Implications for fracture healing of current and new osteoporosis treatments: an ESCEO consensus paper.

Osteoporotic fracture healing is critical to clinical outcome in terms of functional recovery, morbidity, and quality of life. Osteoporosis treatments may affect bone repair, so insights into their impact on fracture healing are important. We reviewed the current evidence for an impact of osteoporosis treatments on bone repair. Treatment with bisphosphonate in experimental models is associated with increased callus size and mineralization, reduced callus remodeling, and improved mechanical strength. Local and systemic bisphosphonate treatment may improve implant fixation. No negative impact on fracture healing has been observed, even after major surgery or when administered immediately after fracture. Experimental data for denosumab and raloxifene suggest no negative implications for bone repair. The extensive experimental results for teriparatide indicate increased callus formation, improved biomechanical strength, and greater external callus volume and total bone mineral content and density. Case reports and a randomized trial have produced mixed results but are consistent with a positive impact of teriparatide on clinical fracture healing. Studies with strontium ranelate in models of fracture healing indicate that it is associated with improved bone microstructure, callus volume, and biomechanical properties. Finally, there is experimental evidence for a beneficial effect of some of the agents currently being developed for osteoporosis, notably sclerostin antibody and DKK1 antibody. There is currently no evidence that osteoporosis treatments are detrimental for bone repair and some promising experimental evidence for positive effects on healing, notably for agents with a bone-forming mode of action, which may translate into therapeutic applications.

Development of a score set to measure function and quality of life in patients suffering from elbow pathology.

INTRODUCTION: Daily function plays an important role in the quality of life for patients suffering from pathology of the upper extremity. The recovery of functions of daily living determines the success or failure of the treatment for the patient. The goal of this study was to establish and validate a score set measuring quality of life, and objective and subjective function in general elbow pathologies. METHODS: A literature review was performed, in order to find a patient-based elbow specific questionnaire. The score set was tested and validated in a cross-sectional setting. RESULTS: The patient-rated elbow evaluation (PREE) was chosen as the patient-based elbow specific questionnaire. For measuring general health and subjective arm function, the short form-36 mental health (SF-36 MH) and the shortened disabilities of the arm, shoulder and hand questionnaire (quick DASH) were chosen, respectively. To measure objective function, several clinical tests were implemented. The score set was tested in 66 patients, of which 56.1% had function restrictions due to pain. The correlation between the PREE-function and quick DASH was found to be the highest (r = 0.74*). Between the PREE and quick DASH, the correlation was good (r = 0.70*) and between the PREE-pain and quick DASH, the correlation was moderate (r = 0.58*). The lowest correlation (r = 0.18) was found between the PREE and SF-36 MH (*p < 0.01). CONCLUSION: General health, subjective and objective function can be measured in elbow pathology patients using a score set containing the SF-36 MH, quick DASH, PREE, and several clinical tests. Further testing of the score set needs to be executed in a prospective study.

Survivorship of second-generation metal-on-metal primary total hip replacement.

BACKGROUND: Second generation metal-on-metal total hip replacements (THR) were introduced in the late 1980s and various studies reported conflicting data on their outcome. METHODS: Implant survival of 1,270 second-generation 28 mm metal-on-metal primary THR in 1,121 patients followed prospectively at a mean of 6.8 years postoperatively was evaluated retrospectively. The probability of survival at 10 years was estimated using the method of Kaplan and Meier, and relative risk factors including age, gender, BMI, type of implant fixation and component size were calculated using the Cox proportional-hazards model. RESULTS: Sixty-three (5%) THRs were revised, these being 28 hips for aseptic loosening and 35 for reasons other than aseptic loosening. The probability of survival at 10 years, with revision for any reason as the endpoint, was 0.90 (95% confidence interval (CI) 0.86-0.94) for the THR as a whole, 0.91 (95% CI 0.87-0.95) for the cup, and 0.96 (95% CI 0.94-0.98) for the stem. No demographic factors or covariates were found to significantly affect the implant survivorship. DISCUSSION: As there was no superior probability of survival, and there have been concerns on putative local and systemic toxicity of metal debris, the use of second-generation metal-on-metal articulations for primary THR remains moot.

