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PubMed1992

A study on bone induction in hydroxyapatite combined with bone morphogenetic protein.

Our present study consisted of an implantation of artificially made hydroxyapatite (HAP) ceramic pellets under the periosteum of the rabbit skull with subsequent inspection of further progress of bone formation and also of an evaluation of the effects of bone morphogenetic protein (BMP). The results revealed that the alkali phosphatase (AL-P) activity of the pellets was elevated only in those of the bone morphogenetic protein group. The results of determination of bone mineral density at the site of the pellets revealed that the increase in bone mineral density was the most remarkable in the bone morphogenetic protein group rather than the control group. The results of the histopathologic examinations revealed that marginal bone formation was found in the pores on the surface between the pellets and the skull in the control group and in the collagen group, whereas in the bone morphogenetic protein group very active bone formation was found not only on the interface in contact with the skull but also surrounding the whole pellet. It also was noted in the animals in the bone morphogenetic protein group that the pellets were corrupted from the peripheries and then absorbed into the newly formed bone. From these results, the efficacy of the hydroxyapatite-collagen-bone morphogenetic protein complex was made clear, and applications in clinical practice are expected in the near future.

Alkaline Phosphatase↗
PubMed2005

No negative effects of bone impaction grafting with bone and ceramic mixtures.

Reconstructing large loaded bone defects with ceramic bone graft extenders is tempting considering the expected future donor bone shortage. However, whether there are negative effects is unknown. Standardized large defects in the acetabulum of goats were created and subsequently reconstructed with metal mesh and impacted morselized cancellous bone grafts or a 50/50% volume mixture of tricalcium phosphate-hydroxyapatite granules and morselized cancellous bone grafts using the bone impaction grafting technique. Subsequently, a cemented total hip prosthesis was inserted. Clinically, no differences were observed between groups. Most of the morselized cancellous bone graft had been resorbed and incorporated into new bone after 15 weeks. The large tricalcium phosphate-hydroxyapatite granules were integrated, the smaller crushed tricalcium phosphate-hydroxyapatite granules were surrounded by osteoclasts or engulfed by macrophages and giant cells. The cement penetration into the reconstructive layer and the quality of the bone based on a semiquantitative score were similar in both groups. We found no suggestion of tricalcium-hydroxyapatite granule-induced third-body wear in this short-term followup study. No negative effects were observed in this study, and therefore, it seems reasonable to use tricalcium-hydroxyapatite granules in a 50/50% volume mix with morselized cancellous bone graft as a bone graft extender in acetabular revision surgery with the bone impaction grafting technique.

Acetabulum↗
PubMed2006

Involvement of neuronal cannabinoid receptor CB1 in regulation of bone mass and bone remodeling.

The CB1 cannabinoid receptor has been implicated in the regulation of bone remodeling and bone mass. A high bone mass (HBM) phenotype was reported in CB1-null mice generated on a CD1 background (CD1(CB1-/-) mice). By contrast, our preliminary studies in cb1-/- mice, backcrossed to C57BL/6J mice (C57(CB1-/-) mice), revealed low bone mass (LBM). We therefore analyzed CB1 expression in bone and compared the skeletons of sexually mature C57(CB1-/-) and CD1(CB1-/-) mice in the same experimental setting. CB1 mRNA is weakly expressed in osteoclasts and immunoreactive CB1 is present in sympathetic neurons, close to osteoblasts. In addition to their LBM, male and female C57(CB1-/-) mice exhibit decreased bone formation rate and increased osteoclast number. The skeletal phenotype of the CD1(CB1-/-) mice shows a gender disparity. Female mice have normal trabecular bone with a slight cortical expansion, whereas male CD1(CB1-/-) animals display an HBM phenotype. We were surprised to find that bone formation and resorption are within normal limits. These findings, at least the consistent set of data obtained in the C57(CB1-/-) line, suggest an important role for CB1 signaling in the regulation of bone remodeling and bone mass. Because sympathetic CB1 signaling inhibits norepinephrine (NE) release in peripheral tissues, part of the endocannabinoid activity in bone may be attributed to the regulation of NE release from sympathetic nerve fibers. Several phenotypic discrepancies have been reported between C57(CB1-/-) and CD1(CB1-/-) mice that could result from genetic differences between the background strains. Unraveling these differences can provide useful information on the physiologic functional milieu of CB1 in bone.

