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The use of hydroxyapatite and autogenous cancellous bone grafts to repair bone defects in rats.

Bone grafts are frequently used in the treatment of bone defects. Bone harvesting can cause postoperative complications and sometimes does not provide a sufficient quantity of bone. Therefore, synthetic biomaterials have been investigated as an alternative to autogenous bone grafts. The objective of this study was to evaluate the repair of bone defects by autogenous cancellous bone grafts or porous bioceramic discs of hydroxyapatite/phosphate cement mixture. Two 5-mm diameter defects were made in the skulls of rats and filled with the bioceramic material or cancellous bone. The rats were sacrificed 2, 4, 8 and 24 weeks after surgery and tissue samples were analyzed by radiography and histology. By the 24th week, the defects filled with autogenous cancellous bone grafts or bioceramic material showed similar volumes of bone tissue within the defect. However, defects treated with bioceramic material were almost completely closed as a result of the joining of ceramic fragments and the neoformed bone tissue, while those filled with autogenous grafts showed several areas filled with connective tissue. These results indicated that the osteointegration of bioceramic fragments allowed the reconstruction of parietal bone defects without the need for a bone graft.

Animals↗

Effects of gonadotropin-releasing hormone agonists on bone metabolism markers and bone mineral density in patients with prostate cancer.

OBJECTIVES: To better understand bone metabolism and predict bone loss in treatment using gonadotropin-releasing hormone agonist for patients with prostate cancer. METHODS: The changes in bone mineral density and blood levels of bone metabolism markers and the level of pyridinoline cross-linked carboxy-terminal telopeptide of type I collagen, a specific marker of bone resorption, and carboxy-terminal pro-peptide of human type I procollagen, a specific marker of bone formation, were examined in 27 consecutive patients with prostate cancer without bone metastasis. RESULTS: After 2 years of gonadotropin-releasing hormone treatment, the bone mineral density was significantly lower (median 0.937 g/cm2) than before treatment. Pyridinoline cross-linked carboxy-terminal telopeptide of type I collagen began to increase significantly 6 months after the start of treatment (3.0 to 8.3 ng/mL, median 4.6, at baseline versus 3.4 to 8.2 ng/mL, median 5.2, after 6 months). Carboxy-terminal pro-peptide of human type I procollagen began to show a significant rise 1 year after the start of treatment (from 72.8 to 221.5 ng/mL, median 102.0, at baseline to 82.7 to 293.4 ng/mL, median 132.0, at 1 year). CONCLUSIONS: Functional coupling between bone resorption and formation was noted, and a decrease in bone mass, even in men, owing to androgen deficiency, was biochemically demonstrated. Fluctuations in these two bone metabolism markers preceded the decrease of bone mineral density. Therefore, these markers might be a predictor of bone loss.

Adenocarcinoma↗

Bone growth stimulators. New tools for treating bone loss and mending fractures.

In the new millennium, humans will be traveling to Mars and eventually beyond with skeletons that respond to microgravity by self-destructing. Meanwhile in Earth's aging populations growing numbers of men and many more women are suffering from crippling bone loss. During the first decade after menopause all women suffer an accelerating loss of bone, which in some of them is severe enough to result in "spontaneous" crushing of vertebrae and fracturing of hips by ordinary body movements. This is osteoporosis, which all too often requires prolonged and expensive care, the physical and mental stress of which may even kill the patient. Osteoporosis in postmenopausal women is caused by the loss of estrogen. The slower development of osteoporosis in aging men is also due at least in part to a loss of the estrogen made in ever smaller amounts in bone cells from the declining level of circulating testosterone and is needed for bone maintenance as it is in women. The loss of estrogen increases the generation, longevity, and activity of bone-resorbing osteoclasts. The destructive osteoclast surge can be blocked by estrogens and selective estrogen receptor modulators (SERMs) as well as antiosteoclast agents such as bisphosphonates and calcitonin. But these agents stimulate only a limited amount of bone growth as the unaffected osteoblasts fill in the holes that were dug by the now suppressed osteoclasts. They do not stimulate osteoblasts to make bone--they are antiresorptives not bone anabolic agents. (However, certain estrogen analogs and bisphosphates may stimulate bone growth to some extent by lengthening osteoblast working lives.) To grow new bone and restore bone strength lost in space and on Earth we must know what controls bone growth and destruction. Here we discuss the newest bone controllers and how they might operate. These include leptin from adipocytes and osteoblasts and the statins that are widely used to reduce blood cholesterol and cardiovascular damage. But the main focus of this article is necessarily the currently most promising of the anabolic agents, the potent parathyroid hormone (PTH) and certain of its 31- to 38-aminoacid fragments, which are either in or about to be in clinical trial or in the case of Lilly's Forteo [hPTH-(1-34)] tentatively approved by the Food and Drug Administration for treating osteoporosis and mending fractures.