A functional outcome study comparing total ankle arthroplasty (TAA) subjects with pain to subjects with absent level of pain by means of videofluoroscopy.

BACKGROUND: Total ankle arthroplasty (TAA) subjects often suffer pain on the anteromedial side of their ankle joint. Whether this prevalent pain is caused by a changed motion pattern of the TAA is unclear. Therefore, this study assessed the kinematic differences in the motion of the TAA components during gait, comparing TAA subjects with elevated versus absent levels of pain. METHODS: Eleven TAA subjects (5 with pain vs. 6 without pain), all with unilateral Mobility™ TAA and at least two years post-operation, were recruited and stratified based on standard clinical assessed patient data. The 3D motion of the TAA was assessed by means of videofluoroscopy during level, uphill and downhill walking. RESULTS: The hypothesis that the pain group shows a different kinematic motion pattern than the no pain group could not be confirmed. CONCLUSIONS: The same kinematic motion pattern causes pain in some patients, but not in others. Further investigation concerning ligament stresses is needed.

Balloon kyphoplasty and vertebroplasty in the management of vertebral compression fractures.

Vertebral compression fractures (VCFs) are the most prevalent fractures in osteoporotic patients. The classical conservative management of these fractures is through rest, pain medication, bracing and muscle relaxants. The aim of this paper is to review prospective controlled studies comparing the efficacy and safety of minimally invasive techniques for vertebral augmentation, vertebroplasty (VP) and balloon kyphoplasty (BKP), versus non-surgical management (NSM). The Fracture Working Group of the International Osteoporosis Foundation conducted a literature search and developed a review paper on VP and BKP. The results presented for the direct management of osteoporotic VCFs focused on clinical outcomes of these three different procedures, including reduction in pain, improvement of function and mobility, vertebral height restoration and decrease in spinal curvature (kyphosis). Overall, VP and BKP are generally safe procedures that provide quicker pain relief, mobility recovery and in some cases vertebral height restoration than conventional conservative medical treatment, at least in the short term. However, the long-term benefits and safety in terms of risk of subsequent vertebral fractures have not been clearly demonstrated and further prospective randomized studies are needed with standards for reporting. Referral physicians should be aware of VP/BKP and their potential to reduce the health impairment of patients with VCFs. However, VP and BKP are not substitutes for appropriate evaluation and treatment of osteoporosis to reduce the risk of future fractures.

A combination of shear and dynamic compression leads to mechanically induced chondrogenesis of human mesenchymal stem cells.

There is great interest in how bone marrow derived stem cells make fate decisions. Numerous studies have investigated the role of individual growth factors on mesenchymal stem cell differentiation, leading to protocols for cartilage, bone and adipose tissue. However, these protocols overlook the role of biomechanics on stem cell differentiation. There have been various studies that have applied mechanical stimulation to constructs containing mesenchymal stem cells, with varying degrees of success. One critical fate decision is that between cartilage and bone. Articular motion is a combination of compressive, tensile and shear deformations; therefore, one can presume that compression alone is unlikely to be a sufficient mechanical signal to generate a cartilage-like tissue in vitro. Within this study, we aimed to determine the role of shear on the fate of stem cell differentiation. Specifically, we investigated the potential enhancing effect of surface shear, superimposed on cyclic axial compression, on chondrogenic differentiation of human bone marrow-derived stem cells. Using a custom built loading device we applied compression, shear or a combination of both stimuli onto fibrin/polyurethane composites in which human mesenchymal stem cells were embedded, while no exogenous growth-factors were added to the culture medium. Both compression or shear alone was insufficient for the chondrogenic induction of human mesenchymal stem cells. However, the application of shear superimposed upon dynamic compression led to significant increases in chondrogenic gene expression. Histological analysis detected sulphated glycosaminoglycan and collagen II only in the compression and shear group. The results obtained may provide insight into post-operative care after cell therapy involving mesenchymal stromal cells.

