Germany has a high demand in meniscal allograft transplantation but is subject to health economic and legal challenges: a survey of the German Knee Society.

PURPOSE: To determine the current status and demand of meniscal allograft transplantation (MAT) in Germany among members of the German Knee Society (= Deutsche Kniegesellschaft; DKG). METHODS: An online survey was conducted between May 2021 and June 2021 and sent to all members of the DKG. The survey questionnaire consisted of 19 questions to determine the demand and technical aspects of MAT among the participants and to identify areas of improvement in MAT in Germany. RESULTS: Overall, 152 participants, 136 (89.5%) from Germany, 8 (5.3%) from Switzerland, 6 (4.0%) from Austria, and 2 (1.3%) from other countries completed the online survey, with the majority working in non-academic institutions. According to the regulations of the DKG, 87 (57.2%) participants were board certified as specialized knee surgeons and 97 (63.8%) worked primarily in the field of orthopedic sports medicine. MAT was considered clinically necessary in Germany by 139 (91.5%) participants. Patient age (83.6%), post-meniscectomy syndrome in isolated lateral (79.6%) and medial (71.7%) meniscus deficiency, and functional and athletic demands (43.4%) were the most important determinants to consider MAT in patients. Participants reported that reimbursement (82.9%), jurisdiction over the use of donor grafts (77.6%), and the availability of meniscal allografts (76.3%) are the main challenges in performing MAT in Germany. The most frequently used meniscal allograft types by 54 (35.5%) participants who had already performed MAT were fresh-frozen grafts (56.6%), peracetic acid-ethanol sterilized grafts (35.9%), and cryopreserved grafts (7.6%). Participants reported to perform suture-only fixation more often than bone block fixation for both medial (73.6% vs. 22.6%) and lateral (69.8% vs. 24.5%) MAT. CONCLUSION: More than 90% of the responding members of the DKG indicated that MAT is a clinically important and valuable procedure in Germany. Reimbursement, jurisdiction over the use of donor grafts, and the availability of meniscal allografts should be improved. This survey is intended to support future efforts to facilitate MAT in daily clinical practice in Germany. LEVEL OF EVIDENCE: Level V.

Reaming in treatment of non-unions in long bones: cytokine expression course as a tool for evaluation of non-union therapy.

UNLABELLED: The analysis of peripheral serum cytokine expression patterns has been shown to be a possible method for demonstrating changes in bone metabolism. The aim of this study is to evaluate the effectiveness of this method within the treatment of long bone non-union with intramedullary reaming, a well-established non-union treatment concept. MATERIALS AND METHODS: Three groups were added to this study: group one (G1) suffered from long bone non-unions, treated successfully with intramedullary reaming; group two (G2) consisted of long bone fractures with proper fracture healing; and group three (G3) included long bone fractures resulting in non-unions. We took blood samples on day 2, and after week 1, 4, 6, month 3 and 6 after initial treatment. Clinical and radiological follow-up were provided for 6 months. We measured transforming growth factor ß-1 (TGFß-1), platelet-derived growth factor (PDGF-AB), and insulin like growth factor-1 (IGF-1) at all-time points. RESULTS: TGF-ß1 levels in G1 and G2 increased from day 2 to 6 weeks after surgery. In general, G1 and G2 showed parallel TGF-ß1 expression patterns, and G3 had a significant peak during first week compared to G1 (p = 0.023). PDGF peaked in G3 during first week after treatment, whereas G1 had its maximum after 4 weeks and G2 after 6 weeks. We were able to detect a significantly lower PDGF concentration at 3 months in G1 compared to G3 (p = 0.029). IGF-1 showed a peak concentration in G1 during the first 4 weeks. Afterwards, concentration levels in both G1 and G2 were higher. CONCLUSIONS: Our study was able to show that the cytokine expression pattern in physiological bone healing is similar to that in successful non-union treatment with intramedullary reaming. Our results show that the effect of non-union therapy could be observed objectively by measuring cytokine expression patterns in peripheral blood even in a small group of patients.

