Healing Of Bone Lesions Research Articles

Pulp revascularization procedure for external inflammatory dental root resorption treatment

To assess the effectiveness of pulp revascularization procedure in children with external inflammatory root resorption (EIRR) after constant teeth injury. The study comprised 17 children aged 6-10 years diagnosed with EIRR as a long-term complication of dental trauma in 19 teeth. EIRR was diagnosed with periapical radiographs and CBCT was performed to further assess the pathology extension. Pulp revascularization was carried out in all 19 teeth. There was no resorption progression in all cases. EIRR areas were substituted by bone. In 10 from 19 teeth with early stages of root development bone or cement-like tissue ingrowth into the root canal was observed radiologically. In cases of severe EIRR this ingrowth may partially compensate for lost tissues which is confirmed by a high percentage (94.7%) of functional teeth during mean follow up time of 38±10 months. Pulp revascularization is an effective method for retaining teeth with EIRR for a relatively long period of time and allows maintaining alveolar bone volume both due to functional tooth preservation and healing of bone lesions in periapical and resorption areas.

Discussion on the common issue about regenerative endodontic treatment, apexification or apical barrier

Regenerative endodontic treatment, apexification or apical barrier can all eliminate the signs and symptoms induced by pulp necrosis with or without apical periodontitis of young permanent teeth, and promote the healing of bone lesions. Although regenerative endodontic treatment may promote the continued development of the root in affected teeth, it is difficult to predict the prognosis as influenced by various factors. And calcification is common after regenerative endodontic treatment. Moreover, the views that apexification may increase the risk of root fracture and that apexification or apical barrier cannot promote the further development of the roots are biased. For some cases, apexification or apical barrier are still good choices. In clinic, when the treatment plan is made, the factors such as the medical condition of the patients, the degree of root development of the affected teeth, the cause and the course of diseases, the amount of residual dental tissues should be fully considered to obtain the best prognosis for the affected teeth.

Hyaluronan hydrogels delivering BMP-6 for local targeting of malignant plasma cells and osteogenic differentiation of mesenchymal stromal cells

Multiple myeloma is a malignant disease characterized by accumulation of clonal plasma cells in the bone marrow. Uncoupling of bone formation and resorption by myeloma cells leads to osteolytic lesions. These are prone to fracture and represent a possible survival space for myeloma cells under treatment causing disease relapse. Here we report on a novel approach suitable for local treatment of multiple myeloma based on hyaluronic acid (HA) hydrogels mimicking the physical properties of the bone marrow. The HA hydrogels are complexed with heparin to achieve sustained presentation and controlled release of bone morphogenetic protein 6 (BMP-6). Others and we have shown that BMP-6 induces myeloma cell apoptosis and bone formation. Using quartz crystal microbalance and enzyme-linked immunosorbent assay, we measured an initial surface density of 400 ng BMP6/cm2, corresponding to two BMP-6 per heparin molecule, with 50% release within two weeks. HA-hydrogels presenting BMP-6 enhanced the phosphorylation of Smad 1/5 while reducing the activity of BMP-6 antagonist sclerostin. These materials induced osteogenic differentiation of mesenchymal stromal cells and decreased the viability of myeloma cell lines and primary myeloma cells. BMP-6 functionalized HA-hydrogels represent a promising material for local treatment of myeloma-induced bone disease and residual myeloma cells within lesions to minimize disease relapse or fractures. Statement of SignificanceMultiple myeloma is a hematological cancer characterized by the accumulation of clonal plasma cells in the bone marrow and local suppression of bone formation, resulting in osteolytic lesions and fractures. Despite recent advances in systemic treatment of multiple myeloma, it is rare to achieve a targeted suppression of myeloma cells and healing of bone lesions. Here we present hydrogels which mimic the physico-chemical properties of the bone marrow, consisting of hyaluronic acid with crosslinked heparin for the controlled presentation of bioactive BMP-6. The hydrogels decrease the viability of myeloma cell lines and primary myeloma cells and induces osteogenic differentiation of mesenchymal stromal cells. The presentation of BMP-6 in the hyaluronan hydrogels enhances the phosphorylation of Smad1/5 while reducing the activity of the BMP-6 antagonist sclerostin. As such, BMP-6 functionalized hyaluronan hydrogels represent a promising material for the localized eradication of myeloma cells.

