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Differences in bone mineral in young Asian and Caucasian Americans may reflect differences in bone size.

Bone mineral content (BMC) and areal bone mineral density (BMD) have been reported to be lower in Asian than in Caucasian adults. To determine if racial differences in bone mass are present in younger subjects and whether they reflect differences in estimated volumetric bone density or in bone size, we compared measurements of bone mineral in healthy young Asian- and Caucasian-American males and females. Bone mineral was measured at the lumbar spine (L2-L4), femoral neck (FN), and whole body (WB) by dual-energy X-ray absorptiometry (DXA) in 99 Asians (49 females, 50 males) and 103 Caucasians (54 females, 49 males) ages 9-26 years. Results were expressed as BMC, BMD, and apparent density (BMAD), an estimate of volumetric bone density that reduces the effect of bone size. Subjects were compared on the basis of chronological age as well as by Tanner stage to correct for potential differences in the timing of puberty. Habitual dietary intake and physical activity were also assessed and correlated with bone mineral. The Asian and Caucasian cohorts differed in body size, diet, and physical activity. Asian females were shorter than the Caucasian females at all stages of puberty and weighed less at pre-/early puberty (p < 0.05). Asian males were older than Caucasians at midpuberty (p < 0.01) and weighed less than the Caucasian males at pubertal maturity (p = 0.001). Asian youths also consumed less calcium and reported less weight-bearing activity. Racial differences were most apparent when comparing BMC data. Asian males had greater spine BMC at midpuberty and lower WB BMC at maturity (p < 0.05). Asian females had lower FN BMC through midpuberty and lower WB BMC in pre-/early puberty (p < 0.05). WB BMD and WB BMC/height values were significantly lower in mature Asian versus Caucasian males. No significant racial differences in BMAD were observed. Multivariate regression analysis indicated that the differences in BMD and BMAD between Asian and Caucasian subjects were largely attributable to differences in weight and pubertal stage, and, at the FN, in weight-bearing activity. Further, the explanatory variables were less strongly associated with BMAD than with BMD. In summary, no significant differences in BMD were found between Asian and Caucasian youths through midpuberty; however, WB BMD and WB BMC/height values were lower in Asian males at sexual maturity. We conclude that observed differences in bone mineral between Asians and Caucasians may be partially attributed to the smaller bone size of Asians.

Absorptiometry, Photon↗

Bone repair using a new injectable self-crosslinkable bone substitute.

A new injectable and self-crosslinkable bone substitute (IBS2) was developed for filling bone defects. The IBS2 consisted of a chemically modified polymer solution mixed with biphasic calcium phosphate (BCP) ceramic particles. The polymer hydroxypropylmethyl cellulose was functionalized with silanol groups (Si-HPMC) and formed a viscous solution (3 wt %) in alkaline medium. With a decrease in pH, self-hardening occurred due to the formation of intermolecular -Si-O- bonds. During setting, BCP particles, 40 to 80 microm in diameter, were added to the polymer solution at a weight ratio of 50/50. The resulting injectable material was bilaterally implanted into critically sized bone defects at the distal femoral epiphyses of nine New Zealand White rabbits. The IBS2 filled the bone defects entirely and remained in place. After 8 weeks, bone had grown centripetally and progressed towards the center of the defects. Newly formed bone, ceramic, and nonmineralized tissue ratios were 24.6% +/- 5.6%, 21.6% +/- 5.8%, and 53.7% +/- 0.1%, respectively. Mineralized and mature bone was observed between and in contact with the BCP particles. The bone/ceramic apposition was 73.4% +/- 10.6%. The yield strength for the IBS2-filled defects was 16.4 +/- 7.2 MPa, significantly higher than for the host trabecular bone tissue (2.7 +/- 0.4 MPa). This study showed that BCP particles supported the bone healing process by osteoconduction while the Si-HPMC hydrogel created intergranular space for bone ingrowth. This new injectable and self-crosslinkable bone substitute could be used conveniently in orthopedic surgery for filling critical-size bone defects.

Animals↗

Plasma osteopontin in comparison with bone markers as indicator of bone metastasis and survival outcome in patients with prostate cancer.

