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Changes in bone mass as determined by ultrasound and biochemical markers of bone turnover during pregnancy and puerperium: a longitudinal study.

In a longitudinal study, we analyzed the speed of sound (SOS) and broadband ultrasound attenuation (BUA) of the os calcis as an index of bone mineral density (BMD) to define the effects of pregnancy and lactation on bone metabolism. We used an ultrasound bone densitometer and measured 6 biochemical markers of bone turnover in 18 healthy women throughout pregnancy and puerperium. The measurement of SOS and BUA by such an ultrasound device was clinically advantageous; not only is it radiation-free technology, but it also correlates highly with BMD measured by conventional X-ray bone densitometry. While a significant decrease in SOS was found in the 3rd trimester of pregnancy as compared with the early stage of pregnancy, there was no difference in both SOS and BUA between the breast-feeding women and the principally formula-feeding women during a 6-month period of puerperium. The analysis of biochemical markers revealed that both bone formation and bone resorption were elevated in the 3rd trimester of pregnancy as well as during puerperium, and that the breast-feeding women had significantly higher bone metabolism than the principally formula-feeding women. These results indicate that bone mass decreases as bone turnover itself is enhanced during pregnancy, while lactation does not substantially affect bone mass during at least 6 months of puerperium, although bone turnover is active.

Adult↗

Alterations in bone turnover and impaired development of bone mineral density in newly diagnosed children with cancer: a 1-year prospective study.

In the present study, longitudinal changes in bone mineral density, bone turnover, and bone hormonal metabolism were evaluated in newly diagnosed children with cancer. Lumbar spine (L2-L4) and femoral neck bone mineral densities (grams per cm2) were measured by dual energy x-ray absorptiometry in 28 children (age, 2.9-16.0 yr; median, 8.0 yr; 10 acute lymphoblastic leukemias, 18 solid tumors) at diagnosis and after a 1-yr follow-up. Apparent volumetric density (grams per cm3) was calculated to minimize the effect of bone size on BMD. Serum levels of osteocalcin (OC), type I collagen carboxyl-terminal propeptide (PICP), and type I collagen carboxyl-terminal telopeptide were measured serially during the study. Serum 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, insulin-like growth factor I (IGF-I), and IGF-binding protein-3 were analyzed at diagnosis and at 1-yr follow-up. A significant decrease in femoral bone mineral density and apparent volumetric density was observed during the year after diagnosis [(mean (SD), -10.1% (8.8%) and -11.3% (8.1%) respectively; P < 0.01], whereas age- and sex-matched controls showed annual increments of +5.4% (7.7%; P < 0.01) and +0.7% (5.7%; P = NS) respectively. The markers of bone formation (PICP and OC) were significantly decreased at diagnosis. By the end of the follow-up, PICP and OC were normalized, whereas the marker of bone resorption (type I collagen carboxyl-terminal telopeptide) was significantly increased. Reduced levels of 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, and IGF-binding protein-3 were observed during the study. To conclude, increased bone resorption and impaired development of femoral bone density were observed in children with cancer during chemotherapy. Deficient accumulation of bone mass may lead to impaired development of peak bone mass and predispose children with cancer to increased risk of osteoporosis and diminished skeletal resistance to fractures later in life.

Absorptiometry, Photon↗

Treatment of senile osteoporosis in SAMP6 mice by intra-bone marrow injection of allogeneic bone marrow cells.

