences observed between HBO and non-HBO treated groups. This study indicated that HBO treatment was beneficial for the tissue incorporation of c.p. titanium implants when placed immediately in free autogenous bone grafts.

Animals↗

Plasma levels of bone Gla-protein reflect bone formation in patients on chronic maintenance dialysis.

Predictive value of plasma levels of bone Gla-protein (BGP) for bone histology was evaluated in 30 chronically dialyzed patients. All patients underwent bone biopsies and serum biochemical parameters, including BGP, parathyroid hormone, and alkaline phosphatase; calcium and phosphate were measured at the time of biopsy. Bone histology showed renal osteodystrophy with low bone turnover and osteomalacia (LT-ROD) in 13 patients, and renal osteodystrophy with high bone turnover and prevailing hyperparathyroid bone disease (HT-ROD) in 17 patients. Values for BGP were above normal in LT-ROD (47.3 +/- 7.9 vs. 6.8 +/- 0.2 ng/ml) and extremely elevated in HT-ROD (831 +/- 170 ng/ml). Similar differences were not found with the other serum biochemical parameters, even though BGP correlated with parathyroid hormone (r = 0.64) and alkaline phosphatase (r = 0.85). There were significant correlations between BGP and cellular and non-cellular parameters of bone formation (r = 0.73 to 0.91). Weaker or no correlations were found between BGP and histologic parameters of bone, reflecting mainly mineralization or resorption. These correlations and the finding of significant differences in plasma BGP between LT-ROD and HT-ROD indicate that plasma levels of BGP reflect bone formation in uremia and predict underlying bone histology.

Adolescent↗

Cytogenetic-morphologic correlations in aneurysmal bone cyst, giant cell tumor of bone and combined lesions. A report from the CHAMP study group.

Aneurysmal bone cyst and giant cell tumor of bone are relatively rare bone tumors that sometimes coexist. We examined the karyotypes of 3 aneurysmal bone cysts, 12 giant cell tumors, and 3 combined lesions. All aneurysmal bone cysts showed involvement of chromosome segments 17p11-13 and/or 16q22. In addition, in 1 of the 3 giant cell tumors with secondary aneurysmal bone cyst, both chromosome bands were rearranged as well, albeit not in a balanced translocation. Seven out of 12 giant cell tumors were characterized by telomeric associations. One giant cell tumor showed a dup(16)(q13q22), suggesting the presence of a (minor) secondary aneurysmal bone cyst component, despite the absence of histological proof. Our results, combined with literature data further substantiate that segments 16q22 and 17p11-13 are nonrandomly involved in at least some aneurysmal bone cysts, irrespective of subtype (primary, secondary, intra/extraosseous, solid or classic). These findings strongly suggest that some aneurysmal bone cysts are true neoplasms. In addition, telomeric associations are the most frequent chromosomal aberrations in giant cell tumor of bone, the significance of which remains elusive. In combined giant cell tumor/aneurysmal bone cyst each component seems to retain its own karyotypic abnormality.

Adolescent↗

Stanozolol stimulates remodelling of trabecular bone and net formation of bone at the endocortical surface.

1. We studied the mechanism of action of the anabolic steroid, stanozolol, in 23 patients with osteoporosis, using a combination of biochemical and histomorphometric techniques. 2. Treatment with stanozolol (5 mg/day) for 1 year was associated with a marked and significant decrease in the fasting urinary excretion of calcium (P less than 0.01) but not with changes in the serum concentrations of calcium and phosphate, the serum activity of alkaline phosphatase, the renal tubular reabsorption of calcium or the urinary excretion of hydroxyproline. 3. Histological examination of trabecular bone showed an increase in bone turnover and the bone formation rate increased twofold (P less than 0.02). There were no significant changes in bone volume or wall thickness after treatment. Tetracycline labelling was used to discriminate bone structural units completed before and during treatment. Measurements of the wall thickness of those bone structural units formed during treatment showed no significant change. 4. Measurements made on the endocortical surface also showed an increase in bone turnover, but in contrast to trabecular bone, the bone structural units formed at endocortical sites during treatment had a significantly greater wall thickness than those formed before treatment (P less than 0.05). 5. We conclude that stanozolol increases the turnover of trabecular bone and increases the endocortical apposition of bone.

Aged↗

Bone gap healing in the dog using recombinant human bone morphogenetic protein-2.

