Histological evaluation of the influence of magnetic field application in autogenous bone grafts in rats.

BACKGROUND: Bone grafts are widely used in oral and maxillofacial reconstruction. The influence of electromagnetic fields and magnets on the endogenous stimulation of target tissues has been investigated. This work aimed to assess the quality of bone healing in surgical cavities filled with autogenous bone grafts, under the influence of a permanent magnetic field produced by in vivo buried devices. METHODS: Metal devices consisting of commercially pure martensitic stainless steel washers and titanium screws were employed. Thirty male Wistar rats were divided into 3 experimental and 3 control groups. A surgical bone cavity was produced on the right femur, and a bone graft was collected and placed in each hole. Two metallic washers, magnetized in the experimental group but not in the control group, were attached on the borders of the cavity. RESULTS: The animals were sacrificed on postoperative days 15, 45 and 60. The histological analysis of control and experimental samples showed adequate integration of the bone grafts, with intense bone neoformation. On days 45 and 60, a continued influence of the magnetic field on the surgical cavity and on the bone graft was observed in samples from the experimental group. CONCLUSION: The results showed intense bone neoformation in the experimental group as compared to control animals. The intense extra-cortical bone neoformation observed suggests that the osteoconductor condition of the graft may be more susceptible to stimulation, when submitted to a magnetic field.

Effects of bisphosphonate treatment on bone repair under immunosuppression using cyclosporine A in adult rats.

UNLABELLED: The effect of cyclosporine A on bone turnover remains unclear. Using adult rats with vascularized bone transplantation, we show that long-term cyclosporine A administration increases bone turnover and zoledronic acid treatment enhances the reconstruction of cyclosporine A-administered skeleton. Bisphosphonates might be efficacious in human bone repair under immunosuppression using cyclosporine A. INTRODUCTION: Bisphosphonate treatment effectively prevents bone loss after transplantation. However, recent evidence from gain- and loss-of-function experiments has indicated that calcineurin inhibitors, such as cyclosporine A (CsA), reduce bone turnover, and severely suppressed bone turnover might delay the union of human fractured bone. The purpose of this study was to investigate the effects of bisphosphonate treatment on the repair of CsA-administered skeleton. METHODS: After skeletal reconstruction by vascularized tibial grafting, adult recipient rats were treated with intramuscular CsA (10 mg/kg/day) and low-dose (0.2 microg/kg/week) or high-dose (2 microg/kg/week) subcutaneous zoledronic acid alone or in combination for 8 weeks. Biochemical parameters were measured in blood and urine. The reconstructed skeleton was analyzed using soft X-ray, histology, dual energy X-ray absorptiometry, and three-point bending test. RESULTS: CsA induced mild renal dysfunction, hyperparathyroidism and high bone turnover. High-dose zoledronic acid delayed cortical bone union at the distal host-graft junction, but its combination with CsA did not cause such a delay. High-dose zoledronic acid prevented CsA-induced bone loss and bone fragility in the reconstructed skeleton. CONCLUSION: In this rat model, long-term CsA administration increases bone turnover, at least partly, through hyperparathyroidism and high-dose zoledronic acid treatment does not impair the union of CsA-administered bone.

Morphology of autogenous bone graft and castor oil polyurethane in the infraorbital rim of rabbits: a comparative study / Estudo morfológico comparativo do enxerto ósseo autógeno e polímero de mamona em rebordo infra-orbitário de coelhos

PURPOSE: Morphological study comparing castor oil polyurethane and autogenous bone graft to repair bone defect in zygomatic bone of rabbits. METHODS: Twenty-four adult, male New Zealand rabbits were randomly distributed between two groups of twelve. Bone defects of 5mm in diameter were cut through the zygomatic bone and filled with polyurethane discs in the experimental group or autogenous bone harvested from the tibia in the control group. Animals were sacrificed after 30, 60 or 90 days, and the zygomatic bones were macro- and microscopically analyzed. Student's, Fisher's, chi-squared and McNemar's tests were used for statistical analysis. RESULTS: Both the castor oil polyurethane and the autograft adapted well to the defect, with no need for fixation. Fibrous connective tissue encapsulated the polyurethane, but no inflammation or giant cell reaction was observed. Acidophilic and basophilic areas were observed inside the micropores of the polyurethane, suggesting cell nuclei. After 90 days, bone repair with a lamellar pattern of organization was observed in the control group. CONCLUSION: The castor oil polyurethane was biocompatible and did not cause inflammation. It may be considered an alternative to fill bone defects.