A substrain of the senescence-accelerated mouse, SAMP6 (senescence-accelerated mouse prone 6), spontaneously develops osteoporosis early in life. Therefore, this strain is a useful animal model for developing new strategies for the treatment of osteoporosis in humans. We succeeded in treating osteoporosis in SAMP6 mice after the onset of this disease, using a newly developed method of bone marrow transplantation (BMT): Allogeneic bone marrow cells obtained from normal mouse strains were directly injected into the bone marrow cavity of irradiated SAMP6 mice (intra-bone marrow BMT [IBM-BMT]). After the treatment with IBM-BMT, hematolymphoid cells were completely reconstituted by donor-derived cells, and bone marrow stromal cells were also found to be of donor origin. The treated SAMP6 mice showed histologically-normal trabecular bone. In addition, bone mineral density and urinary deoxypiridinoline, a hallmark of bone destruction, were normalized. When the message levels of cytokines (tumor necrosis factor alpha, interleukin-6 [IL-6], IL-11, and receptor activator of nuclear factor-kappa B ligand [RANKL]) were examined, IL-11, RANKL (from bone marrow stromal cells), and IL-6 (from osteoclasts), which regulate bone remodeling, were restored to levels similar to those in normal B6 mice. These findings indicate that not only the hemopoietic system but also the bone marrow microenvironment were normalized after IBM-BMT, resulting in an amelioration of the imbalance between bone absorption and formation.

Amino Acids↗

Evaluation of 2 novel approaches for assessing the ability of demineralized freeze-dried bone allograft to induce new bone formation.

BACKGROUND: Because of the wide variation in the ability of human demineralized freeze-dried bone allograft (DFDBA) to reproducibly induce new bone formation, there is a need for a reliable measure of bone induction activity. In this study we examined an immature osteoprogenitor cell line for its potential utility in measuring the activity of DFDBA in vitro. METHODS: We characterized the response of 2T9 cells, an immature osteoprogenitor cell line derived from the calvariae of transgenic mice containing the SV40 T-antigen driven by the mouse bone morphogenetic protein (BMP)-2 promoter, to recombinant human BMP-2 by measuring alkaline phosphatase specific activity, osteocalcin production, and matrix mineralization. Responses were compared to those obtained with 1,25-(OH)2D3. In addition, 2T9 cells were cultured with active or inactive human DFDBA in the presence or absence of BMP-2. We also tested the hypothesis that radio-opacity of tissue following implantation of DFDBA in vivo correlates with the ability of human DFDBA to induce new bone. DFDBA from 9 different donors, stratified by age, were implanted subcutaneously in the thorax of 18 nude (nu/nu) mice. Tissue was harvested at 36 days postoperatively and examined histologically and biochemically for calcium and phosphorus uptake. RESULTS: 2T9 cells exhibited a dose- and time-dependent response to soluble BMP-2. Proliferation was decreased and alkaline phosphatase activity, osteocalcin production, and mineralized nodule formation were increased. The effects were dose- and time-dependent. Peak effects on alkaline phosphatase and osteocalcin were noted on day 8, whereas mineral deposition did not begin to occur until day 12. 1,25-(OH)2D3 did not regulate these effects unless used with BMP-2. When the cells were exposed to active or inactive DFDBA in the presence or absence of BMP-2, no effect on 2T9 cell differentiation was observed. This indicated that DFDBA released no soluble factors with bone inductive ability and that if any active factors were adsorbed to the DFDBA, they were inactivated. When DFDBA was implanted subcutaneously in the thorax of nude mice, there was no histologic evidence of new bone formation. However, there was a donor age-dependent decrease in Ca and P uptake of the implanted tissue, reflecting a donor age-dependent decrease in remineralization of DFDBA. CONCLUSIONS: These data indicate that cell culture assays like the one used in this study may not be appropriate indicators of bone induction ability by DFDBA since soluble factors may not be responsible for bone induction in vivo. Nonetheless, in vitro assays are still needed. While Ca and P uptake by DFDBA-implanted tissue in the present study correlated with the age-dependent decrease in bone induction at intramuscular sites in a previously reported study, these data show that early x-rays may actually detect remineralization and not new bone formation. Thus, assessment of bone induction ability may still depend on histologic analysis of animal models.

Age Factors↗

Qualitative and quantitative expression of bovine bone mineral in experimental bone defects. Part 2: Morphometric analysis.