Adrenergic Fibers↗
PubMed1990

Attenuated bone aluminum deposition in nonuremic beagles with reduced bone remodeling.

Excess bone aluminum accumulates in uremic subjects after parathyroidectomy. To evaluate whether decreased bone remodeling caused by parathyroidectomy augments bone aluminum deposition, we administered aluminum chloride (0.75 mg/kg iv 3 times/wk) or vehicle to thyroparathyroidectomized (TPTX) and sham-operated (Sham) nonuremic beagles for 8 wk. TPTX alone effectively lowered plasma parathyroid hormone concentrations (8.2 +/- 2.8 vs. 27 +/- 2.2 pg/ml) and consequently suppressed bone remodeling, as evidenced by the diminished resorptive surface (0.8 +/- 0.3 vs. 4.0 +/- 0.5%), osteoid surface (0.5 +/- 0.2 vs. 13.3 +/- 2.3%), and bone formation rate (1.8 +/- 0.6 vs. 15.5 +/- 2.2%/yr) compared with untreated Shams. Aluminum treatment resulted in no further suppression of bone remodeling in TPTX dogs and did not cause osteomalacia. Aluminum-treated TPTX dogs, however, accumulated much less total bone (28.1 +/- 4.5 micrograms/g) and surface aluminum (3.8 +2- 1.4%) than similarly treated Shams (61.4 +/- 5.6 micrograms/g; 12.2 +/- 2.7%, respectively) despite displaying higher plasma aluminum concentrations (1,209 +/- 330 vs. 181 +/- 18 micrograms/l). These observations illustrate that diminished bone turnover retards rather than augments bone aluminum accumulation. Thus bone aluminum deposition after parathyroidectomy in uremic subjects is not likely to be the result of passive aluminum accumulation on inactive bone surfaces. Further studies are needed to determine whether factors, such as prior bone aluminum accumulation and/or the degree of preexistent hyperosteoidosis, modulate aluminum accumulation after parathyroidectomy.

Alkaline Phosphatase↗
PubMed1975

Human bone marrow lymphocytes. I. Distribution of lymphocyte subpopulations in the bone marrow of normal individuals.

This study was undertaken to determine the proportions and in vitro immune capacities of lymphocyte populations in the bone marrows of normal humans. Relatively pure mononuclear cell suspensions were obtained from bone marrow aspirates by linear sucrose gradient centrifugations. Simultaneous peripheral blood and bone marrow specimens from each individual were assayed for lymphocyte surface markers and mitogen responsiveness. Maximal possible contamination of bone marrow aspirates by peripheral blood was determined by performing aspirates on individuals who had received 51chromium-labeled autologous erythrocytes. Rhymus-derived (T) lymphocytes, as determined by the sheep red blood cell (E) rosette assay, comprised 8.6-(plus or minus 1.6)% of the total bone marrow lymphocyte pool. Bone marrow-derived (B) lymphocytes, as determined by the presence of a complement receptor, made up 15.4-(plus or minus 1.9)% of the lymphocyte pool whereas 74.6 (plus or minus 2.4)% of mononuclear cells lacked easily detectable surface markers. These findings could not be explained by contamination with peripheral blood lymphocytes since contamination was corrected for in the calculations. Lymphocyte-enriched suspensions of bone marrow cells responded to stimulation with phytohemagglutinin, concanalin A, and particularly pokeweed mitogen. In vitro incubations of bone marrow and peripheral blood lymphocytes with tritiated thymidine followed by determinations of E and erythrocyte antibody complement (EAC) rosettes were performed. Simultaneous rosetteradioautographs demonstrated that the proliferative potential of bone marrow B lymphocytes was greater than peripheral blood B lymphocytes (P less than 0.01). On the other hand, the proliferative potential of bone marrow T lymphocytes was the same as that of peripheral blood T lymphocytes. These findings demonstrate that in addition to containing B lymphocytes the normal bone marrow contains a small fraction of T lymphocytes similar to the mature T lymphocyte pool found in the peripheral blood. These T cells most probably enter the bone marrow parenchyma as part of the normal recirculating lymphocyte pool.

Adult↗
PubMed2005

Early changes in biochemical markers of bone formation correlate with improvements in bone structure during teriparatide therapy.