[Western Ontario shoulder instability index (WOSI): translation and cross-cultural adaptation for use by German speakers]. / "Western Ontario Shoulder Instability Index" (WOSI) : Ubersetzung und transkulturelle Anpassung für den deutschsprachigen Gebrauch.

BACKGROUND: Outcome assessment after orthopaedic interventions is becoming more and more important. However, there are no disease-specific instruments for patient self-assessment of shoulder instability. The goal of our study was to translate and test the Western Ontario Shoulder Instability Index (WOSI) using a standardised approach. The guidelines of the American Association of Orthopedic Surgeons were used for the translation and cross-cultural adaptation process. MATERIAL AND METHOD: Understanding was tested in 20 healthy subjects, and reliability and validity were quantified in 30 patients with shoulder instability. The quality of the translated version was described using the criteria of homogeneity, reliability, and construct validity. RESULTS: The test-retest reliability of the total score [intraclass correlation coefficient (ICC), 0.87] and of the subscores with the ICC (sports, leisure, and work 0.73; sensitivity 0.81; physical symptoms 0.82; and behaviour 0.90) was high. The internal consistency of the total scale was also high (Cronbach's alpha 0.89). CONCLUSIONS: The WOSI covers a broad range of symptoms and impaired functioning in patients with shoulder instability. The German translation shows good results regarding understanding, homogeneity, reliability, and validity. Therefore, it is a useful instrument for self-assessment in patients with shoulder instability.

Trabecular bone structures in the edentulous diastema of osteoporotic sheep.

The edentulous ovine diastema represents a suitable region for implantological research. Due to distinctive embryonic origin and mechanical loading, the edentulous diastema may respond differently to osteoporosis than tooth-bearing areas. To test this assumption, we subjected geriatric sheep to ovariectomy, calcium-/vitamin-D-restricted diet, and methylprednisolone administration. Adult control sheep remained untreated. Structural parameters and bone mineral density were determined by microcomputed tomography and conventional computed tomography, respectively. We report that the trabecular microstructure in the diastema was preserved from catabolic changes. In contrast, the premolar maxillary region of osteoporotic sheep had diminished trabecular bone mineral density, with the corresponding structural deteriorations. These results suggest that maxillary trabecular bone of the edentulous diastema does not respond to catabolic changes which occur in the tooth-bearing area in osteoporosis. Our findings imply that regional anatomic domains must be considered in the planning of pre-clinical studies, taking osteoporotic changes into account.

A sheep model for fracture treatment in osteoporosis: benefits of the model versus animal welfare.

Animal models are necessary to evaluate new options for the treatment of fractures in osteoporotic bone. They permit both the biological response of a living system and the influence of the pathological processes to be taken into account. A sheep model for osteoporosis was established by combining oestrogen deficiency, calcium and vitamin D-deficient diet with steroid medication. Bone mineral density (BMD) was reduced by >30% after 12 weeks of combined treatment. Osteoporosis similar to the human situation with corresponding changes in the micro-architecture and mechanical properties of bone was observed. This publication focuses on the impressive results obtained with the model and contrasts them with considerations of animal welfare. Considerable side-effects associated with steroid medication became manifest. Animals in the treatment groups showed signs of infection of various degrees due to the immunosuppressive effect of the medication. The infections were mostly caused by Corynebacterium pseudotuberculosis. Antibody testing revealed a 100% prevalence of infection in this breed of sheep. A modification of the steroid treatment, i.e. less-frequent injections, reduced the incidence of side-effects. This sheep model shows a significant and reproducible reduction in cancellous BMD of >30%, including relevant changes in biomechanical properties and increased fracture risk. However, the severity of the side-effects cannot be overlooked. The model must be improved if it is to be used in the future. Options to reduce the side-effects are discussed.

Key factors for a successful National Arthroplasty Register.

Since the introduction of the first National Arthroplasty Register in Sweden in 1975, many other countries have tried to adopt the successful Scandinavian system. However, not all have overcome the political and practical difficulties of establishing a working register. We have surveyed the current registries to establish the key factors required for an effective database. We have received detailed information from 15 arthroplasty registers worldwide. The legal conditions under which they operate together with the methods of collection and handling of the data differ widely, but the fulfilment of certain criteria is necessary achieve a high degree of completeness of the data to ensure the provision of statistically relevant information.

