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Influence of bone resorption on the mobilization of lead from bone among middle-aged and elderly men: the Normative Aging Study.

Bone stores of lead accrued from environmental exposures and found in most of the general population have recently been linked to the development of hypertension, cognitive decrements, and adverse reproductive outcomes. The skeleton is the major endogenous source of lead in circulating blood, particularly under conditions of accelerated bone turnover and mineral loss, such as during pregnancy and in postmenopausal osteoporosis. We studied the influence of bone resorption rate on the release of lead from bone in 333 men, predominantly white, middle-aged and elderly (mostly retired) from the Boston area. We evaluated bone resorption by measuring cross-linked N-telopeptides of type I collagen (NTx) in 24-hr urine samples with an enzyme-linked immunosorbent assay. We used K-X-ray fluorescence to measure lead content in cortical (tibia) and trabecular (patella) bone; we used graphite furnace atomic absorption spectroscopy and inductively coupled plasma mass spectroscopy to measure lead in blood and urine, respectively. After adjustment for age and creatinine clearance, the positive relation of patella lead to urinary lead was stronger among subjects in the upper two NTx tertiles (beta for patella lead > or =0.015) than in the lowest NTx tertile (beta for patella lead = 0.008; overall p-value for interactions = 0.06). In contrast, we found no statistically significant influence of NTx tertile on the relationship of blood lead to urinary lead. As expected, the magnitude of the relationship of bone lead to urinary lead diminished after adjustment for blood lead. Nevertheless, the pattern of the relationships of bone lead to urinary lead across NTx tertiles remained unchanged. Furthermore, after adjustment for age, the relation of patella lead to blood lead was significantly stronger in the upper two NTx tertiles (beta for patella lead > or =0.125) than in the lowest NTx tertile (beta for patella lead = 0.072). The results provide evidence that bone resorption influences the release of bone lead stores (particularly patella lead) into the circulation.

Adult↗

Sympathectomy, which induces membranous bone remodeling, has no effect on endochondral long bone remodeling in vivo.

Sympathectomy has been shown to induce resorption within the membranous middle ear bone of gerbils. It is unknown whether sympathectomy exerts a similar effect on endochondral long bone. In the present study, guanethidine sulfate (GS) and 6-hydroxydopamine (HDA) were administered to gerbils to induce sympathectomy. One week later, samples of middle ear bulla bone and radial long bone were harvested and assessed for osteoclastic activity. Histomorphometric analysis showed both pharmacologic sympathectomy with GS and chemical sympathectomy with HDA significantly increased the osteoclast counts and osteoclast surfaces of bulla bone samples but not radial long bone samples, respectively. In contrast, HDA but not GS increased the osteoclast profile area of both long bone and membranous bone samples when compared with vehicle-treated controls. Sympathectomy, induced both chemically and pharmacologically, thus has been shown to increase resorption in membranous bone but not endochondral long bone in the gerbilline model.

Animals↗

The hormonal milieu in early stages of bone cell differentiation modifies the subsequent sex-specific responsiveness of the developing bone to gonadal steroids.

