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[The role of fetus decalcified bone matrix (FDBM) in inducing pure titanium-bone implant integration].

Because of its high biological compatibility, titanium has been a good biomaterial. The implanted artificial bone made from titanium can contact with the vital and mature osseous tissue directly within 3-6 months, the so-called osteointergration. In order to promote the process of osteointergration, FDBM of rabbit was prepared and was combined with pure titanium so as to speed up osteointergration. The study focused on bone density, bone intergration rate, new bone growth rate around the pure titanium, and the Ca2+ and PO(4)3- density of titanium-bone interface. A control group of pure titanium inplant without FDBM was set up. The results showed FDBM had no antigenicity. It could induce and speed up the new bone formation at titanium-bone interface. The titanium-bone intergration time was within 2 months. It was suggested that there were more bone morphogenesis protein (BMP) or other bone induction and bone formation factors in brephobone than that in child and adult bone. As a kind of bone induction material, FDBM was easy prepared, cheap in price, easy to storage, no antigenicity and obvious bone-inductive function.

Animals↗

[Effects of long-term ethanol intake on the bone mass on femoral bone of mice: a microdensitometrical study].

This report on the effects of ethanol intake on bone tissue in ICR strain mice. The authors let male and female ICR mice take 16% ethanol solution (Sake) ad lib for 472 days beginning at the age of 38 days. Observations were using radiograph on bone density of hind legs, we were measured at the middle of the femur densitometer. The effects of indices. Observations were carried out on bone density were analyzed using six indices: the maximum density of the middle of the bone cortex (h1, h2) (the maximum density of the bone cortex (h1 + h2)/2 [hmax]); the minimum density of the middle of the bone marrow (h3) (minimum density of the bone marrow [hmin]); the bone cortical width (d1 + d2); the bone marrow width (d); the cortical bone index (the ratio of cortical bone width to bone width [CBI]); and the radial trabecular index (the ratio of bone width to hmin [RTI]). The results were as follows: In male mice, hmax, hmin, d1 + d2, CBI and RTI were significantly lower than controls (p < 0.01, p < 0.01, p < 0.01, p < 0.01, p < 0.05). In females, hmax, hmin, d1 + d2 and CBI were significantly lower than controls (p < 0.01, p < 0.01, p < 0.01, p < 0.05). The number of osteocytes in the femur diaphysis did not significantly differ between groups. These findings suggest that ethanol intake affects kidney tissues, and decreased reabsorption of calcium were caused by damaging the kidneys, thereby increasing excretion of Ca to the urine. Bone resorption occurred in order to homeostasis of Ca concentration in blood.

Alcoholism↗

Ingrowth of bone into absorbable bone cement: an in vivo microscopic evaluation.

The purpose of the study reported here was to use an in vivo rabbit model to evaluate the rate of bone ingrowth into remodelable calcium phosphate bone cement. We evaluated an in vivo bone chamber placed in a rabbit tibia with its ingrowth compartment filled with absorbable calcium phosphate bone cement (Norian Skeletal Repair System; Norian Corp, Cupertino, Calif). Five New England white rabbits had a single bone chamber implanted into the proximal right tibia. Observations were made and photomicrographs taken on a weekly basis. Results of morphological analysis showed sequential loss of cement and subsequent bone ingrowth over a testing period of up to 30 weeks. Resorption of bone cement was complete in 1 rabbit. The other rabbits had significant bone ingrowth, which reaffirms the biocompatibility of this material. Results of this study showed that using in vivo microscopy with the rabbit bone chamber model was useful in evaluating bone ingrowth and replacement of absorbable bone cement. This model may make it possible to evaluate various combinations of bone cement and bone growth factors, which could serve as an alternative to autogenous bone grafting.

Animals↗

[Preparation of gentamicin-impregnated bone allograft and experimental study on treatment of infective bone defect].

