Magnus Tägil's research while affiliated with Skåne University Hospital and other places

Introduction With a rapidly ageing population, the number of distal radius fractures (DRFs) in the elderly will increase dramatically. The aim of this retrospective register study was to examine the 1- and 5-year mortality in DRF patients aged 80 years or more and correlate the overall survival to factors not related to the fracture itself. Material and Methods Patients aged ≥80 diagnosed with DRFs in Lund University Hospital in Sweden in the period 2010-2012 were extracted from the prospective Lund Distal Radius Fracture register. One- and 5-year standardised mortality rates (SMRs) were calculated using the Swedish standard population as a reference. Medical records were searched for non-fracture-related factors including comorbidity, medications, cognitive impairment and type of living. Cox proportional hazard regression models were used to identify prognostic factors for all-cause mortality. Results The study cohort included 240 patients, with a mean age of 86. The overall 1-year mortality was 5% (n = 11/240) and the 5-year mortality was 44% (n = 105/240). The 1-year SMR was .44 (CI .18-.69, P < .01) when indirectly adjusted for age and gender and compared to the Swedish standard population. The 5-year SMR was .96 (CI .78-1.14). The patients’ ability to live independently in their own home had the highest impact on survival. Discussion The 1-year mortality rate among the super-elderly DRF patients was only 44% of that expected. Possibly, a DRF at this age could be a sign of a healthier and more active patient. Conclusions The DRF patients aged 80 or more had a substantially lower mortality rate 1 year after fracture compared to the age- and gender-matched standard population. Patients living independently in their own homes had the longest life expectancy. Treatment should not be limited solely because of old age, but individualised according to the patient’s ability and activity level.

Recombinant human bone morphogenetic protein-2 (rhBMP-2) has been FDA-approved for lumbar fusion, but supraphysiologic initial burst release due to suboptimal carrier and late excess bone resorption caused by osteoclast activation have limited its clinical usage. One strategy to mitigate the pro-osteoclast side effect of rhBMP-2 is to give systemic bisphosphonates, but it presents challenges with systemic side effects and low local bioavailability. The aim of this in vivo study was to analyze if posterolateral spinal fusion (PLF) could be improved by utilizing a calcium sulfate/hydroxyapatite (CaS/HA) carrier co-delivering rhBMP-2 and zoledronic acid (ZA). Six groups were allocated (CaS/HA, CaS/HA + BMP-2, CaS/HA + systemic ZA, CaS/HA + local ZA, CaS/HA + BMP-2 + systemic ZA, and CaS/HA + BMP-2 + local ZA). 10-week-old male Wistar rats, were randomly assigned to undergo L4-L5 PLF with implantation of group-dependent scaffolds. At 3 and 6 weeks, the animals were euthanized for radiography, μCT, histological staining, or biomechanical testing to evaluate spinal fusion. The results demonstrated that the CaS/HA biomaterial alone or in combination with local or systemic ZA didn't support PLF. However, the delivery of rhBMP-2 significantly promoted PLF. Combining systemic ZA with BMP-2 didn't enhance spinal fusion. Notably, the co-delivery of rhBMP-2 and ZA using the CaS/HA carrier significantly enhanced and accelerated PLF, without inhibiting systemic bone turnover, and potentially reduced the dose of rhBMP-2. Together, the treatment regimen of CaS/HA biomaterial co-delivering rhBMP-2 and ZA could potentially be a safe and cost-effective off-the-shelf bioactive bone substitute to enhance spinal fusion.