Donor lymphocyte infusions to leukemic bone lesions are therapeutically effective in a Ph+ ALL patient with post-HSCT relapse

A Philadelphia chromosome positive (Ph+) acute lymphoblastic leukemia (ALL) case was maintained in remission with the use of chemo-immunotherapy. The latter involved sibling bone marrow transplant (BMT) (three procedures) followed by intravenous (IV) donor lymphocyte infusion (DLI). The third relapse responded to routine chemotherapy and again DLI was employed. During hematological and molecular remission verified at the level of iliac crest aspiration, extra-medullary relapse in the bones was apparent. A novel procedure of donor lymphocyte injection to the bone leukemic lesions was developed and employed. A dose of 106 donor lymphocytes/kg body weight (BW) of the recipient were each time injected to the plane of the right and left tibia, the head of the humerus, and the calcaneus, which resulted in healing of the destructive process. In consequence of this novel approach, in addition to the healing of bone lesions, an accumulation of cytotoxic activated T-cells in the marrow was documented, which was mirrored by an increase in the number of transcripts for interferon (IFN)-γ, interleukin (IL)-17, as well as RORγt. The local administration of DLI directly to the leukemic lesions requires a lower dose that diminishes the toxicity due to the general immune system activation.

Treatment of Metaphyseal Pathologic Fractures of Long Bone Using Locking Compression Plate in Children

Purpose: To evaluate the results of operative treatment for metaphyseal pathologic fracture of long bone in children using Locking Compression Plate (LCP). Materials and Methods: Six children were enrolled in this study. The locations of fracture were proximal femur in five children and distal femur in one child. Pathologic diagnosis was aneurysmal bone cyst, in three children and simple bone cyst, enchondroma, and nonossifying fibroma, in other three children. All six children were underwent curettage of bone lesion and bone grafting, then the fractures were internally fixed using LCP. Results: All fractures were united at six to ten weeks after operation. Healing of bone lesions except one case was observed. There were no mechanical complications, no loss of reduction and malunion. Also, we couldn't find any complication associated with physeal injury, such as leg length discrepancy of lower extremities. Conclusion: Internal fixation of metaphyseal pathologic fracture of long bone using LCP in children is technically easy and offers secure fixation despite anatomic and biologic characteristics of this type of fracture due to biologic and biomechanical advantages of LCP.

Long term results of liver-kidney transplantation in children with primary hyperoxaluria

From 1990 to 2000, we performed eight liver-kidney transplants in eight children, aged 1-16 years, with end-stage renal failure (ESRF) due to primary hyperoxaluria (PH1). The duration of dialysis before transplantation ranged from 2 to 42 months (mean 14 months) and was <1 year in four patients. Only the first patient underwent postoperative hemodialysis; in the other five, we chose to induce maximal diuresis from the first hours with intravenous and intragastric hyperhydration (> or =3 l/m2 per day). High water intake with nocturnal tube hydration was maintained for 6 months to 5 years, as long as oxaluria exceeded 0.5 mmol/day. A quadruple sequential immunosuppressive regimen was used. Two patients died during liver graft surgery. The other six patients are alive and well, with a mean follow-up of 7.4 years (range 5-11 years). Patient and graft survival is 75% at 5 years. At latest follow-up, liver tests were normal in all six patients; creatinine clearance ranged from 55 to 95 ml/min per 1.73 m2 (mean=74). Oxaluria was lower than 0.4 mmol/day in all patients (mean=0.22). The six patients underwent 15 renal biopsies, 1-11 years after transplantation. Chronic transplant nephropathy was present in four patients and mild cyclosporin nephrotoxicity in another. No oxalate crystals were seen and repeat ultrasonography has been consistently normal in all patients. The three patients with bone oxalosis showed progressive complete healing of bone lesions. All six children or adolescents now live a normal life. From this series, we conclude that early combined liver-kidney transplantation is the treatment of choice for children with ESRF due to primary hyperoxaluria.

Prognostic factors for healing of bone lesions in histiocytosis X.

Healing characteristics and rates of resolution were retrospectively reviewed in 38 bone lesions in 18 patients with histiocytosis X. Signs which tended to indicate future healing were a change from a nontrabecular pattern to a trabecular pattern by 10 weeks, a nonsclerotic lesion to one with sclerosis by 13 weeks, and loss of distinct margins by 24 weeks. Complete healing then occurred within 36 to 40 weeks after development of these favorable signs. The earliest occurrence of a favorable sign was 6 weeks. A trabecular pattern was found in 90% of the lesions, outside the skull, which eventually healed. Fifty-eight percent (22 of 38) of the lesions completely healed in an average of 13.6 months. Five months was the most rapid occurrence of healing in any of our cases.