OBJECTIVE: To study and prepare a new kind of bone graft, which has osteogenesis, local anti-infective function and low immunogenicity. METHODS: Gentamicin-impregnated bone was prepared by means of ultrasonic and vacuum, the release of gentamicin in vivo was measured by inhibition bacteria. Ten healthy male adult sheep were made animal infection models of thigh bone or humerus defect of 6 mm x 6 mm x 20 mm at size, and the defect was inoculated into 1 ml 5 x 10(10) CFU/ml Staphylococcus aureus. The animals were randomly divided into the experimental group (n=5, the bone graft with gentamicin was implanted) and the control group (n=5, the bone graft without gentamicin). Macroscopic, WBC count, radiological, and histological investigations were carried out to evaluate the anti-infective and osteosis capability. RESULTS: The concentrations of gentamicin were 46.1 microg/ml in bone allograft and 17.3 microg/ml in muscles after 1 day. The concentrations of gentamicin exceeding the minimum inhibitory concentration lasted for 14 days in vivo. WBC in the control group was higher than that in the experimental group. In the control group, 1 case died owing to septicemia 3 weeks after operation. The implanted bones were wrapped in pus 4 and 6 weeks, and the defects were filled with fibre tissue 8 and 10 weeks after operation. In the experimental group, 1 case was infected, the others had a good concrescence. The bone allografts began to integrate with adjacent bone after 4-8 weeks and integrate well after 12 weeks. The X-ray and histological observation showed that new bone formed and took the place of bone allograft. CONCLUSION: The gentamicin-impregnated bone allograft was of a good sustained release feature in vivo, local anti-infection and osteogenesis. It might be an ideal bone grafting material for bone defects with infection.

Animals↗

[Studies on the possibility of using lyophilized in vitro autogenic bone marrow derived stromal cells to stimulate healing of bone lesions in the jaws].

The authors describe a new method of stimulation of regeneration of bone tissue using autografts of autologous bone marrow supplemented with autologous bone marrow stromal fibroblastoid cells (with osteogenic potential) grown in vitro and lyophilized allogenic bone. Such composite grafts have been used in the treatment of 10 patients with lesion in jaw bone. Bone healing was evaluated using clinical and radiological parameters and was compared with healing in 30 similar lesions treated using composite grafts of autologous bone marrow and allogenic lyophilized bone as well as the spontaneous healing of 45 post-cystic lesions. These data indicate, that composite grafts of autologous bone marrow supplemented with in vitro grown autologous bone marrow stromal cells and lyophilized allogenic bone have excellent capacities accelerating bone healing. In smaller lesions, composite grafts of fresh autologous bone marrow and allogenic lyophilized bone (which are easier to prepare) are also useful.

Adolescent↗

[Future of bone allografts in massive bone resection for tumor].

Currently cryopreservation offers the best means of preserving bone tissue for allografts. At -196 degrees C all enzyme activity is halted and tissue preservation is unlimited. Perfect sterilization, adapted cryoprotection and controlled freezing and thawing are now part of the well-controlled process of bone preservation in bone banks. At implantation, the mechanical properties of cryopreserved bone is as good as or better than fresh bone, although the diaphyseal cortical bone is more fragile. Anatomic and physiologic reconstruction of the graft area is a major factor in graft resistance. It takes approximately three weeks for vessels to penetrate cancellous allografts and at least one month for total revascularization. The delay may reach several years for cortical bone. The immune response of the host is determined by the antigenic properties of the leukocytes in the bone marrow as well as the blood vessels and nerves. The protein-mineral complex itself has little antigenic effect. A certain number of non-specific immune reactions result from transfusions almost always performed with bone grafting. At the present time, there is no artificial material capable of providing a mechanically acceptable substitute for allograft bone in limb reconstruction. Allograft bone currently stocked in bone banks provides a biologically and clinically acceptable means of reconstruction after major bone loss. Other factors such as public acceptance and administrative authorizations will also play an important role in the future of massive reconstruction with bone allografts.

Bone Neoplasms↗

Effects of a bisphosphonate on the expression of bone specific genes after autogenous free bone grafting in rats.