We have established previously that rat bone tissue, as well as rat and human-derived bone cells in culture, show a sex-specific response to gonadal steroids in stimulation of the specific activity of the BB isozyme of creatine kinase (CK) and DNA synthesis. This response could be modified by manipulation of the endocrine environment during early stages in rat development. To further examine the influence of changing hormonal steroid milieu and vitamin D status on the action of gonadal steroids in developing bone tissue, we used two models of ectopic bone formation: demineralized tooth matrix (DTM) implanted under the skin, and femoral bone marrow (BM) transplanted under the kidney capsule of a syngeneic recipient mouse. The response to gonadal steroids in ossicles developed from implanted DTM depended on the recipient's gender; injection of estradiol 17beta (E2; 5 microg) into young female mice 21 days after DTM implantation increased, 24 h later, CK activity in the newly formed ossicles by approximately 60%, whereas injection of dihydrotestosterone (DHT; 50 microg) had no effect on CK activity. In contrast, in male mice, DHT but not E2 increased CK activity in the ossicles by approximately 50%. This sex-specific response was abolished in gonadectomized mice resulting in a similar response of the ossicles to both E2 and DHT. When DTM was implanted into vitamin D- deficient female mice, there was a lower basal CK activity and a significantly diminished response to E2 in the newly formed bone tissues. When BM, which contains mesenchymal and stromal cells and committed osteoprogenitor cells, was transplanted into 6-week-old intact or gonadectomized female or male mice, the response of the newly formed bone ossicles, 21 days after transplantation, to E2 or to DHT was according to the gender of the donor. Bone formed from BM obtained from female mice responded to E2 only and those formed from male BM responded to DHT only. Ossicles developed from BM obtained from gonadectomized mice showed lack of response to either gonadal steroid. Furthermore, only approximately 25% of the BM transplants obtained from castrated (CAST) male donors developed into ossicles. Ossicles formed from BM obtained from vitamin D-deficient female donors showed lack of response to gonadal steroids. These findings suggest that the manipulation of the hormonal milieu in early stages of the differentiation sequence of bone cells modifies the subsequent selective responsiveness of the developing bone tissue to gonadal steroids.

24,25-Dihydroxyvitamin D 3↗

Effects of occlusal loading on ankylosis, bone, and cementum formation during bone morphogenetic protein-2-stimulated periodontal regeneration in vivo.

BACKGROUND: The purpose of this study was to investigate the influence of occlusal loading on recombinant human bone morphogenetic protein-2 (BMP-2)-induced bone and cementum formation in a previously established rat model of periodontal regeneration during the early and late stages of wound healing. METHODS: 64 Wistar rats were divided into 8 groups and had surgically created fenestrated defects on the right side of the mandible involving the removal of bone and exposure of the first and second molar roots. Four groups had their right maxillary molars extracted 2 weeks prior to surgery. Ten microl of 100 ug/ml BMP-2 in a collagen membrane was placed in extracted (hypofunctional) and non-extracted (functional) groups (BMPe and BMPf, respectively) while control groups had collagen membrane only (CONe and CONf). Groups were sacrificed at 10 (BMPe, BMPf, CONe, CONf) or 35 days (BMP35e, BMP35f, CON35e, CON35f) postoperatively and tissues processed for histological examination. Transverse 5 microm sections were stained for identification of new bone, ankylosis and cementum formation. RESULTS: At 10 days, CONe developed greater bone growth compared with CONf (P<0.05), while both BMP groups developed greater bone compared with controls. However, BMPe developed more ankylosis compared with both CONe and CONf while BMPf was significantly greater than CONf only (P<0.05). BMPf only developed significantly greater new cementum compared with controls. At 35 days, BMP35f developed greater bone growth compared with all other groups including BMP35e (P<0.05) and unlike results at 10 days, no differences were apparent between CON35f and CON35e. Unwanted bone growth beyond the defect margin anteriorly was significantly greater in BMP35f. CONCLUSIONS: Results suggest hypofunction stimulates early bone formation. Furthermore, hypofunction and BMP-2 increase the development of transient ankylosis. However, after wound healing is complete, function augments the early effects of BMP-2-induced new bone growth indicating remodeling to physiological levels does not occur. Finally, occlusal loading is both an important stimulus for remodeling and establishment of the periodontal ligament space during early wound healing as well as enhancing BMP-2-induced cementogenesis.

Animals↗

The influence of nacre surface and its modification on bone apposition: a bone development model in rats.