Improved anchorage in osteoporotic vertebrae with new implant designs.

The goal of our study was to evaluate two newly developed implant designs and their behavior in terms of subsidence in lumbar vertebral bodies under cyclic loading. The new implants were evaluated in two different configurations (two small prototypes vs. one large prototype with similar load-bearing area) in comparison to a conventional screw-based implant (MACS TL). A pool of 13 spines with a total of 65 vertebrae was used to establish five testing groups of similar bone mineral density (BMD) distribution with eight lumbar vertebrae each. In additional to BMD assessment via dual-energy X-ray absorptiometry, cancellous BMD and structural parameters were determined using a new generation in vivo 3D-pQCT. The specimens were loaded sinusoidally in force control at 1 Hz for 1000 cycles at three load levels (100, 200, and 400 N). A survival analysis using the number of cycles until failure (Cox regression with covariates) was applied to reveal differences between implant groups. All new prototype configurations except the large cylinder survived significantly longer than the control group. The number of cycles until failure was significantly correlated with the structural parameter Tb.Sp. and similarly with the cancellous BMD for three of five implants. In both large prototypes the cycle number until failure significantly correlated with the preoperative distance to the upper endplates. Although the direct relationship between bone structure or density and mechanical breakage behavior cannot be conclusively proven, all the prototypes adapted for poor bone structure performed better than the comparable conventional implant.

Rupture of the subscapularis tendon (isolated or in combination with supraspinatus tear): when is a repair indicated?

Ruptures of the subscapularis tendon, isolated or combined, are rare, and the treatment modalities are controversial. Of 1345 patients who underwent rotator cuff repair in a 7-year period, 73 had either an isolated rupture of the subscapularis or a subscapularis rupture combined with rupture of the supraspinatus. All reconstructions were performed through a deltopectoral approach. Reinsertion of the subscapularis was combined with reconstruction of the supraspinatus in 32 patients. Of the patients, 63 (86%) were re-examined at a mean follow-up of 35 months. The modified Constant score improved from 62% preoperatively to 91% at follow-up. Isolated or combined reconstructions did not result in significant differences with respect to the Constant score. Of the patients, 62 (98%) were satisfied with the operation. Rerupture was found by ultrasound in 8 subscapularis tendons (13%) and 4 supraspinatus tendons (13%). The rerupture rate showed a significant correlation with the Goutallier stage of fatty degeneration and the interval between injury and operation.

Problematic bone fixation with pyrocarbon implants in proximal interphalangeal joint replacement: short-term results.

Seventeen pyrocarbon PIP prostheses were implanted into 14 patients, followed prospectively and reviewed clinically. The patients were assessed after a mean follow-up of 20.5 months subjectively by a VAS pain scale and radiographically. Significant pain relief was noted in all patients from a mean of 7.6 pre-operatively to 1.3 at final follow-up. Migration of one, or both, components was observed radiographically in eight joints and radiolucent lines were evident in three more cases. The clinical results of the implants which had migrated were less favourable for range of motion and grip strength than the stable joints of this series, although, statistically, the results were not significant. The number of possibly unstable prostheses in this series raises the question as to whether pyrocarbon is suitable for uncemented pressfit fixation in combination with early functional rehabilitation.

Ultrasound melted polymer sleeve for improved screw anchorage in trabecular bone--A novel screw augmentation technique.

