Aim: According to Swedish and Danish law interventions must be based on evidence, and evidence related to rest orthoses in contracture management is limited and inconclusive, making justification of using rest orthoses difficult. The aim is to understand the clinicians’ perceptions of the benefit of rest orthoses when managing wrist and hand contractures, to shape a basis for clinical evidence.Method: A qualitative interview study was made and a total of 13 participants with 2 to 40 years of experience was included. Interviews were transcribed and translated into English. A thematic analysis was undertaken by two researchers. Three themes and seven subthemes were identified and discussed. Results: There was congruence among the participants that rest orthoses can maintain RoM when used but they need to be used at least 6 to 8 hours every day. Combination of botox and rest orthoses has a good effect in many patients with spasticity for maintaining RoM and some function. Many patients gain a benefit in maintaining hygiene, a reduction in pain and easier for patients getting dressed. Conclusion: The interviewed clinicians perceived that rest orthoses can impact pain and prevent contracture formation however evidence was inconclusive, but it merits further research. / Syfte: Enligt svensk och dansk lag måste insatser baseras på evidens, och evidensen relaterad till viloortoser i kontrakturhantering är begränsad och motsägelsefull, vilket gör det svårt att motivera användningen av viloortoser. Syftet är att förstå klinikernas uppfattningar om fördelarna med viloortoser vid hantering av hand- och handledskontrakturer, för att skapa en grund för klinisk evidens. Metod: En kvalitativ intervjustudie genomfördes och totalt 13 deltagare med 2 till 40 års erfarenhet inkluderades. Intervjuerna transkriberades och översattes till engelska varpå en tematisk analys utfördes av två forskare. Tre teman och sju underteman identifierades och diskuterades. Resultat: Det fanns samstämmighet bland deltagarna att viloortoser kan bibehålla rörelseomfång när de används, men de måste användas minst 6 till 8 timmar varje dag. Kombinationen av botox och viloortoser har god effekt hos många patienter med spasticitet för att bibehålla rörelseomfång och viss funktion. Många patienter får fördelar i form av bibehållen hygien, minskad smärta och det blir lättare för patienter att klä på sig.Slutsats: De intervjuade klinikerna ansåg att viloortoser kan påverka smärta och förhindra kontrakturbildning, men evidensen är ofullständiga och kräver ytterligare forskning.

Bakgrund: Stressfrakturer utgör 10–20 % av alla idrottsskador och 10% av alla ortopediska skador, av samtliga stressfrakturer lokaliseras upp till 49% i tibia. För att ställa diagnosen korrekt behövs en magnetröntgen, benskanning eller datortomografi. Syfte: Syftet med denna litteraturöversikt var att kartlägga tillförlitligheten hos kliniska tester för att diagnostisera stressfrakturer i tibia. Metod: En litteraturöversikt med narrativ design tillämpades, sökningen utfördes i Pubmed, Sportdiscus, Pedro & Cinahl, inklusionskriteriet var att studierna skulle ha minst ett radiologiskt referenstest. Kvalitén av studierna bedömdes med Quadas mätinstrument. Resultat: 17 artiklar inkluderades i översikten, totalt var det åtta olika tester som undersöktes. Tre studier valde att kombinera flera tester vid diagnostiseringen av stressfrakturer i tibia. Inget ensamt test eller testkombination hade både en hög specificitet och sensitivitet. Flertalet studier fick en hög sensitivitet vid palpation, även kombinerade tester gav en hög sensitivitet. Konklusion: Enbart kliniska tester verkar inte kunna diagnostisera stressfrakturer i tibia då testerna har en låg specificitet. Eventuellt kan en kombination av tester utesluta stressfrakturer i tibia och därav minska behovet av röntgenundersökning. Flertalet studier hade metodologiska brister därför behövs mer forskning för att kunna dra säkrare slutsatser gällande testernas tillförlitlighet. / Background: Stress fractures make up 10-20% of all sports injuries and 10% of all orthopedic injuries, of all stress fractures up to 49% are in the tibia. To make the diagnosis correctly, an MRI, bone scan or computed tomography is needed.  Aim: The purpose of this study was to investigate the reliability of different clinical tests in the diagnosis of stress fractures of the tibia.  Method: A literature review with narrative design was applied, the search was performed in Pubmed, Sportdiscus Pedro and Cinahl, the inclusion criteria was that the studies had at least one radiological reference test. The quality of the studies was assessed with Quadas measuring instrument.  Results: 17 articles were included in the review, a total of eight different test examined. Three studies chose to combine multiple tests in the diagnosis of tibial stress fractures. No single test or test combination had both a high specificity and sensitivity. Most studies obtained a high sensitivity on palpation, even combined test gave a high sensitivity. Conclusion: Clinical tests alone do not seem to be able to diagnose stress fractures in the tibia as the tests have a low specificity. Possibly, a combination of tests can rule out stress fractures in the tibia and therefore reduce the need for radiological examination. Most studies had methodological flaws therefore, more research is needed to be able to draw safer conclusions regarding the ability of the tests.

