The comparative efficacy of nerve transfer versus tendon transfer in the management of radial palsy: A systematic review and meta-analysis.

Background: There is no clear census as to which operative technique provides better recovery for radial nerve injuries. Therefore, in this systematic review, we examined the functional recovery, patient-reported outcomes, and complications of tendon transfer (TT) and nerve transfer (NT). Methods: Five electronic databases were searched for studies (>10 cases per study) comparing NT and TT regardless of the study design (observational or experimental). Manual search was also conducted. The quality was assessed by the NIH tool. Outcomes included functional recovery, patient-reported outcomes (DASH score, satisfaction, and inability to return to work), and complications. The prevalence was pooled across studies using STATA software, and then, a subgroup analysis based on the intervention type. Results: Twenty-one studies (542 patients) were analyzed. Excellent recovery, assessed by the Bincaz scale, was higher in the TT group (29 % vs. 11 %) as well as failure to extend the fingers (49 % vs. 9 %). No significant difference was noted between both groups regarding DASH score (mean difference = -2.76; 95 % CI: -12.66: 6.93). Satisfaction was great in the TT group (89 %) with a limited proportion of patients unable to return to work (7 %). Complications were slightly higher in the TT group (8 % vs. 7 %) while 18 % of patients undergoing TT requiring revision surgery. Radial deviation was encountered in 18 % of patients in the TT group and 0 % in the NT group. The quality was good, fair, and poor in 2, 13, and 6, respectively. Conclusions: In radial nerve injuries, although tendon transfer may seem to provide better functional motor recovery than nerve transfer, it is associated with a higher rate of failure to extend the finger. Given the large confidence interval, the accuracy of this finding is questioned. However, a great proportion of those patients require revision surgery afterward. Additionally, tendon transfer is associated with a greater complication rate than nerve transfer, particularly radial deviation.

Sagittal correction after short percutaneous fixation for thoracolumbar compression fractures: comparison of the combination of SpineJack® kyphoplasty and fractured vertebra screw fixation.

PURPOSE: The aim of this study was to compare two percutaneous pedicle fixations for the treatment of thoracolumbar fractures: one associating a jack kyphoplasty (SpineCut) and the other using intermediate screws (Trident). METHODS: All adult patients treated for single-level Magerl/AO type A thoracolumbar traumatic fractures in four orthopaedic departments, with SpineCut or Trident, with a one year minimum follow-up, were retrospectively included. Neurological disorders and osteoporotic fractures were not included. The following data were collected: age, sex, Magerl/AO type, type of surgery, and complications. Radiological parameters were analyzed on pre-operative CT scan, and on standing X-rays before discharge, at three months and one year post-operative: vertebral wedge angle (VWA), regional kyphosis angle (RKA), and traumatic regional angulation (TRA: difference between RKA and physiological values for each vertebra). RESULTS: Eighty patients were included, with 42 patients in SpineCut group and 38 in Trident group. Mean age was 41 ± 15.7 years. TRA correction did not differ between the groups: respectively 11.2 ± 8.1° in SpineCut versus 10.2 ± 9.1° in Trident group (p = 0.52). TRA loss of correction between early post-operative and three months was statistically higher in Trident group: -4 ± 5.1° versus -1.5 ± 3.8° (p = 0.03). After 3 months, TRA correction loss was comparable between the groups. Multivariate analysis demonstrated that pre-operative VWA was the only factor significantly associated with early TRA correction loss (p = 0.01). VWA correction and loss of correction did not differ significantly between the groups. No complications were observed. CONCLUSION: Percutaneous pedicle fixations of traumatic thoracolumbar fractures associating jack kyphoplasty and intermediate screws are both safe and efficient techniques.

Early injection of autologous bone marrow concentrates decreases infection risk and improves healing of acute severe open tibial fractures.