OBJETIVO: Estudo morfológico comparativo do implante de poliuretana de mamona e enxerto ósseo autógeno em defeito ósseo padrão em osso zigomático de coelhos. MÉTODOS: Vinte e quatro coelhos Nova Zelândia, machos, adultos, foram distribuídos aleatoriamente em dois grupos de 12. Defeitos de 5mm de diâmetro, perenes, foram confeccionados em osso zigomático e preenchidos com discos pré-fabricados de poliuretana no grupo experimento ou osso autógeno extraído da tíbia no grupo controle. Os animais foram sacrificados após 30, 60 e 90 dias e as peças anatômicas foram avaliadas macro e microscopicamente. Foram utilizados os testes de Student, Fisher,qui-quadrado e McNemar para a análise estatística dos resultados. RESULTADOS: A poliuretana e o osso autógeno se adaptaram ao defeito sem necessidade de fixação. Houve formação de tecido conjuntivo fibroso envolvendo a poliuretana, sem reação inflamatória ou presença de células gigantes. Verificaram-se áreas acidófilas e basófilas nos poros do material implantado, sugestivas de núcleos celulares. No grupo controle, observou-se aos 90 dias o reparo ósseo de padrão lamelar clássico. CONCLUSÃO: A poliuretana de mamona foi biocompatível e não causou reação inflamatória deletéria. Pode ser uma alternativa para o preenchimento de defeitos ósseos.

Morphology of autogenous bone graft and castor oil polyurethane in the infraorbital rim of rabbits: a comparative study.

PURPOSE: Morphological study comparing castor oil polyurethane and autogenous bone graft to repair bone defect in zygomatic bone of rabbits. METHODS: Twenty-four adult, male New Zealand rabbits were randomly distributed between two groups of twelve. Bone defects of 5mm in diameter were cut through the zygomatic bone and filled with polyurethane discs in the experimental group or autogenous bone harvested from the tibia in the control group. Animals were sacrificed after 30, 60 or 90 days, and the zygomatic bones were macro- and microscopically analyzed. Student's, Fisher's, chi-squared and McNemar's tests were used for statistical analysis. RESULTS: Both the castor oil polyurethane and the autograft adapted well to the defect, with no need for fixation. Fibrous connective tissue encapsulated the polyurethane, but no inflammation or giant cell reaction was observed. Acidophilic and basophilic areas were observed inside the micropores of the polyurethane, suggesting cell nuclei. After 90 days, bone repair with a lamellar pattern of organization was observed in the control group. CONCLUSION: The castor oil polyurethane was biocompatible and did not cause inflammation. It may be considered an alternative to fill bone defects.

Autogenous bone graft with or without a calcium sulfate barrier in the treatment of Class II furcation defects: a histologic and histometric study in dogs.

BACKGROUND: The purpose of this study was to histologically evaluate the healing of surgically created Class II furcation defects treated using an autogenous bone (AB) graft with or without a calcium sulfate (CS) barrier. METHODS: The second, third, and fourth mandibular premolars (P2, P3, and P4) of six mongrel dogs were used in this study. Class II furcation defects (5 mm in height x 2 mm in depth) were surgically created and immediately treated. Teeth were randomly divided into three groups: group C (control), in which the defect was filled with blood clot; group AB, in which the defect was filled with AB graft; and group AB/CS, in which the defect was filled with AB graft and covered by a CS barrier. Flaps were repositioned to cover all defects. The animals were euthanized 90 days post-surgery. Mesio-distal serial sections were obtained and stained with either hematoxylin and eosin or Masson's trichrome. Histometric, using image-analysis software, and histologic analyses were performed. Linear and area measurements of periodontal healing were evaluated and calculated as a percentage of the original defect. Percentage data were transformed into arccosine for statistical analysis (analysis of variance; P <0.05). RESULTS: Periodontal regeneration in the three groups was similar. Regeneration of bone and connective tissue in the furcation defects was incomplete in most of the specimens. Statistically significant differences were not found in any of the evaluated parameters among the groups. CONCLUSION: Periodontal healing was similar using surgical debridement alone, AB graft, or AB graft with a CS barrier in the treatment of Class II furcation defects.