Animals↗

Endosteal new bone formation in the long bones of adjuvant treated rats.

Histopathological changes were examined mainly in the diaphyseal parts of long bones, especially femur in adjuvant-treated male Lewis-SPF rats, with reference to clinical symptoms of chronic osteoarthritis. The diaphyseal bone marrow of long bones in these rats sequentially showed three different processes of chronic pathological changes, which, however, partly overlapped each other. Initially, multiple epitheloid cell granulomas or granulomatous lesions containing fibrin deposits began to appear in the marrow space about 22 days after adjuvant injection, when the joint score of arthritis reached a peak in severity. Secondly, about a week after appearance of the granulomas, there occurred the intramembranous endosteal new bone formation proceeding from the endosteum towards the granulomatous lesions. The bone formation reached a maximum about 64 days after the treatment, when the redness of joints of feet and hands was already sedated. Finally, about 40 days after occurrence of the second event, the newly growing bone matrix began to be actively resorbed simultaneously. On the other hand, in the bone marrow of metaphyseal parts of long bones in these rats, severe acute osteomyelitis was observed from an early stage, with marked destruction of bone trabeculae and simultaneous new bone formation. In the diaphyseal bone marrow of affected long bones, the epitheloid cell granulomas appear to induce the endosteal new bone formation.

Adjuvants, Immunologic↗

Healing of segmental bone defects with granular porous hydroxyapatite augmented with recombinant human osteogenic protein-1 or autologous bone marrow.

Hydroxyapatite is a synthetic bone graft, which is used for the treatment of bone defects and nonunions. However, it is a rather inert material with no or little intrinsic osteoinductive activity. Recombinant human osteogenic protein-1 (rhOP-1) is a very potent biological agent, that enhances osteogenesis during bone repair. Bone marrow contains mesenchymal stem cells, which are capable of new bone formation. Biosynthetic bone grafts were created by the addition of rhOP-1 or bone marrow to granular porous hydroxyapatite. The performance of these grafts was tested in a sheep model and compared to the results of autograft, which is clinically the standard treatment of bone defects and nonunions. A 3 cm segmental bone defect was made in the tibia and fixed with an interlocking intramedullary nail. There were five treatment groups: no implant (n=6), autograft (n=8), hydroxyapatite alone (n=8), hydroxyapatite loaded with rhOP-1 (n=8), and hydroxyapatite loaded with autologous bone marrow (n=8). At 12 weeks, healing of the defect was evaluated with radiographs, a torsional test to failure, and histological examination of longitudinal sections through the defect. Torsional strength and stiffness of the healing tibiae were about two to three times higher for autograft and hydroxyapatite plus rhOP-1 or bone marrow compared to hydroxyapatite alone and empty defects. The mean values of both combination groups were comparable to those of autograft. There were more unions in defects with hydroxyapatite plus rhOP-1 than in defects with hydroxyapatite alone. Although the differences were not significant, histological examination revealed that there was more often bony bridging of the defect in both combination groups and the autograft group than in the group with hydroxyapatite alone. Healing of bone defects, treated with porous hydroxyapatite, can be enhanced by the addition of rhOP-1 or autologous bone marrow. The results of these composite biosynthetic grafts are equivalent to those of autograft.

Animals↗

Bone healing and graft resorption of autograft, anorganic bovine bone and beta-tricalcium phosphate. A histologic and histomorphometric study in the mandibles of minipigs.