INTRODUCTION: Open fractures are at risk of nonunion; surgeons are reluctant to propose early standard bone grafting after open fractures, preferring to wait in order to adequately assess the facture status of infection. Bone marrow contains mesenchymal stem cells (MSCs) and granulocyte and macrophage precursors identified in vitro as colony forming units-granulocyte macrophage (CFU-GM), both of which have a prophylactic action against infection. We therefore tested the hypothesis that early injection of bone marrow concentrate would be useful in these fractures. METHODS: We evaluated a series of 231 patients who had received early percutaneous implantation of bone marrow concentrate (BMC) to treat open fractures (with gap less than 10 mm) that were Gustilo-Anderson Type II or III. The results were compared with those of 67 control (no early graft) patients and with those of 76 patients treated with an early, standard of care, iliac bone graft. All patients were treated with external fixation and were considered to have an aseptic fracture at the time of early grafting, but the actual status of infection was re-assessed at the time of grafting by histology and/or analysis of the aspirate. The bone marrow graft contained after concentration 49,758 ±â€¯21,642 CFU-GM-derived colonies/cc and 9400 ±â€¯1435 MSCs/cc which represents an important increase compared to the level of CFU-GM cells and MSCs present in a standard auto-graft. Healing was evaluated at 9 months. RESULTS: The rate of unsuspected infections was higher than 15% in the 3 groups. Bone union and removal of external fixation was achieved at 9 months by 50.7% of patients in the Control Group, by 86.8% of patients in the group with a standard bone graft, and by 87.4% of patients in the bone marrow group. A 90% risk reduction (p = 0.005) in the need for an invasive standard bone graft to treat a nonunion and in the risk of infection was observed when bone marrow was proposed as early injection to the treatment of type II or type-III tibial fractures. CONCLUSION: Bone marrow concentrate for early grafting in open fractures with limited gap was efficient for healing while decreasing infection.

Spinal metastases from thyroid cancer: Some prognostic factors.

BACKGROUND: Spinal metastases (SpMs) from thyroid cancers (TC) significantly reduce quality of life by causing pain, neurological deficits in addition to increasing mortality. Moreover, prognosis factors including surgery remain debated. METHODS: Data were stored in a prospective French national multicenter database of patients treated for SpM between January 2014 and 2017. Fifty-one consecutive patients affected by TC with 173 secondary SpM were included. RESULTS: Mean overall survival (OS) time for all patients from the diagnosis of a thyroid SpM event was 9.1 years (SD 8.7 months). The 1-year, 5-year and 10-year survival estimates were 94% (SD 3.3), 83.8.0% (SD 5.2), and 74.5% (SD 9.9). The median period of time between primary thyroid tumor diagnosis and the SpM event was 31.4 months (SD 71.6). In univariate analysis, good ECOG-PS (status 0 and 1) (p < 0.0001), ambulatory status (Frankel score) (p < 0.0001) and no epidural involvement (p = 0.01), were associated with longer survival, whereas cancer subtype (p = 0.436) and spine surgery showed no association (p = 0.937). Cox multivariate proportional hazard model only identified good ECOG-PS: 0 [HR: 0.3, 95% CI 0.1-0.941; p < 0.0001], 1 [HR: 0.8, 95% CI 0.04-2.124; p = 0.001] and ambulatory neurological status: Frankel E [HR: 0.262, 95% CI 0.048-1.443; p = 0.02] to be independent predictors of better survival. CONCLUSION: For cases presenting SpM from TC, we highlighted that the only prognostic factors were the progression of the cancer (ECOG-PS) and the clinical neurological impact of the SpM (Frankel status). Surgery should be discussed mainly for stabilization and neurological decompression.

Are spine metastasis survival scoring systems outdated and do they underestimate life expectancy? Caution in surgical recommendation guidance.

OBJECTIVE: Survival scoring systems for spine metastasis (SPM) were designed to help surgical practice. The authors sought to validate the prognostic accuracy of the main preoperative scoring systems for SPM. METHODS: It was hypothesized that true patient survival in SPM was better than that predicted using prognosis scores. To investigate this hypothesis, the authors designed a French national retrospective study of a prospectively collected multicenter database involving 739 patients treated for SPM between 2014 and 2017. RESULTS: In this series, the median survival time for all patients from an SPM diagnosis was 17.03 ± 1.5 months. Sensitivity and specificity were estimated using the area under the curve (AUC). The AUC of Tomita's prognosis score was the lowest and poorest (0.4 ± 0.023, range 0.35-0.44), whereas the AUC of the Tokuhashi score was the highest (0.825). The Lei score presented an AUC of 0.686 ± 0.022 (range 0.64-0.7), and the Rades score showed a weaker AUC (0.583 ± 0.020, range 0.54-0.63). Differences among AUCs were all statistically significant (p < 0.001). The modified Bauer score and the Rades score had the highest rate of agreement in predicting survival, with a weighted Cohen's kappa of 0.54 and 0.41, respectively, indicating a moderate agreement. The revised Tokuhashi and Lei scores had a fair rate of agreement (weighted Cohen's kappa = 0.24 and 0.22, respectively). The van der Linden and Tomita scores demonstrated the worst performance, with only a "slight" rate of agreement (weighted Cohen's kappa = 0.19 and 0.16, respectively) between what was predicted and the actual survival. CONCLUSIONS: The use of prognostic scoring systems in the estimation of survival in patients with SPM has become obsolete and therefore underestimates survival. Surgical treatment decisions should no longer be based on survival estimations alone but must also take into account patient symptoms, spinal instability, and quality of life.