Time course of 25(OH)D3 vitamin D3 as well as PTH (parathyroid hormone) during fracture healing of patients with normal and low bone mineral density (BMD).

BACKGROUND: Until now the exact biochemical processes during healing of metaphyseal fractures of healthy and osteoporotic bone remain unclear. Especially the physiological time courses of 25(OH)D(3) (Vitamin D) as well as PTH (Parathyroid Hormone) the most important modulators of calcium and bone homeostasis are not yet examined sufficiently. The purpose of this study was to focus on the time course of these parameters during fracture healing. METHODS: In the presented study, we analyse the time course of 25(OH)D3 and PTH during fracture healing of low BMD level fractures versus normal BMD level fractures in a matched pair analysis. Between March 2007 and February 2009 30 patients older than 50 years of age who had suffered a metaphyseal fracture of the proximal humerus, the distal radius or the proximal femur were included in our study. Osteoporosis was verified by DEXA measuring. The time courses of 25(OH)D(3) and PTH were examined over an eight week period. Friedmann test, the Wilcoxon signed rank test and the Mann-Withney U test were used as post-hoc tests. A p-value ≤ 0.05 was considered significant. RESULTS: Serum levels of 25(OH)D(3) showed no differences in both groups. In the first phase of fracture healing PTH levels in the low BMD level group remained below those of the normal BMD group in absolute figures. Over all no significant differences between low BMD level bone and normal BMD level bone could be detected in our study. CONCLUSIONS: The time course of 25(OH)D(3) and PTH during fracture healing of patients with normal and low bone mineral density were examined for the first time in humans in this setting and allowing molecular biological insights into fracture healing in metaphyseal bones on a molecural level. There were no significant differences between patients with normal and low BMD levels. Hence further studies will be necessary to obtain more detailed insight into fracture healing in order to provide reliable decision criteria for therapy and the monitoring of fracture healing.

Inhibition of osteoclast generation: a novel function of the bone morphogenetic protein 7/osteogenic protein 1.

Monocytes have the potential to differentiate to either macrophages, dendritic cells, or to osteoclasts. The microenvironment, particularly cytokines, directs the monocyte differentiation. Receptors of NFκB (RANK) ligand, tumor necrosis factor (TNF) α, or interleukin- (IL-) 8 have be identified as inducers of osteoclastogenesis, whereas others, such as IL-10 or transforming growth factor (TGF)ß inhibit osteoclast generation or induce differentiation towards a dendritic cell type. We now describe that bone morphogenetic protein (BMP) 7/osteogenic protein- (OP-) 1 inhibited the differentiation of human CD14+ monocytes to osteoclasts. In the presence of BMP7/OP-1 the transcription factors c-Fos and NFATc1, though upregulated and translocated to the nucleus in response to either RANKL or IL-8, did not persist. In parallel, MafB, a transcription factor expressed by monocytes and required for differentiation to macrophages but inhibiting osteoclast generation, was preserved. Because both persistence of NFATc1 and downregulation of MafB are crucial for osteoclastogenesis, we conclude that BMP7/OP-1 inhibits the generation of osteoclasts by interfering with signalling pathways.

Infiltration of the Hoffa's fat pad with stromal vascular fraction in patients with osteoarthritis of the knee -Results after one year of follow-up.