Effect of platelet-rich plasma with autogenous bone graft for maxillary sinus augmentation in a rabbit model.

PURPOSE: To evaluate the effect of platelet-rich plasma (PRP) on autogenous bone graft remodeling during sinus augmentation in a rabbit model. MATERIALS: Twelve New Zealand White rabbits were divided randomly into 3 groups based on their time of sacrifice (2, 4, and 8 weeks). All animals underwent a general anesthetic and harvesting of an autogenous bone graft from the right iliac crest with subsequent bilateral maxillary sinus augmentation. PRP was prepared via standard approved technique by acquiring 21 cc of autogenous blood and performing differential centrifugation to obtain PRP. One cc of PRP was produced that was mixed with bovine topical thrombin and calcium chloride. The left maxillary sinus received only autogenous bone, while the right maxillary sinus received a mixture of PRP mixed with autogenous bone, thus each animal acted as its own control. Equal volumes of bone were inserted in each maxillary sinus. Animals were sacrificed at 2, 4, and 8 weeks and all specimens were harvested for peripheral quantitative computed tomography (pQ-CT), static, and dynamic and histomorphometric analysis. RESULTS: Student t tests were performed comparing bone density via pQ-CT analysis, histomorphometric parameters of total bone area, and bone apposition rate. PRP had no statistically significant effect on bone graft healing in maxillary sinus augmentation when compared using standard pQ-CT, static, and dynamic histologic criteria. CONCLUSION: This study fails to find a direct stimulatory effect of PRP on healing of autogenous bone grafts using pQ-CT, static, and dynamic histomorphometric analyses.

Fourier and fractal analysis of maxillary alveolar ridge repair using platelet rich plasma (PRP) and inorganic bovine bone.

This report concerns the regeneration of the maxillary alveolar process in a 17-year-old patient who had lost the upper central incisors together with alveolar bone as a result of a car accident. Three months later, GBR (guided bone regeneration) was started with the use of autogenic platelet rich plasma (PRP) and inorganic bovine bone. The regenerated bone was analysed after 10 months and compared with intact bone using Fourier analysis of radiograms. The radial and spatial distribution of Fourier transforms showed that the original trabecular pattern existing in the intact bone on both sides of the defect was replicated in an evident way in the regenerated bone. Fractal analysis of intact and regenerated bone showed a higher fractal dimension for intact bone in comparison with regenerated bone, confirming a lower complexity of the newly formed trabecular structures. Replication of the original trabecular pattern in regenerated bone allows us to conclude that genetic mechanisms are influencing the organization of the trabecular pattern of regenerated bone tissue, probably under the influence of the growth factors contained in autologous PRP.

Effect of low level laser therapy on the repair of bone defects grafted with inorganic bovine bone.

The aim of this study was to assess histologically the effect of LLLT (lambda 830 nm) on the repair of standardized bone defects on the femur of Wistar albinus rats which were grafted with inorganic bovine bone Gen-ox(R). Three randomized groups were studied: group I (control, n=6); group II (Gen-ox, n=9) and group III (Gen-ox + LLLT, n=9). The animals were irradiated every 48 h during 15 days; the first irradiation was performed immediately after the procedure. The animals were irradiated transcutaneuosly at four points around the defect. At each point a dose of 4 J/cm(2) was given (Ø approximately 0.6 mm, 40 mW) and the total dose per session was 16 J/cm(2). The animals were killed by an overdose of general anesthetic 15, 21 and 30 days after surgery. The specimens were routinely processed by embedding in paraffin, serially cut and stained with H&E and Picrosirius and analyzed under light microscopy. The results showed evidence of a more advanced repair in the irradiated group when compared to the non-irradiated groups. The repair of the irradiated group was characterized by both increased bone formation and amount of collagen fibers around the graft within the cavity from the 15th day after surgery, also considering the osteoconductive capacity of the Gen-ox. We conclude that LLLT had a positive effect on the repair of bone defects implanted with inorganic bovine bone.