CONTEXT: Biochemical markers of bone turnover may reflect bone structure during anabolic treatment. OBJECTIVE: The objective was to evaluate associations between changes in biochemical markers and structural and dynamic bone parameters during teriparatide treatment. DESIGN: This study was a randomized, multicenter, double-blind, placebo-controlled fracture prevention trial, with 20-month median treatment duration for biopsy subset. SETTING: The trial was conducted at 11 clinical study sites. PATIENTS: Sixty-one postmenopausal women with osteoporosis who had paired transiliac biopsy specimens participated in the study. INTERVENTIONS: Once-daily sc injections of either placebo or teriparatide (20 or 40 microg) were administered. MAIN OUTCOME MEASURES: The study measured: 1) serum and urinary biochemical markers of bone formation [bone alkaline phosphatase and procollagen I C-terminal propeptide (PICP)] and resorption (N-telopeptide and deoxypyridinoline); and 2) structural and dynamic analyses of bone biopsies, including two-dimensional (2D) histomorphometry and three-dimensional (3D) micro-computed tomography evaluations measured at baseline (n = 57) and 12 (n = 21) or 22 (n = 36) months. RESULTS: U-N-telopeptide/creatinine and serum-PICP correlated with bone structure and dynamic indices at baseline, respectively. Changes in bone alkaline phosphatase at 1 month correlated with changes at 22 months in 2D wall thickness (r = 0.73; P = 0.001), trabecular bone volume (trabecular bone volume per total volume, BV/TV) (r = 0.58; P < 0.05), marrow star volume (r = -0.51; P = 0.05); 3D trabecular thickness (r = 0.49; P < 0.05), and BV/TV (r = 0.54; P < 0.05). Changes in PICP at 1 month correlated with changes in wall thickness (r = 0.60; P = 0.01), and 2D BV/TV (r = 0.51; P < 0.05) at 22 months. Changes in markers at 6 or 12 months were not associated with changes in structural or dynamic parameters. CONCLUSIONS: Early (1-month) changes in biochemical markers of bone formation, but not resorption, correlated with improvements in bone structure after 22 months of teriparatide therapy.

Aged↗
PubMed1998

Effect of obesity on estradiol level, and its relationship to leptin, bone maturation, and bone mineral density in children.

The purpose of this study was to investigate 24-h estradiol and leptin levels in obese and nonobese children to further understand the roles of estradiol and leptin in obesity and puberty. We measured serum estradiol, leptin, insulin, glucose, and GH levels every hour for 24 h in 18 obese (12 females and 6 males) and 30 nonobese (11 females and 19 males) prepubertal and early pubertal (stages 1-2) children. Bone age and dual energy x-ray absortiometry (DEXA) were obtained upon completion of the 24-h study. Obese children were significantly younger than nonobese children, with no difference in pubertal stage, height, or bone age between the 2 groups. Obese children had greater bone age to chronological age ratios than nonobese children, indicating a more advanced rate of bone maturation. Mean 24-h estradiol levels correlated significantly with chronological age and bone age as well as with insulin-like growth factor I, insulin-like growth factor-binding protein-3, dehydroepiandrosterone sulfate, mean 24-h GH, and lean body mass. Mean 24-h estradiol levels did not differ between obese and nonobese children [1.65+/-1.47 us. 2.75+/-3.30 pmol/L (0.45+/-0.40 vs. 0.75+/-0.90 pg/mL), respectively]. Similar mean 24-h estradiol levels in obese and nonobese children are consistent with the increased bone maturation of the obese children. Estradiol did not correlate significantly with DEXA fat mass, body mass index, or arm fat measures of adiposity. Obese children had higher 24-h mean leptin concentrations than nonobese children (28.6+/-17.4 vs. 6.8+/-7.1 ng/mL; P < 0.001). Leptin concentrations positively correlated with DEXA fat mass, body mass index, and arm fat measurement of adiposity. Girls had higher 24-h mean leptin levels than boys when controlling for adiposity. Estradiol and leptin concentrations fluctuated over a 24-h period in both groups, with all children having higher leptin concentrations at night and higher estradiol concentrations in the morning. This diurnal rhythm was of a similar pattern, but at higher levels for leptin and lower levels for estradiol in the obese children compared to nonobese children. There was no significant correlation between estradiol and leptin levels. Bone mineral density, as measured by DEXA, did not differ between obese and nonobese children. Similar bone mineral density values in obese and nonobese children are consistent with the increased bone maturation of the obese children. Bone mineral density was not correlated with estradiol or leptin level in these children. In conclusion, obese children had similar estradiol levels and equivalent bone ages at a younger chronological age than nonobese children. Leptin was higher in these obese children, but did not correlate with estradiol level or bone age. These findings suggest that the role of leptin in both obesity and pubertal development is not directly correlated with the estradiol level.

