Demineralized Bone Matrix Injection in Consolidation Phase Enhances Bone Regeneration in Distraction Osteogenesis via Endochondral Bone Formation

Background

Distraction osteogenesis (DO) is a promising tool for bone and tissue regeneration. However, prolonged healing time remains a major problem. Various materials including cells, cytokines, and growth factors have been used in an attempt to enhance bone formation. We examined the effect of percutaneous injection of demineralized bone matrix (DBM) during the consolidation phase on bone regeneration after distraction.

Methods

The immature rabbit tibial DO model (20 mm length-gain) was used. Twenty-eight animals received DBM 100 mg percutaneously at the end of distraction. Another 22 animals were left without further procedure (control). Plain radiographs were taken every week. Postmortem bone dual-energy X-ray absorptiometry and micro-computed tomography (micro-CT) studies were performed at the third and sixth weeks of the consolidation period and histological analysis was performed.

Results

The regenerate bone mineral density was higher in the DBM group when compared with that in the saline injection control group at the third week postdistraction. Quantitative analysis using micro-CT revealed larger trabecular bone volume, higher trabecular number, and less trabecular separation in the DBM group than in the saline injection control group. Cross-sectional area and cortical thickness at the sixth week postdistraction, assessed using micro-CT, were greater in the regenerates of the DBM group compared with the control group. Histological evaluation revealed higher trabecular bone volume and trabecular number in the regenerate of the DBM group. New bone formation was apparently enhanced, via endochondral ossification, at the site and in the vicinity of the injected DBM. DBM was absorbed slowly, but it remained until the sixth postoperative week after injection.

Conclusions

DBM administration into the distraction gap at the end of the distraction period resulted in a significantly greater regenerate bone area, trabecular number, and cortical thickness in the rabbit tibial DO model. These data suggest that percutaneous DBM administration at the end of the distraction period or in the early consolidation period may stimulate regenerate bone formation and consolidation in a clinical situation with delayed bone healing during DO.     

Outcome of rail fixator system in reconstructing bone gap

Background:

Bone loss following open fracture or infected gap nonunion is a difficult situation to manage. There are many modes of treatment such as bone grafting, vascularized bone grafting and bone transport by illizarov and monolateral fixator. We evaluated the outcome of rail fixator treatment in reconstructing bone and limb function. We felt that due to problems such as heavy apparatus, persistent pain, deformity of joints and discomfort caused by an Ilizarov ring fixator, rail fixator is a good alternative to treat bone gaps.

Materials and Methods:

20 patients (17 males and 3 females with mean age 30.5 years) who suffered bone loss due to open fracture and chronic osteomyelitis leading to infected gap nonunion. Ten patients suffered an open fracture (Gustilo type II and type III) and 10 patients suffered bone gap following excision of necrotic bone after infected nonunion. There were 19 cases of tibia and one case of humerus. All patients were treated with debridement and stabilization of fracture with a rail fixator. Further treatment involved reconstructing bone defect by corticotomy at an appropriate level and distraction by rail fixator.

Result:

We achieved union in all cases. The average bone gap reconstructed was 7.72 cm (range 3.5-15.5 cm) in 9 months (range 6-14 months). Normal range of motion in nearby joint was achieved in 80% cases. We had excellent to good limb function in 85% of cases as per the association for the study and application of the method of ilizarov scoring system[ASAMI] score.

Conclusion:

All patients well tolerated rail fixator with good functional results and gap reconstruction. Easy application of rail fixator and comfortable distraction procedure suggest rail fixator a good alternative for gap reconstruction of limbs.     

Long bone reconstruction using multilevel lengthening of bone defect fragments

Purpose

This paper presents experimental findings to substantiate the use of multilevel bone fragment lengthening for managing extensive long bone defects caused by diverse aetiologies and shows its clinical introduction which could provide a solution for the problem of reducing the total treatment time.

Methods

Both experimental and clinical multilevel lengthening to bridge bone defect gaps was performed with the use of the Ilizarov method only.

Results

The experimental findings and clinical outcomes showed that multilevel defect fragment lengthening could provide sufficient bone formation and reduction of the total osteosynthesis time in one stage as compared to traditional Ilizarov bone transport. The method of multilevel regeneration enabled management of critical-size defects that measured on average 13.5 ± 0.7 cm in 78 patients.