Ankle osteonecrosis in fifty-one children and adolescent's leukemia survivors: a prospective randomized study on percutaneous mesenchymal stem cells treatment.

PURPOSE: Corticoid treatment associated with haematologic treatments can lead to ankle osteonecrosis in children's survivors of acute leukemia (ALL). Based on the efficiency of mesenchymal stem cells (MSCs) in hip osteonecrosis, we performed an evaluation of this treatment in 51 children and adolescents who had symptomatic ankle osteonecrosis after therapy for haematologic cancer. MATERIAL AND METHODS: The 51 patients had a total of 79 osteonecrosis sites on MRI, with 29 talus sites, 18 metaphyseal tibia sites, 12 epiphyseal tibia sites, eight calcaneus sites, six fibula sites, four navicular sites, and two cuboid sites. In this prospective randomized trial, 37 ankles were addressed for cell therapy, 37 others for core decompression alone, and 20 were considered as a control group without treatment. We analyzed the outcome of this treatment osteonecrosis, the number and characteristics of bone marrow mesenchymal cells (MSCs) that could be transplanted, and the risks of tumorigenesis in these patients with haematologic cancers. The patients were operated on over a period of ten years from 2000 to 2010 and were monitored through December 31, 2019. RESULTS: Despite a normal systemic blood cells count, MSCs in the iliac crest (counted as CFU-F) were in low number (1021 MSCs/mL; range 314-3015) and were of host origin after even allogeneic bone marrow transplantation. Better clinical outcomes (pain, foot and ankle deformity) and osteonecrosis repair on MRI with absence of collapse were obtained in ankles that received cell therapy as compared with those with core decompression alone or those without initial surgery. No tumour was found on MRI at the sites of injection and this study found no increased risk of recurrence or of new cancer in this population after an average follow-up of 15 years. CONCLUSIONS: These results suggest that autologous MSCs can improve the quality of life of leukemia survivors with ankle osteonecrosis.

Spine Metastasis in Elderly: Encouraging Results for Better Survival.

MINI: The incidence of spinal metastasis (SpM) is increasing, and life expectancy for patients with malignancy is also rising. The "elderly" represent a population with steady growth in SpM proportion. Bracing is associated with lower survival. We believe that surgery should be considered, regardless of the patient's age.

Multicentric prospective study. Through this study, we aimed to clarify and update the prognostic assessment of elderly with spine metastasis (SpM). The incidence SpM is rising, in parallel life expectancy is getting longer and the number of elderly patients presenting malignancy is increasing. Elderly patients with SpM constitute a growing heterogeneous population The patient data used in this study were obtained from a French national multicenter database of patients treated for SpM between 2014 and 2017. Two hundred and forty-three consecutive patients >70 years' old were diagnosed. Median overall survival (OS) time for elderly patients following the event of SpM was 16.3 months. First, we identified significantly worse survival prognostic factors for elderly patients with SpM: poor WHO status 3/4: (hazard ratio [HR]: 2.245, 95% confidence interval [CI] 1.899­2.655; P  < 0.0001), >80 years (HR: 1.758, 95% CI 1.117­2.765; P  = 0.015) no-ambulatory neurological status (Franckel A/B status [HR: 3.219, 95% CI 1.621­6.390; P  < 0.0001)], gastrointestinal cancer (HR: 3.530, 95% CI 1.75­7.1; P  < 0.0001), lung cancer (HR: 3.452, 95% CI 1.784­6.680; P  < 0.0001), orthopedic brace treatment (HR: 1.329; 95% CI 1.050­1.683; P  = 0.018), and epiduritis (HR: 1.52, 95% CI 1.041­2.22; P  = 0.03) were independently poor prognostic factors of survival. The only good prognosis factor identified was thyroid cancer (HR: 0.257, 95% CI 0.07­0.952; P  = 0.04). Prognosis factors concerning the survival of elderly patients seem to be the same as those for the general population such as primary cancer histology, neurological status, WHO status, and epiduritis. Age >80 years also appears to be an independently poor prognosis factor. Our data suggest that orthopedic brace treatment is also associated with lower survival. Level of Evidence: 2.

Spine metastasis in patients with prostate cancer: Survival prognosis assessment.