OBJECTIVE: The purpose was to qualitatively and quantitatively compare the bone formation and graft resorption of two different bone substitutes used in both orthopedic and oral surgery, with autogenous bone as a positive control. MATERIALS AND METHODS: Three standardized bone defects were prepared in both mandibular angles of 12 adult minipigs. The defects were grafted with either autograft, anorganic bovine bone (ABB), or synthetic beta-tricalcium phosphate (beta-TCP). Sacrifice was performed after 1, 2, 4, and 8 weeks for histologic and histomorphometric analysis. RESULTS: At 2 weeks, more new bone formation was seen in defects filled with autograft than with ABB (P approximately 0.0005) and beta-TCP (P approximately 0.002). After 4 weeks, there was no significant difference between beta-TCP and the two other materials. Defects grafted with ABB still exhibited less bone formation as compared with autograft (P approximately 0.004). At 8 weeks, more bone formation was observed in defects grafted with autograft (P approximately 0.003) and beta-TCP (P approximately 0.00004) than with ABB. No difference could be demonstrated between beta-TCP and autograft. beta-TCP resorbed almost completely over 8 weeks, whereas ABB remained stable. CONCLUSION: Both bone substitutes seemed to decelerate bone regeneration in the early healing phase as compared with autograft. All defects ultimately regenerated with newly formed bone and a developing bone marrow. The grafting materials showed complete osseous integration. Both bone substitutes may have a place in reconstructive surgery where different clinical indications require differences in biodegradability.

Animals↗

Osteoprotegerin regulates bone formation through a coupling mechanism with bone resorption.

Deficiency of osteoprotegerin (OPG), a soluble decoy receptor for receptor activator of nuclear factor-kappaB ligand (RANKL), in mice induces osteoporosis caused by enhanced bone resorption, but also accelerates bone formation. We examined whether bone formation is coupled with bone resorption in OPG-deficient (OPG-/-) mice using risedronate, an inhibitor of bone resorption. Histomorphometric analysis showed that bone formation-related parameters (e.g. mineral apposition rate and osteoblast surface/bone surface) in OPG-/- mice sharply decreased with suppression of bone resorption by daily injection of risedronate for 30 d. OPG-/- mice exhibited high serum alkaline phosphatase activity and osteocalcin concentration, both of which were decreased to the levels in wild-type mice by the risedronate injection. Serum levels of RANKL were markedly elevated in OPG-/- mice, but were unaffected by risedronate. The ectopic bone formation induced by bone morphogenetic protein-2 implantation into OPG-/- mice was not accelerated even with a high turnover rate of bone, but attenuation of mineral density from the ectopic bone was more pronounced than that in wild-type mice. These results suggest that bone formation is coupled with bone resorption at local sites in OPG-/- mice, and that serum RANKL levels do not reflect this coupling.

Animals↗

Alveolar ridge augmentation with rhBMP-2 and bone-to-implant contact in induced bone.

The objective of this study was to examine alveolar ridge augmentation following implantation of recombinant human bone morphogenetic protein (rhBMP-2) with an allogeneic freeze-dried demineralized bone matrix (DBM) mixed with autologous blood. A second objective was to evaluate bone-to-implant contact in induced bone. Bilateral surgically created supraalveolar ridge defects in five young adult beagle dogs were implanted with the rhBMP-2-DBM-blood device. Transmucosal dental implants were placed at weeks 8 and 16 postsurgery The animals were euthanized 24 weeks following ridge augmentation. Healing was uneventful in all animals. Radiographic observations indicated substantial bone formation, including regions of radiolucency, at week 8. At week 16, the radiolucencies were generally resolved, and the trabecular structure of the induced bone resembled that of the adjacent residual bone. There were no remarkable differences in radiographic observations between weeks 16 and 24 after ridge augmentation. Histologic analysis revealed dense woven and lamellar induced bone. Any residual DBM appeared remineralized, at least in part. A large portion of the dental implants (approximately 70%) were housed in induced bone with evidence of limited crestal resorption. There was no significant difference in bone density between induced and residual bone, and the levels of bone-to-implant contact were similar (approximately 55%). The rhBMP-2 construct used in this study has a potential to augment alveolar ridge defects. Also, no difference in levels of osseointegration may be expected in induced and residual bone following a two-stage procedure of rhBMP-2-induced ridge augmentation and dental implant placement.