Conclusions

The experimental and clinical results proved the efficiency of the Ilizarov non-free multilevel bone plasty that can be recommended for practical use.     

Reconstruction by bone transport after resection of benign tumors of tibia: A retrospective study of 38 patients

Background:

The commonly used reconstructive options after post resection defects in bone tumors like megaprosthesis, autograft, allograft, bone graft substitutes and recycled bone have their own demerits on a long term. Bone transport that regenerates patient''s own bone is a less explored option of reconstruction after resection of benign bone tumors and reports on this are limited. This technique is very much relevant in tibia where Ilizarov fixator is surgeon and patient friendly. We report our experience.

Materials and Methods:

This is a retrospective series of resection and bone transport in 38 patients with benign tumor of tibia. There were 14 males and 24 females with mean age of 23.40 years (range 9–40 years). Lesion was located in proximal third tibia in 27, middle third in two and distal third in nine patients. The diagnosis was giant cell tumor in 32, chondroblastoma in three, chondromyxoid fibroma, enchondroma and desmoplasic fibroma in one patient each. The resection was intercalary in 28 and transarticular in 10 patients. Osteosynthesis was monofocal in three, bifocal in 31 and polyfocal in four cases.

Results:

Mean followup was 7.22 years (range 1.5–15 years). Mean resection length was 10.21 cm (range 3–22 cm). The mean duration of external fixator was 308.03 days (range 89–677 days) and mean external fixator index was 36.14 days/cm (range 16.84–97.43 days/cm). Twelve patients had difficulties in the form of 11 problems and five obstacles that were successfully managed. None of the patients had local recurrence of tumor or any long term complication. Mean Musculo-skeletal Tumour Society score at final followup was 27.18 (90.60%).

Conclusions:

Bone transport is an excellent option after resection of benign tumors of tibia with good local control and functional outcome, despite minor difficulties that need timely management.     

Ilizarov bone transport as a treatment of congenital pseudarthrosis of the tibia: a long-term follow-up study

Purpose

Most studies on congenital pseudarthrosis of the tibia (CPT) report on the short-term union rate and refracture rate but do not take into account the long-term outcome. This review includes patients treated with an Ilizarov bone transport, who all reached skeletal maturity. It describes long-term results and highlights any prognostic factors that could predict the final outcome.

Methods

The records of patients with CPT treated with an Ilizarov bone transport in our institution were retrospectively evaluated.

Results

A total of 12 consecutive patients were studied. The mean follow-up was 24.5 years (range 6–39 years). Primary consolidation was seen in ten patients (83 %). Half of these patients had a refracture. At final follow-up, eight patients experienced union and four remained un-united, of whom one had an amputation.

Conclusions

The present data confirm a good primary healing rate. However, tibial union at final follow-up was only seen in 67 %, indicating that refracture is the main issue. United bone is often of inferior biological and mechanical quality, so lifetime protection with intramedullary devices, braces or a combination of both is recommended.     

Early Union of Grafted Bone in Ankylosing Spondylitis: Comparative Study with Degenerative Spinal Disease

Background

Patients with ankylosing spondylitis (AS) achieve early bone union compared to those with other spinal diseases. This study compared the time to bone union after surgery between AS patients and degenerative spinal disease patients.

Methods

Patients with degenerative spinal diseases (control group) and AS (experimental group) underwent pedicle subtraction osteotomy followed by posterolateral fusion, and decompression and posterolateral fusion, respectively. There were 10 patients in the experimental group. The control group included 26 patients who were less than 50 years of age and underwent two-level autogenous grafting after decompression and spinal fusion. Autogenous grafts and a range of bone substitutes were used in the experimental group, whereas only autogenous grafts were used in the control group. Bone union was determined on the radiographs and 3-dimensional CT scan images. The level of union was assessed using the Lenke''s and Christensen''s classification systems.