BACKGROUND: Patients presenting spine metastasis (SpM) from prostate cancer (PC) form a heterogeneous population, through this study, we aimed to clarify and update their prognostic assessment. METHODS: The patient data used in this study was obtained from a French national multicenter database of patients treated for PC with SpM between 2014 and 2017. A total of 72 patients and 365 SpM cases were diagnosed. RESULTS: The median overall survival time for all patients following the event of SpM was 28.8 months. First, we identified three significant survival prognostic factors of PC patients with SpM: good Eastern Cooperative Oncology Group/World Health Organization personnel status (Status 0 hazard ratio [HR]: 0.031, 95% confidence interval [CI]: 0.008-0.127; p < .0001) or (Status 1 HR: 0.163, 95% CI: 0.068-0.393; p < .0001) and SpM radiotherapy (HR: 2.923, 95% CI: 1.059-8.069; p < .0001). Secondly, the presence of osteolytic lesions of the spine (vs. osteoblastic) was found to represent an independent prognosis factor for longer survival [HR: 0.424, 95% CI: 0.216-0.830; p = .01]. Other factors including the number of SpM, surgery, extraspinal metastasis, synchrone metastasis, metastasis-free survival, and SpM recurrence were not identified as being prognostically relevant to the survival of patients with PC. CONCLUSION: Survival and our ability to estimate it in patients presenting PC with SpM have improved significantly. Therefore, we advocate the relevance of updating SpM prognostic scoring algorithms by incorporating data regarding the timeline of PC as well as the presence of osteolytic SpM to conceive treatments that are adapted to each patient.

Subchondral bone or intra-articular injection of bone marrow concentrate mesenchymal stem cells in bilateral knee osteoarthritis: what better postpone knee arthroplasty at fifteen years? A randomized study.

PURPOSE: There is an increasing number of reports on the treatment of knee osteoarthritis (OA) using mesenchymal stem cells (MSCs). However, it is not known what would better drive osteoarthritis stabilization to postpone total knee arthroplasty (TKA): targeting the synovial fluid by injection or targeting on the subchondral bone with MSCs implantation. METHODS: A prospective randomized controlled clinical trial was carried out between 2000 and 2005 in 120 knees of 60 patients with painful bilateral knee osteoarthritis with a similar osteoarthritis grade. During the same anaesthesia, a bone marrow concentrate of 40 mL containing an average 5727 MSCs/mL (range 2740 to 7540) was divided in two equal parts: after randomization, one part (20 mL) was delivered to the subchondral bone of femur and tibia of one knee (subchondral group) and the other part was injected in the joint for the contralateral knee (intra-articular group). MSCs were counted as CFU-F (colony fibroblastic unit forming). Clinical outcomes of the patient (Knee Society score) were obtained along with radiological imaging outcomes (including MRIs) at two year follow-up. Subsequent revision surgeries were identified until the most recent follow-up (average of 15 years, range 13 to 18 years). RESULTS: At two year follow-up, clinical and imaging (MRI) improvement was higher on the side that received cells in the subchondral bone. At the most recent follow-up (15 years), among the 60 knees treated with subchondral cell therapy, the yearly arthroplasty incidence was 1.3% per knee-year; for the 60 knees with intra-articular cell therapy, the yearly arthroplasty incidence was higher (p = 0.01) with an incidence of 4.6% per knee-year. For the side with subchondral cell therapy, 12 (20%) of 60 knees underwent TKA, while 42 (70%) of 60 knees underwent TKA on the side with intra-articular cell therapy. Among the 18 patients who had no subsequent surgery on both sides, all preferred the knee with subchondral cell therapy. CONCLUSIONS: Implantation of MSCs in the subchondral bone of an osteoarthritic knee is more effective to postpone TKA than injection of the same intra-articular dose in the contralateral knee with the same grade of osteoarthritis.

Safety of simultaneous versus staged bilateral opening-wedge high tibial osteotomy with locked plate and immediate weight bearing.

PURPOSE: With advances in technology and particularly locked screws, patients with high tibial osteotomy (HTO) are frequently allowed full weight bearing for a  unilateral procedure. We are aware of no reports comparing the safety of a simultaneous bilateral HTO with staged bilateral HTO. The purpose of this study was to retrospectively compare these two strategies. MATERIAL AND METHODS: Ninety patients were treated with bilateral HTO surgery for osteoarthritis from 2009 to 2013; they had opening-wedge HTO and fixed with the same plate fixation and locked screws. A comparison of the outcomes after simultaneous bilateral HTO (35 patients) and after sequential staged bilateral HTO (55 patients) was performed. We considered four measures of medical safety: hypotension, serious intra-operative adverse event, heterologous blood transfusion, and thrombophlebitis. We considered also four measures of orthopaedic safety: infection, patient's inability to walk full weight bearing, changes in correction, and nonunion. RESULTS: For the same duration of operation, the duration of anaesthesia and the time in the operating room were 35% longer for patients having a staged bilateral HTO. Blood loss was higher in patients undergoing simultaneous bilateral HTO compared with those who underwent a staged bilateral HTO. For patients undergoing simultaneous bilateral HTO, thrombophlebitis frequency and length of anticoagulation were lower than the sum of each event in the staged bilateral HTO. The patients with simultaneous bilateral HTO had a longer total period of time for crutches than patients with staged bilateral HTO. Patients in the simultaneous bilateral cohort did not develop an infection within one year as patients in the planned-stage cohort. The simultaneous bilateral cohort had a lower rate of delayed union than the planned-stage cohort did. CONCLUSION: On the basis of this analysis, simultaneous bilateral HTO is a reasonable treatment option. Individuals who undergo staged bilateral HTO face the risk of complications twice, in addition to two hospitalizations. Patients who undergo simultaneous bilateral HTO have a higher risk of blood transfusion.