BACKGROUND: The study was undertaken to evaluate the diagnostic and prognostic value of plasma osteopontin (OPN) in comparison to bone markers as well as the relationships between the markers and clinico-pathological factors in prostate cancer (PCa) patients. METHODS: OPN and the bone markers carboxyterminal-telopeptide of type I collagen, bone-specific alkaline phosphatase (bALP), and aminoterminal-propeptide of type I procollagen (PINP) were measured in 90 PCa patients with and without bone metastases, 35 patients with benign prostatic hyperplasia, and 29 healthy men. RESULTS: OPN and bone markers were significantly elevated in patients with bone metastases compared to the other groups. Significant correlations were found between all four-bone markers (r(s) = 0.43-0.79, all P < 0.01). OPN correlated with tumor grade (r(s) = 0.23, P < 0.05). In receiver-operating characteristics (ROC) analyses, OPN and bone markers were effective in distinguishing PCa patients with and without bone metastases showing areas under the curve (AUC) between 0.80 and 0.88 (all P < 0.001). OPN had an AUC of 0.85 that increased in combination with bALP up to 0.93 providing at the point with the highest diagnostic accuracy both a sensitivity and specificity of about 90%. Kaplan-Meier analyses and Cox proportional hazards regression models showed decreased survival of patients with high OPN and bone marker levels, while only high OPN and PINP were independent negative prognostic factors for PCa-related death. CONCLUSIONS: OPN alone or in combination with bone markers is useful as diagnostic marker in the detection of bone metastases and as prognosticator in the survival prediction in PCa patients.

Adult↗

Bone progenitor cell deficits and the age-associated decline in bone repair capacity.

Aging bone shows a progressive decline in mass and strength. Previous studies have suggested that bone marrow stem cells are reduced with aging and that this could be responsible, in part, for age-associated bone deficits. We measured the number of osteoprogenitor cells present in the bone marrow from adult and aged rats as well as their ability to differentiate in vitro and to form bone in vivo. We found that the number of adherent colony-forming cells was significantly lower (65%) in marrow cells isolated from aged compared with adult rats. Furthermore, 88% of the colonies obtained from aged rats were alkaline phosphatase (AP) positive, whereas virtually all the colonies from adult rats were positive. The addition of dexamethasone to the culture medium decreased the proliferation of the adherent cells and reduced the number of colonies obtained from both adult and aged bone marrow, all of which were AP positive. No significant differences were found in the expression of certain major bone cell marker genes as a function of donor age. However, dexamethasone treatment increased expression of osteopontin (OP) by fivefold. Adult stromal cells not treated with dexamethasone and implanted subcutaneously in recipient rats exhibited about 10-fold greater formation of bone compared with cells from aged rats. In contrast, dexamethasone-treated cells exhibited high levels of bone formation, irregardless of donor age or the age of the recipient into which the cells were grafted. These studies are consistent with a deficit of osteoprogenitor cells in the bone marrow site as a contributing, perhaps correctable factor in the decline in bone repair and bone mass with age.

Aging↗

Evolution of spinal bone loss and biochemical markers of bone remodeling after menopause in normal women.

The main objective of this study was to describe longitudinal patterns of spinal bone loss in normal women who undergo a natural menopause. The second objective was to determine if a proportion of women suffer excessively rapid postmenopausal bone loss from the spine. If this was the case it was the aim to devise a means of predicting the woman at excess risk; but if all women lost bone at similar rates, the aim was to document changing loss rates over the first 5-8 postmenopausal years. Responding women in six suburban general practices recalled for cervical smears who had their last menstrual period 9- 36 months previously were invited to participate in a longitudinal study of bone loss and the biochemical markers plasma osteocalcin and urinary hydroxyproline. Sixty-four subjects agreed to participate, a response rate of 80%. In the ensuing 5 years, six received hormone replacement therapy and are not reported on. The main outcome measures were rates of spinal bone loss over 5 years, measured by dual photon absorptiometry, and radial bone loss over the first 2 years measured to quantitative computed tomography. Spinal bone loss was similar between individuals, with 94% of the variability in the data being accounted for by a statistical model that assumed parallel rates of bone loss. A less restrictive model allowing women to have different rates of spinal bone loss accounted for 12% more of the remaining variance in the data than the previous model. However, rates of radial bone loss were more dissimilar between women than rates of spinal loss. The results of the biochemical data collected serially showed that the plasma osteocalcin rose slowly to a plateau at 5 years postmenopause; in contrast, the hydroxyproline fell progressively with time over the whole period of study. These results were interpreted as being consistent with diminishing rates of bone destruction which gradually reequilibrated with bone formation as time passed after menopause.

