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Histomorphometric evaluation of bone regeneration using allogeneic and alloplastic bone substitutes.

PURPOSE: The purpose of this investigation was to assess bone regeneration in critical sized defects in the rabbit calvarium using allogeneic and alloplastic bone substitutes. MATERIALS AND METHODS: Thirty New Zealand White rabbits were divided into 3 groups of 10 animals each. Bilateral 15 mm x 17 mm calvarial defects were made in the parietal bones of each animal. Group 1 had demineralized bone matrix (DBM) gel placed in one defect, while the other defect was left unfilled and served as the control. Group 2 had one defect filled with calcium hydroxide (CaOH)-treated DBM gel and the other defect filled with DBM gel. Group 3, the calcium-phosphate cement group, had Norian CRS (Norian Corp, Cupertino, CA) placed on one side and Bone Source (Howmedica Leibinger, Dallas, TX) placed on the contralateral side. Five animals in each group were killed at 6 and 12 weeks. Data analysis included qualitative assessment of the calvarial specimens and radiographic evaluation. Histomorphometric analysis was used to quantify the amount of new bone within the defects. RESULTS: Histomorphometric analysis showed that DBM gel-treated defects had significantly more new bone at 12 weeks compared with all other groups. There was no significant difference between defects filled with CaOH-treated DBM gel and those filled with DBM gel at 12 weeks. In group 3, Norian CRS- and Bone Source-treated defects were not statistically different from the unfilled controls. CONCLUSION: DBM gel was an effective allogeneic bone substitute that showed reliable osseous healing of critical size defects in the rabbit calvarium. The addition of CaOH to DBM gel did not significantly improve the bone regenerative capacity of the DBM gel. Both Norian CRS and Bone Source did not promote bone regeneration in this animal model.

Animals↗

Healing of autogenous intramembranous bone in the presence and absence of homologous demineralized intramembranous bone.

This study was designed to examine the osteogenecity of demineralized bone matrix (DBM) prepared from intramembranous (IM) bone and to quantitatively assess the amount of new bone formed by IM autogenous bone grafts with or without DBM(IM). Forty-two defects were created in 42 New Zealand White rabbits. Twenty-one defects were grafted with IM bone alone, and the other 21 defects were grafted with composite IM-DBM(IM). Eleven rabbits, 22 defects were used as controls, where 11 defects were left empty (passive control) and the other 11 defects were filled with rabbit skin collagen (active control). Tissues were retrieved on days 1, 2, 3, 4, 5, 6, 7, and 14 for qualitative and quantitative analysis. Cells involved in the healing of composite IM and IM-DBM(IM) bone grafts were identified. No cartilage cells were detected during the healing of either grafts. Appearance of small blood vessels into the newly formed matrix was seen on day 5 in IM bone grafts and on day 4 in composite IM-DBM(IM) bone graft. Quantitative analysis was performed by means of image analysis on 100 sections of tissues retrieved after 14 days. Approximately 204% more new bone was formed in defects grafted with composite IM-DBM(IM) than in those grafted with IM bone alone (P <.0001). No bone was formed across the defects in either active or passive controls. In conclusion, DBM(IM) significantly increases the osteogenicity of IM bone grafts.

Analysis of Variance↗

Bone marrow imaging of bone marrow transplanted multiple myeloma patients.

Eighteen bone marrow transplanted multiple myeloma patients had imaging studies on 24 occasions with radiography as well as bone and bone marrow scintigraphy within 2 months. Twelve of the radionuclide bone marrow studies were performed with Tc-99m human serum albumin colloid and 12 were performed with a Tc-99m tagged monoclonal antigranulocyte antibody. The total detection rate of bone marrow lesions increased by 5% when the findings on bone marrow scintigraphy were combined with the findings and at radiography bone scintigraphy. For lesions in the spine and sacrum, the increase was 25% and 33% respectively, including patients with focal radiotherapy. Peripheral red bone marrow expansion was noted in 17 patients. In a comparison of Mab and Tc-99m HSA colloid imaging, Mab resulted in a higher bone marrow to soft tissue uptake and to a much smaller part of the skeleton being obscured by liver and spleen uptake. It is concluded that bone marrow imaging is valuable for showing red bone marrow distribution. It thereby shows possible sites for malignant lesions; it also shows that Mab imaging is superior to Tc-99m HSA colloid imaging in bone marrow transplanted multiple myeloma patients.