Vitamin D history part III: the "modern times"-new questions for orthopaedic practice: deficiency, cell therapy, osteomalacia, fractures, supplementation, infections.

PURPOSE: The nutritional basis for rickets was described between 1880 and 1915, at the same period of discovery of other "vital substances" or vitamins. In contrast, rickets could also be prevented or cured by sunshine. But as the capacity to produce vitamin D depends on exposure to ultraviolet B rays (UVB) from sunlight or artificial sources, vitamin D became one of the most frequently used "drugs" in the twentieth century to compensate for insufficient exposure to UVB of humans. Furthermore, as the understanding of vitamin D metabolism grew during the twentieth century, other concerns than rickets occurred for the orthopaedic surgeon: In recent history, deficiency is explored as being an associated factor of different bone pathologies as fracture or prosthetic infection. The aim of this review is to analyze these new data on vitamin D. MATERIALS AND METHODS: During the twentieth century, there were many concerns for the orthopaedic surgeon: sources and synthesis of vitamin D, regulation of the calcium deposition process for both children and adults, when vitamin D deficiency is observed, and what the best method of vitamin D supplementation is. As target genes regulated by vitamin D are not limited to those involved in mineral homeostasis, orthopedists recently discovered that vitamin D might prevent periprosthetic infection. RESULTS: The primary source (80%) of vitamin D is dermal synthesis related to the sun. Dietary sources (20%) of vitamin D are fat fishe, beef, liver, and eggs. Vitamin D is produced industrially to be used in fortified foods and supplements. Maintenance of skeletal calcium balance is mediated through vitamin D receptors. Progenitor cells, chondrocytes, osteoblasts, and osteoclasts contain these receptors which explains the role of vitamin D in cell therapy, in the prevention of rickets and osteomalacia. Despite fortified foods, the prevalence of deficiency remains endemic in north latitudes. However, the definition of vitamin D insufficiency or deficiency remains controversial. Vitamin D has been evaluated in patients undergoing fractures and elective orthopaedic procedures Although supplementation may not be able to prevent or cure all the orthopaedic pathologies, oral supplementation is able to improve the vitamin D levels of deficient patients. These vitamin D level improvements might be associated with better functional and clinical outcomes after some surgical procedures and improvement of immunity to decrease the risk of infection in arthroplasties. CONCLUSION: Vitamin D deficiency is frequent and concerns millions of people in the world. It is therefore normal to find hypovitaminosis in various orthopaedic populations including trauma and arthroplasties. However, we do not know exactly if this phenomenon only reflects the general prevalence of vitamin D deficiency or has an influence on the outcome of some pathologies on specific populations at risk. After the success of treatment of rickets, it is disappointing that we are still wondering in the twenty-first century whether supplementation of a substance synthetized millions of years ago by plankton and necessary for growth of all the animals may improve (or not) clinical and functional outcomes of a simple fracture in humans.

Vitamin D: part II; cod liver oil, ultraviolet radiation, and eradication of rickets.

PURPOSE: After Glisson's description of rickets, it took two centuries to realize that rickets was due to the absence of antirachitic nutrients in the diet or lack exposure of the skin to ultraviolet rays. This bone disease caused by vitamin D deficiency was one of the most common diseases of children 100 years ago. This paper explores how the definition, diagnosis, and treatment of rickets shifted in the first decades of the twentieth century. MATERIAL AND METHODS: Although benefits of cod liver oil as food were known as early as the seventh century, cod liver oil was only proposed as medicinal for rickets in Northern Europe at the end of the eighteenth century. The relationship between rickets and nutritional deficiency was suspected and demonstrated between 1880 and 1915, at the same time of the discovery of other vital substances (vitamins) needed to prevent beriberi, scurvy, and pellagra. Understanding that the lack of photosynthesized vitamin D or the lack of dietary vitamin D was a similar risk of rickets was an important turn in the comprehension of the disease. We look at the sequence and turn of events related to the discovery of vitamin D. RESULTS: Rickets has been recognized first as a disease of urban living people. Cod liver oil had been used since 1700 as a nonspecific treatment for a range of diseases. Generations of children in cities of the north of Europe had learned to hate the taste and smell of the black oily liquid and then grown up to be parents who, in turn, hated to force it down their children's throats. Occasional papers before 1900 pointed to its efficacy for rickets, and most textbooks of the early 1900s mentioned it only as a treatment option. The discovery in the early 1900s that artificial and natural ultraviolet rays had both antirachitic activity allowed to produce antirachitic foods just by food irradiation with artificial ultraviolet irradiation. Clinical guidelines were adopted to propose exposure to sunlight or to artificial ultraviolet radiation to prevent rickets in children. By the mid-1920s, rickets was promoted as universal, at times invisible to non-experts, but present to some degree in nearly every young child regardless of race or class. It was thus used to promote the young disciplines of preventive medicine, pediatrics, and public health. Innovative advances were made in the understanding of vitamin D synthesis from 1915 to 1935. A public health campaign of the 1930s was a success to eradicate rickets, using irradiated ergosterol from yeast to enrich milk and other foods with vitamin D, ensuring that the general population was consuming sufficient vitamin D. CONCLUSION: Rickets therefore provides an excellent window into the early politics of preventive health and the promotion of targeted interventions in the world. It is also a relevant historical counterpoint for current debates over the role of risk factors (absence of light or sun) for disease (today's so-called "lifestyle" diseases).