Objectives: Cell therapy using multipotential stromal cells (MSCs) is being used in a variety of clinical settings to induce tissue regeneration. Promising results have also been achieved in the therapy of osteoarthritis. MSCs have been demonstrated to be safe (Borakati et al., 2018). They can be used in a one step procedure as minimally manipulated mesenchymal stem cells or after in vitro expansion. The in vitro step allows for the selection of a more homogeneous cell population, meeting the standard criteria for MSC identification (Lv et al., 2014). In vitro expansion of MSCs is cost intensive, time consuming and furthermore associated with gradual accumulation of senescent cells (Wagner et al., 2008), telomere erosion (Baxter et al., 2004), and changing phenotypes (Jones et al., 2010; Halfon et al., 2011). These disadvantages could be surpassed by the use of "minimally manipulated mesenchymal stem cells" from bone marrow or adipose tissue (Di Matteo et al., 2019) such as the adipogenic stromal-vascular fraction (SVF).The study investigates whether infiltration of the Hoffa fat pad with autologous SVF is an effective and safe treatment option for patients with gonarthrosis. Furthermore, the number and vitality of the injected cells as well as the clinical efficacy will be evaluated. Materials and methods: We conduct a prospective study. Patients with osteoarthritis of the knee receive infiltration of SVF into the Hoffa fat pad. The number and vitality of the cells are measured with a cell counter. The clinical outcome is checked using VAS, KOOS and SF12 questionnaires with a follow-up period of 1 year. Results: A total of 33 patients and 36 knees were included in this Study. An average of 45 million cells were injected with a standard deviation of 2,5 million Cells. After 6 months a significant improvement of the VAS and the respective subscales of the KOOS could be observed compared to the baseline. After one year of follow-up, a significant improvement in all KOOS subscales compared to baseline was still observed. A significant correlation between reduced knee pain on the VAS and the number of injected cells could be observed as well. Thus, patients injected with a higher number of cells seem to have a better outcome. The average viability of the cells was 64,4% with a standard deviation of 15,9%. A correlation between higher cell viability and better outcome on the QOL subscale of the KOOS was observed. There were no major complications or side effects. Discussion: These initial results indicate that treatment with SVF is a safe therapeutic option that has the potential to relieve joint pain and significantly improved function. The cell number and vitality of the injected cells appear to be important factors influencing the success of the therapy.

Clinical application of BMP 7 in long bone non-unions.

BACKGROUND: Non-unions of long bone fractures are a therapeutic and economic problem of increasing frequency. Aside from conservative treatment options such as ultrasound, impulse waves, and casts, the basic surgical options are autogenous cancellous bone grafting, rod dynamization, reamed nailing, plate fixation, and bone transport techniques. If these methods fail to work, there is a need for alternative treatment options. METHODS: Since May 2001, treatment with recombinant human bone morphogenic protein 7 (BMP 7 or osteogenic protein 1) in combination with a type-one collagen carrier has been the subject of increasing interest. BMP 7 induces the formation of new bone by stem cell differentiation, thereby initiating the reaction cascade of osteogenesis. Non-unions over 9 months and unsuccessful bone grafting constitute the indication for this treatment. RESULTS: We report our experience with 54 patients who had atrophic non-union of long bone fractures. Between May 2002 and May 2006, 57 units of BMP 7 were used. The localization of the non-unions included 21 in the femur, 26 in the tibia, 3 in the humerus and 7 in the forearm. In 36 cases, BMP 7 was used in combination with osteosynthesis revision and bone grafting; in 9 additional patients, BMP 7 was used with bone grafting alone. In 12 patients, BMP 7 was applied as a single procedure without any bone grafting or any change in osteosynthesis. CONCLUSIONS: There were no perioperative or postoperative complications. Follow-up was obtained for a minimum of 6 months. 47 of the 57 (82%) implantations were successful, with bony healing confirmed by clinical and radiological evaluation. In summary, our results support BMP 7 as an additional innovative therapy for long bone non-unions.

Arthroscopic suture bracing of posterior cruciate ligament in a multiple ligament knee injury - A technical report.

The optimum therapy of a torn PCL in multiligamental-injured knees is controversially discussed in literature. As conservative treatment and PCL reconstruction alone mostly lead to long-term immobilization, we performed a single stage PCL bracing with ACL reconstruction using ACL TightRopes® and Fiber-/TigerTapes® to accelerate back-to-sport after multiligamental knee injury with bicrucial tears. The brace consisted of two FiberTapes which were looped in an ACL TightRope and transosseously fixed with a Dog Bone-Button®. The ACL reconstruction was performed by a fourfolded semitendinosus graft in TightRope® technique. We chose an active rehabilitation-protocol with immediately allowed knee flexion to 90° in an ACL brace. This led to excellent results with resumption of sports after 6 months and good subjective and objective knee stability measured with a KT-1000. Our results hint that our method of bracing a torn PCL in multiligamental knee injuries may lead to faster rehabilitation with comparable knee stability.

