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Effect of sodium fluoride, calcium carbonate, and vitamin D on the skeleton in multiple myeloma.

Fifteen patients with multiple myeloma were treated with sodium fluoride (50 mg twice daily) plus calcium carbonate (1 g four times daily) or with the same fluoride-calcium dosage plus vitamin D (50,000 U twice weekly). All patients had increased bone formation, as shown by microradiography and videodensitometry. Ten patients had osteosclerosis demonstrated by roentgenograms. Compressive strength of the vertebral bodies was greater among those who received fluoride-calcium than among controls. Densitometry studies were not helpful. Side-effects were minimal and consisted of nausea and fibrositic symptoms. Hypocalcemia occurred less frequently in patients who received vitamin D along with fluoride-calcium. Administration of sodium fluoride and calcium carbonate produces an increase in bone mass and is a useful adjunct treatment for patients with multiple myeloma.

Bone Diseases↗

Influence of treatment with APD-bisphosphonate on the bone lesions in the mouse 5T2 multiple myeloma.

The effects of the treatment of multiple myeloma (MM) with APD-bisphosphonate on bone destruction, the dissemination pattern of the MM, and toxicity for normal and malignant cells were investigated in an animal model, the 5T2 MM. This mouse MM very closely resembles the human disease, including the typical bone lesions. It was demonstrated by radiography, microradiography, and histologic investigation that the treatment of the 5T2 MM with APD-bisphosphonate protected the mice against a loss of bone to a significant extent. It seemed that the treatment with APD not only diminished the bone destruction by the MM but also led to the formation of new bone in already-affected bone tissue. The growth pattern of the MM was not substantially influenced by the treatment, even though there was an indication that APD exerts some cytotoxic effect on the MM cells.

Animals↗

In vivo testing of a new in situ setting beta-tricalcium phosphate cement for osseous reconstruction.

A new in situ setting tricalcium phosphate cement was implanted in 1.5-mm trepanation defects in rat femurs. Empty cavities and autologous bone grafts were used as controls. Cement resorption and new bone formation were evaluated in undecalcified sections with histologic examination, contact microradiographies, radiodensitometry, and scanning electron microscopy after 1 and 3 weeks. The mechanical integrity was tested in a three-point bending test. The amount of new bone formation over time was determined by intravital fluorescence staining. With the in situ setting substance, a good filling of the whole trepanation defect was achieved without leakage of the paste-like cement. Slow resorption of the cement and new bone formation beginning at the edge of the defect were seen after 1 week. After 3 weeks, resorption was advanced and there was ingrowth of new bone, with close contact between cement particles and bone, as shown in histologic sections and with a calcium/phosphorus analysis by quantitative line scans of an electron microanalysis (SEM-EPMA). This new self-hardening cement is bioactive, resorbable, and osteotransductive. It may be usable for the filling of stable defects, such as cysts or benign tumors, or for bone supplementation in revision arthroplasty.

Animals↗

On the functional morphology of the human petrous bone.

In this study the human petrous bone was investigated to find out whether and in what way it is adapted to mechanical stress by inner bone structure. Three normally formed petrous bones were cut in serial sections and examined by means of microradiography and circular polarized light with respect to mineralization, distribution of bone structure, and collagen fiber arrangement over the cross section. It has been shown that the human petrous bone can be divided morphologically into four different bony layers: 1) endosteal; 2) enchrondral ; 3) inner periosteal layers, which together form the labyrinthine capsule and which are characterized by a higher level of mineralization and show no clear indication of bone remodeling; and 4) outer periosteal layer, in which numerous osteons indicate appositional and resorptional growth processes. The collagen fibers in the labyrinthine capsule are arranged in an irregular web-like pattern, whereas in the outer periosteal layer they run predominantly parallel to the surfaces of the petrous bone, probably to minimize the mechanical stress in the form of a tension band. These results support the assumption that in the human petrous bone, the outer periosteal layer is adapted to resorb elastic deformation, whereas the brittle labyrinthine capsule is better adapted to the functions of an auditory and vestibular organ.

Adaptation, Physiological↗

A reexamination of rat ductuli efferentes.

In 33 testes from a random selection of rats a 10% suspension of India ink in normal saline was introduced through the rete testis into the emergent ductuli efferentes. Low-power microscopy and microradiography confirmed the individually independent origin of each ductule. Five ductules were isolated in each of 17 testes, 4 ductules in 6, 6 ductules in 8, and in 2 testes, 7 and 9 ductules, respectively. In six animals minor variations existed as between the right and left testes +/- 1 in 4 and +/- 2 in 2. It is necessary to exercise great caution in the interpretation of results of experimental work on alteration of the ductuli, because of variability between colonies and within strains of rats.