Absorptiometry, Photon↗

Longitudinal evaluation of perimenopausal femoral bone loss: effects of a low-dose oral contraceptive preparation on bone mineral density and metabolism.

To characterize the pattern of biochemical markers of bone metabolism and femoral bone mineral density in eumenorrheic and oligomenorrheic perimenopausal women, and assess the effects of a low-dose oral contraceptive (OC) on bone metabolism and femoral bone density, bone biochemical markers and femoral bone density (measured at the neck, Ward's triangle and trochanter regions) were evaluated in a longitudinal 2-year follow-up study. The study was conducted in healthy, normally menstruating perimenopausal women (n = 18), perimenopausal oligomenorrheic women (n = 18), and perimenopausal oligomenorrheic women treated with an OC containing 20 microg ethinylestradiol plus 0.15 mg desogestrel (n = 19). The results were analyzed by factorial or repeated measures analysis of variance, as appropriate. During the observation period, in normally menstruating women there were no changes in the menstrual cycle, plasma FSH and estradiol levels, biochemical markers of bone turnover or femoral bone density. In oligomenorrheic untreated women an increase in cycle length with a concomitant decrease in plasma estradiol and an increase in plasma FSH levels were found (p < 0.05). In this group a significant increase in urinary excretion of hydroxyproline and in plasma osteocalcin levels with a concomitant significant decrease in femoral bone density (p < 0.05) occurred. In OC-treated women, osteocalcin plasma levels and urinary excretion of hydroxyproline significantly (p < 0.05) decreased, leading to a significant (p < 0.05) increase in femoral bone density. It is concluded that perimenopausal OC administration can avoid the increase in bone turnover and the decrease in femoral bone density due to the perimenopausal impairment of ovarian function.

Absorptiometry, Photon↗

A comparison of two types of free bone grafts as transport discs in segmental distraction for reconstruction of calvarial bone defects: an experimental study.

INTRODUCTION: Several investigations over the past few years have shown that the importance of preserving the blood supply of the transport disc during segmental distraction has been overestimated. It was clearly demonstrated that distraction osteogenesis by local bone transportation could be achieved even with free bone grafts. So far, there have been no systematic investigations into how different types of free bone grafts vary in their function and suitability as transport discs in segmental craniofacial distraction. The aim of this study was to develop criteria to aid the clinician in selecting the most suitable free bone graft for distraction purposes. MATERIALS AND METHODS: Under general anesthesia, calvarial defects measuring 6 x 5 cm were created in 12 adult black head sheep in order to reconstruct them by segmental distraction using two different types of bone grafts as transport discs. Group 1 (n=6) received autotopical membranous bone of the calvarium as the transport segment, while group 2 (n=6) received heterotopical enchondral material from the iliac crest. Distraction was started postoperatively after 5 days at 0.6 mm/day and continued for 7 weeks. After a further 6 weeks of consolidation, the animals were killed and specimens examined macroscopically, radiographically and histologically. RESULTS: The significantly better quality of bone regenerates of group 1 was clearly influenced by the significantly better stability of the transport disc's connection to the distraction device, the calvaria grafts showing better volume stability and better mechanical resistance during transport than the iliac bone. The influence of both types of bone grafts on the macro- and microstructure of the newly formed bone was clearly evident. The mineralization density of group 2 regenerates was significantly lower than that of group 1 specimens. CONCLUSION: High mechanical stability of the bone graft is a very important point to consider when selecting a free graft for use as transport disc in local bone transport, especially if transport is necessary over long distances.

Animals↗

Family 2 cystatins inhibit osteoclast-mediated bone resorption in calvarial bone explants.