The purpose of this study was to evaluate the clinical availability of a bisphosphonate in autogenous free bone grafts. Bisphosphonate (0.01 mg/kg/day) was administered daily after an autogenous free bone graft on a rat calvarium. The effects of a bisphosphonate on the resorption of grafted bone and mRNA expression in bone specific genes, i.e. bone morphogenetic protein 2, bone morphogenetic protein 4, alkaline phosphatase, osteocalcin, osteoclast inhibitory factor and calcitonin receptor, were studied via a reverse transcription-polymerase chain reaction (RT-PCR), real time RT-PCR and tartrate-resistant alkaline phosphatase (TRAP) staining. In a clinical and histomorphological review, bone resorption decreased in the experimental group in contrast to the control group where active bone resorption was observed. Bisphosphonate altered not only the mRNA expression of the bone resorption associated genes but also the bone formation associated genes. The expression of the calcitonin receptor (CTR) mRNA was not detected and the osteoclast inhibitory factor (OCIF) was significantly up-regulated in the experimental group as opposed to the control group. The expressions of osteocalcin and alkaline phosphatase mRNAs were also higher in the experimental group. However, there was no significant difference in the mRNA expression of bone morphogenetic proteins between the two groups. The data suggest the possibility of a clinical application of bisphosphonates for decreasing resorption of grafted bone.

Acid Phosphatase↗

Lack of evidence for an increase in interleukin-6 expression in adult murine bone, bone marrow, and marrow stromal cell cultures after ovariectomy.

Interleukin-6 (IL-6) has been implicated as a mediator of postmenopausal bone loss. In vitro studies of bone and bone marrow cells have suggested that estrogen regulates bone turnover by controlling the production of IL-6, a potent stimulator of osteoclastogenesis and bone resorption. To investigate this hypothesis in an in vivo model, we examined the effect of ovariectomy or estrogen replacement on IL-6 mRNA and protein expression in adult mouse bone and bone marrow in vivo and in marrow stromal cell cultures. Eight-week-old CD-1 mice were sham-operated (SHAM), ovariectomized (OVX), or ovariectomized and subcutaneously implanted with 21-day slow-release pellets containing 10 micrograms of 17 beta-estradiol (O + E). Placebo pellets were implanted in the SHAM and OVX mice. Uterine weights at 1, 2, or 3 weeks after surgery were significantly decreased (68-76%) in OVX animals compared with SHAM or O + E. In mice sacrificed at 1 or 3 weeks after surgery, we found by nonquantitative reverse transcribed polymerase chain reaction (RT-PCR), that SHAM, OVX, and O + E calvariae (CALV) constitutively expressed IL-6 mRNA. In contrast, IL-6 mRNA was either barely detectable or absent in the tibia (TIB) and bone marrow (BM). In the mice sacrificed 3 weeks after surgery, we determined by quantitative RT-PCR that IL-6 mRNA in the CALV from the OVX and O + E groups were decreased by 81 and 92%, respectively, compared with SHAM. IL-6 protein levels in the flushed bone marrow (BMSups) were detectable and were not significantly different among the groups. In bone marrow cells that were cultured for 1 week, basal levels of IL-6 protein were low and did not differ significantly among the SHAM, OVX, or O + E groups sacrificed 1, 2, or 3 weeks after surgery. After the addition of hrIL-1 alpha, IL-6 protein levels increased 100- to 1300-fold over control. IL-6 levels in cells from animals sacrificed 2 weeks after surgery were significantly lower in the hrIL-1 alpha-stimulated OVX and O + E groups than in hrIL-1 alpha-stimulated SHAM cell cultures. In conclusion, in this model we could find no increase in IL-6 production with in vivo estrogen withdrawal in calvaria, long bones, bone marrow, or marrow stromal cell cultures. If increases in IL-6 expression are involved in the effects of estrogen withdrawal on bone, the magnitude of these changes are relatively small and below the limits of detection of the assays that we employed.