Expression of TRAIL and the death receptors DR4 and DR5 correlates with progression of degeneration in human intervertebral disks.

Intervertebral disks degenerate far earlier than other musculoskeletal tissues and apoptosis has been suggested to have a vital function in promoting the degeneration process that is strongly associated with back pain. However, the molecular mediators of apoptosis in the intervertebral disk are poorly understood. Fas/FasL, TRAIL/DR4, TRAIL/DR5 and TNF-alpha/TNFR1 are ligand/receptor pairs of the tumor necrosis factor/nerve growth factor family, which are able to induce apoptosis by trimerization of the receptor by its corresponding ligand. We investigated which of these molecules are expressed in intervertebral disks and whether their expression correlates to disk degeneration. Intervertebral disks from 28 donors (age 12-70 years) suffering from scoliosis, vertebrae fracture or disk degeneration were scored histologically for degeneration and analyzed for gene expression of FasL/Fas, TRAIL/DR4, TNF-alpha/TNFR1 and caspase 8. Protein expression of FasL and TRAIL was assessed by immunohistology and apoptotic cell death was quantified by poly(ADP-ribose) polymerase (PARP) p85 staining. Isolated disk cells were analyzed by flow cytometry for Fas, FasL, TRAIL, DR4 and DR5 expression. Gene expression of TRAIL (P=0.002) and caspase 8 (P=0.027) significantly correlated with degeneration. TRAIL expression further correlated with cellularity (P=0.04), muccoid matrix changes (P=0.009) and tears and cleft formation (P=0.019). FasL and TRAIL expression was confirmed by immunohistology and PARP cleavage was significantly associated with degeneration (P=0.027). Flow cytometry on isolated disk cells revealed correlations between DR4 and degeneration (P=0.014), DR4/DR5 double-positive cells and degeneration (P=0.019), as well as DR5 and changes in tissue granularity (P=0.03). This is the first study that shows that intervertebral disk cells express TRAIL, DR4 and DR5, which correlate to the degenerative state of the disk. Therefore, disk cells inherit the molecular machinery to induce and undergo cellular apoptosis, and the frequency of cytokine expression suggests that the TRAIL/DR4/DR5 axis is an important molecular mediator of apoptosis induction in disk tissue.

The systemic angiogenic response during bone healing.

INTRODUCTION: Angiogenesis is known to be a critical and closely regulated step during bone formation and fracture healing driven by a complex interaction of various cytokines. Delays in bone healing or even nonunion might therefore be associated with altered concentrations of specific angiogenic factors. These alterations might in turn be reflected by changes in serum concentrations. METHOD: To determine physiological time courses of angiogenic cytokines during fracture healing as well as possible changes associated with failed consolidation, we prospectively collected serum samples from patients who had sustained surgical treatment for a long bone fracture. Fifteen patients without fracture healing 4 months after surgery (nonunion group) were matched to a collective of 15 patients with successful healing (union group). Serum concentrations of angiogenin (ANG), angiopoietin 2 (Ang-2), basic fibroblast growth factor (bFGF), platelet derived growth factor AB (PDGF-AB), pleiotrophin (PTN) and vascular endothelial growth factor (VEGF) were measured using enzyme linked immunosorbent assays over a period of 24 weeks. RESULTS: Compared to reference values of healthy uninjured controls serum concentrations of VEGF, bFGF and PDGF were increased in both groups. Peak concentrations of these cytokines were reached during early fracture healing. Serum concentrations of bFGF and PDGF-AB were significantly higher in the union group at 2 and 4 weeks after the injury when compared to the nonunion group. Serum concentrations of ANG and Ang-2 declined steadily from the first measurement in normal healing fractures, while no significant changes over time could be detected for serum concentrations of these factures in nonunion patients. PTN serum levels increased asymptotically over the entire investigation in timely fracture healing while no such increase could be detected during delayed healing. CONCLUSION: We conclude that fracture healing in human subjects is accompanied by distinct changes in systemic levels of specific angiogenic factors. Significant alterations of these physiologic changes in patients developing a fracture nonunion over time could be detected as early as 2 (bFGF) and 4 weeks (PDGF-AB) after initial trauma surgery.