Osteoclastic bone resorption depends on the activity of various proteolytic enzymes, in particular those belonging to the group of cysteine proteinases. Biochemical studies have shown that cystatins, naturally occurring inhibitors of these enzymes, inhibit bone matrix degradation. Since the mechanism by which cystatins exert this inhibitory effect is not completely resolved yet, we studied the effect of cystatins on bone resorption microscopically and by Ca-release measurements. Calvarial bone explants were cultured in the presence or absence of family 2 cystatins and processed for light and electron microscopic analysis, and the culture media were analyzed for calcium release. Both egg white cystatin and human cystatin C decreased calcium release into the medium significantly. Microscopic analyses of the bone explants demonstrated that in the presence of either inhibitor, a high percentage of osteoclasts was associated with demineralized non-degraded bone matrix. Following a 24-h incubation in the presence of cystatin C, 41% of the cells were adjacent to areas of demineralized non-degraded bone matrix, whereas in controls, this was only 6%. If bone explants were cultured with both PTH and cystatin C, 60% of the osteoclasts were associated with demineralized non-degraded bone matrix, compared to 27% for bones treated with PTH only (P < 0.01). Our study provides evidence that cystatins, the naturally occurring inhibitors of cysteine proteinases, reversibly inhibit bone matrix degradation in the resorption lacunae adjacent to osteoclasts. These findings suggest the involvement of cystatins in the modulation of osteoclastic bone degradation.

Animals↗

Maturity- and sex-related changes in tibial bone geometry, strength and bone-muscle strength indices during growth: a 20-month pQCT study.

During growth, bone strength is conferred through subtle adaptations in bone mass and geometry in response to muscle forces. Few studies have examined the changes in bone geometry, strength and the bone-muscle strength relationship across maturity in boys and girls. Our aims were to describe (i) 20-month changes in bone geometry and strength at the tibial midshaft across three maturity groups of boys and girls, (ii) differences in these adaptations between sexes at the same approximate level of maturity and (iii) the bone-muscle strength relationship across maturity groups of boys and girls and between sexes. We used peripheral quantitative computed tomography (pQCT, Stratec XCT-2000) to measure change in total bone cross-sectional area (ToA, mm(2)), cortical area (CoA, mm(2)), average cortical thickness (C.Th., mm), section modulus (mm(3)) and muscle cross-sectional area (mm(2)) at the tibial midshaft (50% site) in 128 EARLY-, PERI- and POST-pubertal girls (n = 69, 11.9 +/- 0.6 years) and boys (n = 59, 12.0 +/- 0.6 years) across 20 months. We also calculated two bone-muscle strength indices (BMSI) for compression (CoA/MCSA) and bending [strength index/MCSA; where strength index = Z / (tibial length / 2)]. EARLY boys and girls had smaller ToA at baseline than same sex PERI or POST participants. There were no sex differences in ToA or CoA at baseline; however, boys increased both parameters significantly more than girls in every maturity group (8.5-11.1%, P < 0.01). These changes in bone geometry conferred greater gains in bone strength for boys compared with girls in each maturity group (13.8-15.6%, P < 0.01). Baseline BMSIs did not differ between sexes for EARLY and PERI groups, whereas BMSIs were significantly higher for POST boys compared with POST girls (P < 0.05). BMSIs decreased for EARLY and PERI girls (-7.4-(-1.1%)) whereas the ratios remained stable for EARLY and PERI boys (-0.6-2.5%). This sex difference in BMSI change was due to a relatively greater increase in CoA among EARLY and PERI boys compared with same-maturity girls. BMSIs remained stable in POST girls and decreased in POST boys due to relatively greater gains in MCSA. This study provides novel longitudinal descriptions of the maturity- and sex-specific changes in bone geometry, strength and bone-muscle strength indices.

Adolescent↗

Evaluation of bone volume following bone grafting in patients with unilateral clefts of lip, alveolus and palate using a CT-guided three-dimensional navigation system.

PURPOSE: In cleft patients the eruption of the permanent canine depends very much on the amount of bone available following bone grafting. The purpose of this study was to evaluate the initial defect in alveolar clefts and the volume of bone bridging found in unilateral clefts which had undergone bone grafting. PATIENTS AND METHODS: To determine the fate of the bone graft in cleft palate patients a three-dimensional CT-based Navigation System (Zeiss, Aalen, Germany) was used. CT scans of 16 patients with unilateral clefts were taken immediately preoperatively and 1 year postoperatively. The patients underwent surgery between the age of 9 and 14 years using iliac crest bone grafts. The data was transferred to the work station of the navigation system. Using the STN software, the defect at the alveolar clefts and volume of the bone grafts were determined in each case. Three-dimensional models were created showing the amount of bone immediately preoperatively and 1 year postoperatively. RESULTS: The size of the cleft defect did not correlate with the success rate of the alveolar bone grafting. The form of the transplant remained almost constant when the permanent canine erupted spontaneously into the graft. In cases of absence of the permanent tooth or when the permanent canine required orthodontic treatment, significant bone loss could be observed in the buccopalatal direction. CONCLUSION: Three-dimensional reconstruction of bone grafts using a navigation system enables a valuable objective assessment of graft volume. Bone formation can be assessed in all three dimensions showing a high grade of resorption in patients lacking physiological load.