Animals↗

Increased bone density and decreased bone turnover, but no evident alteration of fracture susceptibility in elderly women with diabetes mellitus.

Bone density, bone turnover and fracture susceptibility were evaluated in 1,132 randomly recruited women, all 75 years old. Seventy-four of the women had diabetes, while 1,058 women did not. Areal bone mineral density (aBMD) of the hip and lumbar spine was investigated by dual energy X-ray absorptiometry (DXA), and bone mass of the calcaneus was measured by ultrasound. Urinary deoxypyridinoline/creatinine (U-DPD/Crea) and serum C-terminal cross-linked telopeptide of type 1 collagen (S-CTX) were assessed as markers of bone resorption. Serum bone-specific alkaline phosphatase (S-bone ALP) and serum osteocalcin (S-OC) were assessed as markers of bone formation. Also, serum 25(OH) vitamin D and serum parathyroid hormone (S-PTH) were assessed. Fracture susceptibility was evaluated retrospectively and prospectively for up to 6.5 years. In diabetic women, the aBMD of the femoral neck was 11% higher (p<0.001), and BMD of the lumbar spine was 8% higher (p=0.002) than in non-diabetic women. There was no difference in bone mass by ultrasound of the calcaneus. Women with diabetes had higher BMD of the femoral neck (p<0.001) and lumbar spine (p=0.03) also after correction for differences in body weight. In diabetic women, U-DPD/Crea, S-CTX, and S-OC were decreased when compared with non-diabetic women (p=0.001 or less). After correction for covariance of body weight and plasma creatinine, S-CTX (p<0.001) and S-OC (p<0.001) were still lower in the diabetic women. Diabetic patients had hypovitaminosis D (p=0.008), a difference explained by differences in time spent outdoors and body weight. S-PTH did not differ between the groups. Women with diabetes had no more lifetime fractures (52%) than women without diabetic disease (57%), (p=0.31). This study shows that elderly women with diabetes and without severe renal insufficiency have high bone mass and low bone turnover. The high bone mass and low bone turnover is not likely to have a strong influence on fracture susceptibility.

Absorptiometry, Photon↗

Lower bone cellular activities in male and female mature C3H/HeJ mice are associated with higher bone mass and different pyridinium crosslink profiles compared to C57BL/6J mice.

The female inbred strains of C3H/HeJ (C3H) and C57BL/6J mice (B6), having high and low femoral peak bone mass, respectively, were proposed as models for studying the genetic regulation of bone mass. Here, we compared the known bone phenotype, in 4.5-month-old C3H versus B6 mice, in both genders. Femoral bone mineral content, trabecular bone mass, and thickness at the distal metaphysis were higher in C3H mice. In the long bones, deoxypyridinoline content was lower and pyridinoline/deoxypyridinoline ratios were greater in C3H. Intrafibrillar collagen packing is different not only within strains but also within sexes. Bone resorption activity, evaluated by urinary pyridinium crosslinks and active resorption surfaces in the femoral metaphysis, was lower in C3H. Bone formation activity, evaluated by serum osteocalcin and alkaline phosphatase (ALP) levels, as well as histomorphometric indices of bone formation in the femoral metaphysis and the cortical tibia, was lower in C3H. Conversely, the ALP- and Von Kossa-positive colony-forming units were more numerous in bone marrow cell cultures originating from male C3H. In both strains, resorption and formation activities were lower in males than in females. In C3H, males had lower bone mass than females whereas the opposite was seen in B6. In conclusion, we found that the lower cellular activities in C3H were associated with high cancellous bone mass and pyridinium crosslink levels, which might account for the more mineralized bone in C3H mice compared to that in B6 mice.

Amino Acids↗

Bone mass and comparative rates of bone resorption and formation of fibular autografts: comparison of vascular and nonvascular grafts in dogs.