Effect of low level laser therapy on the repair of bone defects grafted with inorganic bovine bone

O objetivo deste trabalho foi avaliar histologicamente a influência da radiação laser não-cirúrgica (830 nm) sobre o reparo ósseo de defeitos padronizados em fêmur de ratos Wistar albinus e submetidos a implante de osso bovino inorgânico Gen-ox. Foram estabelecidos três grupos de animais: grupo I (controle, n=06); grupo II (Gen-ox, n=09) e grupo III (Gen-ox + LLLT, n=09). Os animais foram irradiados a cada 48 horas, sendo a primeira irradiação realizada imediatamente após a cirurgia. Os animais foram irradiados transcutaneamente em quatro pontos em torno da ferida. Cada ponto recebeu uma dose de 4 J/cm2 e a dose total por sessão foi de 16 J/cm2. Os sacrifícios foram realizados 15, 21 e 30 dias após a cirurgia. Os espécimes foram removidos e fixados para procedimento laboratorial, sendo corados com HeE e Picrosirius e analisados em microscopia de luz. Os resultados mostraram evidência de um reparo ósseo mais avançado nos espécimes irradiados em relação aos não irradiados. O reparo nos espécimes irradiados foi caracterizado por uma maior neoformação óssea, bem como por uma maior proliferação de fibras colágenas no interior do defeito já a partir de 15 dias após a cirurgia, também considerando a capacidade osteocondutiva do Gen-ox. Conclui-se que a LLLT resultou num efeito de biomodulação positiva sobre o reparo do defeito ósseo submetido a implante de osso bovino inorgânico.

Enhancement of osteoblast proliferation in vitro by selective enrichment of demineralized freeze-dried bone allograft with specific growth factors.

Decalcified freeze-dried bone allograft (DFDBA), believed to serve as a matrix for new bone growth and to contain various bone-inducing growth factors, is currently used to regenerate periodontal defects and to restore and maintain dental alveolar ridges. Growth factors within DFDBA are extracted during the demineralization process, thus rendering the allograft incapable of spontaneous osteogenesis; however, exogenous growth factor addition to DFDBA may enhance the osteogenic capacity of native osteoblasts. This study's purpose is to evaluate murine osteoblast proliferation in the presence of various exogenous soluble growth factors as measured by fluorescence units. Osteoblasts harvested from mouse pup calvaria were cultured with 2% residual calcium-DFDBA and supplemented by one of the following growth factors or combinations of these factors: transforming growth factor-beta (TGF-beta), insulin-like growth factor-I (IGF-I), platelet-derived growth factor (PDGF), fibroblast growth factors basic (bFGF), or vascular endothelial growth factors (VEGF). Osteoblast proliferation rates indicate that the in vitro supplementation of 2% residual calcium-DFDBA with the combination of IGF and TGF-beta, IGF and PDGF, and PDGF and TGF-beta significantly (P < or = .05) enhance murine osteoblast activity and proliferation at 7 days compared with the control containing no exogenous growth factors.

Bone regeneration with calcium sulfate: evidence for increased angiogenesis in rabbits.

Autologous bone is the preferred bone graft material because it carries proteins as bone-enhancing substrates, minerals, and vital bone cells. Calcium sulfate (CS) is a well-tolerated, biodegradable, osteoconductive bone graft substitute and is a reasonable alternative to autogenous bone graft. Blood vessels are an important component of bone formation and maintenance. The process of vascular induction is called angiogenesis, and it plays a key role in all regenerative processes. Bone tissue differentiation is related to the local presence of blood vessels. One method to evaluate the presence of blood vessels in a tissue is to count the microvessels to evaluate microvessel density (MVD). The aim of the present study was to conduct a comparative evaluation of microvessel density in sites treated with CS and autologous bone in rabbits, with or without e-PTFE nonresorbable membranes (Gore-Tex, Flagstaff, Ariz). Nine New Zealand rabbits, each weighing about 2.5 kg, were used in this experiment. Three 6-mm wide defects were created in each tibial metaphysis. The defects were filled in a random way. The defects of group 1 (3 rabbits) were filled with CS granules (Surgiplaster, Classimplant, Rome, Italy) and covered with e-PTFE membranes. The defects in group 2 (3 rabbits) were filled with CS granules (Surgiplaster). The defects in group 3 (3 rabbits) were filled with autologous bone. A total of 54 defects were filled (18 with CS and e-PTFE membranes, 18 with CS alone, and 18 with autologous bone). No postoperative deaths or complications occurred. All nine animals were sacrificed at 4 weeks. MVD results were as follows: in the first group, 9.88 +/- 4.613; in the second group, 7.92 +/- 1.998; and in the third group, 5.56 +/- 1.895. P = .000 was highly significant. Statistically significant differences were found between groups 1 and 3, 1 and 2, and 2 and 3. The presence of more blood vessels in the sites treated with CS could help to explain the good results reported in the literature with the use of CS.