Alveolar Process↗

[Repair of bone defect with benign tumor by embryonic bone transplantation].

OBJECTIVE: To evaluate the clinical results of repair of bone defect by embryonic bone transplantation. METHODS: From January 1994 to June 1999, 148 cases of bone defect were repaired by embryonic bone transplantation following alcohol treatment, there were 63 cases with bone cyst, 42 cases with fibrous dysplasia of bone, 26 cases with giant cell tumor of bone, and 17 cases with enchondroma among them. The maximal bone defect was 3.5 cm x 10.0 cm, while the minimal defect was 0.5 cm x 1.0 cm. RESULTS: All of those bone defect with benign tumor were bone union used by embryonic bone transplantation after 3 months to 1 year of operation, the average healing course was 6.2 months, followed up 1 to 6 years, averaged 14 months, no tumor recurrence and no obvious local or system response were observed. CONCLUSION: Embryonic bone can be used as a good repairing material of postoperative bone defect of benign tumors, the clinical results are satisfactory.

Adolescent↗

[Bone histology and clinical diagnostic criteria in aluminum-induced bone disease].

Bone remodeling and aluminum (Al) staining were carried out in 429 bone biopsies from patients with uremic bone disease, 273 cases were Al positive (64%). In high-turnover, low-turnover and mixed type of renal osteodystrophy the Al-positive rate was 29%, 75% and 80%, and Al deposition on bone surfaces was 44 +/- 33%, 80 +/- 30% and 62 +/- 35% respectively. Thus the low-turnover and mixed type have a higher Al-positive rate and more Al deposition than the high-turnover type. Animal experiments using decalcified bone matrix implants showed that Al inhibited all bone remodeling processes except cartilage formation. These and other data indicate that Al induces low-turnover bone disease, i.e., osteomalacia or aplastic bone disease. Osteomalacia in our series showed increased osteoid area and mineralization lag time, and decreased calcified bone area, bone mineralization rate and cells number. Aplastic bone disease was similar with that but had reduced osteoid and a normal ratio of steroid to calcified bone. The relationship of these studies to clinical diagnostic criteria of Al-induced bone disease is discussed.

Adolescent↗

Phosphotungstic acid-iron-haematoxylin staining method for osteoid, boundary bone and bone components in paraffin sections.

A new staining technique which stains osteoid and bone tissue differentially and also demonstrates boundary bone, pathological osteoid and the changes in ageing, pathological and dead bone matrix in decalcified paraffin or low-viscosity-nitrocellulose bone sections was developed. This phosphotungstic acid-iron-haematoxylin (PTAIH) method is based on pretreating the sections with phosphotungstic acid followed by an iron alum mordant and staining in haematoxylin with subsequent timed differentiation, at certain stages of which the features listed above appear. Van Gieson's picrofuchsin is then used as a counterstain. After standard differentiation osteoid appears red in sharp contrast with the black bone, young and woven bone, old and lamellar bone, and allows one to demonstrate changes in stainability of diseased osteoid and bone matrix, and dead bone. With the differentiation done individually and interrupted at certain stages it is possible to distinguish between various bone components depending on the amount and quality of their in vivo mineralisation. Comparison with controls showed that in this respect the method is more sensitive than the curremt staining techniques of undecalcified bone sections since it demonstrates not only unmineralised and fully mineralised tissues but also shows the poorly calcified, demineralised and ill-calcified bone components. The advantages of the method compared with those using undecalcified sections are its simplicity, suitability for fixed and decalcified material in any unspecialised histological laboratory and the fact that osteoid and other bone components can be studied in sections of unlimited size and in undisturbed relationship to their surrounding soft tissues.

Aging↗

Enveloping the tendon graft with periosteum to enhance tendon-bone healing in a bone tunnel: A biomechanical and histologic study in rabbits.