Interferons in the treatment of multiple myeloma

A review of the clinical studies in which interferons have been involved has shown that they may have a role in the treatment of multiple myeloma. Twelve studies, each of which involved at least 10 evaluable cases (352 in total) with various dose schedules involving leukocyte, lymphoblastoid and recombinant alpha-IFNs, reported 8-33% objective responses. The response duration was rather short but, in a few cases, it lasted for more than a year. In addition to a decrease in the levels of M-protein and/or urine Bence-Jones protein, a decrease in the number of plasma cells in the bone marrow, disappearance of bone pain, healing of bone lesions, increase of hemoglobin and/or restoration of normal immunoglobulins were observed. Higher doses of recombinant alpha-interferons seemed to exert a stronger effect. No clear difference in response rate was observed between myeloma which had been previously treated and that which was not treated. At least clinically, therefore, there seems to be no cross-resistance between alpha-interferons and conventional anti-tumor drugs. A randomized study comparing low-dose leukocyte interferon with intermittent high-dose melphalan-prednisone has given a lower response rate for interferon. Beta- and gamma-interferons have not yet been extensively studied. They have been used at low doses producing an objective response in 7% of 68 and 2% of 45 evaluable cases, respectively. Since the myelosuppression of interferons is transient and, after discontinuation of interferon therapy, peripheral blood cells usually recover within a week, it may be possible to use interferon in combination with agents that have strong myelosuppressive effects provided there is no synergism.

Phase II study of recombinant alpha-2 interferon in resistant multiple myeloma.

A multicenter phase II study of INTRON, recombinant alpha-2 interferon (Schering Corp, Kenilworth, NJ), in patients with relapsing or refractory myeloma was initiated. Patients received either intravenous therapy for two weeks followed by subcutaneous therapy or subcutaneous dosing from initiation of treatment. Of 38 evaluable patients, 19 were refractory and 19 had relapsed at entry. Twenty-five of 38 had received prior treatment with multiple drugs. Responses were seen among 2/19 refractory patients and 5/19 relapsing patients. Three of seven responders continue to respond for more than one year while receiving maintenance therapy. Most patients experienced improvement in bone pain, and one patient, with a complete response, had healing of bone lesions. Survival curves show a statistically significant improvement in survival for responders v nonresponders. INTRON was well-tolerated with only four patients discontinuing treatment due to adverse effects. Thirty-two percent of patients had hematologic toxicity requiring dose adjustment; however, there was no evidence of cumulative hematologic toxicity. No patients developed serum neutralizing factors to interferon. Additional trials are warranted to study the activity of INTRON in previously untreated patients.

Healing of bone lesions with 1,25-dihydroxyvitamin D3 in the young X-linked hypophosphatemic male mouse.

The X-linked hypophosphatemic (Hyp) mouse presents with biochemical and skeletal abnormalities similar to those of human vitamin D-resistant rickets and hence is considered as a model of the human disease. In an attempt to correct osteomalacia, young (21-day-old) mutant male mice were infused continuously for 4 weeks with 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3; 0.05--0.25 microgram/kg . day]. Mineral and skeletal changes were assessed by serum, urinary, and bone ash concentrations of calcium, phosphorus, and magnesium and by histomorphometric analysis of bone formation measured on histological sections of tetracycline dual labeled undecalcified caudal vertebrae. Treatment with 1,25-(OH)2D3 produced a dose-dependent elevation of serum phosphorous that could be assigned to increased intestinal phosphate absorption. Concomitantly, epiphyseal, endosteal, and periosteal bone mineralization were improved in correlation with both the dosage of 1,25-(OH)2D3 and the serum phosphorus level. Normalization of serum calcium and phosphorus but not of urinary phosphate excretion were achieved together with complete healing of bone mineralization when the highest doses of 1,25-(OH)2D3 (0.175--0.35 microgram/kg . day) were given. The data show that rickets and osteomalacia, which characterize the young Hyp mouse, can be healed by 1,25-(OH)2D3 in doses high enough to normalize serum mineral concentrations. Unlike the renal phosphate leak, the phenotypic expression of the Hyp gene pertaining to bone mineralization is then corrected by 1,25-(OH)2D3 supplementation.

25-Hydroxyvitamin D 3 (calcifediol) therapy of juvenile renal osteodystrophy: Beneficial effect on linear growth velocity

A prospective study of renal osteodystrophy in moderate renal insufficiency was undertaken to assess the effects of 25(OH)D3 (Calcifediol) on healing of bone lesions and improvement of linear growth. One year after entering the study, the mean group growth velocity increased into the normal range and remained there in the next two therapy years. A significant correlation existed between pretherapy and one-year therapy values of growth velocity and serum 25(OH)D3 concentration. Qualitative bone histology obtained by transilial bone biopsy was also evaluated during the course of study. Catch-up growth was not seen, but potential for such growth may exist in later years in our patients.

Chemotherapy in the management of extramedullary plasmacytoma

The results of chemotherapy in 24 patients with extramedullary plasmacytoma are reported. Complete regressions, including disappearance of monoclonal paraprotein and healing of bone lesions, were seen in 12 of 20 (60%) patients with disseminated disease. Extramedullary plasmacytoma responds better to chemotherapy than myeloma, and treatment should be pursued with vigour until all signs of disease have disappeared. Sensitivity to single-agent chemotherapy may vary, and if treatment fails with one agent, others should be tried.