BACKGROUND: The purpose of this study was to evaluate morphometrically the rate of resorbability of an inorganic bovine bone material in a standardized intrabony defect in dogs whether protected or unprotected by a bioabsorbable membrane at different healing periods, and to assess histomorphometrically the amount of osteoconductivity of this material and final healing site configuration. METHODS: In eight mongrel dogs, four round intrabony defects (5 x 4 mm) were made on the lateral mandibular angle, bilaterally at a different given time. Bovine bone mineral randomly filled two sites, while the other two were left with blood clot. A bioabsorbable collagen membrane covered each type of defect. The blood clotted uncovered sites served as controls. Section blocks for histology were made at 3, 6, 12, and 24 months. Following the non-decalcification method and staining with Stevenel's blue and van Gieson's picro fuchsin, morphometric analysis was performed on each specimen lesion type. RESULTS: Average bone area fraction at the bovine bone mineral uncovered sites (BBM) was 23.1%, 44%, 63.4%, and 58.8% at 3, 6, 12, and 24 months, respectively. Differences were statistically significant between 3 to 6 and 6 to 12 months (P<0.001). Average particle area fraction was 35.6%, 29%, 27.6%, and 26.8% at the respective periods. Differences were statistically significant between 3 to 6 months (P<0.05). In the bovine bone mineral membrane-protected (BBMM) sites, average bone area fraction was 26.4%, 51.7%, 61.2%, and 52.4% at 3, 6, 12, and 24 months, respectively. Differences were statistically significant between 3 to 6 months (P<0.05). Average particle area fraction was 37.9%, 29.8%, 26.8%, and 33.7%, respectively. Differences between the two sites with regard to the newly formed bone and particle presence were insignificant. In both, the increasing pattern of osteoconduction as expressed by the osteoconductivity test along the different healing periods was similar, as well as the decreasing pattern of the remaining concavity of the healing site configuration. Multiple comparison analysis of bone area fraction disclosed statistically significant superiority (P<0.05) of the membrane-ungrafted sites over BBM sites at 3 and 6 months and over BBMM sites at 6 months. Bone area fraction of the BBMM sites (51.7%) was statistically higher than the control sites (37.5%) (P<0.05). At 12 months, all test sites were statistically superior over the controls with regard to the regenerated bone and its healing configuration; i.e., remaining concavity of the defect. The healing site configuration of the test sites was persistently different from the control sites at 24 months. CONCLUSIONS: Newly formed bone and complete healing were evident in the BBM and BBMM sites. The membrane contributed no substantial benefits. Bovine bone particle resorptive phase was observed up to 6 months. Thereafter, there was no continued resorption up to 24 months observation.

Alveolar Bone Loss↗

Autogenous cultured bone graft--bone reconstruction using tissue engineering approach.

Maniatopoulos et al. reported the formation of calcified bone-like tissue when rat bone marrow cells were cultured in the presence of dexamethasone and beta-glycerophosphate. We have succeeded to construct the in vitro cultured bone on the porous framework of hydroxyapatite ceramics (HA). After 2 weeks of the culture, the construct showed the existence of mineralized collagen fibers on the surface of HA determined by Scanning Electron Microscopy. The construct also demonstrated high alkaline phosphatase (ALP) activity together with noticeable level of osteocalcin. The results indicate that the construct consisted of thin layer of bone matrix covered hydroxyapatite surface and abundant bone forming active osteoblasts. After the in vivo implantation of the construct, volume of the matrix increased and obvious bone tissue was detected by ordinal microscopy even one-week after implantation and its high osteogenic activity was maintained for a long term (one year). The in vivo bone is biologically active tissue evidenced by Northern blot analysis of the implanted construct which showed ALP and osteocalcin mRNA expression comparable to those of normal cancellous bone. These results demonstrate that the in vitro fabricated cultured bone/HA construct can possess new bone forming capability in in vivo situations. We have also succeeded to fabricate the construct using aged human marrow cells and the construct showed thick lamellar bone formation after the in vivo implantation. Based on these findings, we propose alternative approach for bone reconstruction surgery using the autogenous cultured bone/HA construct. Importantly, we can fabricate the implantable autogenous bone tissue derived from patient's marrow cells and the cells can be obtained by needle aspiration without damaging the patient's normal tissue.