PURPOSE: This study investigated bone gap healing in a zygomatic arch defect using recombinant human bone morphogenetic protein-2 (rhBMP-2; Genetics Institute, Andover, MA) in an absorbable collagen sponge (ACS) carrier. METHODS: Zygomatic arch osteotomies were completed 15 mm apart and the arch was mobilized in 6 adult female mongrel dogs. The segment was then repositioned laterally 8 to 10 mm and secured with a titanium reconstruction plate. Bone gaps in either the right or left arches received rhBMP-2, with the contralateral side being left empty in 4 animals and the defects received buffer/ACS without rhBMP-2 in 2 animals as controls. Submentovertex radiographs were taken immediately postoperatively and every 4 weeks until killing at 12 weeks. RESULTS: Clinical evaluation indicated no significant differences in the degree of inflammation between the groups. However, the rhBMP-2 sites were found to be firm on palpation, in contrast to a soft tissue defect palpated in the control sites. Radiographic examination showed significant bone formation in all rhBMP-2 grafted sites as early as 4 weeks. The radiopacity of the bone continued to increase over the time of this study. Five of six control sites did not show bone formation through the course of this study. In addition to lack of bone formation, 5 of 6 control sites showed collapse of the repositioned arch. All arches in the rhBMP-2 sites remained in their lateral position and formed bone in the gaps. In 2 animals, bone formation moderately exceeded the confines of the gap, and in 2 animals excessive bone formation occurred. CONCLUSIONS: This study confirms that rhBMP-2 has the potential to be used to stimulate bone gap healing in the craniofacial complex.

Animals↗

The complex of recombinant human insulin-like growth factor-I (rhIGF-I) and its binding protein-5 (IGFBP-5) induces local bone formation in murine calvariae and in rat cortical bone after local or systemic administration.

The influence of recombinant human insulin-like growth factor-I (rhIGF-I), its binding protein-5 (IGFBP-5) or their equimolar complexes on calvarial osteogenesis was investigated by quantitative radiography and histomorphometry after local administration to adult mice or mature rats. The systemic effects of these proteins were investigated in aged Sprague-Dawley rats with regard to their ability to prevent or restore bone mass in ovariectomy induced osteopenia as assessed by radiography, dual-energy X-ray absorptiometry (DEXA) analyses, peripheral computerized tomography (pQCT) and mineral analyses after daily s.c. administration for 3 or 8 weeks following a bone depletion period of 8 weeks. Bone mass of murine calvariae was significantly increased in a dose-dependent manner by the complex 7 days after discontinuation of local administration for 19 days in mice, whereas IGF-I alone expressed only weak effects. IGFBP-5 alone was ineffective in this respect. In the same model, only the complex had a weak osteogenetic potential in 7 week or 5 month old rats. Systemic long-term treatment with the complex of rhIGF-I/IGFBP-5 (2.0/7.6 mg/kg/day, s.c.) for 8 weeks resulted in significantly increased cortical thickness, area and mineral density in femoral midshaft or tibial metaphysis suggesting periosteal bone formation. This was obviously related to increased muscle strength since these effects were parallelled by increased body weight. No effect on trabecular bone occurred as demonstrated by site-specific analyses (vertebrae, proximal tibia) using DEXA, pQCT and radiography. This selective action of rhIGF-I/IGFBP-5 on periosteal bone formation is unique for an IGFBP. Femoral ash and calcium content, both corrected for tissue volume, increased slightly. However, when the increase in cortical thickness and bone mass was corrected for bone size, the effects are nearly abolished, suggesting an additional effect of bone growth. This potential deserves further evaluation in order to differentiate between effects on cortical bone via muscle strength and lack of efficacy on trabecular bone balance.

Age Factors↗

Radiography and bone scintigraphy in bone marrow transplant multiple myeloma patients.

PURPOSE: To compare conventional radiography and bone scintigraphy in relation to clinical outcome in bone marrow transplant multiple myeloma patients. MATERIAL AND METHODS: A total of 70 radiographies and 70 bone scintigraphies were compared in 35 patients. RESULTS: The skull, the extremities, the iliac and public bones were better assessed with radiography. For new vertebral lesions and for lesions in the ribs and sternum, bone scintigraphy proved superior. For the sacrum, the methods were equal. When bone scintigraphy was used as a complement to radiography, 4% more pathological sites were found. No patient had both a normal radiography and a pathological bone scintigraphy, but 5 patients had both a normal bone scintigraphy and a pathological radiography. The results of the radiological examinations did not always correlate with the clinician's grading of the patient's disease. The radiological examinations had no prognostic value for the 7 patients examined on several occasions. CONCLUSION: The ability of conventional radiography and bone scintigraphy to disclose myeloma lesions varies, depending on location and size of the lesions. Radiography should remain the primary examination modality also for bone marrow transplant multiple myeloma patients. Bone scintigraphy can serve as a complement for investigating unexplained pain, e.g. caused by lesions in vertebrae or ribs.