BACKGROUND: Bone graft substitutes are currently used individually or in various combinations in reconstructing bone defects. Nacre, marine mineralized structure, was recently proposed as a very biocompatible and osteoinductive material for use in periodontal and implant surgery. Our aim was to investigate the interaction between natural nacre and fresh bone marrow, during bone development, in an ectopic site of DA rats. Surface modifications of nacre were tested. METHODS: Demineralized bone matrix (DBM) cylinders (demineralized cortex of diaphysis) prepared from rat femurs were filled with fresh marrow, which was removed from other 2-month old DA rat femurs. Natural nacre particle or nacre which was treated with HCl, phosphate buffer saline (PBS), and Ca(OH)2 to modify its surface was placed into the DBM cylinders. The cylinders were implanted subcutaneously at the thoracic region of growing DA rats. After 4 weeks the cylinders were surgically removed, fixed in buffered formalin, and x-rayed. Scans of the microradiographs and histological evaluation of the DBM cylinders including bone developed at the interface of nacre and its surface modifications were compared to marrow controls. RESULTS: The results show that natural nacre is a poor conductive biomaterial in a bone developmental environment. Nacre surface treated with Ca(OH)2 and PBS was found to be most biocompatible. In this group, new bone was apposed directly on the nacre surface and the total amount of bone was highest in comparison to other treatment groups. CONCLUSIONS: This study does not support previous observations that nacre is osseoinductive. Our model system seems to be very sensitive and capable of testing interaction between surface modifications of biomaterials and fresh marrow in the process of new bone development.

Analysis of Variance↗

Effect of bone porosity on the mechanical integrity of the bone-cement interface.

BACKGROUND: Osteopenia is one factor that may influence the decision about the type of implant fixation to use in total hip arthroplasty. However, clinical studies generally do not associate the outcome of an arthroplasty with the degree of osteopenia. The mechanical integrity of the cement fixation of an implant may be affected by the relative degree of osteopenia, which could account for some of the variable long-term results after total hip arthroplasty performed with cement. The purpose of this study was to determine the effects of bone porosity, trabecular orientation, cement pressure, and cement penetration depth on fracture toughness at the bone-cement interface. METHODS: Trabecular bone from the proximal part of bovine femora was used with a single brand of commercial acrylic bone cement to form compact-tension interface specimens representing a range of bone porosities, orientations, and cement pressures within a clinically achievable range. All specimens were loaded to failure with use of a servohydraulic testing machine, and fracture toughness at the interface was calculated. After testing, images of a representative sample of specimens were made with use of computed tomography to measure the penetration depth of the cement into the bone. RESULTS: Significant correlations were found between fracture toughness and bone porosity, trabecular orientation, and cement pressure, with bone porosity having the strongest effect (p < 0.000015). Examination of the computed tomographic images also showed a significant correlation between fracture toughness and maximum cement penetration depth (p < 0.033), as well as significant partial correlations between maximum and mean penetration depth and bone porosity (p < 0.0037 and p < 0.0028). CONCLUSION: The fracture resistance of the bone-cement interface is greatly improved when the ability of the cement to flow into the intertrabecular spaces is enhanced.

Animals↗

Bone-specific drug delivery systems: approaches via chemical modification of bone-seeking agents.

Despite several decades of progress, bone-specific delivery is still limited by the unique anatomical features of bone, which mainly consists of inorganic hydroxyapatite. A practical approach to this problem is to produce targeted drugs that have a high affinity for hydroxyapatite. Bisphosphonates are a class of synthetic compounds structurally related to pyrophosphate. Bisphosphonates rapidly localise on the bone surface after being administered either intravenously or orally, since the P-C-P portion of the bisphosphonate structure has high affinity for hydroxyapatite. Therefore, bisphosphonate modification might be a promising method for targeting drugs selectively to the bone. Bisphosphonate-conjugated drugs are hydrophilic and highly water-soluble due to the acidic nature of the bisphosphonate moiety at physiological pH, and therefore they hardly permeate through the biological membrane of soft tissues. These physicochemical changes also reduce the intrinsic susceptibility of the drug to metabolism, promoting urinary or biliary excretion as unchanged drug. All these physicochemical and pharmacokinetic alterations contribute to the exceptional skeletal disposition of bisphosphonate-conjugated drugs. Bisphosphonate conjugation is based on chemical modification of the targeting molecule, and therapeutically optimised bisphosphonate derivatives have to be custom-developed on a case-by-case basis. The bisphosphonate moiety is usually coupled with the targeting drug through a specific linkage. The high affinity of bisphosphonate conjugates for the bone is not simply dependent on the bisphosphonate moiety but on the resultant molecule as a whole, including the linker and the linked drug. Lipophilicity (represented as log P) appears to be an appropriate index for predicting the osteotropic properties of bisphosphonate derivatives. Several strategies using bisphosphonate-conjugated drugs have been investigated at a laboratory level with the aim of obtaining therapeutically optimised treatments for conditions such as osteoporosis, osteoarthritis and bone cancer. In each case, the intention is to achieve prolonged local exposure to high concentrations of the targeting drug, thereby improving therapeutic index by enhancing pharmacological efficacy and minimising systemic adverse effects. Although most examples of bone-specific drug delivery via bone-seeking agents still remain in preclinical studies, several phosphonate-coupled radiopharmaceuticals, such as samarium-153 complexed to tetraphosphonate, are expected to be an effective pain palliation therapies for metastatic bone cancer and are currently being developed in clinical trials. Furthermore, recent reports on bisphosphonate-modified proteins have illustrated the feasibility of bone-specific delivery of biologically active protein drugs, such as cytokines and growth factors.