The metabolic fate of whole grafts that were either vascularized or nonvascularized were compared. This study was designed to quantify and correlate changes in bone resorption, formation, and mass in orthotopic, stably fixed, weight-bearing autografts. The grafts were 8-cm segments of the fibula that were internally fixed. Fibula segments subjected to sham operations, nonvascularized autografts, and vascularized autografts were studied in 16 dogs at three months after surgery. Three months prior to surgery the dogs were labeled repeatedly over two months with 3H-tetracycline and 3H-proline. Metabolic turnover of whole grafts was evaluated by quantifying loss of 3H-tetracycline for measuring postoperative resorption of bone mineral and loss of 3H-collagen for resorption of bone collagen. Net changes in bone dry weight, calcium, and collagen per whole grafts were obtained to determine differential changes in the mineral and matrix mass. The difference in change between bone resorption and bone mass was used to determine the amount of new bone formation that had replaced the resorbed bone. Vascularized autografts lost more mass (12%), and had more bone resorption (40%) and more bone formation (28%) than sham operated and unoperated fibulas. Nonvascularized grafts lost much more bone mass (48%) because resorption was large (61%) and formation was relatively small (13%). More new bone was formed in vascularized autografts than in nonvascularized autografts. During the incorporation of bone grafts, resorption is an early and rapid process, whereas formation is a late and slow process.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

The 'Functional Muscle-Bone Unit': probing the relevance of mechanical signals for bone development in children and adolescents.

The present text deals with the relationship of muscle force and mass to bone mass and geometry in the developing skeleton of children and adolescents. Recent results of the last ten years are discussed with reflection on Harold Frost's 'mechanostat hypothesis'. Bone mass and geometry follow the development of body size and muscle force in children and adolescents. Thereby, bone is adapted to the tissue strain due to biomechanical forces. This process is modified by hormonal signals (i.e., estrogens and androgens). Therefore, the quantified relationship of muscle force to bone stability is a reasonable approach to distinguish between primary and secondary bone diseases. Primary bone diseases are characterized by a disturbed adaptation of bone to biomechanical forces. In contrast, secondary bone diseases show a correct adaptation of bone to loaded forces in combination with a decline of muscle force. Therefore, the 'Functional Muscle-Bone Unit' was introduced into the diagnostics of pediatric bone diseases. The ratio of two parameters--referred to bone strength on the one and to biomechanical forces on the other side--is a reasonable diagnostic approach to distinguish between primary and secondary bone diseases.

Adolescent↗

In vitro study of osteogenic differentiation of bone marrow stromal cells on heat-treated porcine trabecular bone blocks.

This in vitro study investigated the potential of the heat-treated porcine trabecular bone block as a bone substitute for the treatment of bone defects or related diseases. Chemical, mechanical, and morphological studies of bone blocks were performed. The resultant properties were compared with the properties of currently available commercial products from bovine trabecular bones. The major component of the bone block was hydroxyapatite, and the ratio of Ca/P was 1.65-1.66. The average values of the compressive Young's modulus and the ultimate strength were 346.33 +/- 83.15 and 6.66 +/- 1.62 MPa, respectively. The pore size of the heat-treated bone blocks was approximately 300-500 microm. For the biological investigations, expanded bone marrow stromal cells (BMSCs) were isolated from the femurs of New Zealand White rabbits and were dynamically seeded into the heat-treated porcine bone block (10x10x5 mm3). Before the cells were seeded, the heat-treated porcine bone blocks were divided into two groups: collagen coated blocks (n=16) and uncoated blocks (n=16). Within each group, the blocks were again divided into two groups, depending on the culture method, i.e., static or rotating culture. Cells were cultured in the blocks for up to 6 weeks. Scanning electron microscopic examination after 4 weeks showed that the cell layers attached to the porcine bone block. Proliferation and osteogenic differentiation were analyzed by cell counting, an MTT assay, alkaline phosphatase activity, and total protein content. The deposition of extracellular substances and osteoid formation surrounded by osteoblast-like cuboidal cells were confirmed through histochemical staining and transmission electron microscopy. Based on the results of this study, we conclude that heat-treated porcine trabecular bone has great potential as a bone substitute and may even be superior to currently available commercial products.