Adolescent↗

Rationale for the use of bone scans in selected metastatic and primary bone tumors.

Since the introduction of bone scans in 1951, there have been many studies comparing biologic and physical characteristics of new bone-imaging agents and the results of scintigraphy and radiology in large numbers of patients. Relatively speaking, there have been fewer studies detailing the health benefits and financial cost associated with the use of skeletal scintigraphy. This review concerns these aspects in patients with malignancies of various sites and stages. About 2% of patients with stage I or II breast cancer have bone metastases at the time they first present, whereas nearly 28% of patients with stage III disease have bone metastases. A large percentage of patients with initially negative scans develop bone metastases during the first 3--4 yr; many of them develop them within the first 12--18 mo after initial diagnosis. For patients with lung cancer, the use of bone scans in staging their disease is somewhat controversial. Several studies indicate that the yield of positive bone scans may range from as low as 2% to as high as 35%. Data on the use of bone scans in staging prostatic cancer initially are similar to those in patients with breast cancer, that is, yields of 7% in patients with stage I or II disease and a yield of about 20% with stage III disease. Children with osteosarcoma or Ewing's sarcoma rarely have bone disease distant from the site of their primary bone lesion at presentation. However, a large percentage of them (30%--40% or so) develop bone metastases during the follow-up period. As in the case with patients with breast cancer, about half of these bone metastases are evident by 12--18 mo.

Bone Neoplasms↗

Usefulness of bone markers for detection of bone metastases in lung cancer patients.

OBJECTIVES: Lung cancer commonly causes destructive bone metastases. The aim of this study was to compare efficiency of biochemical bone markers in the detection of bone metastases in lung cancer patients. DESIGN AND METHODS: We measured serum calcium (Ca), alkaline phosphatase (ALP), bone isoenzyme of alkaline phosphatase (BALP), osteocalcin (OC) and urine deoxypyridinoline crosslinks (DPD) levels in 52 lung cancer patients; 27 patients with the evidence of bone metastases, 25 without metastases in bone when they were first diagnosed. BALP, OC and DPD were measured by specific immunoassays. ALP, Ca and urine creatinine levels were determined by colorimetric methods. RESULTS: Ca, ALP, BALP, OC and DPD levels were significantly higher in the patients with bone metastases than those without bone metastases (p < 0.01 for BALP and OC, p < 0.001 for Ca, ALP and DPD). The sensitivity and specificities of all markers as follows: 89%-44% for BALP, 52%-88% for OC, 81%-76% for DPD, respectively. ROC curves were generated separately for BALP, OC and DPD to assess the diagnostic efficiency of markers in a different manner. DPD showed the best curve characteristics among the studied bone markers, followed by the BALP curve. OC curve showed poor characteristics. CONCLUSIONS: Our results suggest that the measurement of DPD and BALP may be useful in detecting bone metastases in lung cancer patients. Also it could help in the follow-up of bone metastases from lung cancer since they can be repeated more often than roentgenography and bone scintigraphy, at less cost and with less discomfort to the patients.

Adult↗

Tensile strength of the cement-bone interface depends on the amount of bone interdigitated with PMMA cement.

An experimental investigation was performed to (1) determine the general mechanical behavior and in particular, the post-yield behavior of the cement-bone interface under tensile loading, (2) determine where interface failure occurs, and (3) determine if the mechanical properties of the interface could be related to the density of bone at the interface and/or the amount of cement-bone interdigitation. Seventy-one cement-bone test specimens were machined from human proximal femurs that had been broached and cemented using contemporary cementing techniques. The amount of cement-bone interdigitation was documented and the quantitative computed tomography equivalent mineral density (QCT density) of the bone with cement was measured. Specimens were loaded to failure in tension under displacement control and exhibited linear elastic behavior with some reduction in stiffness until the peak tensile stress was reached (1.28 +/- 0.79 MPa). A substantial amount of strain softening (negative tangent stiffness) with an exponential-type decay was found after the peak stress and continued until there was complete debonding of the specimens (at 0.93 +/- 0.44 mm displacement). Interfacial failure most often occurred at the extent of cement penetration into the bone (56% of specimens) or with small spicules of cement left in the bone (38% of specimens). The results showed that the post-yield tensile behavior contributes substantially to the energy required to cause failure of the cement-bone interface, but the post-yield behavior was not well correlated with the amount of interdigitation or density of bone. Linear regression analysis revealed a moderate (r2 = 0.499, p < 0.0001) positive relationship between the tensile strength of the cement-bone interface and the quantity of bone interdigitated with the cement.