Biocompatible Materials↗

The molecular genetics of bone formation: implications for therapeutic interventions in bone disorders.

Skeletal biology is a complex process involving the developmental commitment and differentiation of chondrocytes and osteoblasts which produce and mineralize cartilage and bone matrix during growth and postnatal life. Several genes are involved in controlling osteogenesis by acting on target cells in a very complex manner. Manipulation of genes in mice and studies of genetic mutations affecting the skeleton in humans have enabled the assessment of the role of transcription factors, bone matrix proteins and regulatory factors involved in the control of chondrocyte and osteoblast differentiation, and have considerably improved our understanding of the bone formation process. Clinical studies and gene polymorphism analyses suggest that the variable expression of particular genes may be linked to clinical osteoporosis. A major challenge in the future will be to develop molecularly targeted approaches to stimulating bone formation and increasing bone mass. The use of mouse strain models and transgenic animals with variable bone density may be useful to identify genetic determinants of bone mass which may serve as a basis for drug discovery and development. On the other hand, the availability of gene microarrays and other emerging genomic techniques are promising tools to identify genes that are distinctly expressed in health and disease. These technologies may also serve to test the mechanisms of action of drugs aimed at increasing bone formation. Genetic studies of the molecular signaling pathways involved in normal and pathological osteogenesis may also help to identify genes that could be targeted for therapeutic intervention. Candidate approaches include selective gene transfection in target cells and the use of drugs acting on gene promoters to selectively enhance gene expression in osteoblasts. The development of these strategies is expected not only to bring new insight into the molecular mechanisms that govern bone formation in normal and pathological situations but, in the long term, may also result in the identification of novel molecular targets for therapeutic interventions for bone formation disorders.

Bone Development↗

Bone induction by fetal and adult human bone matrix in athymic rats.

In the rat the intramuscular implantation of demineralized rat bone matrix induces local bone formation. In adult primates, however, allogenous bone matrix induces little or no bone formation in extraskeletal sites. To assay inductive properties, human demineralized bone matrix from 6 adult donors and 4 fetuses was implanted intramuscularly in athymic rats for 6 weeks. Fetal and adult matrix implants yielded about the same amount of bone: about half of the bone yield from rat or rabbit matrix in the same model. We conclude that human bone matrix has inductive properties and that failures to induce bone formation in adult primates may be due to an inability by the recipients to respond to inductive stimuli of adult bone matrix.

Adolescent↗

Measurement of bone morphogenetic proteins and other growth factors in demineralized bone matrix.