Animals↗

Integration of endochondral bone grafts in the presence of demineralized bone matrix.

The use of endochondral bone grafts (EC) and demineralized bone matrix (DBM), which contains a potent osteoinductive matrix, may promote the repair of nonregenerative defects. The purpose of the current work is to assess qualitatively and quantitatively the effect of DBM on the healing of EC bone grafts and to compare it to the healing of EC bone grafts alone. Twenty-four defects in rabbit skulls were filled with EC bone grafts alone, DBM alone, or combined EC and DBM. Histologic and immunohistologic changes were examined in 2 weeks. The amount of new bone formation was quantified by image analysis. Healing of all the groups was characterized by the presence of a cartilage intermediate stage. In the EC bone grafts alone, healing was localized to the host bone/graft interface. In the composite group, amalgamation of the new bone, DBM, and bone graft progressed throughout the whole width and depth of the defect, uniting the graft to the recipient bed. The amount of new bone formed was significantly greater (47%) in the composite group than the EC group. In conclusion, DBM powder augments the bone-induction capacity of the recipient bed as well as the bone graft. The composite EC bone grafts and added DBM possess properties required for an effective graft material and merit further clinical evaluation.

Animals↗

Expression of CD31, Met/hepatocyte growth factor receptor and bone morphogenetic protein in bone metastasis of osteosarcoma.

The mechanism of metastasis of osteosarcoma cells to other bones has not yet fully been clarified. The purpose of the present study was to examine whether various factors involve the formation of osteosarcoma metastatic foci in other bones. Immunohistochemically, CD31 expression in osteosarcoma with no bone metastasis and osteosarcoma with bone metastasis was noted in 10 and 75% of cases, respectively. Met/hepatocyte growth factor (HGF) receptor expression in osteosarcoma with no bone metastasis and osteosarcoma with bone metastasis was noted in 90 and 25% of cases, respectively. Bone morphogenetic protein (BMP) expression in osteosarcoma with no bone metastasis and osteosarcoma with bone metastasis was noted in 20 and 75% of cases, respectively. Metastasis of osteosarcoma cells to other bones was significantly correlated with expression of BMP and CD31 and with no expression of Met/HGF receptor protein in osteosarcoma cells. In contrast, expression of insulin-like growth factor receptor in osteosarcoma cells did not correlate significantly with bone metastasis. These results suggest that formation of metastatic foci of osteosarcoma cells in other bones is regulated by CD31, which is associated with migration between endothelial cells, by BMP, which can induce and activate various mesenchymal cells affecting bone formation, and by escape of effect by HGF, which promotes differentiation of osteosarcoma cells.

Adolescent↗

Interleukin 10-deficient mice develop osteopenia, decreased bone formation, and mechanical fragility of long bones.

BACKGROUND & AIMS: Bone loss is a common complication of human inflammatory bowel disease (IBD), but its mechanisms are not understood completely. We investigated bone metabolism in interleukin-10-deficient ( IL-10-/- ) mice, an animal model with IBD features. METHODS: IL-10-/- male mice (8- and 12-weeks-old) and their age-matched wild-type counterparts (C57BL/6J) were studied. Bone mass of the femur was determined by ashing. Tibial cancellous and cortical bone mass and formation was measured by static and dynamic histomorphometry. Biomechanical strength of the femur was tested. Primary bone marrow stromal cell cultures were used to assess osteoblast generation. Serum levels of 25-OH vitamin D 3, insulin-like growth factor-1 (IGF-1), parathyroid hormone, osteocalcin, and deoxy-pyridinoline cross-links were measured. The presence of colitis was determined histologically, and by IL-12 and interferon-gamma (IFN-gamma) secretion from cultured colonic explants. RESULTS: Eight- and 12-week-old IL-10-/- mice developed osteopenia of both cancellous and cortical bone, evidenced by lower femoral ash weight, cancellous bone area and surface, trabecular number, and decreased cortical bone area and width. Osteopenia was associated with mechanical fragility, manifested by decreased stiffness and mechanical load at fracture, and was caused by suppressed bone formation, indicated by decreased cancellous double-labeled surface, mineralizing surface, serum osteocalcin level, and mineralized nodule number in bone marrow stromal cell cultures. IL-10-/- mice with colitis had significantly less bone mass compared with IL-10-/- mice without colitis. CONCLUSIONS: IL-10-/- mice develop the hallmarks of osteoporosis, that is, reduced bone mass, increased mechanical fragility, and suppressed bone formation. The presence of colitis is an important contributor to osteoporosis in IL-10-/- mice.