Animals↗

Alpha-particle doses to cells of the bone remodeling cycle from alpha-particle-emitting bone-seekers: indications of an antiresorptive effect of actinides.

There are indications that alpha-particle-emitting bone-seekers such as plutonium or americium could enhance bone mass by suppressing bone resorption. To assess this possibility, this study calculates doses from alpha-particle emitters to the cells involved in trabecular bone turnover. Alpha-particle energy deposition in tissue from a bone surface source was calculated by Monte Carlo modeling. This was combined with bone surface cellular geometry to yield dose rates to cells during the remodeling cycle. Bone-resorbing osteoclasts receive on average 50 times the dose rate that bone-forming osteoblasts receive. Newly formed bone shields osteoblasts from alpha particles emitted by the buried deposit of alpha-particle emitters. However, at alpha-particle bone-seeking radionuclide intakes known to cause changes in remodeling (about 3700 Bq/kg body weight), the alpha-particle dose to osteoclasts corresponds to an extremely low rate of cell traversals (0.07% per cycle). It is therefore unlikely that perturbation of bone remodeling by alpha-particle bone-seeking radionuclides is directly caused by alpha-particle traversals of remodeling cells; some other indirect mechanism might be involved.

Actinoid Series Elements↗

[Ectopic osteogenesis of bone marrow stromal cells induced by bone morphogenetic protein].

OBJECTIVE: To investigate the ectopic osteogenesis of bone marrow stromal cells (MSC) induced by bone morphogenetic protein(BMP) in vitro and in vivo, providing the experimental evidence for making an artificial bone with its own capacity of bone formation. METHODS: MSC were separated and cultured from bone marrow of Wistar rats, MSC were co-cultured with BMP in vitro (cultured in plate and diffuse chamber). Artificial coral hydroxyapatites (CHA) with MSC and BMP were implanted into dorsal muscles of Wistar rats, their bone formation were observed by morphological examination, histochemistry and immunohistochemistry. RESULTS: Only cartilaginous matrix were produced by MSC in vitro (cultured in plate and diffuse chamber), and both cartilaginous and bone matrix production within the combined grafts were seen. The bone formation of experimental groups (CHA + BMP + MSC) was stronger than that of control A(CHA + MSC) and control B(CHA). CONCLUSION: It may be possible to produce an artificial bone with its own capacity of bone formation by combined graft (CHA + BMP + MSC). There may be multiple factors as well as BMP inducing bone formation both in the whole body and the location of the implantation. Further research on these factors will have the significance for making the ideal artificial bone.

Animals↗

[Experimental study of the thermic effect on bone at 60 degrees C, as applied to bone allograft].

Bone reconstruction methods increasingly often require using bank bone. These massive bone fragments can be taken only from dead subjects or those in irreversible coma. Surgical sterility of the samples does not always guarantee the absence of an HIV infection, for which seroconversion often occurs very late. B. Spire's work has shown the effectiveness of a 30-minute heat treatment at 56 degrees C to inactivate HIV in blood products. Our study has therefore evaluated the effectiveness of a heat treatment method for bone to inactivate HIV on one hand, and the mechanical and histologic consequences of this treatment on rabbit bone. All bone fragments in this study were frozen at -80 degrees C to reproduce the same conditions of use as in current bone banks. Heating deep-frozen fragments of spongious tissue and of bone marrow from seropositive subjects in a 60 degrees C humid heat allowed confirming thermal sterilization of HIV, but a greater number of case is required to support this technique, as well as a verification with cortical bone. Thermal sterilization of bone allografts does not alter the mechanical properties nor the possibilities of bone regrowth in allografts. Application to human bone allografts should be confirmed by a greater number of cases, but it appears as a simple means to suppress the current disadvantage of late seroconversion control.