Adult↗

Laminin, VEGF, and bone matrix protein expression in uroepithelial bone induction--a canine model.

A biological and embryological bone induction from epithelial-mesenchymal cell interactions has been noticed in some developing tissues. However, the mechanism for bone formation induced by the epithelial-mesenchymal cell interactions is not clear. The aim of our study was to reveal the role of laminin, vascular endothelial growth factor (VEGF), and bone matrix proteins in mesenchymal cell differentiation during uroepithelial bone induction using a well-established canine model. In this model, a myoperitoneal muscle flap from the abdominal rectus sheath was transplanted into the bladder wall. After 6 weeks, the bladder samples were removed and assessed by histology and immunohistochemistry. This study demonstrated that bone formation occurred in two different directions with two distinct mechanisms. We noted that bone-forming cells in two types of bone formation derived from mesenchymal stem cell differentiation induced either from uroepithelium or bone autoinduction. Laminin was only expressed in peripheral regions of uroepithelium bone formation. Type II collagen was expressed both intracellularly and extracellularly around hypertrophic chondrocytes, whereas VEGF was mostly expressed in proliferating chondrocytes. This study indicates that components in basement membrane like laminin play a role in transitional epithelium-induced differentiation of mesenchymal cells to chondrocytes in muscle tissue. The sequential expression of bone matrix proteins by differentiated osteogenetic cells indicates a subsequent sequence of bone autoinduction.

Animals↗

Tissue-engineered bone repair of goat-femur defects with osteogenically induced bone marrow stromal cells.

Tissue engineering can generate bone tissue and has been shown to provide a better means of repairing weight-bearing bone defect. Previous studies, however, have heretofore been limited to the use of nonosteogenically induced bone marrow stromal cells (BMSCs) or the application of slow-degradation scaffolds. In this study, weight-bearing bone was engineered using osteogenically induced BMSCs. In addition, coral was used as a scaffold material, due to its proper degradation rate for the engineering and repair of a goat femur defect. A 25 mm long defect was created at the middle of the right femur in each of 10 goats. The rates of defect repair were compared in an experimental group of ten goats receiving implants containing osteogenically induced BMSCs and in the control group of goats (n = 10) receiving just coral cylinders. In the experimental group, bony union was observed by radiographic and gross view at 4 months, and engineered bone was further remodeled into newly formed cortexed bone at 8 months. There was increased gray density of radiographic rays in the repaired area, which was significantly different (p < 0.05) from that of the control group. H&E staining demonstrated that trabecular bone was formed at 4 months. Moreover, irregular osteon was observed at 8 months. Most importantly, the tissue-engineered bone segment revealed a similarity to the left-side normal femur in terms of bend load strength and bend rigidity, showing no significant difference (p > 0.05). In contrast, the coral cylinders of the control group showed no bone formation. Furthermore, almost complete resorption of the carrier had occurred, being evident at 2 months in the control group. H&E staining demonstrated that a small amount of residual coral particle was surrounded by fibrous tissue at 4 months whereas the residues disappeared at 8 months. Based on these results, we conclude that engineered bone from osteogenically induced BMSCs and coral can ideally heal critical-sized segmental bone defects in the weight-bearing area of goats.

Animals↗

Longitudinal changes in bone metabolism and bone mineral content in children with celiac disease during consumption of a gluten-free diet.

