Jörg Goldhahn

Influence of osteoporosis on fracture fixation - a systematic literature review

SummaryThe goal of our systematic literature search was to prove whether the experimentally shown influence of osteoporosis on fracture fixation could be confirmed in clinical studies. Despite significant effects in several studies, this is not supported by pooled data due to lack of accurate osteoporosis assessment and complication definitions.IntroductionThe fact that osteoporosis causes fractures is well-known; the assumption that it aggravates their orthopaedic treatment has not been proven. The goal of our systematic literature search was to find out whether the experimentally proven influence of osteoporosis on fracture fixation could be confirmed in clinical studies.MethodsA systematic electronic database search was performed identifying articles that evaluated complications after fracture fixation among patients suspected of having osteoporosis as measured by BMD or surrogates including Singh index or risk factors. To determine complications risks (relative risk within 95% confidence interval) data were pooled across studies, weighted by sample size and stratified by treatment type.ResultsTen studies out of 77 randomized controlled trials (51 hip, 23 distal radius and three proximal humerus studies) and three systematic reviews finally met eligibility criteria. Despite significant differences of the relative complication risk between osteoporotic and non-osteoporotic patients in several studies, this could not be proven in the pooled data.ConclusionsIn contrast to biomechanical evidence that local osteoporosis affects anchorage of implants, this could not be reproduced in clinical studies, due to the lack of accurate osteoporosis assessment, missing complication definitions and heterogeneous inclusion criteria in these studies. Prospective studies are required that address specifically the correlation between local bone status and the risk of fixation failure.

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.

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.

What counts: outcome assessment after distal radius fractures in aged patients.

Objectives: Outcome of surgical interventions at the distal radius does not only depend on the type of intervention used, it also depends on the way the outcome is measured. Substantial differences in outcome assessment between different measurement tools and poor correlation among them result in the question about the best instrument for the evaluation of treatment after distal radius fractures. The aim of the review is to discuss pros and cons of the parameters that are available to assess the outcome after distal radius fractures. The review should help to choose the appropriate instruments for a given research question in aged patients with distal radius fractures. Data Sources and Synthesis: Objective and subjective measures were reviewed with respect to their suitability in outcome assessment. Radiological parameters like inclination, palmar slope, and length of the radius are most common and used to determine especially surgical success. Grip strength and range of motion are considered objective and used as study endpoints in many studies. Functional tests like the Jebsen test provide a realistic feedback about disability but require special skills and resources of the testing personnel. Patient self-assessment adds perceived patient benefit. The patient-rated wrist evaluation (PRWE) provides a reliable and valid instrument for subjective outcome assessment. Conclusions: A combination of objective and subjective parameters should be used to assess the outcome of different treatment strategies due to the known discrepancies. Objective parameters like shortening, radial shift, or others should be clearly defined in the study methodology.

Implant stability is affected by local bone microstructural quality

It is known that low bone quality, caused for instance by osteoporosis, not only increases the risk of fractures, but also decreases the performance of fracture implants; yet the specific mechanisms behind this phenomenon are still largely unknown. We hypothesized that especially peri-implant bone microstructure affects implant stability in trabecular bone, to a greater degree than more distant bone. To test this hypothesis we performed a computational study on implant stability in trabecular bone. Twelve humeral heads were measured using micro-computed tomography. Screws were inserted digitally into these heads at 25 positions. In addition, at each screw location, a virtual biopsy was taken. Bone structural quality was quantified by morphometric parameters. The stiffness of the 300 screw-bone constructs was quantified as a measure of implant stability. Global bone density correlated moderately with screw-bone stiffness (r2=0.52), whereas local bone density was a very good predictor (r2=0.91). The best correlation with screw-bone stiffness was found for local bone apparent Youngs modulus (r2=0.97), revealing that not only bone mass but also its arrangement in the trabecular microarchitecture are important for implant stability. In conclusion, we confirmed our hypothesis that implant stability is affected by the microstructural bone quality of the trabecular bone in the direct vicinity of the implant. Local bone density was the best single morphometric predictor of implant stability. The best predictability was provided by the mechanical competence of the peri-implant bone. A clinical implication of this work is that apparently good bone stock, such as assessed by DXA, does not guarantee good local bone quality, and hence does not guarantee good implant stability. New tools that could quantify the structural or mechanical quality of the peri-implant bone may help improve the surgical intervention in reaching better clinical outcomes for screw fixation.

Clinical evaluation of medicinal products for acceleration of fracture healing in patients with osteoporosis.

Pre-clinical studies indicate that pharmacologic agents can augment fracture union. If these pharmacologic approaches could be translated into clinical benefit and offered to patients with osteoporosis or patients with other risks for impaired fracture union (e.g. in subjects with large defects or open fractures with high complication rate), they could provide an important adjunct to the treatment of fractures. However, widely accepted guidelines are important to encourage the conduct of studies to evaluate bioactive substances, drugs, and new agents that may promote fracture union and subsequent return to normal function. A consensus process was initiated to provide recommendations for the clinical evaluation of potential therapies to augment fracture repair in patients with meta- and diaphyseal fractures. Based on the characteristics of fracture healing and fixation, the following study objectives of a clinical study may be appropriate: a) acceleration of fracture union, b) acceleration of return to normal function and c) reduction of fracture healing complications. The intended goal(s) should determine subsequent study methodology. While an acceleration of return to normal function or a reduction of fracture healing complications in and of themselves may be sufficient primary study endpoints for a phase 3 pivotal study, acceleration of fracture union alone is not. Radiographic evaluation may either occur at multiple time points during the healing process with the aim of measuring the time taken to reach a defined status (e.g. cortical bridging of three cortices or disappearance of fracture lines), or could be obtained at a single pre-determined timepoint, were patients are expected to reach a common clinical milestone (i.e. pain free full weight-bearing in weight-bearing fracture cases). Validated Patient Reported Outcomes (PROs) measures will need to support the return to normal function co-primary endpoints. If reduction of complication rate (e.g. non-union) is the primary objective, the anticipated complications must be defined in the study protocol, along with their possible associations with the specified fracture type and fixation device. The study design should be randomized, parallel, double-blind, and placebo-controlled, and all fracture subjects should receive a standardized method of fracture fixation, defined as Standard of Care.