Systemic response of the GH/IGF-I axis in timely versus delayed fracture healing.

The GH-IGF axis has profound effects on the local and systemic regulation of bone metabolism and may be important for quality of fracture healing. To test the hypothesis that deficiency of the GH/IGF axis may play a role in the pathogenesis of fracture non-union we investigated whether alterations of serum concentrations of the GH-IGF axis could be related to failed fracture healing compared to timely fracture healing in trauma patients. Serum probes were prospectively collected from 186 patients with surgical treatment of long bone fractures up to 6 months after surgery. Samples from 14 patients with atrophic type of non-union have been compared to 14 matched patients with normal bone healing. Postoperative time courses of serum concentrations have been analyzed using commercially available chemiluminescence sandwich assays (GH), fully automated assay systems (IGF-I, IGFBP-3) or sandwich immunometric assays (ALS). Comparison between both collectives revealed significantly lower serum concentrations of GH dependent ALS during early (1st week after surgery) and of both IGFBP-3 and ALS during late stages of fracture healing (6 and 8 weeks after surgery) in non-union patients, coinciding clinically with failed fracture healing. Tendentially lower serum levels of IGF-I in the non-union group over the entire investigation period were statistically not significant. We have been able to show time courses of serum concentrations of the GH/IGF-I axis during normal and failed fracture healing in humans. An impairment of the GH/IGF-I axis might be involved in the biochemical mechanisms determining delayed or failed fracture healing.

Non-unions treated with bone morphogenic protein 7: introducing the quantitative measurement of human serum cytokine levels as promising tool in evaluation of adjunct non-union therapy.

BACKGROUND: In this study we sought to determine if application of bone morphogenic protein 7 (BMP-7) promotes physiological bone healing of non-unions and to investigate if serum cytokine analysis may serve as a promising tool in the analysis of adjunct non-union therapy. Therefore we analyzed the influence of BMP-7 application on the serum cytokine expression patterns on patients with impaired bone healing compared to patients that showed proper bone healing. METHODS: Our study involved analyzing blood samples from 208 patients with long bone fractures together with patients that subsequently developed non-unions. From this large pool, 15 patients with atrophic non-union were matched to 15 patients with atrophic non-union treated with local application of BMP-7 as well as normal bone healing. Changes in the cytokine expression patterns were monitored during the 1st, 2nd, 4th, 8th, 12th and 52nd week. The patients were followed both clinically and radiologically for the entire duration of the study. Serum cytokine expression levels of transforming growth factor beta (TGF-ß), platelet-derived growth factor (PDGF) and basic fibroblast growth factor (bFGF) were analyzed and compared. RESULTS: Serum expression of TGF-ß were nearly parallel in all three groups, however serum concentrations were significantly higher in patients with proper bone healing and those treated with BMP-7 than in patients with non-unions (p < 0.05). bFGF serum concentrations increased initially in patients with proper bone healing and in those treated with BMP-7. Afterwards, values decreased; bFGF serum concentrations in the BMP-7 group were significantly higher than in the other groups (p < 0.05). PDGF serum concentration levels were nearly parallel in all groups, serum concentrations were significantly higher in patients with proper bone healing and those treated with BMP-7 than in patients with non-unions (p < 0.05). CONCLUSION: Treatment with BMP-7 in patients with former non-unions led to similar cytokine expression patterns after treatment as those found in patients with proper bone healing. Our results suggest that treatment with BMP-7 promote healing of non-unions. Furthermore, quantitative measurement of serum cytokine expression is a promising tool for evaluating the effectiveness of additional non-union therapies such as adjunct application of growth factors.