The development of a vasculature within a tissue-engineered construct is one of the largest hurdles to successful bone regeneration. This thesis investigates methods to increase vasculature of such transplanted constructs, based on in vivo transplant studies and in vitro analysis of cell behaviors. A syngeneic mouse model in immunocompetent mice was developed and analyzed for both osteogenesis and hematopoiesis. This study demonstrates that syngeneic bone marrow stromal cells (BMSCs) are not rejected by the host, provided the strain of mice is sufficiently inbred. Additionally, an effective protocol was developed for the isolation of endothelial cells (ECs) from the bone marrow of mice. Two different sets of materials for this study were analyzed, both collagen based, and the GelfoamTM scaffold was found to possess advantages over synthesized collagen or collagen/hydroxyapatite composites, although only for mouse and not human bone transplantation. In order to gain rapid and integrated vasculature formation within the transplant, attempts were made to increase both (de novo) vasculogenesis and angiogenesis (ingrowth) from the surrounding tissue. For the former, transplant studies were combined with in vitro osteogenic calcification studies. Direct co-culture of the BMSCs and ECs increased osteogenic calcification and was monitored by using both alizarin red S quantification and quantitative polymerase chain reaction. Angiogenesis (as assessed by cell migration) was studied by various motility and chemotaxis assays in vitro, as well as through use of a directed in vivo angiogenesis assay. Growth factors, particularly TGF-β1 and BMP-4, were found to increase cell movement in these systems. In conclusion, we show that although much work remains to be done in order to increase the vasculature in bone transplants, systematic combination of in vivo and in vitro assays can elucidate the nature behind this crucial process in this context.

Cam-type Femoro-Acetabular Impingement (FAI) is a common cause of hip osteoarthritis (OA). In this condition a bony abnormality at the head-neck junction of the femoral head, called the “cam”, abuts against the acetabulum causing labral damage and articular cartilage delamination, which in turn may lead to progressive degeneration and OA. The understanding of the damage mechanism is currently at a conceptual level. The aim of the thesis is to develop a more detailed understanding of the underlying mechanism so as to improve methods of detection and treatment of cam-type FAI and thus to help prevent hip OA. A geometric-kinematic model combining hip joint motion and hip joint geometry was cre- ated to determine what motions, activities or cam shapes give rise to cam-type impingement, which was quantified by the proximity of the acetabular and femoral bony surfaces. Five normal subjects and five symptomatic cam-type FAI patients were modelled. The FAI patients experienced early impingement during the impingement test but did not have impingement during common functional activities. The early impingement was possibly due to the larger coverage and protrusion of their cams and the smaller overall proximity in their hip joints. A 2D finite element (FE) model was created to simulate cam-type FAI. As idealised 2D rectangular and circular geometries did not reproduce the damage seen clinically, subject- specific geometry, loads, and motions were introduced. Under some circumstances, as the cam entered the hip joint, large shear strains developed near the cartilage-bone interface of the acetabulum which would result in cartilage delamination. In vitro experiments were undertaken to validate the FE model and verify the damage mech- anism by which cam-type FAI leads to cartilage delamination. Porcine cartilage-bone samples were loaded under conditions similar to those generated by a cam (shear and compression). A validation FE model was created that used the same material and contact representations and analysis framework as the impingement FE model but mimicked the experimental setup. The cartilage shear strains assessed with a video-based method were similar to predicted FE results. In vitro damage experiments demonstrated that delamination can be caused by repetitive shear and compressive loading that lead to large shear strains near the cartilage-bone interface. The impingement FE model was used to further explore the effect of cam anatomy. In hips with low clearance, cams with large protrusions (75% hip joint clearance) would not enter into the hip joint, but caused high shear strains in the labrum, which would result in labral tears. A narrower cam caused damage to the labral tip, whereas a wider cam caused damage to the labral-bone junction. In contrast, cams with small protrusion (25% hip joint clearance) were able to enter the joint and caused damage at the articular cartilage-bone interface, which would result in cartilage delamination. The wider the cam, the further into the hip joint the damage was initiated. The FE model was used to explore the effect of different labral anatomy and of reshaping surgery. A labrum connected to the articular cartilage resulted in shear strains of up to five times greater in the articular cartilage and labrum compared to an unconnected labrum and was more likely to cause articular cartilage delamination. For a cam that damages the articular cartilage, surgical removal of the cam reduced shear strains. For a cam that abuts the labrum, surgical removal of the cam eliminated labral abutment and increased the range of motion of the hip, but resulted in greater shear strains in the articular cartilage. It is not known whether these shear strains are normal or could possibly be damaging. Also, reshaping the head to be spherical resulted in slightly reduced shear strains in the articular cartilage compared to the current surgical practice of cutting deeper into the femoral head when removing the cam. This study has, for the first time, using a validated FE model demonstrated the mechanism by which a cam can cause articular cartilage delamination and labral tearing. Further analysis using the geometric and FE model should help identify cam deformities that would be likely to cause OA and the best way to treat them surgically so as to prevent OA.

This thesis is based on studies of the ten-year community-based intervention programme entitled, the Vadstena Osteoporosis Prevention Project (VOPP). The specific aims of the research were to describe the effects of physical activity and training programmes on bone mass and balance performance in adults, to determine whether a fall risk prevention programme could motivate personal actions among the elderly, to ascertain whether the intervention programme could reduce the incidence of forearm and hip fractures. Two studies addressed training programmes for middle-aged and old people. First, VOPP participants who were aged 40–70 years and had low forearm bone mineral density (BMD) values were invited to take part in a one-year weight-bearing training study. Thirty of those individuals were included in the investigation. Additional bone mass measurements were performed at the hip and the lumbar spine, and balance and aerobic capacity were also tested. The training programme was performed twice a week (I). In the second study, healthy persons aged 70–75 years were invited to participate in a balance-training study. Fifteen persons joined an exercise group, and another fifteen were controls. The training programme comprised specific balance exercises and was carried out twice a week for nine weeks (II). The association between forearm BMD values and several lifestyle factors was explored in random samples of the population aged 20–72 years (n=880) in a cross-sectional study (III). Another study explored the association between calcaneal stiffness, forearm BMD, and lifestyle factors amongst participants aged 20–79 years (n=956) at the final registration of the VOPP (V). Effects of the VOPP interventions directed at environmental risk factors for falls and the promotion of physical activity were examined in people aged ≥ 65 years (IV). The incidence of forearm and hip fractures was studied amongst middle-aged and elderly individuals in the intervention and the control communities during the study period 1987–2001 (VI). The exercise group (n=15) in the weight-bearing training study showed increases in BMD at the greater trochanter (p<0.01), one-leg stance balance with the eyes closed and coordination tests (p<0.05), and aerobic capacity (p<0.05). No significant difference was found when the groups were compared concerning changes in the different tests during the intervention period (I). In the balance-training study, the exercise group showed post-training improvement in the following tests: standing on the right leg with eyes closed (p<0.01), standing on the right leg (p<0.01) and on the left leg (p<0.05) while turning the head, and walking 30 metres (p<0.01). There were significant differences between the groups in these tests when changes were compared at the post-intervention test (II). Age (p<0.0001) and body mass index (p≤.0001) were associated with forearm BMD in both sexes. Reported moderate physical activity levels in men were positively associated with forearm BMD (p<0.05) (III). In both sexes, reported moderate (p<0.05) and high (women p<0.05 and men p<0.001) physical activity levels were positively associated with calcaneal stiffness. The correlation coefficient between forearm BMD and calcaneal stiffness