Animals↗

Degradation characteristics of alpha and beta tri-calcium-phosphate (TCP) in minipigs.

In seven Goettingen minipigs 3.5--4.7-ml cancellous bone defects were created in the area of the tibial head on both sides. The defects were filled with alpha-TCP or beta-TCP (tricalciumphosphate). ITI implants (Straumann, Freiburg, Germany) of 3.2 x 12-mm length were inserted into the underlying ceramic substitutes. Two additional pigs were used as control. Within the periods of observation (4, 16, 20, 28, 46, 68, and 86 weeks) fluorescent dyes were applied. Nondecalcified thin-sliced sections were examined by means of light and fluorescence microscopy. In addition microangiography and microradiography were performed. Bony regeneration occurred basally and on the sides of the defect according the angiogenetic reossification pattern. Resorption was due to a hydrolytic and cellular degradation process. After 46 weeks histomorphological evaluation showed an incomplete osseointegration of the simultaneously implanted dental implants. The bone contact surface ratio was lower than 25%. After 86 weeks 95--97% of both alpha- and beta-TCP were resorbed. Ceramic residuals stayed within the newly formed trabeculae thus resisting further degradation until remodeling occurred. Both alpha- and beta-TCP show a comparable degradation process. At the 86-week postoperative point only small residuals of the ceramic can be found. These residuals stay within the newly formed trabeculae, which show a functional orientation. In comparison control defects showed only sparse reossification. The beta-TCP material shows an accelerated degradation mode and has an optimal reactivity with the surrounding tissues. According to the results of this animal experiment both materials can be classified as bone-rebuilding materials.

Animals↗

Tissue ingrowth of Replamineform implants.

The Replamineform process, a new technique for the fabrication of porous hard tissue implant materials which replicates the skeletal configuration of certain marine invertebrates, was used to manufacture 1 cm long by 0.5 cm diam cylinders. The inherent advantages of porous configurations obtained through this process are controlled, uniform pore size, controlled pore-microstructure ratio, and complete interconnection of pores. The specific materials studied were chrome-cobalt-molybdenum alloy, alphaA103, hydroxyapatite prepared by hydrothermal conversion, and the basic (aragonite) CaCO3 skeleton of the coral genus Porities. The implants were placed in the canellous bone of the distal femora and proximal tibiae of adult, mongrel dogs and analyzed at 8 weeks for tissue response and ingrowth. Uniformly, new bone was found to grow into the pores of these materials and become normally mineralized. These findings were determined by microradiography, scanning electron microscopy, electron microprobe analysis, and histology. No evidences of infection, rejection, or encapsulation were seen. In the case of those CaCO3 implants left in place for 1 year, there was almost complete resorption of the cylinders, with both bony trabeculae and unmineralized collagen (presumably osteoid) found at the sites of insertion.

Aluminum↗

Two-year biocompatibility study of ORNL graphite.

A new grade of graphite-isotropic, fine-grained, and of superior strength-has been produced at the Oak Ridge National Laboratory. The possibility of using this material in orthopedic implants is under study at the University of Illinois. As part of this program, plugs 1/8 in. in diam were inserted in holes drilled in the proximal femur of 2 groups of 8-week old male rabbits. The groups were sacrificed at the end of 1 and 2 years. A single i.m. injection of achromycin was given 2 days prior to sacrifice. Thin sections of the plugs and surrounding tissue were examined by microradiography and optical microscopy (white light, polarizing, and fluorescent). All bone was normal. Minimal evidence of irritation or fibrous encapsulation appeared.

Animals↗

Bone growth into porous high-density polyethylene.

The purpose of this study was to delineate the process by which bone comes to fill the pores of porous high-density polyethylene (PHDPE) implants. PHDPE (450 mu pore size) pellets 4 mm in diameter and 1 cm long were implanted into the femurs of dogs. A bone biopsy procedure was utilized to obtain PHDPE pellets implanted for periods of 3 days through 8 weeks. A one-year biopsy specimen taken from the PHDPE coating on the stem of a canine total-hip prosthesis was also studied. The results demonstrated that significant amounts of bone formed within the PHDPE pellets as early as 14 days after implantation. Bone was identified throughout the specimens after 4 weeks. After 6 weeks, the tissue in hematopoietic marrow. Scanning electron microscopy was utilized in conjunction with light microscopy and microradiography to study the ultrastructural features of the bone ingrowth process.

Animals↗

Structure and function of the human patella: the role of cancellous bone.