The treatment of nonunions with application of BMP-7 increases the expression pattern for angiogenic and inflammable cytokines: a matched pair analysis.

The local application of bone morphogenetic protein-7 (BMP-7) in combination with the transplantation of autologous bone graft improves the outcome in nonunion treatment; however, the specific reasons remain unclear. In this study, we sought to determine if the local application of BMP-7 contributes to improved bone regeneration in nonunion therapy by modulation of the angiogenic and inflammable cytokine expression patterns of the early inflammation response. Therefore, we utilized the analysis of serological cytokine expression patterns. As a matched pair analysis, best-fitting patients who were treated with transplantation of autologous bone graft (G1, n=10) were compared with patients who were treated with additional application of BMP-7 (G2, n=10). The changes in the cytokine expression patterns were monitored and correlated to clinical data of bone healing. Significant differences in angiogenesis potential (vascular endothelial growth factor [VEGF] serum levels) could be found in the first days after surgery (P<0.05). Furthermore, the increase and absolute amount of VEGF levels in the BMP-7 group were considerably higher than in the control group during the first 2 weeks after surgery. The expression pattern of inflammable cytokines showed noticeable differences in the time point of significant elevated levels, in particular, inflammable cytokines showed an earlier peak in G2. Furthermore, interleukin-6 was significantly elevated within the first week only, comparing G2 to G1 (P<0.05). Our findings indicate that BMP-7 induces an early and more intense expression of VEGF via a direct and postulated indirect pathway, thereby providing a favorable environment for bone healing. Moreover, application of BMP-7 leads to an earlier expression of known proinflammatory cytokines. The results of this study show that application of BMP-7 leads to costimulatory effect on both angiogenic and inflammable cytokine expression patterns that may serve as a possible stimulus for bone regeneration.

Quantification of TGF-ß1, PDGF and IGF-1 cytokine expression after fracture treatment vs. non-union therapy via masquelet.

INTRODUCTION: Biochemical processes during bone regeneration can be analysed via quantification of peripheral serum cytokine levels. To date, serum levels of cytokines in patients treated with masquelet technique and patients with normal bone healing have not been compared. This comparison is supposed to deliver novel insights into the process of bone regeneration. Our aim was to validate this established method in the monitoring of bone regeneration after non-union treatment in masquelet technique. MATERIALS AND METHODS: Between 04/2008 and 01/2014 three groups were recruited: G1 (10 patients) with long bone non-unions, treated successfully with masquelet therapy, G2 (6 patients) with unsuccessful masquelet therapy and G3 (10 patients) with long bone fractures and normal bone healing. Peripheral blood samples were collected over a period of six months following a standardised time pattern in combination with clinical and radiologic follow up. TGF-ß1, PDGF-AB and IGF-1 were measured using commercially available immunoassays. RESULTS: TGF-ß1 levels in G1 and G2 demonstrated a parallel and lower overall concentration over time compared to G3. G3 showed a significant TGF-ß1 peak 2 weeks after surgery compared to G1 (p=0.0054). PDGF-AB concentrations were always lower in G2 than in G1 and G3. G3 peaked at week 2 with a significant higher value than in G2 (p=0.0177). IGF-1 showed lower overall serum concentrations in G2 than in G1 and G3. G1 had a peak level during the fourth week of follow-up. Compared to G2 this peak was significant (p=0.0015). CONCLUSIONS: This study shows that successful bone regeneration via masquelet technique only partially imitates cytokine expression of physiological bone healing. High expressions of IGF-1 correspond to a successful masquelet therapy while TGF-ß seems to play a minor role. These results assume that objective analysis of an effective non-union therapy with cytokine expression analysis is possible even with a small number of patients.