was 0.58 in women and 0.34 in men (V). Persons aged ≥ 65 years at the follow-up in 1994 reported more use of shoe/cane spikes and moderate physical activity levels compared to controls (IV). There was no change in the general incidence of forearm and hip fractures between the communities for the study period. However, there was a tendency towards decreasing incidence of forearm and trochanteric hip fracture in both sexes during the late intervention period in the intervention community (VI). A community-based intervention programme aimed at reducing the incidence of osteoporotic fractures must be regarded as a long-term project and should preferably be monitored over an extended post-intervention period. / On the day of the public defence the statuses of articles IV and V were Submitted and VI was Manuscript

Degenerative disorders of the rotator cuff tendons account for nearly 75% of all shoulder pain, causing considerable pain and morbidity. Given the strong correlation between age and tendinopathy, and unprecedented population aging, these disorders will become increasingly prevalent. Improved understanding of tendon degeneration will guide the development of future diagnostic and treatments, and is therefore urgently needed. However, the aetiology and pathology of rotator cuff tendinopathy remain unclear. The complicated mechanical environment of the rotator cuff is hypothesised to influence the susceptibility of the tendons to degeneration and tearing. Studies have reported biological adaptations in torn cuff tendons indicative of increased compressive loading within the tendon. The material adaptations of healthy and degenerative cuff tendons are largely unreported but will provide further insight into the role of the mechanical environment in rotator cuff aetiology and pathology. This thesis examined the material adaptations of healthy and diseased tendons to explore the role of mechanical loading in rotator cuff pathology. The material adaptations of healthy animal tendons, and healthy and delaminated human cadaveric rotator cuff tendons, in response to different loading environments were characterised. The effects of age, tears, steroid injection and subacromial decompression surgery on the structural adaptations of human cuff tendons were also studied, as was the effect of tendon cell proliferation on the mechanical properties and degradation behaviour of collagen scaffolds. Loading environment significantly affected the structural adaptations of healthy tendons. Regions exposed to compressive and shear strains exhibited thinner fibres, shorter crimp lengths and thinner, less aligned fibrils compared with regions exposed to tensile strains alone. In healthy rotator cuff tendons, the inhomogeneous loading environment produced topographically inhomogeneous structural adaptations. The tendons of a delaminated rotator cuff exhibited less topographical variation in properties and thinner, less aligned fibrils compared with healthy cuff tendons. Torn cuff tendons exhibited thinner fibrils and shorter crimp lengths compared with control samples. These adaptations were identifiable early in the disease progression, and neither steroid injection nor subacromial decompression surgery significantly influenced these adaptations at seven weeks post‐treatment. Significant correlations between decreasing dimensions and increasing tear size were found when age was included as a confounding factor, reflecting the importance of age and tear size in determining the material properties of tendons. Tendon cell proliferation influenced the mechanical properties and degradation behaviour of the collagen scaffolds, emphasising the integral role of cells in the functional adaptation of biological materials. These results demonstrate the effect of mechanical environment on the material adaptations of tendons. They also indicate the importance of the complicated mechanical environment experienced by the rotator cuff tendons in predisposing the tendons to degeneration and tearing. The observed material adaptations of degenerative and torn tendons suggest that rotator cuff pathology is associated with increased levels of compressive and/or shear strains within the tendon. These changes begin early in the disease progression and neither steroid injection nor sub‐acromial decompression surgery are capable of reversing the changes in the timeframe investigated. These findings highlight the urgent clinical need for pre‐rupture diagnostic techniques for the detection of early pathological changes in the rotator cuff. They also emphasize the requirement for new intervention strategies that restore the healthy mechanical environment and reverse early pathological adaptations in order to prevent catastrophic failure of the tendons.