PURPOSE: Fixing and incorporating the tendon graft within the bone tunnel is a major concern when using grafts for ligament reconstruction. The periosteum contains multipotent stem cells and has the potential to form osteogenic and chondrogenic tissues. This study uses histologic and biomechanical analyses to examine the effect of periosteum on tendon-bone healing within a bone tunnel. TYPE OF STUDY: Experimental study in an animal model. METHODS: In this study, 36 adult New Zealand White rabbits were used. The long digitorum extensor tendon was transplanted into a bone tunnel of the proximal tibia. The periosteum from the proximal tibia was sutured on the surface of the tendon portion. The tendon was pulled through a drill-hole in the proximal tibia and attached to the medial aspect of the tibia. Histologic examination of the tendon-bone interface and biomechanical test for maximal pullout load were evaluated at 4, 8, and 12 weeks after operation. RESULTS: Histologic analysis of the tendon-bone interface showed a fibrous layer formed between the tendon and the bone by the periosteum. This layer became progressively integrated with the tendon and bone surface during the healing process. At 4 weeks, the cancellous bone lining in the bone tunnel was interdigitated with the fibrous interface tissue. At 8 weeks, progressive new bone grew into the interface fibrous layer. At 12 weeks, collagen fibers anchored to the bone and organization with fibrocartilage formation developed between the tendon and bone. Biomechanical testing revealed higher maximal pullout strength in the periosteum-enveloped group at all time points, with a statistically significant difference at 8 and 12 weeks. The periosteum-treated group had a higher interface strength-to-length ratio and significant increase at 8 weeks and 12 weeks. CONCLUSIONS: The histologic and biomechanical studies demonstrated that, if periosteum was sutured on the tendon that was transplanted within a bone tunnel, it resulted in a superior healing process and better healed strength. When doing ligament reconstruction with a tendon graft, the periosteum can be sutured to the graft to enhance tendon-bone healing.

Animals↗

In vitro expression of osteoblastic markers in cells isolated from normal fetal and postnatal human bone and from bone of patients with osteogenesis imperfecta.

We studied the expression of osteoblastic markers in cultured cells isolated from the bone of 15 patients with different clinical forms of osteogenesis imperfecta (OI) and of seven fetal and postnatal controls. Cultured bone cells of ten OI patients produced abnormal collagen type I. Similar to controls, OI bone cells produced predominantly collagen type I with traces of collagen types III and V. The 1,25(OH)2 vitamin D3-stimulated synthesis of osteocalcin, a specific osteoblastic marker protein, was similar in OI bone cells and age-matched controls. Bone cells from fetal controls and from patients with the perinatal lethal OI type II produced less osteocalcin than bone cells from postnatal controls and surviving OI patients. OI bone cells responded to parathyroid hormone (PTH) by increased production of cAMP similar to controls. Bone cells from fetal controls and from OI type II donors showed a decreased response to PTH. Activity of the bone-liver-kidney isoenzyme alkaline phosphatase (AP) was detected in all control and OI bone cells. The expression of all osteoblastic markers was similar in bone cells producing abnormal collagen type I. These observations show that OI bone cells in vitro express a pattern of osteoblastic markers similar to age-matched control bone cells indicating that osteoblastic differentiation is not altered by the underlying defects of collagen type I metabolism in OI bone cells.

Alkaline Phosphatase↗

Neuronal regulation of bone metabolism and anabolism: calcitonin gene-related peptide-, substance P-, and tyrosine hydroxylase-containing nerves and the bone.