Bone Density↗
PubMed2004

Isosorbide mononitrate increases bone formation and decreases bone resorption in postmenopausal women: a randomized trial.

UNLABELLED: NO regulates bone remodeling in cellular and animal models. We examined the effect of administering ISMO, a NO donor, on bone turnover in 144 postmenopausal women. After 3 months, women randomized to ISMO had a greater decrease in bone resorption and a greater increase in bone formation compared with placebo. NO donors may prevent postmenopausal bone loss. INTRODUCTION: NO both stimulates bone formation and inhibits bone resorption in vitro. NO donors (nitrates) are inexpensive and widely available, but their value for postmenopausal osteoporosis has never been evaluated in a randomized trial. MATERIALS AND METHODS: We randomly assigned 144 healthy postmenopausal women with a hip BMD T score between 0 and -2.5 to 5 or 20 mg/day of isosorbide mononitrate (ISMO) or placebo for 12 weeks. We measured urine N-telopeptide (NTx), a marker of bone resorption, and serum bone-specific alkaline phosphatase (BSALP), a marker of bone formation. Markers were measured immediately before randomization and after 12 weeks of treatment. We calculated the percent change in NTx and BSALP for each of the treatment groups (placebo, 5 mg ISMO, and 20 mg ISMO). Our primary outcome was the percent change in NTx and BSALP in the 5- and 20-mg ISMO groups compared with placebo. RESULTS AND CONCLUSIONS: Compared with women randomized to placebo, women randomized to 20 mg of ISMO had a 45.4% decrease in NTx (95% CI, 25.8-64.9) and a 23.3% increase (95% CI, 8.9-37.8) in BSALP. Women randomized to 5 mg of ISMO had a 36.3% decrease in NTx (95% CI, 14.8-57.8) and a 15.9% increase in BSALP (95% CI, 1.1-30.7). ISMO decreases bone resorption and increases bone formation. These findings suggest that nitrates may be useful for the prevention of postmenopausal osteoporosis.

Aged↗
PubMed1998

Bone marrow composition and bone microarchitecture and turnover in blacks and whites.

We examined the relationship between bone histomorphometric variables versus marrow cellularity, marrow adiposity (among hemopoietic cells), and fatty degeneration (areas of only fat) of bone marrow in iliac crest bone samples from 98 normal black (n = 53) and white (n = 45) males and females. We found blacks to have greater marrow cellularity (p = 0.0001), less marrow adiposity (among hemopoietic cells, p = 0.0001), greater values for bone volume (p = 0.030), trabecular thickness (p = 0.002), and static bone turnover variables (osteoid volume, p = 0.001; osteoid surface, p = 0.001; osteoid thickness, p = 0.001; eroded surface, p = 0.0006) than whites. Marrow cellularity correlated positively with static bone turnover variables osteoid volume (r = 0.257, p = 0.011), osteoid surface (r = 0.265, p = 0.008), osteoid thickness (r = 0.217, p = 0.032), and eroded surface (r = 0.273, p = 0.007) when all 98 cases were analyzed together. These findings suggest that marrow cells may influence bone turnover. The extent of fatty degeneration, but not that of adipose tissue, increased with age in blacks (r = 0.476, p = 0.0003) and whites (r = 0.476, p = 0.001), as did bone loss. There was no racial difference in the extent of fatty degeneration. We conclude that the lesser extent of adiposity in blacks is a racial characteristic that is unaffected by aging, whereas fatty degeneration which may have partly occupied space vacated by bone loss, is an aging phenomenon, unrelated to race. Greater bone turnover in blacks may be expected to lead to more frequent renewal of fatigue-damaged bone, which together with sturdier bone structure may contribute to the lower fragility fracture rates in blacks.

Adult↗
PubMed1998

The diuretic indapamide increases bone mass and decreases bone resorption in spontaneously hypertensive rats supplemented with sodium.