Background: The application of a bioresorbable calcium sulfate/hydroxyapatite (CaS/HA) ceramic at the interface of fenestrated screws and osteoporotic bone significantly enhances the immediate mechanical anchorage compared with non-augmented controls. However, the anchoring effectiveness of different screw augmentation techniques in spines with varying vertebral bone mineral density (BMD) remains uncertain. Purpose: The aim of this study was to investigate the immediate anchoring effectiveness of CaS/HA augmentation with two different application techniques for pedicle screw fixation in spines with varying BMD levels. Methods: Two techniques were applied for pedicle screw augmentation: injecting CaS/HA through a cannulated pre-inserted fenestrated screw (injecting technique) or delivering the material through a partly inserted screw to the predrilled bone canal before the screw was fully inserted (pre-filling technique). All thoracic and lumbar vertebrae from fresh-frozen cadaveric spine specimens of a non-osteoporotic elderly male and an osteoporotic elderly female were collected. The injecting and pre-filling techniques were applied to the left and right sides of each individual vertebra, with 1 mL and 2 mL of CaS/HA paste per unilateral thoracic and lumbar screw, respectively. X-rays and CT scans were applied to monitor the procedures and the cement distribution of the augmented screws. Finally, all vertebrae were subjected to uniaxial pull-out testing. Results: The CaS/HA was effectively distributed around the screws in all vertebrae. The maximum pull-out force was comparable between the techniques in both non-osteoporotic and osteoporotic spines, while the pull-out force was significantly higher in the non-osteoporotic spine compared with the osteoporotic spine, regardless of the augmentation technique applied. Conclusion: The application of CaS/HA augmented cannulated or fenestrated pedicle screws, regardless of the augmentation technique employed, resulted in similar initial anchorage strength in both non-osteoporotic and osteoporotic spine. The vertebral BMD will determine the absolute maximum pull-out strength of the augmented screws.

Although bone morphogenetic protein 2 (BMP-2) has been FDA-approved for spinal fusion for decades, its disadvantages of promoting osteoclast-based bone resorption and suboptimal carrier (absorbable collagen sponge) leading to premature release of the protein limit its clinical applications. Our recent study showed an excellent effect on bone regeneration when BMP-2 and zoledronic acid (ZA) were co-delivered based on a calcium sulphate/hydroxyapatite (CaS/HA) scaffold in a rat critical-size femoral defect model. Therefore, the aim of this study was to evaluate whether local application of BMP-2 and ZA released from a CaS/HA scaffold is favorable for spinal fusion. We hypothesized that CaS/HA mediated controlled co-delivery of rhBMP-2 and ZA could show an improved effect in spinal fusion over BMP-2 alone. 120, 8-week-old male Wistar rats (protocol no. 25-5131/474/38) were randomly divided into six groups in this study (CaS/HA, CaS/HA + BMP-2, CaS/HA + systemic ZA, CaS/HA + local ZA, CaS/HA + BMP-2 + systemic ZA, CaS/HA + BMP-2 + local ZA). A posterolateral spinal fusion at L4 to L5 was performed bilaterally by implanting group-dependent scaffolds. At 3 weeks and 6 weeks, 10 animals per group were euthanized for µCT, histological staining, or mechanical testing. µCT and histological results showed that the CaS/HA + BMP-2 + local ZA group significantly promoted bone regeneration than other treated groups. Biomechanical testing showed breaking force in CaS/HA + BMP + local ZA group was significantly higher than other groups at 6 weeks. In conclusion, the CaS/HA-based biomaterial functionalized with bioactive molecules rhBMP-2 and ZA enhanced bone formation and concomitant spinal fusion outcome Acknowledgements: Many thanks to Ulrike Heide, Anna-Maria Placht (assistance with surgeries) as well as Suzanne Manthey & Annett Wenke (histology).

The majority of patients with a distal radius fracture (DRF) are elderly, a group known to experience difficulties with new technology, partly due to a low level of digital literacy. At the beginning of the coronavirus disease 2019 pandemic, during the spring 2020, patients that underwent DRF surgery had regular follow-ups replaced by video calls from their surgeon and physiotherapist. Afterward, patients answered questionnaires regarding health and digital literacy and took part in semistructured interviews regarding the experience of the virtual follow-up. By systemic text condensation, 2 major categories were identified: (1) The video call-new, but surprisingly simple: All but 1 found it easier than expected, and (2) Video calls-the patient's choice: All but 1 patient preferred video calls to physical visits for follow-up. This is the first mixed methods study to assess patients' experiences of digital follow-up after DRF surgery. This study indicates that digital follow-up was highly appreciated, even among patients with low levels of digital literacy. Digital technologies must be made suitable even for patients with inadequate levels of digital literacy.