Matrix metalloproteinases and failed fracture healing.

During fracture healing and the resulting formation of new bone, an extensive amount of extracellular matrix is synthesized which subsequently undergoes enzymatic remodeling and then mineralization. The remodeling process of mostly collagenous molecules is largely attributable to matrix metalloproteinases (MMPs). A variety of members of this protease family and its respective inhibitors - termed tissue inhibitors of matrix metalloproteinases (TIMP) - have been found to be closely related to the fracture healing process. Delays in bone healing or even nonunion could be related to the concentrations of these enzymes or their behavior over time. In this study, serum samples were prospectively collected from patients who had undergone surgical treatment for limb fracture. Serum probes from 15 patients with nonunion of fractures 4 months after surgery have been compared to 15 matched patients with normal bone healing. Postoperative time courses of serum concentrations of MMP-1/-2/-3/-8/-9/-13 as well as TIMP-1/-2 were analyzed using commercially available enzyme immunoassays. Comparison between both collectives revealed significantly elevated serum concentrations of proMMP-1 in the nonunion group at 2 and 24 weeks after surgery. Similar findings were found for MMP-8 at 2, 4 and 8 weeks. At 1 week after surgery, TIMP-1 serum concentrations were significantly lower in nonunion patients when compared to patients with normal bone repair. We have been able to show for the first time the course of serum concentrations of MMPs and TIMPs during normal and delayed fracture healing. Characteristic time courses of systemic MMP- and TIMP-levels could be a reflection of local enzyme regulatory mechanisms during fracture healing. An altered balance of the MMP/TIMP system in favor of proteolytic activity as shown in our investigation may be involved in the pathophysiological processes leading to fracture nonunion.

Allograft bone matrix versus synthetic bone graft substitutes.

Autologous bone is used very often in the treatment of fresh fractures, delayed unions and non-unions. Alternatives have included allografts and in recent years also demineralized bone matrix. The growing availability of good synthetic bone grafts and their advantages in safety and avoiding donor-site morbidity are the reasons that these products are being used more and more. There are on the market a wide variety of substitutes with different capabilities. Nevertheless autologous bone graft is still considered as the gold standard and will be discussed here in that context. Osteoconductive, osteogenic and osteoinductive products will also be classified and their advantages and disadvantages described.

Cigarette smoking influences the clinical and occupational outcome of patients with tibial shaft fractures.

Tibial shaft fracture is one of the most common types of bone fracture in young patients. In this prospective clinical cohort study, we investigated the effects of cigarette smoking on the clinical, functional, psychosocial and occupational outcomes after isolated lower-leg fracture. We examined 85 patients, including 61 men and 24 women, with a collective mean age of 46 years (range: 18-84 years). Thirty-nine patients had never smoked (G1) and 45 patients were current or previous smokers (G2). The G2 group displayed a significantly increased risk for delayed union or nonunion (G1=3 patients, G2=18 patients; P=0.0007) and increased time required for fracture healing (mean times: G1=11.9 weeks, G2=17.4 weeks; p=0.003) and a markedly increased time out of work (mean times: G1=16.1 weeks, G2=21.5 weeks; p=0.1177 (not significant)). The 18 negatively affected patients in G2 displayed a significant increase in the time required for fracture healing and time out of work (26 weeks (p=0.02) and 31 weeks (p=0.03), respectively). G2 group members had a 3- to 18-fold higher risk of impaired bone healing. The mean Short Form 36 (SF-36) was similar in both groups. The physical-function scores were G1=49.6 and G2=48.6; the mental scores were G1=52.7 and G2=52.8. These findings indicate that smoking significantly increases the risk of impaired fracture healing, which has clinical and occupational consequences for the affected patients. Based on our data, we developed a score to estimate the individual risk of impaired fracture healing. These types of patients must be informed and closely monitored to determine the need for timely re-intervention with additional therapy, such as BMP s or ultrasound.