16: Further evidence for a feed—back loop between parathyroid hormone (PTH) and vitamin D (vit D) metabolites: acute decrease of serum immunoreactive PTH (iPTH) in normocalcemic vitaminD deficient ricket (vit D. D. R.) after vitamin D2 load

The secondary hyperparathyroidism (HPT) present in normocalcemic vit D.D.R. is not clearly understood. Recent studies indicating that a feed-back loop may be present between PTH and 1,25 dihydroxycholeoalciferol, we have examined the acute effect of a vit D load on serum iPTH levels in 5 infants (age 5 to 11 months) with normocalcemic vit D.D.R. They all presented a clinical history compatible with vit D deficiency and marked typical bone lesions of rickets. Serum Ca ranged from 8,9 to 9,6 mg/100ml, serum P from 3,8 to 5,5 mg/100ml and serum alkaline phosphatases(A.Pase) from 84 to 225 iu(N<50). Elevated serum iPTH levels were present: 280 to 670 μlEq/ml(N<100). A unique oral vit D2 load (600 000 u) was given. In all infants a marked decrease in serum iPTH was observed 24 and 48 h later (serum iPTH at 48 h : 115 to 360 μlEq/ml -ΔiPTH : 140 to 450 μlEq/ml) with no consistent changes in serum Ca, P and A.Pase. Normal levels of serum iPTH were found on a control 10 to 18 days later, though serum A. Pase remained elevated and healing of bone lesions was incomplete. These results suggest that the HPTof normocalcemic vit D.D.R. is, at least in part, directly secondary to the lack of active metabolites of vit D, probably 1,25 dihydroxy vit D; they are also consistent with the concept of a feed-back loop between PTH and vitamin D metabolites.

Whole-body in-vivo neutron activation analysis in assessing treatment of renal osteodystrophy with 1-alpha-hydroxycholecalciferol.

Four selected adults with different patterns of osteodystrophy receiving regular dialysis were treated with 1-alpha-hydroxycholecalciferol (1-alpha-OHD3) 0-5-2 mug/day for 10 to 12 months. In two patients, one with osteitis fibrosa and the other with osteomalacia, significant biochemical, radiological, and histological improvements occurred, and total body calcium measured by in-vivo neutron activation analysis increased. In two patients, in whom there were no increases of whole-body calcium, neither biochemical improvement nor healing of bone lesions occurred during the study; in one of these patients the effect of 1-alpha-OHD3 on bone resorption may have contributed to loss of body calcium and deterioration of bone disease. 1-alpha-OHD3 may therefore be a valuable adjunct in the treatment of only some patients with renal osteodystrophy. Whole-body in-vivo neutron activation seems to provide a sensitive and non-invasive index of early response to treatment.

The natural history of extramedullary plasmacytoma and its relation to solitary myeloma of bone and myelomatosis.

From this study I suggest that extramedullary plasmacytoma (EMP) shows several important differences from myelomatosis and solitary myeloma of bone (SMB) which can be summarized as follows: 1. A marked preference for the primary tumor to present in a particular site, namely the upper air passages. 2. A high incidence of metastatic spread to soft tissues. 3. Spread to bone occurs frequently but shows no preference for bones containing active hematopoietic tissue and widespread bone-marrow involvement occurs only occasionally. 4. Prolonged survival may be achieved with therapy for local disease. 5. Vigorous treatment for disseminated disease can be given and may result in longer remissions than those usually seen in myelomatosis. Healing of bone lesions has been observed on several occasions. It is concluded also that SMB constitutes a rather unusual presentation of myelomatosis but is essentially the same disease process.

The effect of environmental temperature on healing of bone lesions in the rat. II. The effect of bone injury on mineral metabolism at 20 degrees c. and 30 degrees c.

Fracture of a radius in rats living at 20° C. and 300° C. leads to a greater whole‐body retention by both groups of a tracer dose of 85Sr injected at the time of fracture, compared to the whole‐body retention found in isothermally housed uninjured controls. A simple small dental drill‐hole lesion of the tibia resulted in an enhanced whole‐body retention of tracer only in rats living at 300° C.There is evidence of skeletal mobilization of calcium on fracture of a bone in rats at 20° C., but not in those at 30° C. However, there were no histologically observable differences in healing of bone lesions between the two groups of rats.

X-Ray Studies of Motility of Gastro-intestinal Tract of Rachitic Rats with Healed Bone Lesions.

ConclusionThe hypomotility of the gastro-intestinal tract of rachitic rats is evident even after the healing of bone lesions. We appreciate that the number of rats used in our experiment is small, but we have received sufficient encouragement for us to continue on with the work.