Adult↗

Influence of preoperative mechanical bone quality and bone mineral density on aseptic loosening of total hip arthroplasty after seven years.

OBJECTIVE: To test mechanical bone quality and bone mineral density of the femoral head at the day of implantation as indicators for femoral prosthesis loosening. METHODS: Mechanical bone quality of a femoral head slice was assessed by destructive compression testing combined with bone mineral density measurements using peripheral quantitative computed tomography. Fourteen patients with walking pains were attainable for a radiographical follow-up mean 7.1 years after implantation. RESULTS: Radiolucent lines along the stem were evident in 11 of 14 femurs, most of them seen in Gruen zones 7, 6, 1, 3, 14, and showed strong correlations to preoperative bone strength (r=-0.80; P<0.001) and axial stiffness (r=-0.75; P=0.002), yet not to bone mineral density (r=-0.67; P=0.009). Slight varus deviations <3 degrees were noted in six femurs. Preoperative strength was reduced in this femurs to 54% (P=0.006), and stiffness to 61% (P=0.038), while bone mineral density did not differ significantly. CONCLUSIONS: Femoral prosthesis loosening after seven years can be predicted by mechanical bone quality of the femoral head at the time of implantation. Bone mineral density measurements may also indicate future stem loosening but have to interpreted carefully, keeping in mind a poorer predictive value. RELEVANCE: Indications and choice of type of hip arthroplasty should be balanced in osteoporotic bones in particular. While preoperative bone mineral density measurement allows the prediction of mechanical bone quality, its relevance in predicting failure in arthroplasty treatment remains unclear.

Aged↗

Bone ingrowth into porous-coated tibial components implanted with autograft bone chips. Analysis of ten consecutively retrieved implants.

Ten asymmetric porous-coated tibial knee components were consecutively retrieved from nine patients with implantation times ranging from 1 week to 48 months. Morselized autograft bone chips were applied to the resected surface of the tibia prior to component implantation. Microradiographic analysis showed bone in contact with 64 +/- 10% of the porous-coated interface. Backscattered electron imaging of the bone-implant interface revealed bone within 8-22% of the porous coating. Although bone in the form of autograft bone chips was observed in the porous coating of the 1 and 3 week specimens, it was not connected to the host bone. By 3 and 6 months, the bone chips were integrated and connected to the host bone providing osseous continuity from the porous coating to the skeleton. This study shows that reproducible bone ingrowth into porous-coated tibial components is achievable using autograft bone chips to promote bone fixation.

Aged↗

Deproteinized bovine bone (Bio-Oss) and bioactive glass (Biogran) arrest bone formation when used as an adjunct to guided tissue regeneration (GTR): an experimental study in the rat.

OBJECTIVES: Grafting of deproteinized bovine bone or bioactive glass has been suggested as an adjunct to guided tissue regeneration (GTR) for the treatment of periodontal and peri-implant bone defects but the influence of these materials on bone formation is not clarified. The aim of the study was to examine the long-term influence of deproteinized bovine bone (Bio-Oss) or bioactive glass (Biogran) on bone formation produced by GTR. MATERIAL AND METHODS: Eighteen rats were used. Following incisions along the inferior border of the mandible, muscle-periosteal flaps were raised to expose the mandibular ramus. Rigid, hemispherical, Teflon capsules (6 mm internal diameter and 1 mm peripheral collar) loosely packed with a standardized quantity of either deproteinized bovine bone (test group 1) or bioactive glass (test group 2), or empty capsules (control group) were then placed with their open part facing the lateral surface of the ramus (one capsule per animal). After 1 year, the capsules were removed by a reentry operation, and the animals were sacrificed. Histological specimens of the augmented sites were prepared, and the volumes of (1). newly formed bone, (2). graft particles, and (3). soft connective tissue in the space originally created by the capsule were estimated by a point-counting technique in three to four histological sections, taken by uniformly random sampling. RESULTS: Limited bone formation was observed in the two test groups. The major part of the space originally created by the capsules was occupied by graft particles embedded in connective tissue. The mean volume of newly formed bone occupied only 23% of the total space in the animals grafted with Bio-Oss and 12.6% in those grafted with Biogran. In the control animals, however, 88.2% (p<0.01) of the space was filled with newly formed bone. There were no signs of ongoing bone formation in any of the three experimental groups. CONCLUSION: It is concluded that grafting of Bio-Oss or Biogran as an adjunct to GTR arrests bone formation.