Results

In the experimental group, the mean age was 41.3 years (range, 30 to 67 years), the mean follow-up period was 21.7 months (range, 12 to 43 months), and bone union was confirmed at an average of 3.5 months (range, 3 to 5 months) after surgery. In the control group, the mean age was 43.1 years (range, 35 to 50 years), the mean follow-up period was 21.8 months (range, 12 to 74 months), and bone union was observed at an average of 5.6 months (range, 4 to 12 months) after surgery. The difference in the time to bone union between the two groups was significant (p = 0.023).

Conclusions

The union of grafted bone was obtained earlier in patients with AS than in those with degenerative spinal diseases. Therefore, future studies should examine the factors affecting the early union in AS patients.     

Acute Suppression of Bone Turnover With Calcium Infusion in Persons With Spinal Cord Injury

Background:

Some people with chronic spinal cord injury (SCI) have low vitamin D levels and secondary hyperparathyroidism.

Objective:

To determine whether, and to what extent, an acute calcium infusion decreased levels of N-telopeptide (NTx), a marker of osteoclastic activity, in individuals with chronic SCI.

Study Design:

Case series.

Subjects:

Eight men with chronic SCI. A relatively low serum 25 hydroxyvitamin D concentration (25[OH]D ≤20 ng/mL) and/or a high parathyroid hormone (PTH) (>55 pg/mL) was a prerequisite for study inclusion.

Methods:

Calcium gluconate bolus 0.025 mmol elemental calcium/kg over 20 minutes followed by a constant infusion of 0.025 mmol/kg per hour for 6 hours was infused; blood samples were collected every 2 hours for measurement of serum total calcium, creatinine, NTx, and PTH.

Results:

All results are expressed as means (± SDs). Baseline serum 25-hydroxyvitamin D level was 14.5 ± 3.5 ng/mL (range: 10.2–19.6 ng/mL); PTH, 70 ± 25 pg/mL (range: 37–100 pg/mL); and NTx, 21 ± 7 nM bone collagen equivalents (BCE) (range: 14–34 nM). At 2, 4, and 6 hours after the calcium infusion, serum calcium rose from 9.3 ± 0.2 to 10.8 ± 0.9, 10.5 ± 0.8, and 10.6 ± 0.6 mg/d; PTH was suppressed from 70 ± 25 pg/mL to 18 ± 12, 16 ± 9, and 15 ± 9 pg/mL, respectively; NTx fell from 21 ± 8 nM BCE to 17 ± 5, 12 ± 4, and 12 ± 3 nM BCE, respectively.

Conclusions:

Serum NTx is a marker for bone collagen catabolism, and its reduction suggests that bone turnover was decreased. A relative deficiency of vitamin D associated with chronically elevated levels of PTH would be expected to increase bone turnover and to worsen the bone loss associated with immobilization.     

The etiology of short stature affects the clinical outcome of lower limb lengthening using external fixation: A systematic review of 18 trials involving 547 patients

Background and purpose

Distraction osteogenesis (DO) has been used to gain height in short statured individuals. However, there have been no studies comparing the clinical outcome of limb lengthening based on the etiology of the short stature. We assessed whether different underlying diagnoses are associated with varied clinical outcomes in these patients.

Methods

We performed a systematic review of the literature pertaining to lower limb lengthening using external fixation for short stature. Clinical outcomes including amount of lengthening, healing index (HI), and complications based on the underlying diagnosis for the short stature were documented.

Results

18 clinical studies were included, with 547 patients who underwent 1,581 lower limb segment lengthening procedures. Mean follow-up was 4.3 years. The average age at lengthening was less for individuals with achondroplasia/hypochondroplasia (A/H) (14.5 years) than for those with Turner’s syndrome (TS) (18.2 years) or with constitutional short stature (CSS) (21.7 years). Mean height gained was greater in patients with A/H (9.5 cm) than in those with TS (7.7 cm) or CSS (6.1 cm) group. The HI was better in A/H (30.8 days/cm) and CSS (32 days/cm) than in TS (45.1 days/cm). The reported complication rate per segment was lower for A/H (0.68) and TS (0.71) than for CSS (1.06).