Animals↗

Dehiscence or thinning of bone overlying the superior semicircular canal in a temporal bone survey.

OBJECTIVE: To determine the incidence and etiology of dehiscences of bone overlying the superior semicircular canal in a temporal bone archive. DESIGN: A microscopic study was performed of 1000 temporal bones from 596 adults in a university hospital registry. Specimens were sectioned vertically in the plane of the superior semicircular canal. Measurements of minimum bone thickness over the superior canal were made in a subset of 108 randomly chosen specimens. All bones were examined for thinning or dehiscence relative to these norms. Clinical histories, when available, were reviewed. RESULTS: Complete dehiscence of the superior canal was identified in 5 specimens (0.5%), at the middle fossa floor (n = 1) and where the superior petrosal sinus was in contact with the canal (n = 4). In 14 other specimens (1.4%), the bone at the middle fossa floor (n = 8) or superior petrosal sinus (n = 6) was no thicker than 0.1 mm, significantly less than values measured in the control specimens (P<.001). Abnormalities were typically bilateral. Specimens from infants demonstrated uniformly thin bone over the superior canal in the middle fossa at birth, with gradual thickening until 3 years of age. CONCLUSIONS: Dehiscence of bone overlying the superior canal occurred in approximately 0.5% of temporal bone specimens (0.7% of individuals). In an additional 1.4% of specimens (1.3% of individuals), the bone was markedly thin (< or =0.1 mm), such that it might appear dehiscent even on ultra-high-resolution computed tomography of the temporal bone. Sites affected were in the middle fossa floor or a deep groove for the superior petrosal sinus, often bilaterally. These abnormalities may arise from failure of postnatal bone development. Thin areas of bone over the superior canal may be predisposed to disruption by trauma.

Adult↗

Bioactive bone cement: comparison of apatite and wollastonite containing glass-ceramic, hydroxyapatite, and beta-tricalcium phosphate fillers on bone-bonding strength.

A study was conducted to compare the bone-bonding strengths of three types of bioactive bone cement, consisting of either apatite- and wollastonite-containing glass-ceramic (AW-GC) powder, hydroxyapatite (HA) powder, or beta-tricalcium phosphate (beta-TCP) powder as an inorganic filler and bisphenol-a-glycidyl methacrylate (Bis-GMA) based resin as an organic matrix. Seventy percent (w/w) filler was added to the cement. Rectangular plates (10 x 15 x 2 mm) of each cement were made and abraded with #2000 alumina powder. After soaking in simulated body fluid for 2 days, the AW cement (AWC) and HA cement (HAC) formed bonelike apatite over their entire surfaces, but the TCP cement (TCPC) did not. Plates of each type of cement were implanted into the tibial metaphyses of male Japanese white rabbits, and the failure loads were measured by a detaching test at 10 and 25 weeks after implantation. The failure loads of AWC, HAC, and TCPC were 3.95, 2.04, and 2.03 kgf at 10 weeks and 4.36, 3.45, and 3.10 kgf at 25 weeks, respectively. The failure loads of the AWC were significantly higher than those of the HAC and TCPC at 10 and 25 weeks. Histological examination by contact microradiogram and Giemsa surface staining of the bone-cement interface revealed that all the bioactive bone cements were in direct contact with bone. However, scanning electron microscopy and energy-dispersive X-ray microanalysis showed that only AWC had contacted to the bone via a Ca-P rich layer formed at the interface between the AW-GC powder and the bone, which might explain its high bone-bonding strength. Neither the HAC nor the TCPC contacted the bone through such a layer between each powder and the bone, although the HAC and TCPC directly contacted with bone. Our results indicate that all three types of abraded and prefabricated cement have bonding strength to bone, but AWC has superior bone-bonding strength compared to HAC and TCPC.