Osteoinductivity of demineralized bone matrix has been attributed to bone morphogenetic proteins (BMP). Other growth factors, including insulin-like growth factor-1 (IGF-1) and transforming growth factor-beta1 (TGF-beta1), have also been detected in demineralized bone matrix. Success of bone graft substitutes containing demineralized bone matrix has been assumed to be closely associated with osteoinductivity of the demineralized bone matrix. Because of differences in bone characteristics between donors and tissue banks, confirmation and measurement of osteoinductivity may play a crucial role in predicting the success of the bone graft substitute. In the current studies, BMP-2, BMP-4, TGF-beta1, and IGF-1 were measured in demineralized bone matrix. A strong association was noted between BMP-2 and TGF-beta1 levels. A strong association was also found between BMP-2 and new bone formation in an ectopic nude rat model.

Bone Demineralization Technique↗

Aluminum deposition in the bone of patients with chronic renal failure--detection of aluminum accumulation without signs of aluminum toxicity in bone using acid solochrome azurine.

In this study, the sensitivity of the aurine tricarboxylic acid (ATA) and acid solochrome azurine (ASA) stain for aluminum were compared under special consideration of the relationship to bone histology in renal osteodystrophy. Al deposition in iliac crest bone biopsies taken from 78 patients with chronic renal failure (CRF) was assessed histochemically using the ATA and ASA stain; the Al accumulation was correlated with bone histology and histomorphometry. Significantly more Al was detectable with the ASA method on trabecular bone surfaces and cement lines (18 +/- 20% vs 4 +/- 12% on surfaces; 13 +/- 18% vs 0.4 +/- 1.3% on cement lines). In 31 cases in which ATA yielded negative results, ASA in contrast indicated Al deposits on up to 20% of the trabecular bone surface. The specimens with more Al on the trabecular bone surface had a significantly higher osteoid volume and osteoid surface. With ATA, these differences were observed at a staining of > or = 10% of the trabecular surface, with ASA at a staining of > or = 40% of the trabecular surface. Therefore, it seems to be possible to detect a very low Al deposition, without any Al-induced changes in bone morphology or signs of Al toxicity in the bone using the ASA method. By contrast, a positive ATA stain is mainly found in biopsies with typical signs of Al-induced changes of histomorphometric bone parameters. We, therefore, recommend the routine use of the ASA stain to detect Al deposition in bone.

Adult↗

Sinus floor elevation using anorganic bovine bone matrix (OsteoGraf/N) with and without autogenous bone: a clinical, histologic, radiographic, and histomorphometric analysis--Part 2 of an ongoing prospective study.

One of the goals of the sinus elevation procedure is the creation of vital bone to effect the osseointegration of dental implants placed in the posterior maxilla. With this goal in mind, in 1993 the Department of Implant Dentistry at New York University College of Dentistry began a long-term clinical, histologic, histomorphometric, and radiographic study of the sinus elevation procedure. The primary parameters included the effects of graft material selection, time allowed for graft maturation, and the effect of barrier membrane placement on the creation of vital bone in the sinus cavity. The effects of these and other parameters on implant survival rates were also to be evaluated. This paper reports the data collected on a subgroup of 113 sinus elevations that used anorganic bovine bone matrix (OsteoGraf/N) alone or in combination with autogenous bone and/or demineralized freeze-dried bone as a graft material. This is the second in a proposed series of papers that will result from this ongoing research project. The results of this study indicate that: OsteoGraf/N appears to be an effective graft material with a 98.2% implant survival rate to date: vital bone formation increased with time; vital bone formation increased moderately when demineralized freeze-dried bone allograft was added, and increased substantially when intraoral autogenous bone was added or when an expanded polytetrafluoroethylene membrane was used; and the increased height achieved by the procedure was stable over a 3-year period. Because of the high overall implant survival rate, it was not possible to determine the relationship between vital bone formation or membrane usage and implant survival.

Animals↗

Bone augmentation by recombinant human BMP-2 and collagen on adult rat parietal bone.