Interface between bone and nacre implants in sheep.

We have investigated the interface between bone and chronic implants of nacre in sheep. There was no foreign body reaction over the period of 10 months and the implants were not broken down. Light microscopy indicated activity within an osteoprogenitor cellular layer lining the implant, resulting in a complete sequence of new bone formation. Nacre appeared to bind directly to newly formed bone without any intervening fibrous tissue. Scanning electron microscopy and energy dispersive photon X-microanalysis showed calcium and phosphate ions lining the nacre within the osteoprogenitor tissue. These studies show a dynamic activity of the bone/nacre interface, leading to continuity between the nacre and the bone.

Changes in the extracellular matrix on the surface of sintered bovine bone implanted in the femur of a rabbit: an immunohistochemical study.

The interface of implanted True Bone Ceramics (TBC; sintered bovine bone; Koken, Tokyo, Japan) was examined. In the primary experiment, TBC was implanted into the bone marrow of a rabbit's femur. The extracellular matrices (types I, II, and III collagens and fibronectin) of decalcified specimens collected 1-48 weeks postoperatively were immunohistochemically examined. Undecalcified sections collected 6 weeks postoperatively were used for line analyses of calcium and phosphorus, by a scanning electron microscope-electron probe microanalysis (SEM-EPMA) method. In a secondary experiment, TBC was implanted into an osteochondral defect of a femoral condyle, harvested 1-12 weeks postoperatively, and decalcified to examine the extracellular matrices at the interface. In the bone marrow in the early phase, TBC had absorbed quantities of fibronectin. Immature bone (containing both types I and III collagens) in direct apposition to the ceramic surface had matured (containing type I collagen alone) in the TBC pores. SEM-EPMA revealed the continuity of high levels of calcium and phosphorus at the TBC-bone interface. In the secondary experiment, enchondral ossification or fibrous tissue formation was observed near the articular surface. However, in the subchondral layer, direct bone formation was observed in the TBC pores. It was concluded that TBC has excellent bioactivity for inducing maturation of new bone matrix on porous surfaces.

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.

Mandibular reconstruction by secondary reimplantation of resected segments: a preliminary report.

This paper presents a new method of reconstructing the mandible after ablative surgery for cancer. This method uses autogenous grafts consisting of the respected part of the mandible, which is hollowed out, defatted in chloroform/methanol, sterilized with ethylene oxide, irradiated with beta-radiation (dose 25 kGy), and stored for 7-10 months. At reimplantation, they were filled with compressed, autogenous, particulate cancellous bone. All grafts took, and four of six host-graft junctions healed.

Evaluation of osseointegration of endosseous implants in radiated, vascularized fibula flaps to the mandible: a pilot study.

PURPOSE: This study clinically evaluated the osseointegration of implants placed into vascularized fibula flaps used in mandibular reconstruction of cancer patients following radiation treatment and subsequent hyperbaric oxygen (HBO) therapy. MATERIALS AND METHODS: Five head and neck cancer patients had mandibular resection and immediate reconstruction with a vascularized fibula flap. Subsequent therapy included greater than 50 Gy of radiation to the fibula flap over a 6 to 8-week period. Two to 6 weeks following radiation therapy each patient received 20 90-minute daily sessions of HBO at 2.4 atmosphere pressure. Stage 1 implant surgery was performed placing two to six implants (15 mm in length and 3.75 to 4.0 mm in width) into each fibula flap. This was followed by 10 postoperative HBO sessions using the previously mentioned protocol. The stage 2 procedure was performed 6 months after the stage 1 procedure. Osseointegration was assessed clinically using manual force and an electronic device at the time the implants were uncovered and monthly over a 6-month period. RESULTS: All 20 implants placed in the fibula flaps were osseointegrated clinically at the time the implants were uncovered and during the 6-month follow-up. CONCLUSION: In this pilot study, mandibular reconstruction with a vascularized fibula flap and endosseous osseointegrated implants, following radiation of the fibula, was successful. It was concluded that factors such as the graft having its own blood supply and the use of HBO contributed to the successful osseointegration of these implants.