BACKGROUND: A gluten-free diet (GFD) rapidly corrects the bone mineral deficit of children with untreated celiac disease. The mechanisms underlying such changes are still poorly understood. OBJECTIVE: In a longitudinal study, we monitored changes in bone metabolism during consumption of a GFD. DESIGN: We studied 22 white patients with celiac disease (11 girls) aged 10.5 +/- 1.0 y at the time of diagnosis. We compared bone metabolism and bone mass values in these patients with those in 428 healthy white children aged 11.3 +/- 0.2 y. Bone-specific alkaline phosphatase (a bone formation index) and N-terminal telopeptide of type I collagen (NTx; a bone resorption marker) were measured at the time of diagnosis and after 2, 6, and 12 mo of the GFD. Bone mineral content was measured at the lumbar spine and for the whole skeleton. RESULTS: The bone mineral content of patients was significantly lower than that of control subjects at the time of diagnosis but not after 1 y of the GFD. Serum bone-specific alkaline phosphatase concentrations of patients were significantly lower than those of control subjects at the time of diagnosis (P = 0.0064) and increased gradually and significantly during the GFD (ANOVA F = 4.71; P = 0.024). Conversely, patients with untreated disease had significantly higher urinary concentrations of NTx than did healthy control subjects (P < 0.0001). Urinary concentrations of NTx were not significantly affected by treatment (P = 0.37). CONCLUSIONS: The rate of bone metabolism is altered in children with untreated celiac disease, and these alterations may be the cause of osteopathy. Remarkable changes occur after the initiation of a GFD, and they result in a more balanced equilibrium.

Alkaline Phosphatase↗

Bone tissue engineering: treatment of cranial bone defects in rabbits using self-reinforced poly-L,D-lactide 96/4 sheets.

This study is one of a series in which the authors evaluate various absorbable sheets to guide bone regeneration in cranial bone defects. The aim was to evaluate the use of self-reinforced poly-L,D-lactide 96/4 (SR-PLA96) sheets for cranial bone tissue engineering in experimental defects in rabbits. Square defects of 10 x 10 mm were created in the right parietal bone. SR-PLA96 implants (15 x 15 mm) were used to cover these defects in 12 New Zealand White rabbits. Similar defects were created in the left parietal bone, but no sheets were used (controls). The rabbits were killed after 6, 24, or 48 weeks. Histology and histomorphometry were used to evaluate healing of the defects. Defects covered with SR-PLA96 sheets showed more abundant bone formation than control (non-covered) defects. At 6 weeks, the defects were occupied mainly by fibrous tissue. At 24 weeks, healing with bone formation was more obvious in the covered defects. At 48 weeks, bone completely bridged defects covered with SR-PLA96 sheets, and incomplete bridging was seen in non-covered control defects. Hence, bone tissue engineering in experimental cranial bone defects in rabbits can be achieved using SR-PLA96 sheets to guide bone regeneration.

Absorbable Implants↗

Diagnostic value of TI-201 and three-phase bone scintigraphy for bone and soft-tissue tumors.

PURPOSE: Although TI-201 is highly sensitive for detecting bone and soft-tissue tumors, its uptake is not specific for malignant lesions. This study assessed the differentiation of malignant and benign lesions and evaluated the sensitivity, specificity, and accuracy of TI-201 imaging and three-phase bone scans. MATERIALS AND METHODS: Forty bone and soft-tissue tumors (16 malignant and 24 benign) were evaluated. TI-201 static images were acquired 10 minutes (early) and 2 hours (delayed) after injection of the radionuclide. Within 14 days, three-phase bone scintigraphy was performed using Tc-99m HMDP with the patient in the same position. The count ratio of the lesion compared with the normal contralateral or adjacent site (L:N ratio) was measured. RESULTS: With TI-201 scintigraphy, mean (+/- SD) values of early and delayed L:N ratios were 3.36 +/- 1.25 and 2.88 +/- 1.20, respectively, in malignant lesions; and 1.88 +/- 1.14 and 1.48 +/- 0.76, respectively, in benign lesions. TI-201 accumulation in benign lesions was significantly less than that of malignancies on early and delayed images. However, an overlap of both ratios between malignant and benign lesions was seen. No such significance was detected on three-phase bone scintigraphy (L:N ratios of malignant and benign tumors were 2.57 +/- 1.22 and 2.24 +/- 2.11, respectively, for blood flow imaging; 2.41 +/- 0.78 and 2.26 +/- 1.54, respectively, for blood pool imaging; and 2.80 +/- 2.10 and 2.89 +/- 4.55, respectively, for bone imaging). When we assumed that the tumor was malignant when the delayed TI-201 L:N ratio exceeded the blood pool phase L:N ratio with bone scintigraphy, the sensitivity rate was 81%, specificity rate was 100%, and accuracy rate was 93%. CONCLUSIONS: TI-201 imaging for bone and soft-tissue tumors was better than three-phase bone scintigraphy alone but was not good enough to clearly differentiate malignant lesions from benign ones. TI-201 scintigraphy, performed in combination with three-phase bone scintigraphy, may be superior to either one of the two imaging procedures alone for bone and soft-tissue tumor diagnosis.

Adolescent↗