Adult↗

Porcine fetal enamel matrix derivative enhances bone formation induced by demineralized freeze dried bone allograft in vivo.

BACKGROUND: Embryonic enamel matrix proteins are involved in the formation of acellular cementum during development of the periodontal attachment apparatus, suggesting that these proteins might be used clinically to promote periodontal regeneration. At present, it is unknown if these proteins are osteoinductive, osteoconductive, or osteopromotive. To address this question, we examined the ability of a commercially prepared embryonic porcine enamel matrix derivative to induce new bone formation in nude mouse calf muscle, or to enhance the bone induction ability of a demineralized freeze-dried bone allograft (DFDBA). METHODS: Porcine fetal enamel matrix derivative (EMD) was implanted bilaterally in the calf muscle of 4 male Nu/Nu mice per treatment group (N = 8 implants): 2 mg EMD alone; 4 mg EMD alone; inactive human DFDBA alone; inactive DFDBA + 2 mg EMD; inactive DFDBA + 4 mg EMD; active DFDBA alone; active DFDBA + 2 mg EMD; and active DFDBA + 4 mg EMD. Implants were harvested after 56 days and examined histologically for bone induction using a semi-quantitative score and histomorphometrically for area of new bone, cortical bone, bone marrow, and residual DFDBA. RESULTS: Implants containing inactive DFDBA, 2 mg EMD, 4 mg EMD, and inactive DFDBA + 2 or 4 mg EMD did not induce new bone. Active DFDBA and active DFDBA + 2 mg EMD induced new bone to a similar extent. In contrast, active DFDBA + 4 mg EMD resulted in enhanced bone induction, area of new bone, and cortical bone. Residual DFDBA was also increased in this group. CONCLUSIONS: EMD is not osteoinductive. However, it is osteopromotive, due in part to its osteoconductive properties, but a threshold concentration is required.

Animals↗

Characterization of bone defect repair in young and aged rat femur induced by xenogenic demineralized bone matrix.

BACKGROUND: The osteoinductive effect of some biomaterials could be affected by those systemic conditions typical of old age. The aim of the present paper was to assess the effects of age on the healing of bone defects treated with demineralized bone matrix (DBM). METHODS: The study was conducted in young (3 month old) and aged (18 month old) rats to assess the efficacy of DBM in the treatment of osseous defects in bone with limited repair capacities. A standard bone defect was created in the distal femoral condyles of male Wistar rats: the left condyle was filled with rabbit DBM granules, while the right condyle was left empty (control). Histological and microhardness analyses were performed at 30 and 45 days after implant surgery. RESULTS: After implantation of xenogenic DBM, bone healing areas of the aged and young groups showed a significant increase in the formation of newly mineralized bone relative to controls. Measurements of trabecular thickness on day 45 revealed no differences between newly formed and preexisting bone in the young group, while control values were lower. Microhardness measurements demonstrated that newly mineralized bone, either induced by DBM or not, and preexisting bone were comparable in terms of trabecular hardness after 45 days. CONCLUSIONS: In conclusion, xenogenic DBM seems to be effective in bone defect healing, since it increases mineralized tissue volume. In both DBM-filled and empty sites, age seems to have a detrimental effect on the volume of new bone formation but no influence on bone maturation.

Aging↗

Bone loss and bone turnover in diabetes.