Interpretation

Patients with A/H tolerated larger amounts of lengthening with fewer complications than those with other diagnoses.Distraction osteogenesis (DO) uses a corticotomy or osteotomy to allow formation of new bone in the gap created by controlled distraction of the bone segments. In 1905, Codivilla proposed limb lengthening through distraction (Codivilla 2008), and this concept was reintroduced in 1969 by Ilizarov (Ilizarov and Deviatov 1969) and in 1977 by Wagner (1977) using external fixation (EF). Since then, DO has been used to address non-unions, skeletal defects, and limb deformities, including limb length discrepancy (Aronson 1997, Liu et al. 2011).More recently, this surgical modality has been used to increase standing height in individuals of short stature (Koczewski et al. 2002). Although there are several challenges associated with DO such as length of treatment, the psychological consequences of treatment, and permanent complications, with advances in DO—including the availability of newer implants and techniques—more individuals with a variety of underlying diagnoses will undergo limb lengthening. However, to our knowledge, there have been no large comparative studies on the clinical outcome of lower limb lengthening for short stature based on the underlying diagnosis.We performed a systematic review of the literature on lower limb lengthening and assessed whether there were any differences in the reported clinical parameters, such as lengthening percentage (LP) and healing index (HI), based on the etiology of short stature. From previous literature (Paley 1988), we hypothesized that patients with achondroplasia and hypochondroplasia would have undergone greater degrees of lengthening with fewer reported complications than those with other diagnoses for their short stature.     

The Effect of Platelet Rich Plasma from Bone Marrow Aspirate with Added Bone Morphogenetic Protein-2 on the Achilles Tendon-Bone Junction in Rabbits

Background

To determine if exogenously injected bone marrow derived platelet-rich plasma (PRP) plus bone morphogenetic protein (BMP)-2 could accelerate the healing of bone-tendon junction injuries and increase the junction holding strength during the early regeneration period.

Methods

A direct injury model of the bone-tendon junction was made using an Achilles tendon-calcaneus bone junction in a rabbit. In the PRP/BMP-2/fibrin group, 0.05 mL of bone marrow derived PRP and 100 ng/mL of BMP-2 both incorporated into 0.1 mL of fibrin glue were injected into Achilles tendon-calcaneus bone junctions. The effect of the intervention was tested by comparing the results of an intervention group to a control group. The results of biomechanical testing, and histological and gross analyses were compared between the 2 groups at the following time points after surgery: 2 weeks, 4 weeks, and 8 weeks.

Results

Histologic examinations showed that woven bone developed in tendon-bone junctions at 2 weeks after surgery in the PRP/BMP-2/fibrin group. Mechanical test results showed no significant difference between the PRP/BMP-2/fibrin and control groups at 2 and 4 weeks after surgery, but the mean maximal load in the PRP/BMP-2/fibrin group was significantly higher than in the control group (p < 0.05) at 8 weeks after surgery.

Conclusions

Bone marrow derived PRP and BMP-2 in fibrin glue accelerated healing in a rabbit model of tendon-bone junction injury.     

Grafting Using Injectable Calcium Sulfate in Bone Tumor Surgery: Comparison with Demineralized Bone Matrix-based Grafting

Background

Injectable calcium sulfate is a clinically proven osteoconductive biomaterial, and it is an injectable, resorbable and semi-structural bone graft material. The purpose of this study was to validate the clinical outcomes of injectable calcium sulfate (ICS) grafts as compared with those of a demineralized bone matrix (DBM)-based graft for filling in contained bony defects created by tumor surgery.

Methods

Fifty-six patients (41 males and 15 females) with various bone tumors and who were surgically treated between September 2003 and October 2007 were included for this study. The patients were randomly allocated into two groups, and either an ICS graft (28 patients) or a DBM-based graft (28 patients) was implanted into each contained defect that was developed by the surgery. The radiographic outcomes were compared between the two groups and various clinical factors were included for the statistical analysis.

Results

When one case with early postoperative pathologic fracture in the DBM group was excluded, the overall success rates of the ICS and DBM grafting were 85.7% (24/28) and 88.9% (24/27) (p > 0.05), respectively. The average time to complete healing was 17.3 weeks in the ICS group and 14.9 weeks in the DBM group (p > 0.05). Additionally, the ICS was completely resorbed within 3 months, except for one case.

Conclusions

Although the rate of resorption of ICS is a concern, the injectable calcium sulfate appears to be a comparable bone graft substitute for a DBM-based graft, with a lower cost, for the treatment of the bone defects created during surgery for various bone tumors.     