Total joint and other prosthesis often require the removal and replacement of considerable quantities of cancellous bone, and often are anchored in place by grouting into cancellous bone. Thus, a possible source of failure or loosening of many types of prostheses may be rooted in the lack of understanding of the structure, properties, and function of this material. In addition, as we have pointed out before, cancellous bone may play an important biomechanical role in the etiology of joint degeneration. With these considerations in mind, the architecture of the cancellous bone in the human patella was studied by serial sectioning and microradiography, using an improved technique developed in our laboratory. Volumes of cancellous bone with apparently different functional roles were identified. Stereological techniques were used to quantify the structural characteristics and geometrical relationships throughout the patella. These results led to a structural model for the cancellous bone of the patella, and a comprehensive picture of the internal architecture. The distribution of mechanical compliance and yield stress was also measured, as a function of location and orientation, by a specially constructed microcompression testing machine. The measurements reflected the distribution of trabecular architecture, and both the properties and architecture reflected the gross biomechanical function of the patella. Furthermore, a true structure-function relationship was derived. Patellar contact area studies were performed on fresh cadavers and mapped for various angles of flexion. The variation in contact areas and the spatial variations in stiffness are discussed relative to the biomechanics and clinical aspects of the patella.

Biomechanical Phenomena↗

The biocompatibility of materials for internal fixation of fractures.

Surgically produced fractures of rabbit tibiae were internally stabilized with intramedullary rods of stainless steel (316LVM), titanium (6A1,4V), polyacetal (Delrin), and polyamide (Nylon 101). Periodic radiographs were taken until sacrifice at 16 weeks after fracture. Structural properties of the tibiae were determined in torsion with the rods in situ, and then the tissue was prepared for histology or microradiography. The results demonstrated that fracture remodeling was adversely affected by the metal rods. New bone was seen to have formed over the ends of the metal rods, and cortical bone resorption was observed in the fracture region, suggestive of transfer of mechanical stress to the rods, resulting in stress shielding of the diaphysis. Negligible osseous response to the polymeric rods was observed; fracture callus remodeling was extensive. The torsional test results demonstrated that fractures with polymeric rods were significantly stronger and tougher than those with metallic rods. With the exception of titanium, the strength of healed fractures was inversely related to the elastic moduli of the implant materials.

Acetals↗

A high-modulus polymer for porous orthopedic implants: biomechanical compatibility of porous implants.

A high-modulus polymer, polysulfone, was evaluated as a porous bone implant material. The bone ingrowth into canine cortical pellets of sintered polysulfone particles was assessed by microradiography and histology. The shear strength of the porous polysulfone-bone interface was determined by push-out and pull-out tests of cortical and trochanteric implants, respectively. Results indicated that the bone ingrowth into porous polysulfone specimens proceeded in such a fashion as to mimic the normal repair at the site. Mechanical testing of cortical and cancellous implants revealed that the interfacial shear strength of the porous polysulfone-bone composite was similar to that achieved using porous metals.

Biocompatible Materials↗

Piezoelectric ceramic implants: in vivo results.

The suitability of barium titanate (BaTiO3) ceramic for direct substitution of hard tissues was evaluated using both electrically stimulated (piezoelectric) and inactive (nonpolarized) test implants. Textured cylindrical specimens, half of them made piezoelectric by polarization in a high electric field, were implanted into the cortex of the midshaft region of the femora of dogs for various periods of time. Interfacial healing and bio-compatibility of the implant material were studied using mechanical, microradiographical, and histological techniques. Our results indicate that barium titanate ceramic shows a very high degree of biocompatibility as evidenced by the absence of inflammatory or foreign body reactions at the implant-tissue interface. Furthermore, the material and its surface porosity allowed a high degree of bone ingrowth as evidenced by microradiography and a high degree of interfacial tensile strength. No difference was found between the piezoelectric and the electrically neutral implant-tissue interfaces. Possible reasons for this are discussed. The excellent mechanical properties of barium titanate, its superior biocompatibility, and the ability of bone to form a strong mechanical interfacial bond with it, makes this material a new candidate for further tests for hard tissue replacement.

Animals↗

Biodegradation behavior of various calcium phosphate materials in bone tissue.

In order to study the biodegradation behavior of calcium phosphate materials, cylinders of standard size were implanted in the tibiae of rabbits. Material parameters were stoichiometry (hydroxyapatite with a Ca/P ratio of 1.67 versus tricalcium phosphate with a Ca/P ratio of 1.50), crystallographic structure (apatite versus beta-whitlockite), microporosity, and macroporosity. The extent of biodegradation was evaluated by radiography, light and fluorescence microscopy, microradiography, and porosity measurements. All calcium phosphate materials were biocompatible in bone tissue. Hydroxyapatite ceramics had a higher osteogenic potential than beta-whitlockite materials. Depending on their porosities, sintered tricalciumphosphate (beta-whitlockite) materials were more or less biodegradable, in contrast to sintered hydroxyapatite materials, which showed no detectable resorption over a period of 9 months of implantation.