BACKGROUND: Screw anchorage in osteoporotic bone is still limited and makes treatment of osteoporotic fractures challenging for surgeons. Conventional screws fail in poor bone quality due to loosening at the screw-bone interface. A new technology should help to improve this interface. In a novel constant amelioration process technique, a polymer sleeve is melted by ultrasound in the predrilled screw hole prior to screw insertion. The purpose of this study was to investigate in vitro the effect of the constant amelioration process platform technology on primary screw anchorage. METHODS: Fresh frozen femoral heads (n=6) and vertebrae (n=6) were used to measure the maximum screw insertion torque of reference and constant amelioration process augmented screws. Specimens were cut in cranio-caudal direction, and the screws (reference and constant amelioration process) were implanted in predrilled holes in the trabecular structure on both sides of the cross section. This allowed the pairwise comparison of insertion torque for constant amelioration process and reference screws (femoral heads n=18, vertebrae n=12). Prior to screw insertion, a micro-CT scan was made to ensure comparable bone quality at the screw placement location. FINDINGS: The mean insertion torque for the constant amelioration process augmented screws in both, the femoral heads (44.2 Ncm, SD 14.7) and the vertebral bodies (13.5 Ncm, SD 6.3) was significantly higher than for the reference screws of the femoral heads (31.7 Ncm, SD 9.6, p<0.001) and the vertebral bodies (7.1 Ncm, SD 4.5, p<0.001). INTERPRETATION: The interconnection of the melted polymer sleeve with the surrounding trabecular bone in the constant amelioration process technique resulted in a higher screw insertion torque and can improve screw anchorage in osteoporotic trabecular bone.

Primary stability of various forms of osteosynthesis in the treatment of fractures of the proximal tibia.

The treatment of fractures of the proximal tibia is complex and makes great demands on the implants used. Our study aimed to identify what levels of primary stability could be achieved with various forms of osteosynthesis in the treatment of diaphyseal fractures of the proximal tibia. Pairs of human tibiae were investigated. An unstable fracture was simulated by creating a defect at the metaphyseal-diaphyseal junction. Six implants were tested in a uniaxial testing device (Instron) using the quasi-static and displacement-controlled modes and the force-displacement curve was recorded. The movements of each fragment and of the implant were recorded video-optically (MacReflex, Qualysis). Axial deviations were evaluated at 300 N. The results show that the nailing systems tolerated the highest forces. The lowest axial deviations in varus and valgus were also found for the nailing systems; the highest axial deviations were recorded for the buttress plate and the less invasive stabilising system (LISS). In terms of rotational displacement the LISS was better than the buttress plate. In summary, it was found that higher loads were better tolerated by centrally placed load carriers than by eccentrically placed ones. In the case of the latter, it appears advantageous to use additive procedures for medial buttressing in the early phase.

Biomechanical evaluation of healing in a non-critical defect in a large animal model of osteoporosis.

Current methods for fracture treatment in osteoporosis are not always sufficient. To develop new fixation strategies (both mechanical and biological) requires pre-clinical testing utilizing appropriate models. The aim of this study was to apply a recently developed sheep model of osteoporosis to the study of healing in a non-critical long bone defect. A standardized transverse mid-shaft tibial osteotomy (with a fracture gap of 3 mm) was performed in seven osteoporotic and seven normal sheep and stabilized with a special external fixator for 8 weeks. The fixator was used for weekly in vivo bending stiffness measurements. Ex vivo bending stiffness and torsional stiffness of the callus zone were also determined. Callus area, callus density, and osteoporosis status were determined at 0, 4, and 8 weeks using peripheral quantitative computed tomography. The increase of in vivo bending stiffness of the callus was delayed approximately 2 weeks in osteoporotic animals. A significant difference (33%) in torsional stiffness was found between the osteotomized and contralateral intact tibia in osteoporotic animals, but no significant difference occurred in normal sheep (2%). In osteoporotic animals, ex vivo bending stiffness was reduced 21% (p=0.05). Bending stiffness was correlated with callus density (r=0.76, r=0.53); torsional stiffness was correlated with callus area (r=0.60) and to a lesser extent with callus density (r=0.53). This study demonstrated a delay of fracture healing in osteoporotic sheep tibiae with respect to callus formation, mineralization, and mechanical properties.

Effect of cortical thickness and cancellous bone density on the holding strength of internal fixator screws.