Management of open infected comminuted tibial fractures using Ilizarov concept

Background

Bone loss is very common in high energy trauma. It could be treated either by amputation and prosthesis or by reconstruction of both bony and soft tissue structures. The choice of treatment in a given case must be based on the assessment of the local and general condition of the patient such as regional neurovascular supply, and the residual articular and muscular function. Reconstruction may require bone grafts, tibiofibular synostosis, free microvascular soft tissue or bone transplants. The use of Ilizarov concept gives another option for treatment of bone defects. In this study, infected tibial fractures were treated using Ilizarov concept.

Patients and methods

Twenty-eight patients (20 males and 8 females) with open comminuted infected fracture of the tibia were included. After debridement, all cases had variable amount of bone defects and were treated using Ilizarov technique. Follow-up was for at least 1 year. Filling of the bone defect was achieved either by compression–distraction method in 13 cases (group I) or by means of bone transport in the other 15 cases (group II).

Results

The results were judged as excellent in 16 patients, good in 9 and fair in 2, while one patient was of poor result. Type of fracture, age of the patient and sex had no statistically significant relation with the final end results. Furthermore, there was no significant difference between the two groups. The average external fixator index was 45 days/cm (range from 35 to 70 days/cm). The mean external fixator index was less in group I.

Conclusion

In the management of infected comminuted tibial shaft fractures, bone transport is indicated for the treatment of major bone loss, whereas compression–distraction is suitable only for treating less extensive bone gaps.     

Ilizarov non-free bone plasty for extensive tibial defects

Purpose

The purpose of this study was to present a retrospective comparative overview of the Ilizarov non-free bone plasty techniques of one-stage multilevel fragment lengthening and gradual tibilisation of the fibula used for extensive tibial defect management.

Methods

Extensive tibial defects in 83 patients were managed either by multilevel fragment lengthening (group I, n = 41, mean defect size 13.1 ± 0.9 cm) or gradual tibilisation of the fibula (group II, n = 42, mean defect size 12.5 ± 1.2 cm) using the Ilizarov apparatus. The initial findings, treatment protocols and outcomes of those patients treated within the period 1972–2011 were studied retrospectively by medical records and radiographs, and statistically assessed with Microsoft Excel and Attestat software.

Results

Group I had multilevel fragment lengthening over one stage that averaged 288.0 ± 14.4 days. The mean total period of gradual tibilisation of the fibula in group II was 316.0 ± 29.7 days. The patient’s age in the latter group had an effect on the completeness of leg-length equalisation.

Conclusions

The techniques can be used to manage extensive tibial defects as all the defects bridged, leg-length discrepancy and deformity were corrected and patients were able to load their limbs.     

Evaluation of Bone Mineral Status in Adolescent Idiopathic Scoliosis

Background

Several reports have suggested low bone mineral density (BMD) in patients with adolescent idiopathic scoliosis (AIS). We determined bone mineral status in patients with AIS to evaluate the effect of brace treatment on BMD.

Methods

BMD was measured in 46 patients (mean age, 17.8 ± 4.9 years) with AIS (17 with brace and 29 without brace) by dual-energy X-ray absorptiometry scan and compared the results to an age-matched (mean age, 16.6 ± 3.9 years) control group (n = 54).

Results

The AIS group had significantly lower bone mass at the lumbar spine (Z-score, -1.500 vs. -0.832) and hip (Z-score, -1.221 vs. -0.754) except at the femoral neck. No difference in BMD was found between patients with AIS who used a brace and those who did not.

Conclusions

The results confirmed that BMD was low in AIS patients and it was not affected by brace treatment.     

Tumor Treated by Endoscopy

Background

This study was conducted to examine the clinical usefulness and efficacy of endoscopic curettage on benign bone tumor.

Methods

Thirty-two patients (20 men and 12 women) with benign bone tumor were included in the study. The patients were aged between five and 76 years; the mean follow-up period was 27.05 months (range, 9.6 to 39.9 months). The primary sites include simple bone cyst (9 cases), fibrous dysplasia (6 cases), enchondroma (5 cases), non-ossifying fibroma (4 cases), bone infarct (3 cases), aneurysmal bone cyst (1 case), chondroblastoma (1 case), osteoblastoma (1 case), intraosseous lipoma (1 case), and Brodie abscess (1 case). A plain radiography was performed to assess the radiological recovery. Radiological outcomes, including local recurrence and bone union, were evaluated as excellent, good, poor, and recurred.