A composite of recombinant human bone morphogenetic protein-2 (rhBMP-2) and collagen was implanted beneath the cranial periosteum of 10-month-old rats to observe bone development and absorbent change of carrier collagen. The rhBMP-2/collagen onlay implant resulted in active bone formation and the augmented bone was connected directly with the original bone, whereas the collagen alone resulted in neither bone nor cartilage. The ossification process in the rhBMP-2/collagen occurred directly through bone formation, similar to intramembranous ossification. The carrier collagen fibers were found in the woven bone and were completely absorbed at 8 weeks in the presence of rhBMP-2, while the collagen alone implant remained encapsulated by a thin, fibrous connective tissue. Our results indicate that rhBMP-2/collagen is an effective material as a biological onlay implant, showing osteoinductive properties and being completely replaced by new bone. Carrier collagen not only plays a role in rhBMP-2 delivery, but also provides a cell anchorage for cell differentiation and remains as an artificial matrix in woven bone.

Absorbable Implants↗

Radiographic features of bone in several strains of laboratory mice and of their tumours induced by bone-seeking radionuclides.

The natural radiographic appearance of the various bones of the skeleton are described for several strains of laboratory mice. The Harwell substrains of CBA, A and 101 are generally similar and become osteoporotic on ageing. Harwell C57BL have similar, but more delicately chiseled, bones. Harwell C3H mice have bones with stouter cortices and may show osteosclerosis on ageing. CF1 females (donated by Dr M. Finkel) showed osteosclerosis and osteophytic outgrowths when aged. NMRI mice (donated by Dr A. Luz) appeared larger than the pure-strain Harwell mice. In general, mouse bones are simple tubular structures with an ivory cortex and a marrow cavity. Cancellous trabecular bone is scanty, even in vertebrae, flat bones and the metaphyses of long bones. Bone-seeking radionuclides administered to mice lead to skeletal tumours: (a) osteosarcomata, which are commonly radio-opaque to a variable degree owing to calcified tumour bone, but which may be osteolytic, (b) primitive mesenchymal (angio-) sarcomata which are non-osteogenic and osteolytic, (c) fibrosarcomata--which also are osteolytic--and to local or general lymphomata from irradiation of parental cells in bone marrow, but no special radiological features have been found associated with these last-named tumours.

Aging↗

[Comparison of whole-body MR imaging and bone scintigraphy in the detection of bone metastases from breast cancer].

The aim of this study was to investigate the usefulness of whole body MR imaging (WB-MRI) in the detection of bone metastases from breast cancer and to compare the results with those from bone scintigraphy. In 21 patients with suspected bone metastasis from breast cancer, both bone scintigraphy and WB-MRI were performed. With WB-MRI, coronal images were obtained using a body coil in an FOV of 48 cm, and sequences of fast short TI inversion recovery (STIR) and gadolinium-enhanced fast spoiled GRASS (SPGR) were used in three parts: from the head to the thorax, the abdomen to the pelvis, and the lower extremities. Of the total 105 metastatic bone lesions, 65 (61.9%) were detected by bone scintigraphy, 98 (93.3%) by fast STIR, and 74 (70.5%) by fast SPGR. Thus, the detection of bone metastases by WB-MRI was excellent. However, detectability in the ribs was lower for WB-MRI than for bone scintigraphy. Contrast-enhanced MRI was useful in the differentiation of osteosclerotic lesions, in which high signal intensity is rare, pleural effusion, which has high signal intensity on STIR, and bone metastatic lesions. In conclusion, WB-MRI showed high reliability in the detection of bone metastatic lesions from breast cancer.

Adult↗

Kinetics of bone marrow repopulation in lethally irradiated rats after transplantation of vascularized bone marrow in syngeneic hind limb.