Evidence for anti-osteoporosis therapy in acute fracture situations--recommendations of a multidisciplinary workshop of the International Society for Fracture Repair.

The International Society for Fracture Repair convened a multidisciplinary workshop to assess the current evidence around the interaction between anti-osteoporosis drugs and the healing of incident fractures, with a view to making recommendations for clinical practice. The consensus was that there is no evidence-based reason to withhold anti-resorptive therapy while a fracture heals, whether or not the patient was taking such therapy when the fracture occurred. The workshop also considered existing models of service provision for secondary prevention and concluded that the essential ingredient for reliable delivery is the inclusion of a dedicated coordinator role. Several unresolved issues were defined as subjects for further research, including the question of whether continuous long-term administration of anti-resorptives may impair bone quality. The rapidly changing area requires re-assessment of drugs and their interaction with fracture healing in the near future.

A concept for comprehensively measuring health, function and quality of life following orthopaedic interventions of the upper extremity

The view that subjective complaints rather than “objective” measurements decide on whether to consult the doctor or allow for an intervention to be carried out, should contribute to the decision-making process. This is especially true in diseases with multiple joint impairments. Although a variety of patient self-assessment scores exists, no gold standard is available to measure function and quality of life (QoL) after interventions at the upper extremity. The goal of our concept is to establish a comprehensive score set where patients should rate their generic health resp. quality of life (QoL), function of the upper extremity and specific joint function including activities of daily living, function and pain. A comparison with normative data should be possible in order to estimate how the subjective results of the patient when compared to “healthy” people in the general population. Score sets for measuring intervention effect at the shoulder, elbow and the hand were established after previous methodological testing within an interdisciplinary research project. The provisional sets were defined following a systematic literature search. Each set received a score of measuring the quality of life (SF-36), the whole function of the arm (DASH) and the specific joint function (SPADI/ASES for shoulder, PREE/mASES for the elbow and PRWE/custom for the hand). Individual scores were translated, if necessary according to AAOS-guidelines, and tested for reliability and construct validity. All three score sets were then systematically tested in cross-sectional studies. In addition, characteristic values such as minimal detectable difference and effect size could already be determined in the shoulder set in a long-term study. Definite score sets were defined, which allow quantification of the intervention effect at the upper extremity on function and quality of life after.

Complication Reporting in Orthopaedic Trials

BACKGROUND The nature and frequency of complications during or after orthopaedic interventions represent critical clinical information for safety evaluations, which are required for the development or improvement of orthopaedic care. The goal of this systematic review was to check whether essential data regarding the assessment of the prevalence, severity, and characteristics of complications related to orthopaedic interventions are consistently provided by the authors of papers on randomized controlled trials. METHODS Five major peer-reviewed orthopaedic journals were screened for randomized controlled trials published between January 2006 and July 2007. All relevant papers were obtained, anonymized, and evaluated by two external reviewers. A checklist consisting of three main parts (definition, evaluation, and reporting) was developed and applied for the assessment of complication reporting. The results were stratified into surgical and nonsurgical categories. RESULTS One hundred and twelve randomized controlled trials were identified. Although complications were included as trial outcomes in two-thirds of the studies, clear definitions of anticipated complications were provided in only eight trials. In 83% of the trials, the person or group assessing the complications was not identified. No trial involved a data safety review board for assessment and classification of complications. CONCLUSIONS The lack of homogeneity among the published studies that we reviewed indicates that improvement in the reporting of complications in orthopaedic clinical trials is necessary. A standardized protocol for assessing and reporting complications should be developed and endorsed by professional organizations and, most importantly, by clinical investigators.

Recommendation for measuring clinical outcome in distal radius fractures: a core set of domains for standardized reporting in clinical practice and research.

IntroductionLack of standardization of outcome measurement has hampered an evidence-based approach to clinical practice and research.MethodsWe adopted a process of reviewing evidence on current use of measures and appropriate theoretical frameworks for health and disability to inform a consensus process that was focused on deriving the minimal set of core domains in distal radius fracture.ResultsWe agreed on the following seven core recommendations: (1) pain and function were regarded as the primary domains, (2) very brief measures were needed for routine administration in clinical practice, (3) these brief measures could be augmented by additional measures that provide more detail or address additional domains for clinical research, (4) measurement of pain should include measures of both intensity and frequency as core attributes, (5) a numeric pain scale, e.g. visual analogue scale or visual numeric scale or the pain subscale of the patient-reported wrist evaluation (PRWE) questionnaires were identified as reliable, valid and feasible measures to measure these concepts, (6) for function, either the Quick Disability of the arm, shoulder and hand questionnaire or PRWE-function subscale was identified as reliable, valid and feasible measures, and (7) a measure of participation and treatment complications should be considered core outcomes for both clinical practice and research.ConclusionWe used a sound methodological approach to form a comprehensive foundation of content for outcomes in the area of distal radius fractures. We recommend the use of symptom and function as separate domains in the ICF core set in clinical research or practice for patients with wrist fracture. Further research is needed to provide more definitive measurement properties of measures across all domains.