Results

In our series, there were 27 cases (84.4%) of good or better outcomes, six cases (18.8%) of complications (4 local recurrence, 1 wound infection, and 1 pathologic fracture).

Conclusions

Our results showed that endoscopic curettage and bone graft had a lower rate of recurrence and a higher cure rate in cases of benign bone tumor. It can, therefore, be concluded that endoscopic curettage and bone graft might be good treatment modalities for benign bone tumors.     

Is the Induced-membrane Technique Successful for Limb Reconstruction After Resecting Large Bone Tumors in Children?

Background

Resection of primary malignant tumors often creates large bony defects. In children, this creates reconstructive challenges, and many options have been described for limb salvage in this setting. Studies have supported the use of an induced-membrane technique after placement of a cement spacer to aid in restoration of bone anatomy.

Questions/purposes

We asked: (1) What complications are associated with the induced-membrane technique? (2) How often is bone healing achieved after resection greater than 15 cm using this technique? (3) What is the functional outcome of patients treated with this technique?

Methods

We performed a retrospective evaluation of eight patients with a mean age of 13.3 years (range, 11–17 years) treated for a malignant bone tumor between 2002 and 2012 at our centers. The primary malignant tumors involved the proximal humerus, femur, and tibia. All patients were treated using the induced-membrane technique after a resection with mean bone loss of 18 cm (range, 16–23 cm). The general indication for using the induced-membrane technique during this time was a large diaphyseal defect after resection of the tumor. In addition to using cancellous graft as with the original technique, in the current patients an autogenous nonvascularized fibula was used to enhance stability. The patients were assessed at the last followup using the Musculoskeletal Tumor Society (MSTS) scoring system. Mean followup was 47.1 months (range, 24–120 months), and none of the patients were lost to followup before 2 years.

Results

A total of four unplanned reoperations were performed in these eight patients. A fracture of the reconstruction occurred in three patients and all were treated successfully, two with surgery and one with immobilization. Bone fusion was obtained in all patients within 4 to 8 months (mean, 5.6 months) after the reconstruction. The mean healing index was 0.31 month/cm of reconstruction (range, 0.23–0.5 month/cm). At last followup, the mean MSTS score was 74% (range, 67%–80%).

Conclusions

Our findings suggest that the modified induced-membrane technique is a reasonable alternative to other limb reconstruction techniques for bone tumors in children and has the advantage of not requiring a bone bank or an expensive metal prosthesis. Although more patients will be needed to substantiate our findings, it has become a standard part of our arsenal in the treatment of large bone defects after resection of pediatric primitive bone tumors.

Level of Evidence

Level IV, therapeutic study.     

Metacarpal lengthening by distraction histiogenesis in adults

Background:

Metacarpal lengthening in the hand is a new application for distraction neo-histiogenesis. Metacarpal lengthening with distraction helps in improvement in pinch function. Thumb lengthening is technically easy in comparison to other metacarpals. We present the operative treatment and post-operative outcome in nine patients with amputations and congenital anomalies.

Materials and Methods:

Nine patients underwent distraction osteogenesis for the treatment of amputations of the hand and other congenital anomalies. The dominant right hand was operated in eight cases and the left hand in one case. There were six males and three females. Improvement of function was always the aim of surgery. Age range was between 18 and 23 years. Thumb lengthening was performed in five patients and that of the index finger in four patients. Distraction started on the fifth post-operative day at the rate of 0.25 mm/day. Sensory function and bone consolidation was assessed before fixator removal.

Results:

The mean duration of distraction was 51 days (range, 42–60 days) and the distractor was removed at a mean of 150 days (range, 140 and 160 days) and the bones were lengthened by a mean of 24 mm (range, 20–28 mm) There was improvement of function in all cases.

Conclusion:

The metacarpal lengthening by distraction histiogenesis in congenital and traumatic amputations is safe and simple method to improve pinch function of hand.