Clinical and epidemiological studies suggest that thiazide diuretics can prevent bone loss and decrease the incidence of hip fractures. However, the mechanism of the effect of diuretics on bone is not clearly established. Indapamide (IDP), a sulfonamide diuretic related to thiazides, is used to treat hypertension. Sixty spontaneously hypertensive rats (SHRs) were divided into four groups and treated with or without IDP (1.5 mg/kg/day) during 8 weeks in the presence or absence of a high sodium load (8% NaCl supplementation in the diet). Sodium and calcium excretions were increased in the rats receiving the high sodium load (SHR + 8% NaCl) comparatively with control rats (SHR). IDP decreased and increased, respectively, calcium and sodium excretions. Serum parathyroid hormone (PTH) was unchanged in any group. Bone density was measured at the femur, tibia, and vertebrae, and bone morphometry was performed at the metaphysis of the femur to evaluate bone architecture. Rats fed a high sodium diet had an average 5.5% decreased bone density at every site except the femoral diaphysis. The trabecular bone volume was also decreased (SHR + 8% NaCl vs. SHR, 11.99+/-0.78 vs. 17.51+/-1.5%, p < 0.05). An increase in trabecular separation suggested that these changes were due to increased bone resorption. In the SHR + 8% NaCl + IDP group, IDP increased bone density and trabecular bone volume (SHR + 8% NaCl + IDP vs. SHR + 8% NaCl, 16.52+/-1.04 vs. 11.99+/-0.78%, p < 0.05). Trabecular separation and pyridinoline/creatinine excretion (SHR + 8% NaCl + IDP vs. SHR + 8% NaCl, 136.39+/-9.62 vs. 195.18+/-22.34 nmol/mmol, p < 0.05) were also decreased by IDP. These results show that in rats receiving a high sodium diet, IDP can reverse sodium-induced bone loss and increased bone resorption independently of changes in serum PTH.

Absorptiometry, Photon↗
PubMed1998

Transforming growth factor-beta 1: induction of bone morphogenetic protein genes expression during endochondral bone formation in the baboon, and synergistic interaction with osteogenic protein-1 (BMP-7).

Certain members of the bone morphogenetic protein (BMP) and transforming growth factor-beta (TGF-beta) families are inducers of endochondral bone formation in vivo. TGF-betas, however, do not initiate bone formation when implanted in heterotopic (extraskeletal) sites of rodents. Here we show that platelet-derived porcine TGF-beta 1 (pTGF-beta 1) induces endochondral bone in heterotopic sites of the baboon (Papio ursinus) at doses of 5 microgram per 100 mg of guanidinium-inactivated collagenous bone matrix as carrier, with an inductive efficiency comparable to 5 and 25 micrograms of recombinant osteogenic protein-1 (hOP-1, BMP-7), a well characterized inducer of bone formation. We further demonstrate that pTGF-beta 1 and hOP-1 interact synergistically to induce large ossicles in the rectus abdominis of the primate as evaluated by key parameters of bone formation on day 14 and 30. Tissue generated on day 30 by 5 microgram pTGF-beta 1 or 25 micrograms hOP-1 induced comparable expression levels of OP-1, BMP-3 and type IV collagen mRNA transcripts, whereas TGF-beta 1 and type II collagen expression was 2 to 3 fold higher in pTGF-beta 1-treated implants, as determined by Northern analysis. In ossicles generated by 25 micrograms hOP-1 in combination with relatively low doses of pTGF-beta 1 (0.5, 1.5 and 5 micrograms), type II collagen expression increased in a pTGF-beta 1 dose-dependent manner, whilst type IV collagen was synergistically upregulated with a 3 to 4 fold increase compared to ossicles generated by a single application of 5 micrograms pTGF-beta 1 or 25 micrograms hOP-1. Morphogen combinations (5 micrograms pTGF-beta 1 with 20 micrograms hOP-1, and 5 and 15 micrograms pTGF-beta 1 with 100 micrograms hOP-1 per g of collagenous matrix as carrier) induced exuberant tissue formation and greater amounts of osteoid than hOP-1 alone when implanted in calvarial defects of the baboon as evaluated. on day 30 and 90, with displacement of the temporalis muscle above the defects. Since a single application of TGF-beta 1 in the primate did not induce bone formation in calvarial defects, whilst it induces endochondral bone differentiation in heterotopic sites, our data indicate that the bone inductive activity of TGF-beta 1 is site and tissue specific. mRNA expression of multiple members of the TGF-beta superfamily suggests complex autocrine and paracrine activities of the ligands and different signalling pathways on responding cells during the cascade of endochondral bone formation in the primate. The present findings may provide the basis for synergistic molecular therapeutics for cartilage and bone regeneration in clinical contexts.