Metallosis caused by alumina ceramic screw fixation of grafted bone in a bipolar hip endoprosthesis.

We report a case of metallosis due to ceramic fragments in the inner bearing surface of the polyethylene cup of a bipolar hip prosthesis with fracture of the alumina ceramic screws used for grafted bone fixation. After bone-grafting acetabuloplasty with a Bateman bipolar endoprosthesis, gradual migration of the outer head occurred, and fracture of the screws was observed. Seven years after the operation, radiographs showed severe metallosis of the surrounding tissues. At revision, marked wear of the inner head was seen. Detailed examination revealed that many rough-edged ceramic particles originating from the fractured ceramic screws had become embedded in the inner surface of the polyethylene bearing insert. These extremely hard ceramic fragments had entered the prosthetic joint space during joint movement, thereafter causing continuous abrasion of the metal head. After revision, the concentration of the constituents of the prosthesis alloy in the serum decreased toward control levels. To prevent serious complications like those in the present case, screws should be inserted more than 1 cm from the outer head of a bipolar endoprosthesis, and the outer head should be removed as soon as possible if it comes into contact with the screws.

Effect of dietary phosphate deprivation and supplementation of recipient mice on bone formation by transplanted cells from normal and X-linked hypophosphatemic mice.

The hypophosphatemic (Hyp) mouse is the murine homolog for human hypophosphatemic vitamin D-resistant rickets. We previously reported that bone cells isolated from normal and Hyp mice produced abnormal bone when transplanted intramuscularly into mutant mice. To assess the role of hypophosphatemia on bone formation in transplants, normal and Hyp mouse periostea were pair transplanted into control or phosphate (P)-supplemented Hyp mice and into control or P-deprived normal mice. The bone nodules formed in transplants after 2 weeks were characterized by measuring the thickness of the surrounding osteoid seams and the relative osteoid volume. P restriction in normal recipient mice impaired bone formation by transplanted normal cells and aggravated the defective bone formation by Hyp cells. The osteoid thickness and volume remained significantly higher in Hyp transplants than in normal cotransplants, however. P supplementation of Hyp recipient mice normalized bone formation by transplanted normal cells but not by Hyp cells. However, a marked decrease in osteoid thickness and volume was observed in Hyp transplants down to values observed in normal recipient mice. These results indicate that hypophosphatemia is not the only cause of abnormal bone formation in the Hyp mouse but that an osteoblast dysfunction contributes to the bone disease. These observations further support the concept that the osteoblast may be an important target for the Hyp mutation.

Effects of gallium on bone in the rat.

Gallium nitrate lowers the serum calcium in patients with hypercalcemia caused by malignancy and is available for clinical use. The mechanism for the hypocalcemic action is unknown, however. The present studies were undertaken to determine the effects of gallium on bone metabolism. Normal male rats were implanted subcutaneously with mineralized allogeneic bone matrix. Histomorphometry of the implants and of tibiae was determined after three doses of tetracycline administered at intervals of 1 week. Gallium as nitrate was administered daily by intraperitoneal injection at doses of 0.9, 1.8, and 3.6 mg elemental gallium per kg body weight for 21 days in one study and at 3.5 mg/kg for 33 days in a second study. All the gallium-treated rats gained weight. Rats given gallium at doses of 3.5 mg/kg or more grew at a lower rate than untreated controls (-7 and -10% at doses of 3.5 and 3.6 mg/kg, respectively; p less than 0.05). At a dose of 0.9 mg/kg, gallium did not inhibit bone resorption or lower serum calcium but inhibited bone formation by 32% and bone apposition by 36% at the endosteal surface of the tibia. At a dose of 1.8 mg/kg, gallium produced modest hypocalcemia, prevented a rise in circulating 1,25-dihydroxyvitamin D [1,25-(OH)2D], inhibited bone resorption in implants, and inhibited bone formation by 19% and bone apposition by 18%. At a dose of 3.5 mg/kg, gallium lowered the serum calcium and serum 1,25-(OH)2D, inhibited growth, and accentuated the antiresorptive and antiformative effects seen at the two lower doses.(ABSTRACT TRUNCATED AT 250 WORDS)