Bone alters its metabolic and anabolic activities in response to the variety of systemic and local factors such as hormones and growth factors. Classical observations describing abundance of the nerves fibers in bone also predict a paradigm that the nervous system influences bone metabolism and anabolism. Identification of the nerve-derived signaling molecules, capable of modulating cellular activities of the bone cells, facilitates a novel approach to study the biology of skeletal innervation. Many of the signaling molecules that may act as efferent agents on the bone cells fall into the category of neuropeptides. The present article reviews current understanding of the skeletal innervation and their proposed physiological effects on bone metabolism, with a special interest to calcitonin gene-related peptide (CGRP)-containing nerves fibers. CGRP is abundantly distributed in bone via sensory nerves, especially in the epiphyseal trabecular bones. Its in vitro actions to the cultured osteoblasts and osteoclasts, together with its in vivo localization, strongly support the paradigm that the nervous system influences bone metabolism. In addition, CGRP is recently shown to be expressed endogenously by the osteoblasts. Transgenic mice with osteoblasts overexpressing CGRP are characterized by increased bone formation rate and enhanced bone volume, suggesting that CGRP indeed acts on bone metabolism not only via nervous route but also via autocrine loop. The current article also reviews the distribution of nerve fibers containing substance P (SP), another sensory nerve-specific neuropeptide, and tyrosine hydroxylase (TH), the rate-limiting enzyme of catecholamine. The distinct effects of SP and catecholamines on the bone cells together with their in vivo influences manifested by experimental denervation studies suggest that the sensory and sympathetic nerves play important roles in bone metabolism.

Animals↗

Stimulation of bone resorption results in a selective increase in the growth rate of spontaneously metastatic Walker 256 cancer cells in bone.

To test the hypothesis that bone metastasis is related to the rate of bone remodeling, we have examined the effect of enhanced bone resorption on the growth of spontaneously metastatic Walker 256 (W256) cancer cells. Bone resorption was stimulated in male Fischer rats by injecting Rice H-500 Leydig tumor cells subcutaneously. The resorptive response of the skeleton was confirmed in a pilot study by evaluating parameters of bone morphometry after 4, 7 and 10 days of tumor burden. The distal femoral epiphyses had 35 +/- 10% more osteoclast surface, 83 +/- 11% less osteoblast surface, and 46 +/- 5% less trabecular bone after 10 days of tumor burden, compared to non-tumor-bearing controls. To evaluate the effect of Leydig tumor-induced bone resorption on the growth response of W256 cells, 20 rats were injected intramuscularly with 2 x 10(7) W256 cells, and 20 rats were vehicle-injected. Two days later, 10 rats from each group were injected subcutaneously with Leydig tumor cells. Twelve days after W256/vehicle injection, rats were injected with [3H]thymidine, killed 2 h later, and their femurs, liver, lungs and kidneys were processed for histology. In rats injected with Leydig tumor cells only, enhanced bone resorption was confirmed by a 40 +/- 4% increase in serum calcium concentration, a 48 +/- 8% decrease in trabecular bone content, and a 72 +/- 15% decrease in osteoblast surface, compared with non-tumor-bearing rats. Metastatic W256 cells adjacent to trabecular bone in Leydig tumor-bearing rats had a 56 +/- 18% greater relative [3H]thymidine labeling index (TdR) than did W256 cells in the bones of non-Leydig tumor-bearing rats. The TdRs of W256 cells in the liver, lungs, and kidneys were not affected by Leydig tumor burden. In this model, enhanced bone resorption was associated with the selective growth promotion of metastatic W256 cells in bone, suggesting the existence of a bone-derived factor which is mitogenic to W256 cells.

Animals↗

Mechanical properties, bone mineral content, and bone composition (collagen, osteocalcin, IGF-I) of the rat femur: influence of ovariectomy and nandrolone decanoate (anabolic steroid) treatment.

Nandrolone decanoate (ND) is an anabolic steroid with a positive effect on bone mass in osteoporotic patients. The mechanism of action, (i.e., reduction of bone resorption and/or stimulation of bone formation), the ultimate effect on mechanical properties, and the most effective dosage are not yet clear. To address these issues, dose-related effects of the long-term effect of ND on serum and bone biochemistry, bone mineral content, and bone mechanical properties in ovariectomized (OVX) rats (12 weeks old at the start of the experiment) were studied for 6 months. The results were compared with those obtained in age-matched, intact, and OVX rats. OVX caused in the femur a significant increase in net periosteal bone formation and net endosteal bone resorption of bone collagen content and torsional strength, and of serum alkaline phosphatase, osteocalcin, and insulin-like growth factor-I (IGF-I) levels, whereas cortical bone density and calcium/creatinine and phosphorus/creatinine in 24-hour urine were significantly reduced. Treatment of OVX rats with 1 mg ND/14 days resulted in a significant increase in periosteal bone formation, femur length, cortical and trabecular bone mineral content and density, torsion stiffness and strength, and bone IGF-I content, and a decrease in serum osteocalcin, urinary calcium/creatinine levels, and bone collagen content compared with OVX controls. The higher ND dosage of 2.5 mg/14 days did not improve the results. ND treatment did not reverse all changes induced by OVS to the level of the intact controls. These results indicate that ND acts as an antiresorptive drug and as a home formation stimulating drug.(ABSTRACT TRUNCATED AT 250 WORDS)