There have been conflicting reports about the effect of diabetes on bone density. In 1978, we studied 109 patients, 46 with type I and 63 with type II diabetes; approximately 12 years later we restudied 35 of the 66 surviving patients. In the original study, radial bone density did not differ significantly between patients with either type of diabetes but was significantly lower than in nondiabetic control subjects. In eight osteopenic patients, bone formation rate and other histological indexes of osteoblast recruitment and function were markedly depressed compared with those in nondiabetic control subjects. In patients remeasured approximately 2.5 years (41 patients) and approximately 12.5 years (35 patients) after baseline, bone loss had continued at the expected rate in patients with type I diabetes, with maintenance of the same deficit, but was slower than expected in patients with type II diabetes, such that the initial deficit had been completely corrected. In six of the eight patients who had undergone bone biopsy, one with type I and five with type II diabetes, the mean bone mineral density z-score of the spine and femoral neck approximately 12 years later was > 0 and in one subject was significantly higher than normal at both sites. Based on these data and on previous studies, we propose that in patients with diabetes, low bone formation retards bone accumulation during growth, metabolic effects of poor glycemic control lead to increased bone resorption and bone loss in young adults, and low bone turnover retards age-related bone loss.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Recent advances in bone biology provide insight into the pathogenesis of bone diseases.

Bone is modeled during embryonic development by endochondral and membranous ossification and is continuously remodeled thereafter under the influence of local and systemic factors to provide structural support and assist in calcium homeostasis. Recent studies of knockout and transgenic mice have increased understanding of the regulation of bone modeling during development and of remodeling of mature bone and have shed new light on the pathogenesis of a number of bone disorders. For example, fibroblast growth factor receptor-3, parathyroid hormone-related protein, and tartrate-resistant acid phosphatase affect the function of chondrocytes during endochondral ossification (the latter two by regulating their life spans and thus growth plate thickness and bone length). Some ubiquitously expressed genes seem unexpectedly to have unique functions that are largely confined to bone cells: M-CSF, C-Fos, PU.1, and NF-kappaB are required for osteoclast formation, whereas c-Src and Mitf (microphthalmia transcription factor) are required for osteoclast activity after the cells have formed. Knockout of these genes results in osteopetrosis, a disorder characterized by persistence in marrow cavities of unresorbed osteocartilaginous matrix and, as in some affected humans, by increased mortality. Some proteins seem to act as negative regulators of bone cell function, for example osteoprotegerin (a soluble TNF receptor) in osteoclasts; osteocalcin, bone sialoprotein, and 5-lipoxygenase in osteoblasts. Regulation of osteoclast life span may be an important mechanism by which estrogen and bisphosphonates prevent bone loss in conditions characterized by increased bone resorption, such as postmenopausal osteoporosis. The unique requirement of bone cells for certain gene products raises the possibility that these cells may have specific responses to inhibitory or stimulatory agents, and that signaling molecules in these response pathways could be specific targets for novel therapies to treat or prevent common bone diseases.

Animals↗

An experimental study on rhBMP-2 composite bone substitute for repairing craniomaxillary bone defects.

OBJECTIVE: To measure bone regenerative effects in animal calvarial or mandibular critical-size defects using recombinant human bone morphogenetic protein-2 (rhBMP-2) combined with four selected carriers. MATERIALS AND METHODS: The composite bone grafts were obtained by combining rhBMP-2 with chitin, coral, coral-based porous HA (CHA), and xenogeneic cancellous bone, respectively. These materials were implanted on the calvarial or mandibular defect of rabbits and on the calvarial defect of rats. Each carrier material was also studied as a control group. The animals were examined 2, 4, 8, and 12 weeks after implantation by radiography, histology (under light microscope and scanning electron microscope), immunohistochemistry, and biomechanics. RESULTS: The results showed that the composite graft was absorbed gradually after it was implanted into the defect, during which time new bone was formed within the combined material in the defect site; the amount of new bone increased as time elapsed. At 12 weeks the composite was replaced completely by bone except in the CHA group. In contrast, a large amount of fibrous tissue, and little new bone, formed on the area of the bone defect when the carrier material alone was implanted. CONCLUSIONS: All materials tested seem to be suitable carriers for rhBMP-2, which plays a very important role in new bone formation. These composite bone substitutes may be ideal materials for repairing various bone defects in the craniomaxillofacial region.