Animals↗

Bone-bonding ability of P2O5-free CaO.SiO2 glasses.

An apatite- and wollastonite-containing glass-ceramic (A.W-GC) has been reported to form a tight bond with living bone through an apatite layer formed on its surface. This layer is considered to be formed by dissolution of Ca2+ and HSiO3- ions from the glass-ceramic into the surrounding body fluids. In order to confirm this proposed mechanism for the surface reaction of A.W-GC, three kinds of glass in the systems CaO-SiO2, CaO-SiO2-CaF2, and CaO-SiO2-P2O5 were implanted into the tibiae of rabbits for 3 or 8 weeks. Contact microradiography and SEM-EPMA showed that all three kinds of glass formed a Ca,P-rich layer in combination with a Si-rich layer on their surfaces within 3 weeks and formed a direct bond with bone via these layers. The detaching test, performed 8 weeks after implantation, showed that the loads required to detach the implants from the bone were almost equal for the phosphorus-free and the phosphorus-containing glasses. It was concluded that even P2O5-free CaO.SiO2 glass formed a Ca,P-rich layer on its surface and bonded tightly with living bone. If glasses and glass-ceramics release at least Ca2+ and HSiO3- ions, this would be sufficient for them to form the Ca,P-rich layer on their surfaces in vivo, enabling them to bond directly with bone.

Animals↗

The bonding behavior of calcite to bone.

Plates of calcite (CaCO3) were implanted in rabbit tibiae, and their biocompatibility and bonding ability to bone were studied. The plates were also implanted subfascially in rabbit muscle for 8 weeks, and changes on their surfaces in the body were examined. Contact microradiography and Giemsa surface stain demonstrated direct bonding between calcite and bone without interpositions. The average failure load of the interface between calcite and bone was 4.11 kg, indicating an adequate strength of bonding. However, a Ca-P-rich layer, which formed on the surfaces of other bioactive ceramics in vivo, was not detected by a scanning electron microscope-electron probe x-ray microanalyzer. Scanning electron micrographs of the surface of calcite implanted subfascially for 8 weeks showed marked degradation and a rough surface. However, the surface apatite layer was not detected by thin-film x-ray diffraction analysis and Fourier transform infrared reflection spectroscopy. Calcite is a biodegradable material that bonds to bone without a surface apatite layer. The mechanical bonding provided by the anchoring effect of the newly formed bone into the surface roughness of calcite is considered to be a major factor in calcite-bone bonding.

Animals↗

Behavior of the bone-titanium interface after push-in testing: a morphological study.

Fourteen titanium dental implants (Tioblast) were implanted singly in the proximal tibia of New Zealand rabbits for 120 days. A bone defect was surgically produced and filled with Bio-Oss around six of these implants. After the animals were sacrificed and their organs harvested, bone segments were fixed and methacrylate embedded after the push-in test had been performed. Microradiography was performed on longitudinal sections of the implants, whereas scanning electron microscope analysis was performed on the remaining embedded half-implants using secondary electrons only. The results showed that the implants were apically and coronally surrounded by bone, whether Bio-Oss was used or not. Fractures were evident through the newly formed bone and between the pre-existing and newly formed bone. Some fracture lines propagated through the bone and stopped at the implant surface without continuing along the bone-titanium interface. Detachment between the implant and the bone occurred at the coronal extremity of the implants and along its cervical region. These results highlight the fact that the bone-titanium interface has a high resistance to loading. It exhibited greater resistance than the newly formed bone and seems to behave in a manner similar to the cement lines of osteons.

Animals↗

Salicylic acid-derived poly(anhydride-esters) inhibit bone resorption and formation in vivo.

The objective of this study was to investigate the effects of a novel polymer that biodegrades into salicylic acid (SA) on the healing of critical sized long bone defects. Microspheres of the homopolymer, or a copolymer containing 50% less of the SA, were packed into 5-mm mid-diaphyseal defects in rat femurs. Control animals received collagen sponge implants. After 4 and 8 weeks of implantation, bone healing was evaluated using microradiography and quantitative histomorphometry. Four weeks postsurgery, significantly less new bone was formed in both of the polymer groups (p<0.038). Reduced bone loss was also noted with the polymers at this time, although it was not statistically significant. However, at 8 weeks postsurgery, a statistically significant reduction in bone loss was observed in both of the polymer groups compared with controls (p<0.0072). Both polymers seemed to elicit identical tissue responses because there were no differences detected between the homopolymer and copolymer materials at either time point. These results indicate that locally released SA can significantly reduce both bone loss and bone formation in this animal model.

Anhydrides↗