Animals↗

Abnormal serum bone Gla protein levels in multiple myeloma. Crucial role of bone formation and prognostic implications.

The signification of serum bone Gla protein (serum BGP, osteocalcin) has been investigated in multiple myeloma. As a first step, quantitative iliac crest bone biopsies were performed in 19 patients; the serum BGP levels strongly correlated with histologic parameters of bone formation (r = 0.72-0.84, P less than 0.001) but not with those of bone resorption (r = 0.10). These results confirm that serum BGP is a marker of bone formation in multiple myeloma, as previously described in many other bone disorders. As a second step, serum BGP was measured in 117 patients with multiple myeloma as a systemic indicator of the degree of bone formation. Twenty-one percent of the patients had abnormal serum BGP levels (25 cases). The 14 patients with increased values (mean, 13.2 +/- 2.7 ng/ml) and thus increased bone formation belonged to a subgroup characterized by a lower osteolytic potential and a more indolent disease. On the other hand, the 11 patients with decreased values (mean, 1 +/- 0.3 ng/ml) and thus reduced bone formation had an advanced disease, extensive lytic bone lesions, a hypercalcemia frequently and a poor survival (mean, 4 months; range, 1-12). The biochemical investigations of the whole patient population, including serial studies in individual patients, have shown a large scatter of serum BGP levels, suggesting major differences in the bone formation rates. However, an overall inverse correlation was found between serum BGP and osteolytic potential. These results have confirmed the important role of the inhibition of bone formation in the occurrence of bone lesions in multiple myeloma and the interest of serum BGP to select a myeloma patient subgroup with low osteolytic potential and characterized by abnormally increased levels of this marker.

Adult↗

Strontium distribution and interactions with bone mineral in monkey iliac bone after strontium salt (S 12911) administration.

The analysis of the interaction of strontium (Sr) with bone mineral is of interest because a new agent containing Sr (S 12911) has shown positive effects on bone mass in various animal models of osteoporosis and is currently being developed for preventive and curative treatment of postmenopausal osteoporosis. Iliac bone samples were obtained from 20 male monkeys: 4 untreated control animals, 12 animals sacrificed at the end of a 13-week treatment with high dose levels of S 12911 (750, 275, or 100 mg/kg/day orally), and 4 animals sacrificed 6 weeks after the end of a 13-week treatment with S 12911 (750 or 100 mg/kg/day orally). The distribution of Sr was determined and quantified by X-ray microanalysis. Changes at the crystal level were evaluated by X-ray diffraction and Raman microspectrometry. In the control animals, traces of Sr were found to be homogeneously distributed throughout the bone tissue. In the treated monkeys, Sr could only be detected in calcified matrix. In monkeys sacrificed at the end of the treatment, Sr was found to be dose-dependently incorporated into the mineral substance of the compact and cancellous bone. Sr was heterogeneously distributed with three to four times more Sr in new than in old compact bone, and approximately two and a half times more Sr in new than in old cancellous bone. The bone Sr content dramatically decreased in the animals sacrificed 6 weeks after the end of the treatment. Diffraction showed no significant changes in the characteristics of the crystal lattice. Sr appeared to be easily exchangeable from bone mineral and was slightly linked to mature crystals through ionic substitutions. Even at the highest dose level tested, less than 1 calcium ion out of 10 was substituted by 1 Sr ion in each crystal. In conclusion, taken up by bone, Sr was heterogeneously distributed with a higher concentration in new than in old bone but induced no major modifications of the bone mineral (crystallinity, crystal structure) at the crystal level. As a result, a treatment with S 12911 Sr salt should not induce any alteration of bone mineral.

Administration, Oral↗

Inhibition of PPARgamma prevents type I diabetic bone marrow adiposity but not bone loss.