Animals↗

Enhancement of bone regeneration and graft material resorption using surface-modified bioactive glass in cortical and human maxillary cystic bone defects.

PURPOSE: Bioactive glass bonds to bone through a calcium phosphate layer that mimics the structure of the mineral phase of bone. Formation of this layer is inhibited in the presence of serum protein. The authors hypothesize that creation of a calcium phosphate layer on the surface of bioactive glass before implantation will enhance bone regeneration and graft material resorption in bone defects. MATERIALS AND METHODS: Bioactive glass particles covered with a layer of amorphous calcium phosphate (BG-ACP), bioactive glass particles covered with a layer of hydroxycarbonate apatite (BG-HCA), and unmodified bioactive glass particles (as a control) were prepared and implanted in cortical bone defects in dogs or in human maxillary cavities. Ungrafted sites were also used as a control. RESULTS: Histomorphometric analyses showed significantly more bone tissue regeneration and graft material resorption in the defects filled with BG-HCA than in those filled with BG-ACP or unmodified bioactive glass (P < .0001). Moreover, measurements of radiographic density of the grafted areas suggested a higher rate of bone regeneration in defects filled with the modified bioactive glass than in those filled with unmodified bioactive glass or in the ungrafted control. Bone formation was significantly greater in defects filled with unmodified bioactive glass particles than in ungrafted defects. DISCUSSION: The enhancement of bone regeneration could be explained by the ability of the apatite layer to facilitate bone adsorption and enhance calcium release, which stimulates osteoblast differentiation and bone formation. CONCLUSION: Results of both the clinical and animal studies suggest that the use of surface-modified bioactive glass covered with a hydroxycarbonate apatite layer has the potential to accelerate bone formation and graft material resorption better than unmodified bioactive glass.

Adsorption↗

Quantitative bone histology in 84 normal American subjects. Micromorphometric analysis and evaluation of variance in iliac bone.

Quantitative bone histology was done in undecalcified sections of iliac crest bone specimens obtained from 84 normal American individuals. Samples were obtained within 12 h after death in a vertical and horizontal manner from both the right and left iliac crests. In addition to the determination of normal values of micromophometric parameters of bone in these healthy American subjects, the following studies were carried out: (a) comparison of variance of micromorphometric parameters of bone obtained from the right versus left iliac bone (40 pairs), (b) comparison of micromorphometric parameters of bone obtained in a vertical versus horizontal manner (12 pairs), (c) evaluation of variance with increasing distance from the compact zone in bone samples obtained in a vertical manner (44 pairs), (d) analysis of variation between bone samples obtained more anteriorly versus posteriorly along the iliac crest (N = 40), (e) comparison of differences in micromorphometric parameters obtained from age-matched men versus premenopausal women (N = 12), and (f) plotting of histograms for assessment of distribution of micromorphometric parameters. The results show that histomorphometric data of bone cannot be easily compared when different techniques are employed for obtaining bone samples. Sampling variations are kept smaller when bone specimens are obtained in a vertical manner. Anterior/posterior variation does not cause major sampling error. If ranges of variation are taken into account, quantitative bone histology is a valuable tool for assessment of bone structure and bone cells.

Adolescent↗

Expression of bone morphogenetic protein-4 mRNA during the process of bone formation in embryogenesis and fracture repair.