Animals↗
PubMed2003

[Repair of alveolar bone defect with tissue engineered bone: an experimental study of dogs].

OBJECTIVE: To study the feasibility of repairing experimental horizontal alveolar bone defects by tissue engineering based on bone marrow stromal cells (BMSC). METHODS: Dog bone marrow mononuclear cells were isolated from the bone marrow by gradient centrifugation and then cultured in conditional medium to be induced to become osteogenic. Immunohistochemistry was used to examine the expression of core-binding factor alpha subunit 1 (Cbfa1), osteocalcin (OCN), and type I collagen in the cultured BMSCs. Histochemical technique was used to examine the expression of alkaline phosphatase (AKP) in the BMSCs. Inversed phase-contrast microscopy and electron microscopy were used to observe the morphology and proliferation of the BMSCs. Induced BMSCs at passage 3 were harvested and mixed with calcium alginate to form a gelatin form cell-scaffold construct. A horizontal alveolar bone defect (5 mm high) was created surgically in each buccal side of the mandibular premolars 3 and 4 and molar 1 of 11 dogs. The defects was randomly repaired with a cell-scaffold construct (experimental group, 20 teeth), calcium alginate alone (control group A, 15 teeth), or left untreated (control group B, 12 teeth). At four, twelve, and twenty-four weeks after operation, 2, 7, 2 dogs were killed respectively and block sections of mandibular bones at the defects were collected and processed for gross and histological observation as well as X-ray examination. The status of bone repair 12 weeks after operation in the 3 groups was compared. RESULT: In vitro induced BMSCs exhibited an osteogenic phenotype. Since the passage 3 calcium salt sedimentation could be seen in the extracellular stroma of BMSCs. Cbfa1, type I collagen, and AKP were expressed in the BMSCs in every passage. OCN was expressed since the second passage. Histologically, bone nodule structure was observed in the experimental group 4 weeks after operation. The engineered bone became more mature, similar to the normal bone, 12 weeks after operation. Twelve weeks after operation, the alveolar ridge regeneration amounted to a repair height of 2.43 +/- 0.93 mm, 0.98 +/- 0.87 mm, and 0.78 +/- 0.75 mm and reached 48.59%, 19.74%, and 15.76% of the original height in the experimental group, control group A, and control group B respectively, with a significant difference between the experimental and control groups A and B (all P < 0.01). CONCLUSION: BMSCs can be induced to become osteogenic and be used as seed cells to engineer bone tissue and repair experimental alveolar bone defect.

Alkaline Phosphatase↗
PubMed1992

[An experimental study of the process of bony ingrowth into inorganic bone-particle impregnated bone cement].

A composite of inorganic bone particles formed with bone cement in certain proportion was implanted in the proximal femora of 15 New Zealand rabbits. The animals were sacrificed in batches at different intervals after implantation and specimens were sectioned for scanning electron microscopic (SEM) observation and push-out test. SEM showed that the bone particles in the composite were in contact with each other and forming bony pathways. The gaps between inorganic bone particle bone cement and cortical bone were filled at first with collagen fibrils which were interwoven to form collagen fiber bundles and then mineralized to assume woven bone. The bone particles became smaller in size and were enveloped, absorbed and replaced by new bone structure gradually reaching the depth of bone cement along the pathways formed by bone particles. The shear strength of the cement-bone interface was increased subsequently.

Animals↗
PubMed2004

Sequential analysis of biochemical markers of bone resorption and bone densitometry in multiple myeloma.