Animals↗

[Bone density and bone metabolism regulated by vitamin D receptor allele polymorphism in a German study sample].

BACKGROUND: It has been reported that the spinal bone density is associated with vitamin-D-receptor (VDR) gene polymorphisms. The results of recent studies have been contradictory concerning the predictive power for low bone mineral density (BMD). Regional population-specific influences have been found to affect the vitamin-D-endocrinologic-system, diminishing the influence of VDR polymorphism on BMD and on bone turnover. We have examined the association of bone density, fracture predictivity and biochemical markers of bone turnover with VDR polymorphism in a German population. METHODS: Blood and urine were collected from a heterogeneous subset of 164 caucasian subjects with ethnic German background. Polymerase chain reaction and subsequent digestion with Bsm I were used to examine variations of VDR genotypes. The morning following initial specimen collections, both urinary excretion rate of pyridinoline crosslinks (Pyr) and serum levels of bone alkaline phosphatase (BAP) were determined. For determination of the bone mineral density, the well-established method of dual X-ray absorptiometry was used. FINDINGS: The VDR BB-genotype was associated with low bone mineral density for age-matched subjects (90.1 +/- 15.5%) versus the bb-genotype (100.8 +/- 10.8%) at the lumbar spine and at the Ward's triangle (91.8 +/- 17.9% versus 101.9 +/- 12.1%). 34.2% of BB-genotype subjects, 14.2% of bB-genotype subjects and 12.6% of bb-genotype subjects had Z-score related bone mineral density < 85%. The fracture rate at typical osteoporotic fracture sites was 23.6% for the BB-, 10.8% for the bB- and 0.0% for the bb-genotype. The urinary excretion rate of free pyridinoline crosslinks was higher for the BB-genotype than for the bB- or the bb-, however the difference was not significant. No genotype specific variations were seen for bone alkaline phosphatase. INTERPRETATION: The authors conclude from this study that bone mineral density at the axial skeleton is associated with the vitamin-D-receptor allele polymorphism and that there is an influence on bone turnover and fracture rate in a German subset. CLINICAL RELEVANCE: The analysis of the VDR-genotype can be considered as a new piece in the puzzle of the diagnostic of osteoporosis for we get prognostic hints concerning the rate of fracture.

Adult↗

Targeted disruption of the osteoblast/osteocyte factor 45 gene (OF45) results in increased bone formation and bone mass.

We have previously described osteoblast/osteocyte factor 45 (OF45), a novel bone-specific extracellular matrix protein, and demonstrated that its expression is tightly linked to mineralization and bone formation. In this report, we have cloned and characterized the mouse OF45 cDNA and genomic region. Mouse OF45 (also called MEPE) was similar to its rat orthologue in that its expression was increased during mineralization in osteoblast cultures and the protein was highly expressed within the osteocytes that are imbedded within bone. To further determine the role of OF45 in bone metabolism, we generated a targeted mouse line deficient in this protein. Ablation of OF45 resulted in increased bone mass. In fact, disruption of only a single allele of OF45 caused significantly increased bone mass. In addition, knockout mice were resistant to aging-associated trabecular bone loss. Cancellous bone histomorphometry revealed that the increased bone mass was the result of increased osteoblast number and osteoblast activity with unaltered osteoclast number and osteoclast surface in knockout animals. Consistent with the bone histomorphometric results, we also determined that OF45 knockout osteoblasts produced significantly more mineralized nodules in ex vivo cell cultures than did wild type osteoblasts. Osteoclastogenesis and bone resorption in ex vivo cultures was unaffected by OF45 mutation. We conclude that OF45 plays an inhibitory role in bone formation in mouse.

Animals↗