Bone morphogenetic protein-4 is a potent inducer of ectopic bone and cartilage formation in vivo. Expression of the bone morphogenetic protein-4 gene has been detected in bone cells during fracture repair but not in normal adult bone cells. To examine whether the gene is expressed by bone cells during embryonic development, in situ hybridization and reverse transcription polymerase chain reaction methods were used to detect murine bone morphogenetic protein-4 specific complementary DNA in murine developmental bone tissues. Bone morphogenetic protein-4 messenger RNA was detected in the cells of various developing bone tissues, but it was not detected in these tissues after birth. Combined with previous reports, our findings indicate that the bone morphogenetic protein-4 gene is expressed during embryogenesis and bone repair and suggest that its product may be a potent bone-forming factor in bone development and fracture repair.

Journal Article↗

The assessment of bone formation and bone resorption in osteoporosis: a comparison between tetracycline-based iliac histomorphometry and whole body 85Sr kinetics.

Bone formation and resorption have been measured in patients with idiopathic osteoporosis by histomorphometry of 7.5-mm trephine biopsies and in the whole body by 85Sr radiotracer methodology and calcium balances. The studies were synchronized and most were preceded by double in vivo tetracycline labeling. Correlations between histological and kinetic bone formation indices were better when better when based on the extent of double tetracycline labels than on measurements of osteoid by visible light microscopy. Correction of the kinetic data for long-term exchange, using 5 months' serial whole body counting of retained 85Sr, improved the fit of the kinetic to the histological data. A statistical analysis of the measurement uncertainties showed that the residual scatter in the best correlations (between exchange-corrected bone formation rates and double-labeled osteoid surface indices) could be attributed to measurement imprecision alone. The exchange-corrected resorption rate correlated fairly well with iliac trabecular resorption surfaces, and using a volume referent rather than a surface referent for the histological index improved the statistical fit when patients with therapeutically accelerated bone turnover were included. A much better correlation was obtained by including osteoid volume acting as an independent predictor of bone resorption in a bivariate regression with a resorption surface index. The residual errors could then be accounted for by known measurement uncertainties. Whereas osteoid taking a double label closely predicted the kinetic rate of bone formation, further analysis suggested that osteoid that took no label or a single label was more closely related to bone resorption, presumably as a secondary result of the coupling of bone formation to bone resorption. The idea that continued bone loss in some patients is associated with defective osteoblastic bone formation is supported by the low rates found in some patients by both techniques. Heuristically these studies validate both in vivo tetracycline labeling for dynamic histomorphometry and corrections for long-term exchange in kinetic studies of bone formation, providing a quantitative framework for the design and analysis of future studies of bone remodeling in the osteoporoses.

Adult↗

A study of the mechanical strength of long bone defects treated with various bone autograft substitutes: an experimental investigation in the rabbit.

This study was designed to determine which of several bone grafting materials would be the most efficacious substitute for autogenous bone graft in the treatment of segmental long bone defects. The experimental model was a 1-cm defect in the rabbit ulna. The control group had nothing implanted in the defect. The six grafts tested were: (a) autogenous iliac crest bone, (b) autogenous cortical bone (ulna), (c) hydroxylapatite, (d) hydroxylapatite-demineralized bone matrix (allograft) composite graft, (e) freeze-dried bone (allograft), and (f) demineralized bone matrix (allograft). At 6 weeks postoperatively, the ulnas were harvested, examined radiographically, and tested mechanically in torsion. The radiographic examination proved to be of little value because some materials were radiodense at the time of implantation. The rates (percentage) of union, torques at failure, and energy to failure values were statistically significantly higher than control for all groups except hydroxylapatite. We concluded that demineralized bone matrix and hydroxylapatite-demineralized bone matrix composite graft compare favorably with cortical replacement (autograft) in mechanical strength and rate of union and therefore may be satisfactory substitutes for bone grafting. Freeze-dried bone did not appear to be as satisfactory because of its low mean energy to failure, but statistical analysis failed to confirm this opinion. Hydroxylapatite graft, when used alone, does not appear to be a suitable material for grafting segmental bone defects.

Animals↗

Histopathologic analysis of bone marrow and bone metastasis in murine neuroblastoma.