Background: Several studies of distal radial fractures have investigated final displacement and its association with clinical outcomes. There is still no consensus on the importance of radiographic outcomes, and published studies have not used the same criteria for acceptable alignment. Previous reports have involved the use of linear or dichotomized analyses. Methods: The present study included 438 patients who were managed with either reduction and cast immobilization or surgery for the treatment of distal radial fractures. Radiographic outcomes were determined on the basis of radiographs that were made 3 months after the injury. Clinical outcome was determined on the basis of the QuickDASH (an abbreviated version of the Disabilities of the Arm, Shoulder and Hand [DASH] questionnaire) score, range of motion, and grip strength at 1 year after the injury. Nonlinear relations were analyzed with cubic splines. Results: Three hundred and sixty-six patients (84%) had both radiographic and clinical follow-up. Seventy patients were lost to follow-up. The mean age was 57 years (range, 18 to 75 years), and 79% of the patients were female. Dorsal tilt was the radiographic parameter that was most strongly associated with the QuickDASH score, grip strength, and range of motion. We found nonlinear relations. Clinical outcomes were found to worsen with increasing dorsal tilt, with the cutoff value being approximately 5°. Conclusions: We found that clinical outcomes following distal radial fractures have a nonlinear relationship with dorsal tilt, with worse outcomes being associated with increasing dorsal tilt. The decline in clinical outcome starts at 5°, but there is unlikely to be a noticeable difference in capability as measured with the QuickDASH until 20° of dorsal tilt (based on the minimum clinically important difference) in a population up to 75 years old. Level of evidence: Diagnostic Level II. See Instructions for Authors for a complete description of levels of evidence.

A number of techniques have been developed to improve the immediate mechanical anchorage of implants for enhancing implant longevity. This issue becomes even more relevant in patients with osteoporosis who have fragile bone. We have previously shown that a dynamic hip screw (DHS) can be augmented with a calcium sulphate/hydroxyapatite (CaS/HA) based injectable biomaterial to increase the immediate mechanical anchorage of the DHS system to saw bones with a 400% increase in peak extraction force compared to un-augmented DHS. The results were also at par with bone cement (PMMA). The aim of this study was to investigate the effect of CaS/HA augmentation on the integration of a different fracture fixation device (gamma nail lag-screw) with osteoporotic saw bones. Osteoporotic saw bones (bone volume fraction = 15%) were instrumented with a gamma nail without augmentation (n=8) or augmented (n=8) with a CaS/HA biomaterial (Cerament BVF, Bonesupport AB, Sweden) using a newly developed augmentation method described earlier. The lag-screws from both groups were then pulled out at a displacement rate of 0.5 mm/s until failure. Peak extraction force was recorded for each specimen along with photographs of the screws post-extraction. A non-parametric t-test was used to compare the two groups. CaS/HA augmentation of the lag-screw led to a 650% increase in the peak extraction force compared with the controls (p<0.01). Photographs of the augmented samples shows failure of the saw-bones further away from the implant-bone interface indicating a protective effect of the CaS/HA material. We present a novel method to enhance the immediate mechanical anchorage of a lag-screw to osteoporotic bone and it is also envisaged that CaS/HA augmentation combined with systemic bisphosphonate treatment can lead to new bone formation and aid in the reduction of implant failures and re-operations.

Majority of osteoporosis related fractures are treated surgically using metallic fixation devices. Anchorage of fixation devices is sometimes challenging due to poor osteoporotic bone quality that can lead to failure of the fracture fixation. Using a rat osteoporosis model, we employed neutron tomography and histology to study the biological effects of implant augmentation using an isothermally setting calcium sulphate/hydroxyapatite (CaS/HA) biomaterial with synthetic HA particles as recruiting moiety for systemically administered bisphosphonates. Using an osteoporotic sawbones model, we then provide a standardized method for the delivery of the CaS/HA biomaterial at the bone-implant interface for improved mechanical anchorage of a lag-screw commonly used for hip fracture fixation. As a proof-of-concept, the method was then verified in donated femoral heads and in patients with osteoporosis undergoing hip fracture fixation. We show that placing HA particles around a stainless-steel screw in-vivo, systemically administered bisphosphonates could be targeted towards the implant, yielding significantly higher peri-implant bone formation compared to un-augmented controls. In the sawbones model, CaS/HA based lag-screw augmentation led to significant increase (up to 4 times) in peak extraction force with CaS/HA performing at par with PMMA. Micro-CT imaging of the CaS/HA augmented lag-screws in cadaver femoral heads verified that the entire length of the lag-screw threads and the surrounding bone was covered with the CaS/HA material. X-ray images from fracture fixation surgery indicated that the CaS/HA material could be applied at the lag-screw-bone interface without exerting any additional pressure or risk of venous vascular leakage. : We present a new method for augmentation of lag-screws in fragile bone. It is envisaged that this methodcould potentially reduce the risk of fracture fixation failure especially when HA seeking “bone active” drugs are used systemically.