BACKGROUND AND OBJECTIVES: Bone lesions often occur in multiple myeloma (MM), but no tests have proven useful in identifying patients with increased risk. Bone marker assays and bone densitometry are non-invasive methods that can be used repeatedly at low cost. This study was performed to evaluate these methods in predicting bone events in MM patients. DESIGN AND METHODS: Thirty newly diagnosed MM patients were enrolled. Serum C-terminal telopeptide (ICTP) and urinary N-terminal telopeptide (NTx) of collagen I were measured for assessment of bone resorption, and serum C-terminal (PICP) and N-terminal (PINP) propeptides of procollagen I, bone-specific alkaline phosphatase, and osteocalcin were measured to estimate bone formation. Dual energy X-ray absorptiometry (DEXA) was used to assess bone mineral density (BMD) of the lumbar spine, hip, and whole body. Serum and urine samples were collected every 6 weeks, DEXA-scans performed every 3 months, and skeletal radiographs were done every 6 months as well as when indicated. RESULTS: Serum ICTP and urinary NTx were predictive of progressive bone events. Markers of bone formation, bone mineral density assessments, and M component measurements were less informative. In Cox analysis, ICTP showed the highest predictive value, but should be replaced with NTx in patients with nephropathy. Pretreatment low lumbar BMD was predictive of early vertebral fractures. INTERPRETATION AND CONCLUSIONS: Sequential DEXA-scans showed heterogeneous local BMD changes, and our data do not support routine use of sequential DEXA-scans. However, lumbar DEXA-scans at diagnosis can identify patients with increased risk of early vertebral collapses. Sequential analyses of serum ICTP and urinary NTx are useful for monitoring bone damage.

Absorptiometry, Photon↗
PubMed2006

[Reconstruction of bone defects with autograft after resection of upper extremity bone].

OBJECTIVE: To discuss the reconstructive method of the bone defect after resection of the upper extremity bone tumor and to assess the outcome of the autograft to reconstruct the bone defect after the bone tumor resection. METHODS: From August 1998 to March 2004, 16 patients aged 7-45 years suffering from bone tumor of the upper extremity were treated with the wide resection of the bone tumor and the reconstruction of the bone defect by the autograft. The following diagnoses were confirmed by pathological examination: Ewing's sarcoma and osteosarcoma of the proximal humerus in 1 patient each; Ewing's sarcoma of the distal humerus in 2 patients; giant cell tumor in 8 patients, high-grade chondrosarcoma in 2, malignant fibrohistiocytoma in 1; and osteosarcoma in 1 of the distal radius. Substitution of the proximal humerus with the clavicle was performed in 2 patients, and the distal humerus with the fibula in other 2 patients. Of the 12 patients with tumor in the distal radius, 1 was reconstructed with autograft of the iliac bone and 11 with autograft with the fibula. The functional outcome was evaluated by the MSTS score. RESULTS: The follow-up for 36 and 12 months respectively revealed that in the 2 patients undergoing the autograft with the clavicle in the proximal humerus, good shoulder functions of flexion and extension were obtained although the function of abduction was poor, with the MSTS scores of 23 and 22 respectively. In the 2 patients undergoing the autograft with the fibular in the distal humerus, good elbow function and bone union were observed according to the follow-up for 3 and 4 months respectively, with the MSTS scores of 24 and 19 respectively. Of the 12 patients undergoing the autograft in the distal radius, 11 had an excellent or good function with no complication, with the average MSTS score of 22.6 (ranging from 18 to 27), according to the follow-up for 6-75 months; only 1 had no bone union 10 months after operation and lost the follow-up afterwards. CONCLUSION: Reconstruction of the bone defect with the autograft after the wide resection of the upper extremity bone tumor is an ideal and reliable method for some suitable patients, especially for some children.

Adolescent↗
PubMed1979

Induction of new-bone formation in the host bed by human bone-tumor transplants in athymic nude mice.