Unusual indication of Cell therapy for hip osteonecrosis after pregnancy.

PURPOSE: Osteonecrosis is a rare event during or after pregnancy. Due to the low number of cases, there is no report of long-term results after conservative surgery in this population. METHOD: From 1992 to 2010, 145 consecutive female patients with unilateral symptomatic (94 stage I and 51 stage II) left hip osteonecrosis (ON) related to pregnancy were treated between 4 and 16 months after delivery with percutaneous mesenchymal stem cell (MSC) injection obtained from bone marrow concentration. The average total number of MSCs (counted as number of colonies forming units-fibroblast) injected in the hip was 185 000 ± 65 000 cells (range 95 000-240 000 cells). RESULTS: At the most recent follow-up (average 15 years after hip surgery, range 8-25 years), among the 145 hips included in the study, 4 hips (2.7%) had collapsed and were treated with total hip arthroplasty (THA). Thirty-two of the 94 stage I had progressed to stage II; and 4 of the 51 stage II had progressed to stage III and collapse. The other 141 hips (97.3%) were without collapse and pain free. On MRI, as percentage of the volume of the femoral head, the osteonecrosis had decreased from 34.5% pre-operatively to 6% at the most recent follow-up. For women who had other children after treatment, a subsequent pregnancy was not associated with osteonecrosis. CONCLUSION: Patients with hip osteonecrosis following pregnancy had a low conversion rate to THA when treated early with cell therapy.

Cell therapy versus simultaneous contralateral decompression in symptomatic corticosteroid osteonecrosis: a thirty year follow-up prospective randomized study of one hundred and twenty five adult patients.

PURPOSE: Symptomatic osteonecrosis related to corticosteroids has a high risk of progression to collapse in absence of treatment. The purposes of this study were to evaluate the results of autologous bone marrow grafting of the symptomatic hip in adult patients with osteonecrosis and to compare the results with core decompression alone in the contralateral symptomatic hip. MATERIALS AND METHODS: A total of 125 consecutive patients (78 males and 47 females) with bilateral osteonecrosis (ON) and who had both hips symptomatic and at the same stage on each side (stage I or II) were included in this study from 1988 to 1998. The volume of osteonecrosis was measured with MRI in both hips; the smaller size ON was treated with core decompression, and the contralateral hip with the larger ON was treated with percutaneous mesenchymal cell (MSC) injection obtained from bone marrow concentration. The average total number of MSCs (counted as number of colony forming units-fibroblast) injected in each hip was 90,000 ± 25,000 cells (range 45,000 to 180,000 cells). RESULTS: At the most recent FU (average 25 years after the first surgery, range 20 to 30 years), among the 250 hips included in the study, 35 hips (28%) had collapsed at the most recent follow-up after bone marrow grafting, and 90 (72%) after core decompression (CD). Ninety-five hips (76%) in the CD group underwent total hip replacement and 30 hips (24%) in the bone marrow graft group (p < 0.0001). Hips undergoing only CD were approximately three times more likely to undergo a primary THA (odds ratio: 10.0278; 95% CI: 5.6117 to 17.9190; p < 0.0001) as compared with hips undergoing an initial bone marrow grafting. For the 90 hips treated with bone marrow injection and without collapse, the mean volume of repair evaluated by MRI at the most recent follow-up was 16.4 cm3 (range 12 to 21 cm3) corresponding to a decrease of the pre-operative average volume from 22.4 cm3 (range 35-15 cm3) to 6 cm3 (range 12-0 cm3); as percentage of the volume of the femoral head, the decrease moved from 44.8 to 12%. CONCLUSION: Core decompression with bone marrow injection improved the outcome of the disease as compared with core decompression alone in the same patient.