Diabetes type I is associated with bone loss and increased bone adiposity. Osteoblasts and adipocytes are both derived from mesenchymal stem cells located in the bone marrow, therefore we hypothesized that if we could block adipocyte differentiation we might prevent bone loss in diabetic mice. Control and insulin-deficient diabetic BALB/c mice were chronically treated with a peroxisomal proliferator-activated receptor gamma (PPARgamma) antagonist, bisphenol-A-diglycidyl ether (BADGE), to block adipocyte differentiation. Effects on bone density, adiposity, and gene expression were measured. BADGE treatment did not prevent diabetes-associated hyperglycemia or weight loss, but did prevent diabetes-induced hyperlipidemia and effectively blocked diabetes type I-induced bone adiposity. Despite this, BADGE treatment did not prevent diabetes type I suppression of osteoblast markers (runx2 and osteocalcin) and bone loss (as determined by micro-computed tomography). BADGE did not suppress osteoblast gene expression or bone mineral density in control mice, however, chronic (but not acute) BADGE treatment did suppress osteocalcin expression in osteoblasts in vitro. Taken together, our findings suggest that BADGE treatment is an effective approach to reduce serum triglyceride and free fatty acid levels as well as bone adiposity associated with type I diabetes. The inability of BADGE treatment to prevent bone loss in diabetic mice suggests that marrow adiposity is not linked to bone density status in type I diabetes, but we cannot exclude the possibility of additional BADGE effects on osteoblasts or other bone cells, which could contribute to preventing the rescue of the bone phenotype.

Adipocytes↗

Initial experience with dynamic MR imaging in evaluation of normal bone marrow versus malignant bone marrow infiltrations in humans.

The purpose of this study was (a) evaluation of dynamic contrast-enhanced MR imaging of normal bone marrow versus malignant bone marrow infiltrations in patients with proven B-cell-type chronic lymphocytic leukemia (B-CLL) and (b) correlation with the clinical stage according to Binet (stages A, B, C) and response to therapy. Bone marrow imaging of the lumbar spine, pelvis, and proximal femurs was performed at 1.5 T in 45 patients without known malignancy and in 30 patients with B-CLL. The differences between opposed-phase and in-phase dynamic gradient-echo sequences before and up to 10 minutes after intravenous application of .1 mmol/kg body weight of gadolinium-diethylenetriamine penta-acetic acid (Gd-DTPA) were evaluated in normal bone marrow. The contrast-enhancement patterns of normal and malignant bone marrow were compared using the opposed-phase dynamic gradient-echo sequence. Ten of the patients with bone marrow infiltrations (Binet stage C) additionally underwent MR imaging follow-up during therapy. Opposed-phase gradient echo sequences demonstrated a signal decrease of normal bone marrow, and in-phase gradient echo sequences demonstrated a signal increase of normal bone marrow after administration of Gd-DTPA. The dynamic signal intensity time courses differed significantly (P < .05) between Binet stages B and C and controls as well as among the three Binet stages of B-CLL. In the 10 patients followed during therapy, MR imaging sensitively demonstrated response (n = 6), nonresponse (n = 2), or relapse after initial response (n = 2). In out-of-phase imaging, both normal bone marrow and initial bone marrow infiltration in CLL stage Binet A show signal decrease after administration of contrast agent, whereas there is increase in signal intensity in higher-grade bone marrow infiltration in Binet stage B or C disease. The signal loss of normal bone marrow in out-of-phase imaging is a phase effect rather than a T2* effect. The differentiation of initial from higher-grade bone marrow infiltration on out-of-phase images relies solely on a shift in the fat/water ratio.

Adult↗

Experimental study on vascularized bone allografts for reconstruction of massive bone defects.