Animals↗

MR imaging, bone scintigraphy, and radiography in bone stress injuries of the pelvis and the lower extremity.

PURPOSE: To compare MR imaging, radiography and bone scintigraphy in the diagnosis of stress injuries to bones of the pelvis and lower extremity. MATERIAL AND METHODS: Fifty consecutive conscripts with clinical signs of a stress injury to bone underwent MR imaging and bone scintigraphy. Forty-three patients also had radiographs available. Bone scintigraphy served as a gold standard. RESULTS: Compared to the bone scintigraphy, the sensitivity of radiography was 56%, specificity 94%, accuracy 67%, positive predictive value (PPV) 95%, and negative predictive value (NPV) 48%. The kappa value for radiography and bone scintigraphy was fair (0.39). Correspondingly, the sensitivity of MR imaging was 100%, specificity 86%, accuracy 95%, PPV 93% and NPV 100%. The kappa value for MR imaging and bone scintigraphy was very good (0.89). MR imaging depicted 3 bone stress injuries that were not visible on bone scintigraphy. Positive findings obtained from radiography correlated with MR signs of fracture line or callus (p<0.001). CONCLUSION: MR imaging is more sensitive than two-phase bone scintigraphy, and MR imaging should be used as the gold standard in the assessment of stress injuries of bone. Radiography reveals mainly the late phases of bone stress injuries, such as stress fracture and callus.

Adult↗

Parathyroid hormone-independent osteoclastic resorptive bone disease: a new variant of adynamic bone disease in haemodialysis patients.

BACKGROUND: Osteitis fibrosa cystica (OFC) caused by secondary hyperparathyroidism is the pre-eminent form of uraemic osteodystrophy. In recent years, however, new bone abnormalities have been described. Among them adynamic bone disease (ABD) has become a focus of growing interest. Marked suppression of dynamic bone measurements with normal or near-normal static bone-forming parameters are the hallmarks of this disorder. Depressed parathyroid hormone (PTH) levels, frequently evident in this entity, have been linked causally with low bone turnover. METHODS: We reviewed bone biopsy specimens from 96 patients with end-stage renal disease undergoing chronic haemodialysis. RESULTS: We found OFC in 50% of our patients, 20% had mixed bone disease, 24% showed bone morphology of ABD and a minority (6%) had osteomalacia, mostly due to aluminium accumulation. In the patients that were affected by ABD there was a distinct subgroup with bone morphology featuring a striking increase in osteoclast number and osteoclast surface, whereas the osteoid volume, osteoid thickness, osteoblast surface, tetracycline uptake and bone formation rates were diminished as in ordinary ABD. Similarly the PTH levels in this subgroup were low or undetectable. CONCLUSION: We describe patients undergoing chronic haemodialysis with static and dynamic bone forming parameters, indistinguishable from that of ABD, but differing from the classic ABD by the presence of increased osteoclastic bone resorption. The suppressed PTH levels in this subgroup suggests that factors other than PTH activate osteoclasts in some patients on chronic haemodialysis. Uraemic cytokines and/or toxic metabolites, including beta-microglobulin, may be involved in this disorder. The precise nature of this bone abnormality remains to be defined by further studies.

Adolescent↗