A novel in vivo porcine model of intervertebral disc degeneration induced by cryoinjury.

PURPOSE: Degenerative disc disease involves sequential events that lead to the loss of cells, a decrease in disc matrix production, disc dehydration, and alteration of its biomechanical properties. The aim of this study was to determine whether cryoinjury of the nucleus pulposus performed through endplate perforation contributes to disc degeneration and to compare this technique with standard methods. METHOD: Under general anesthesia, the lumbar discs of six pigs were exposed and randomly submitted to needle puncture of the annulus fibrosus (NeP), isolated endplate injury (EP), or cryoinjury using a 2.5-J Thompson cryoprobe applied through a single endplate perforation (EP+cryo). The remaining discs served as controls. Animals were sacrificed at two months and the harvested lumbar spines were submitted to CT scan and MRI investigations. Histologic analysis was performed to assess the degree of disc degeneration. RESULTS: CT scan showed that decrease in average disc height was more important after cryoinjury (49.3%) than after endplate perforation (16.9%) (P < 0.0001) or needle puncture (19.4%) (P < 0.0001). On MRI, the dehydration ratio was significantly more important after EP+cryo (60%) than after NP (40%) or EP (30%) (P < 0.0001). After cryoinjury, the histologic score developed for this study was significantly higher than after needle puncture or endplate perforation (P < 0.0001). CONCLUSIONS: Imaging and histological analysis showed that disc cryoinjury applied through endplate perforation was superior to the classical NeP and EP models to induce experimental disc degeneration. This model appears suitable for testing safety and efficacy of novel treatments of intervertebral disc degeneration.

History of concentrated or expanded mesenchymal stem cells for hip osteonecrosis: is there a target number for osteonecrosis repair?

PURPOSE: Despite multiple possible treatments, the risk of collapse remains the main problem of osteonecrosis. Heart failure (HF). In an effort to address the reverse this issue, curative strategies with regenerative medicine are increasingly being considered. The aim of this technology is to halt or reverse progression of the disease to collapse. MATERIAL AND METHODS: The pioneering report by Hernigou published in 2002 was the first pilot study suggesting that injection of bone marrow stem cells was a safe approach able to improve osteonecrosis in patients with early stages. Since then, an impressive number of studies and trials employing unselected BM-derived cells (1000 the last 2 years) showed that delivery of those cells to the site of osteonecrosis during core decompression was somehow able to ameliorate the patient with osteonecrosis. In order to translate the promise of this cell therapy into better clinical benefit, many questions need to be addressed. In this review, we therefore analyzed current clinical experience of the literature and our experience of 4000 cases to address these questions and particularly the number of cells that should be injected. RESULTS: After almost 20 years of clinical research in this field, we are still far from having drawn conclusions on the number of cells we should inject in regenerating hip osteonecrosis. Findings are difficult to interpret due to heterogeneity of causes of osteonecrosis, as well as differences in the cells count, sample quality, and stages of osteonecrosis. The authors address specific issues, as cell quality, cell numbers, volume of osteonecrosis, concentration of cells, and ex vivo expansion. Bone marrow mesenchymal stem cells are supposed to be "functionally competent," but are collected from the bon, marrow of patients with diseases and risk factors of osteonecrosis. The recipient organ (bone osteonecrosis) is a tissue where several alterations have already occurred. These questions are addressed in this review. CONCLUSION: In this review, we analyzed current clinical experience regarding cell therapy and address issues that should be a guide for future cell-based therapeutic application in osteonecrosis.

Subchondral stem cell therapy versus contralateral total knee arthroplasty for osteoarthritis following secondary osteonecrosis of the knee.