Anabolic Agents↗

Correlation of different bone markers with bone density in patients with rheumatic diseases on glucocorticoid therapy.

Osteoporosis is a common concomitant disease in patients with rheumatic diseases on glucocorticoid (GC) therapy. Bone status is usually evaluated by determination of bone density in combination with clinical examinations and laboratory tests. However, the strength of individual biochemical bone makers in GC-induced osteoporosis has yet to be fully clarified. For this reason, different bone markers were investigated in correlation with bone density in patients with rheumatic diseases. Approximately 238 patients (212 women, 26 men) with a rheumatic disease and under GC therapy were examined consecutively for the first time with regard to bone density (BMD) and bone markers [osteocalcin, bone-specific alkaline phosphatase (precipitation method/tandem-MP ostase), crosslinks [pyridinoline (PYD), deoxypyridinoline (DPX), N-terminal telopeptide (NTX)]]. The daily glucocorticoid dose was 10 mg prednisone equivalent (median), and the cumulative dose was 12 g prednisone equivalent (median). None of the patients had previously taken medication for osteoporosis. Osteoporosis was demonstrated in 35.3% of the patients, osteopenia in 47.5%, and a normal BMD in 17.2%. The results of tandem-MP ostase correlated with the BMD of the lumbar spine and of the femoral neck. The values for N-terminal telopeptide and pyridinoline correlated only with the bone density of the femoral neck. All results were statistically significant, although the correlation coefficients were low. After classification of the patients according to their BMD values (osteoporosis, osteopenia and normal BMD), there were significantly more patients with bone markers above the norm in the osteoporosis group and in the osteopenia group than in the group with normal bone density. All bone markers recorded behaved similarly in relation to the bone density values. The same analysis was also undertaken for the different disease groups. In these subgroups there was also a correlation between ostase/crosslinks with BMD, but the correlation coefficients were low. A general recommendation for the routine use of a specific bone marker in patients with rheumatic diseases on glucocorticoid therapy cannot be made from a cost-benefit point of view mainly because of limited predictive power (low correlation coefficients, incomplete correlation with different sites of BMD measurement).

Adult↗

A new concept of the pattern of structural changes with bone loss by histomorphometric analysis using bone slabs.

We examined naked bone slabs (1.2 mm thick) from iliac bone biopsied cores obtained from 33 women aged 33-89 years. The number, size, and shape of the pores in the bone slabs were analyzed. The results revealed that the % bone area (the percentage area occupied by bone in the slab) was linearly correlated with age and other parameters, such as the size of pores, irregularity of pores, and pore distance, but was not correlated to the number of pores. We found a second-degree polynomial relationship between the % bone area and the number of pores. Based on three parameters--% bone area, number of pores, and size of pores--cluster analysis was performed and the specimens divided into three groups. The group with sufficient bone mass showed few small round pores, and the group with severe bone loss revealed a few large pores that were caved in. The characteristics of these groups represented the relationship between bone mass and structural change. The remaining group with moderate bone loss was divided into two subgroups, one with an increased number of pores without expansion and one with expanded pores without an increase in number. We presumed that the variations between the groups were caused by differences between fine and rough structures in the trabeculae caused during the process of bone loss. We concluded that this analysis of bone slabs allowed the pattern of trabecular structural change that occurred with bone loss to be determined easily and visually.

Adult↗