To elucidate the development of bone metastasis in human neuroblastoma, bone marrow and bone metastases were analysed histologically in a hematogeneous metastasis model of murine neuroblastoma. The bone marrow metastasis occurred initially in the bone marrow sinusoid where tumor cells adhered and extravasated to bone marrow parenchyma, resulting in the formation of nodular lesions in the medullary cavity. The nodular lesions eventually progressed to diffuse lesions segmentally occupying the medullary cavity. During the establishment of the diffuse lesions, tumor cells invaded cancellous bone and/or bone cortex, resulting in bone metastasis. Such nodular or diffuse bone marrow metastatic lesions occurred sporadically in a variety of bones. To improve the results of treatment for neuroblastoma, the characteristics of the bone marrow and the bone metastases demonstrated in this study should be considered in the diagnosis and treatment of this disease.

Animals↗

Enhancement of crude bone morphogenetic protein-induced new bone formation and normalization of endochondral ossification by bisphosphonate treatment in osteoprotegerin-deficient mice.

Osteoprotegerin (OPG) is a novel secreted member of the tumor necrosis factor receptor family which plays a crucial role in negative regulation of osteoclastic bone resorption. We investigated both the quantity and quality of heterotopic new bone induced by crude bone morphogenetic protein (BMP) as a means of examining bone metabolism by bisphosphonate administration in OPG-/- mice. Four weeks after implantation of crude BMP, the volume of heterotopic new bone in OPG-/- mice without alendronate was significantly less than in wild-type (WT) mice. Alendronate treatment of OPG-/- mice resulted in enhancement of the volume of heterotopic new bone. Histological findings revealed that WT mice showed normal bone formation with persistent cartilage that was interspersed with islands of bone. In contrast, the cartilage was replaced by trabecular bone and bone marrow adipocytes in OPG-/- mice without alendronate. However, some cartilage was still present in OPG-/- mice with alendronate compared to those without alendronate. All bone formation-related parameters and bone resorption-related parameters were significantly lower in OPG-/- mice with alendronate than in those without alendronate. These findings suggest that in stimulated osteoclastogenesis without OPG, osteoinductive activity induced by crude BMP is inhibited and endochondral ossification induced by crude BMP is accelerated. On the other hand, alendronate treatment of OPG-/- mice caused osteoinductive activity induced by crude BMP to increase and endochondral ossification induced by crude BMP to be decelerated. In conclusion, inhibition of stimulated osteoclastogenesis results in the enhancement of new bone formation and normalization of endochondral ossification.

Alendronate↗

Lumbar vertebral cancellous bone is capable of responding to PGE2 treatment by stimulating both modeling and remodeling-dependent bone gain in aged male rats.

Previously we found that PGE2 3 mg/kg in 20-month-old male rats induced massive bone formation mainly by modeling dependent bone gain in cortical bone. It is not known whether cancellous bone will respond similarly; thus, we evaluated the effect of PGE2 on cancellous bone of the same aged rats. Thirty-four 20-month-old Wistar male rats were given PGE2 (3 mg/kg/day) or vehicle subcutaneously for 10 and 30 days. Double fluorescent labels were injected 9 and 2 days prior to the sacrifice. Histomorphometry was performed on 1% toluidine blue stained and unstained sagittal sections of lumbar vertebral bodies. The results demonstrated that 10-day PGE2 treatment increased osteoprogenitor cells, osteoblasts (x 2-fold), osteoid (x 4.5-fold), woven bone formation (0.04%), and 40% more trabecular area; it stimulated modeling (x 2-fold) and remodeling-dependent (x 1.5-fold) bone formation with increase of mineralization lag time (MLT, x 7.5-fold). Thirty-day treatment sustained increases in osteoblast numbers, modeling and remodeling-dependent bone formation and further stimulated woven bone formation (6.6%), turnover (x 3-fold), and trabecular area and number (x 2-fold). Osteoprogenitor cells were undetectable along with 70% less osteoid area compared with 10-day treatment but still was 1.5-fold higher than aging controls. MLT returned to aging control level. It was concluded that the aged cancellous bone of 20-month-old male Wistar rat retains a capability of responding to the anabolic effect of PGE2. Osteoblastogenesis and enhanced modeling and remodeling-dependent woven or lamellar formation contribute to this anabolic action. Bone formation differed in that the endocortical surface of cortical bone was stimulated mainly by modeling whereas both modeling and remodeling-dependent bone gain were equally stimulated at the trabecular surface of the lumbar vertebral body.