To study the healing mechanism of vascularized bone allografts under short-term as well as long-term immunosuppression with cyclosporin A, experimental vascularized intercalary bone allograft transplantation was carried out between inbred rats using the tibiofibula graft model. Bone scintigram and radiographs were used as an indicator for early detection of rejection after transplantation and bone union. In vascularized bone allografts under long-term immunosuppression with cyclosporin A, early bone union and continuous incorporation were similar to that observed in vascularized bone autograft transplantation. When administration of cyclosporin A was discontinued before completion of bone union, the graft was rejected and bone union was delayed. Apparent swelling on the operated limb associated with a decrease in bone scintigram uptake suggested the occurrence of rejection of the allograft. Vascularized bone allograft transplantation is useful for reconstruction of massive bone defects only if immunosuppressants are used and maintained at least until bone union is obtained.

Animals↗

Effect of cadmium on osteogenesis within diffusion chambers by bone marrow cells: biochemical evidence of decreased bone formation capacity.

The biological and biochemical effects of cadmium administration on bone marrow in rats were examined. When young adult rats were administered cadmium (Cd) repeatedly at a dose of 750 micrograms/kg body wt for up to 4 weeks, metallothionein mRNA was detected by a gene expression analysis in their bone marrow at 2 weeks after the first Cd administration, though the amounts were lower than those in liver. To determine the direct effect of cadmium on bone formation, the potential of Cd-treated bone marrow cells and demineralized bone matrix (DBM) to form bone and cartilage was assessed using a diffusion chamber (DC) in vivo, by histological examination, and by biochemical parameters such as alkaline phosphatase (ALP) activity, total calcium and phosphorus content, and the bone-specific vitamin K-dependent Gla-containing protein (BGP) content, relative to mineralization. Diffusion chambers were inoculated with DBM and bone marrow cells from either Cd-treated or nontreated rats (control) and were then implanted subcutaneously into syngeneic nontreated rats. The accumulation of BGP in DCs with Cd-treated bone marrow was significantly lower than that in control DCs. Unlike in control DC, a peak of ALP activity did not occur at 4 weeks postimplantation in DC implants inoculated with Cd-treated bone marrow; the ALP activity and calcium content in these implants were also significantly lower than those of the control bone marrow-containing chambers at the early stage of implantation. Histological examinations of chambers with Cd-treated marrow showed a decreased area of cartilage and bone foci compared with those in control chambers. These findings suggest that Cd administration inhibits the osteoblastic and chondroblastic differentiation pathway in bone marrow through direct effects on these cells.

Animals↗

Longitudinal study of bone loss in pre- and perimenopausal women: evidence for bone loss in perimenopausal women.

Bone loss before and around the time of menopause is not well characterized by longitudinal studies. We measured bone mineral density at various skeletal sites--total body, femoral neck, trochanter, anteroposterior (AP) and lateral spine, and forearm--with dual-energy X-ray absorptiometry in a large prospective cohort of 272 untreated pre- and perimenopausal women aged 31-59 years, at 1 year intervals for 3 years. Sex steroids and the following markers of bone remodeling were measured: serum osteocalcin (OC), procollagen I carboxyterminal extension peptide, bone alkaline phosphatase (BAP) and urinary crosslinks (CTX and NTX). Seventy-six women were classified as perimenopausal and 196 as premenopausal. Over the 3 years, premenopausal women had no significant bone loss at any site and a small but significant increase in bone mineral density at the trochanter, total hip, AP spine and radius. Perimenopausal women significantly lost bone from cancellous and cortical sites, i.e., the femoral neck, trochanter and lumbar spine. In perimenopausal women with increased follicle stimulating hormone, the rate of bone loss at the femoral neck correlated negatively with OC and BAP. In perimenopausal women, serum estradiol levels decreased during the 3 years of follow-up and bone loss from the trochanter and the AP spine was correlated with serum estradiol after 3 years. In conclusion, among premenopausal women there is no bone loss. In contrast, there is a rapid and diffuse bone loss in perimenopausal women, related to decreased estrogen secretion. Bone markers may be useful to identify these women losing bone.

Absorptiometry, Photon↗