Internal fixators are a new class of implants designed to preserve the periosteal blood supply of the bone. In contrast to conventional plate fixation in which the screws have spherical heads and are loaded mainly by axial pullout forces, screws in internal fixators are "locked" within the plate and therefore subjected to axial as well as bending loads. In this study the ultimate loads of screws of a commercially available internal fixator system were tested in a pullout (n = 72) and cantilever bending mode (n = 72) in metaphyseal and diaphyseal regions of four pairs of human tibiae with different bone qualities. Cortical thickness and cancellous bone density were determined at the screw insertion sites. Stepwise multiple linear regression revealed that cortical thickness and cancellous density can explain 93% and 98% of the variance of the ultimate load of the screws in an axial pullout and cantilever bending mode. Screws in internal fixators are better suited to transmit shear forces and thereby make better use of the strength potential of bone than screws used in conventional plate fixation: this is especially advantageous when bone strength is reduced, e.g. due to osteoporosis.

Mechanical boundary conditions of fracture healing: borderline indications in the treatment of unreamed tibial nailing.

Unreamed nailing favors biology at the expense of the achievable mechanical stability. It is therefore of interest to define the limits of the clinical indications for this method. The extended usage of unreamed tibial nailing resulted in reports of an increased rate of complications, especially for the distal portion of the tibia. The goals of this work were to gain a thorough understanding of the load-sharing mechanism between unreamed nail and bone in a fractured tibia, to identify the mechanical reasons for the unfavorable clinical results, and to identify borderline indications due to biomechanical factors. In a three-dimensional finite element model of a human tibia, horizontal defects were stabilized by means of unreamed nailing for five different fracture locations, including proximal and distal borderline indications for this treatment method. The loading of the bone, the loading of the implant and the inter-fragmentary strains were computed. The findings of this study show that with all muscle and joint contact forces included, nailing leads to considerable unloading of the interlocked bone segments. Unreamed nailing of the distal defect results in an extremely low axial and high shear strain between the fragments. The results suggest that mechanical conditions are advantageous to unreamed nailing of proximal and mid-diaphyseal defects. Apart from biological reasons, clinical problems reported for distal fractures may be due to the less favorable mechanical conditions in unreamed nailing. From a biomechanical perspective, the treatment of distal tibial shaft fractures by means of unreamed nailing without additional fragment contact or without stabilizing the fibula should be carefully reconsidered.

Impact of bone density on distal radius fracture patterns and comparison between five different fracture classifications.

OBJECTIVE: To investigate the impact of bone mineral density (BMD) and bone geometry on failure loads and fracture patterns of the distal radius and to compare 5 different fracture classifications. DESIGN: Biomechanical and radiologic in vitro study. SETTING: Research laboratory. MAIN OUTCOME MEASUREMENTS: A total of 118 intact human forearms from elderly donors were examined by means of conventional radiography and peripheral quantitative computed tomography (PQCT) to determine BMD and geometry. The forearms were subjected to a standardized biomechanical test simulating a fall on the outstretched hand. The distal radius fractures were classified from x-rays using the AO ( 33), Cooney ( 9), Fernandez ( 15), Frykman ( 17), and Melone ( 31) classifications. The grading was repeated after preparation and direct visual inspection of the fracture site and was correlated with radiographic results. Fracture patterns also were correlated with BMD and geometry. RESULTS: Correlations between bone properties and fracture patterns (r = 0.09-0.70) suggested an increase in the severity of fractures with decreasing bone quality. The highest correlation between failure load and bone properties was found for the cortical area (r = 0.70) and trabecular density (r = 0.60). Good correlations between radiographic and direct visual classification were obtained for the Cooney ( 9) (r = 0.70), the AO ( 33) (r = 0.68), and the Fernandez ( 15) (r = 0.65) classifications. Smaller values were found for the Frykman ( 17) (r = 0.44) and the Melone ( 31) (r = 0.27) classifications. CONCLUSIONS: With increasing osteopenia, the load to failure decreases, and the severity of fractures increases. Fracture patterns in this patient population can be adequately graded with the AO ( 33) and Cooney ( 9) classifications. The severity of distal radius fractures tends to be underestimated by conventional x-ray examination, which needs to be taken into account when a fracture treatment plan is selected.