PURPOSE: Total knee arthroplasty (TKA) implanted in patients with secondary osteonecrosis (ON) related to corticosteroids have relatively poor outcome (20% revision rate) at a mean follow-up of only eight years. With the hypothesis that subchondral bone marrow injection might improve knees in these patients, we evaluated 30 patients who had bilateral knee osteoarthritis with severe joint space narrowing and received TKA in one knee and subchondral bone marrow concentrate injection in the contralateral knee. MATERIAL AND METHODS: A prospective randomized controlled clinical trial was carried out in 60 knees of 30 patients (mean age 28 years, 18-41) who presented bilateral osteoarthritis secondary to knee ON related to corticosteroids in relation with different severe medical conditions. During the same anesthesia, one knee received TKA; for the other knee, a bone marrow graft containing an average of 6500 MSCs/mL (counted as CFU-F, range 3420 to 9830) was delivered to the subchondral bone of the femur and tibia. The length of anesthesia related to each procedure (bone marrow aspiration and subchondral injection of concentrated bone marrow versus total knee arthroplasty) was measured. Peri-operative outcomes, morbidity, complications, and safety of the two procedures were compared. Subsequent admissions for revision surgery were identified. At the most recent follow-up (average of 12 years, range 8 to 16 years), clinical outcomes of the patient (Knee Society score) were obtained along with radiological imaging outcomes (MRIs for knees with subchondral bone marrow injection). RESULTS: Anesthesia related to the TKA side was longer than for the cell therapy group. Medical and surgical complications were more frequent after TKA. A higher number of thrombophlebitis was observed on the side with TKA (15%) versus none on the side with cell therapy (0%). At the most recent follow-up (average of 12 years, range 8 to 16 years), six (out of 30) TKA knees needed subsequent surgery versus only one with cell therapy. The Knee Score had improved and remained similar in the TKA and cell therapy groups (respectively 80.3 points ± 11 versus 78.3 ± 23); 21 patients preferred the knee with cell therapy and 9 preferred the knee with TKA. Knees with cell therapy had improvement on cartilage and bone marrow lesions observed at the site of bone marrow subchondral injection. CONCLUSIONS: Subchondral autologous bone marrow concentrate was an effective procedure for treating young patients with knee osteoarthritis following secondary ON of the knee related to corticosteroids with a lower complication rate and a quicker recovery as compared with TKA.

Stem cell therapy in early post-traumatic talus osteonecrosis.

PURPOSE: Avascular necrosis of the talus is one of the most notable complications associated with talar neck fractures with frequent evolution of the osteonecrosis into a difficult arthrodesis. We tested whether the injection of bone marrow mesenchymal stem cells (MSCs) could improve the repair process of the osteonecrosis. MATERIAL AND METHODS: Forty-five early (without collapse) post-traumatic talus osteonecroses (group 1; study group) were treated between 1995 and 2012 with percutaneous injection of progenitor cells (autologous bone marrow concentrate from the iliac crest). The number of MSCs transplanted in each ankle of group 1 was 124 × 103 cells (range 101 × 103 to 164 × 103 cells). The evolution of these osteonecroses treated with autologous bone marrow implantation was compared with the evolution of a control group of 34 talar osteonecroses without collapse and treated with only core decompression (group 2; control group) between 1985 and 1995. The outcome was determined by progression in radiographic stages to collapse, by the need of arthrodesis, and by the time to successfully achieve fusion for patients who needed arthrodesis. RESULTS: For the 45 ankles with autologous concentrate bone marrow grafting, collapse frequency was lower (27%, 12 among 45 versus 71%, 24 among 34; odds ratio 0.1515, 95% CI 0.0563-0.4079; P = 0.0002) and follow-up showed longer duration of survival before collapse or arthrodesis, compared to 34 ankles of the control patients with core decompression alone. Furthermore, the time to successfully achieve fusion after arthrodesis was significantly shorter in patients treated with bone marrow progenitors as compared with the other ankles, which had core decompression alone. CONCLUSION: In our study the early conservative surgical treatment with autologous bone marrow grafting improved the natural course of the disease as compared with core decompression alone.

Single-stage treatment of infected tibial non-unions and osteomyelitis with bone marrow granulocytes precursors protecting bone graft.

PURPOSE: Infected non-unions present a clinical challenge, especially with risk of recurrent infection. Bone marrow contains granulocyte precursors identified in vitro as colony forming units-granulocyte macrophage (CFU-GM) have a prophylactic action against infection. We therefore tested the hypothesis that bone marrow concentrated granulocytes precursors added to a standard bone graft could decrease the risk of recurrence of infection when single-stage treatment of infected tibial non-unions is performed with bone graft. METHODS: During a single-stage procedure 40 patients with infected tibial non-union received a spongious bone graft supercharged with granulocytes precursors after debridement (study group). A control group (40 patients) was treated in a single stage with local debridement and standard bone graft obtained from the iliac crest. The antibiotic therapy protocol was the same (60 days) in the two groups. CFU-GM progenitors were harvested from bone marrow aspirated on the opposite iliac crest of the site where the cancellous bone was obtained. Union (radiographs and CT scan), a recurrence of clinical infection, and need for subsequent surgery were evaluated. RESULTS: Thirty-eight (95%) patients who received graft supercharged with granulocytes precursors achieved successful union without recurrence of infection during the seven-year follow-up versus 28 (70%) control patients; for the control group the mean graft resorption volume was 40%, while no bone graft resorption was found for the study group. CONCLUSION: Supercharging the cancellous bone graft with bone marrow granulocytes precursors protect the site of infected non-union from recurrence of infection and bone resorption of the graft.