UNLABELLED: Specimens of twelve osteosarcomas, five chondrosarcomas, one giant-cell tumor, and five extraskeletal soft-tissue sarcomas were transplanted into male athymic nude (nu/nu) mice. Survival of the transplant was determined by the volume-doubling time and the sex chromatin of the tumor cells obtained from two female patients. By these criteria and the similarity of the histological composition of the original tumor and the transplant, survival occurred in four of twelve osteosarcomas and four of five chondrosarcomas. Without any local infiltration of lymphocytes or plasma cells, or other evidence of cell-mediated immunity, the surviving tumors regressed by the fourth week after the operation. Transformed osteoblasts and osteoprogenitor cells were replaced by fibrous connective tissue or fibrogenic tumor-tissue cells. Osteocytes degenerated and disappeared from the lacunae. The one giant-cell tumor transplant survived, growing very slowly, but by the end of the first week after transplantation whorls of mononucleated cells appeared in sites previously occupied by multinucleated cells. Transplants of leiomyosarcoma, liposarcoma, and synovioma (one tumor of each) degenerated. One of two fibrosarcomas survived transplantation. The most striking reaction of the mouse host bed was to encompass six of twelve osteosarcomas and four of five chondrosarcomas in deposits of normal living cartilage, bone, and bone marrow. The incidence of new bone inducedy by living transplants was only slightly greater than by implants of freeze-dried killed osteosarcoma tissue. Not one of five extraskeletal sarcomas, living or dead, induced bone formation. These observations suggest that an osteoinductive agent is transmitted by some osteosarcomas and chondrosarcomas. This agent initiates differentiation of host mesenchymal cells into normal non-tumorous cartilage and bone, which later colonized by bone marrow. CLINICAL RELEVANCE: Our observations present experimental evidence of the origin of the envelope of normal non-tumorous bone that may surround tumorous bone. In 1926, Phemister recognized the clinical significane of this envelope as a pitfall in the differential diagnosis of malignant bone tumors, chondrosarcoma, myositis ossificans circumscripta, and other neoplasms. He emphasized the importance of examining the entire specimen for the distribution of deposits of tumorous and normal bone. The induction of normal bone formation in the host bed surrounding transplants of osteosarcomas and some chondrosarcomas (but not transplants of fibrosarcoma, liposarcoma, or leiomyosarcoma) is evidence of a specific tumor-cell characteristic. Thus, the bone inductive response is not an unspecific reaction to injury from expansion or of tumor growth but a biological response to tumor-cell products. Transplants of human malignant tumors growing in the thymus-deficient mouse can be treated by combinations of radiation, amputation, and new chemotherapeutic agents...

Adolescent↗
PubMed1988

Fluoride and bovine bone extract influence cell proliferation and phosphatase activities in human bone cell cultures.

The effects of fluoride (20 mumol/L) and bovine bone extract (17 micrograms/ml) were determined on cultures of human bone cells, embryonic chick bone cells, and human skin fibroblasts. The incorporation of [3H]thymidine into DNA was measured 16 hours after the addition of factors. After three to five days treatment, Triton X-100 extracts of the cells were assayed for acid phosphatase activity, in the presence and absence of tartrate, and for alkaline phosphatase activity. Fluoride stimulated [3H]thymidine incorporation and specific activity of alkaline phosphatase in human bone cells and chick bone cells but not in human skin cells. Fluoride also stimulated the cell population doubling rate of the human bone cells with an optimum of approximately 20 mumol/L. Bovine bone extract stimulated thymidine uptake into DNA several-fold and decreased alkaline phosphatase activity in all three types of cultured cells. The specific activity of tartrate-resistant acid phosphatase was increased in bone cells but not in skin fibroblasts. These results suggest that fluoride specifically stimulates the proliferation and differentiation of osteoblasts, while the growth factors in bovine bone extract primarily stimulate proliferation of bone cells. Cultures of human bone cells respond similarly to chick calvarial cells when treated with fluoride or bovine bone extract.

Acid Phosphatase↗
PubMed1994

[Influence of bone marrow fat on the determination of bone mineral content by QCT].

Single-energy quantitative CT (SEQCT) is thought to be suitable for long-term observation of changes in bone mineral content in individual patients. However, in patients with osteoporosis, an increase in bone marrow fat cannot be ignored. The relationship between bone marrow fat and bone mineral density (BMD) at different tube voltages of 80 kV and 120 kV was investigated using a set of solution phantoms that we devised, and was also studied in healthy volunteers. On the basis of the results obtained using the solution phantoms, the influence of bone marrow fat accounted for a decrease of 8.9 mg/cm3 in BMD value at 80 kV and of 10.8 mg/cm3 at 120 kV in the presence of 10 vol% fat. These findings suggested that the influence of fat was less at a lower tube voltage. The formulas used to estimate the true bone mineral and fat contents from the BMD values at low and high tube voltages were derived by eliminating the influence of beam hardening. Using these formulas, we studied healthy volunteers, and found that the difference between the true BMD value and the BMD value calibrated for beam hardening averaged 17.8 mg/cm3 at 80 kV and 22.6 mg/cm3 at 120 kV. Moreover, the estimated concentration of bone marrow fat in the volunteers averaged 25.0 vol%. In conclusion, because SEQCT performed at a low tube voltage is less influenced by bone marrow fat, it should be selected for assessment of the clinical response to therapy and for studying sequential changes. However, in patients with a low bone mineral content indicated by SEQCT, it would be worthwhile trying to estimate both true mineral and fat contents in bone using the formulas obtained in this study in order to differentiate decrease in bone mineral from interference by bone marrow fat.

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