Grafting of the recipient with bone marrow cell suspension provides only few stromal cells and no autologous environment for cooperation between hemopoietic and stromal cells. Vascularized bone marrow grafts provide the recipient with bone marrow hemopoietic and stromal cells in their natural spatial relationship. It is expected that such a graft will resume its function soon after transplantation and almost immediately repopulate bone marrow cavities of the irradiated recipient as well as supply the sites of cytopoiesis with the necessary growth factors. The aim of the study was to investigate the process of repopulation of bone marrow cavities and lymphoid organs of irradiated recipient by bone marrow cells from syngeneic hind limb transplant. Lewis rats received total body irradiation of 8 Gy followed by orthotopic transplantation of syngeneic limb or i.v. infusion of equivalent amount of bone marrow cells. In control experiments the hind limb was shielded with lead plate during total body irradiation. Ten days after irradiation and hind limb transplantation the yield of nucleated cells from tibia was reaching values of normal animals. In rats receiving i.v. bone marrow cell infusion it was 40% of control values and in rats repopulated from shielded own hind limb it was 60% of controls. In all groups a higher percentage of early and immediate normoblasts and a reduced pool of juvenile and segmented neutrophils was observed. Thirty days after irradiation and repopulation procedures all parameters were returning to normal levels in each group. The results indicate that bone marrow cell transplantation in hind limb graft is highly effective in lethally irradiated animals in reconstituting bone marrow.

Animals↗

Bone mineral density and bone scintigraphy in adult Saudi female patients with osteomalacia.

OBJECTIVE: This prospective study was conducted to demonstrate the role of bone mineral density (BMD) and bone scan in the management of adult Saudi female patients with established diagnosis of osteomalacia. METHODS: Bone scan using Tc99m methylene diphosphonate (MDP) and BMD of the lumbar spine and femoral neck using dual x-ray absorptiometry (DXA) were performed at the time of diagnosis 6 months and one year after therapy in 96 Saudi female patients attending the metabolic bone disease clinic at King Khalid University Hospital, Riyadh, Kingdom of Saudi Arabia, between January 1997 through to June 1999, aged between 20 and 73-years (mean 42 years). Alkaline phosphatase, calcium and inorganic phosphorus were measured for all patients before and after treatment. 25 Hydroxy Vitamin D was only measured with the first BMD measurements. RESULTS: The bone profile showed typical biochemical abnormalities of osteomalacia. The bone scan showed feature of "superscan" in all patients and "pseudofractures" in 43 patients. Bone mineral density measurements were compared with that of normal Saudi subjects matched for age and sex. The BMD was significantly low at diagnosis and showed significant improvement after therapy. The improvement of bone density in response to therapy was more evident in lumbar spine than in femoral neck bone. CONCLUSION: Our results showed that BMD in adult Saudi female patients with osteomalacia was markedly affected probably due to specific constitutional and environmental factors (inadequate exercise, lack of sun exposure and lack of intake of milk and dairy products). In addition, lumbar BMD and serum calcium appeared to be better markers to monitor therapy. Bone scan helped in demonstrating disease activity, the presence of pseudofractures.

Absorptiometry, Photon↗

Study of gelatinized marrow stroma osteoblasts and true bone ceramic active bone.

OBJECTIVE: To investigate a new method to construct tissue-engineering bone that will be applicable clinically. METHODS: The cultured 5th generation rabbit bone marrow stroma osteoblasts (MSO) was dissolved in 3% sodium alginate solution (the final concentration of sodium alginate in the solution being 1%, and MSO, 5x10(6)/L), and then inoculated into prepared true bone ceramic (TBC) and gelatinized the bone by dribbling with calcium gluconate. The standard bone defect models were made in 48 adult New Zealand rabbit's both radius. Among the 48 rabbits, 24 were in Groups A and B, in which the left radius was implanted with gelatinized MSO-TBC (Group A) and right radius implanted with autograft-bone (Group B); and the other 24 were in control group whose left radius was implanted with non-gelatinized MSO-TBC (Group C) and right radius implanted with gelatinized TBC (Group D). Outcomes of the implanted bones were assessed by radiology, pathological histology, osteogenetic quantitative analysis, and biomechanics at 2, 4, 8, 12 weeks postoperatively. RESULTS: In Groups A and B, a satisfactory bone reparation and bony union was noted within 12 weeks. In Groups C and D, bone reparation was not satisfied compared with Group A in terms of ostogenetic quantity and biomechanics. CONCLUSIONS: Gelatinized MSO-TBC is an ideal artificial active bone that overcomes TBC shortcomings of fragileness and smooth surface that is not eligible for seed cell's adhesion. It is promising to put into clinical use extensively.

Animals↗