Animals↗

Blood perfusion and remodelling activity in canine tibial diaphysis after filling with a new bone cement compared to bone wax and poly(methyl methacrylate) cement.

Six dogs each had one tibia filled with standard poly(methyl methacrylate) (PMMA) bone cement and the contralateral tibia filled with a new methyl methacrylate-n-decyl methacrylate-isobornyl methacrylate (MMA-DMA-IBMA) bone cement (Boneloc) with lowered polymerization heat and monomer leakage. An additional six dogs each had one tibia filled with MMA-DMA-IBMA and the contralateral tibia filled with bone wax. There was a higher diaphyseal blood flow, measured with a microsphere technique, in the legs filled with MMA-DMA-IBMA than in those filled with PMMA. The wax-filled bones presented higher blood perfusion than those with MMA-DMA-IBMA. We found a tendency towards higher 99mtechnetium-labelled methylene diphosphonate (99mTcMDP) uptake, and autoradiograms revealed a tendency towards larger subperiosteal apposition and more blackening, both at the subperiosteal apposition and the cortex, in the bones filled with new bone cement in the first series, but in wax-filled bone in the second series. It is concluded that the new bone cement, compared to standard acrylic bone cement, seems to inhibit the vascular response and bone remodelling activity less, making earlier remodelling possible. However, the new bone cement still seems to inhibit bone blood perfusion compared to bone wax.

Animals↗

Dose in bone and tissue near bone-tissue interface from electron beam.

This work has quantitatively studied the variation of dose both within bone and in unit density tissue near bone-tissue interfaces. Dose upstream of a bone-tissue interface is increased because of an increase in the backscattered electrons from the bone. The magnitude of this effect was measured using a thin parallel-plate ionization chamber upstream of a polymethyl methacrylate (PMMA)-hard bone interface. The electron backscatter factor (EBF) increased rapidly with bone thickness until a full EBF was achieved. This occurred at approximately 3.5 mm at 2 MeV and 6 mm at 13.1 MeV. The full EBF at the interface ranged from approximately 1.018 at 13.1 MeV to 1.05 at 2 MeV. It was also observed that the EBF had a dependence on the energy spectrum at the interface. The penetration of the backscattered electrons in the upstream direction of PMMA was also measured. The dose penetration fell off rapidly in the upstream direction of the interface. Dose enhancement to unit density tissue in bone was measured for an electron beam by placing thermoluminescent dosimeters (TLDs) in a PMMA-bone-PMMA phantom. The maximum dose enhancement in bone was approximately 7% of the maximum dose in water. However, the pencil-beam algorithm of Hogstrom et al. predicted an increase of only 1%, primarily owing to the inverse-square correction. Film was also used to measure the dose enhancement in bone. The film plane was aligned either perpendicular or parallel to the central axis of the beam. The film data indicated that the maximum dose enhancement in bone was approximately 8% for the former film alignment (which was similarly predicted by the TLD measurements) and 13% for the latter film alignment. These results confirm that the X ray film is not suitable to be irritated "edge on" in an inhomogeneous phantom without making perturbation corrections resulting from the film acting as a long narrow inhomogeneous cavity within the bone. In addition, the results give the radiotherapist a basis for clinical judgment when electron beams are used to treat lesions behind bone or near bony structures. We feel these data enhance the ability to recognize the shortcomings of the current dose calculation algorithm used clinically.

Bone and Bones↗