Chondroplasia, the development of cartilage-like characteristics in tendinous tissue, is a form of degeneration found in tendons including those of the rotator cuff. The molecular mechanism of its development is currently unknown. An examination of the features of the torn rotator cuff and the cartilage literature led to the identification of several potential drivers of chondroplasia including cell shape change/actin cytoskeleton and hypoxia. Lovastatin caused actin cytoskeleton disruption and promoted cartilage matrix deposition in the ATDC5 model. It was the most effective member of a panel of cytoskeletal inhibitors, increasing expression of the chondrocytic markers Sox5 and Sox9 and decreasing expression of COL1A1 and COL3A1 in primary human tenocytes. Its effects were dose dependent, reversible by mevalonate addition and long term treatment induced de novo expression of collagen II. Short term hypoxia upregulated VEGF-A and chondrocytic marker gene DEC1 expression but not other chondrocyte markers. Combination treatment with hypoxia did not enhance the effects of lovastatin. These data suggest that modulation of pathways that regulate the actin cytoskeleton and cell shape may alter tenocyte phenotype.

Tendon injury prevalence in both athletic and occupational settings is on the increase. Tendon healing properties are poor, despite the complex biological process triggered by the injury, which makes those injuries incapacitating for months. A significant proportion of these injuries remain difficult to treat, and many patients suffer from decreased performance and longstanding sequelae. While mechanical stabilization has been a hallmark of tendon surgical management, orthobiologics are playing an increasing role in optimizing tendon healing. Platelet rich Plasma (PRP), which is a volume of autologous plasma having platelet concentration above baseline, has been suggested as an accelerant orthobiological agent rich in supraphysiological concentration of growth factors. However, strong evidence of its mode of action and of its clinical efficacy is lacking. The purpose of this thesis is to identify the role of PRP in tendon regeneration in in-vitro and clinical studies. Firstly, the viability and biological components of clinically-prepared PRP were studied in novel experiments. This PRP was used in linked in-vitro studies to investigate the possible mechanism of PRP effect on the injured Achilles tendon cells and tissues. Cell count, viability, proliferation and DNA content were studied. The clinical application of PRP in Achilles tendon rupture was assessed in a randomised clinical pilot study using a combination of PROMs, objective outcome measures and a novel imaging modality called functional ultrasound elastography. This non-invasive technique was developed in a healthy-tendons volunteer study and its feasibility in ruptured tendons was assessed in the pilot trial. In another unique study, the immunohistochemical response to PRP was assessed in biopsies taken under US guidance at week 6 and compared to control to explore the possible mechanism of PRP effects. The findings confirmed that PRP is a viable activatable autologous blood product rich in growth factors. The results also confirmed that leukocytes and platelets are present in very high concentration with reversal of lymphocyte neutrophil ratio. Elastography volunteer study confirmed that FUSE is feasible using clinically applicable ultrasound scan. The improved algorithm allowed visualisation of localised strain within the studied tissues. The clinical application of PRP in Achilles tendon rupture revealed positive efficacy signal that PRP led to faster healing, improved pain and earlier restoration of function. However, the findings of this pilot trial were indicative and not confirmative. Immunohistochemistry analysis showed that PRP enhanced the maturity of the healing tendon tissues by promoting better collagen I deposition, improved Collagen III/Collagen I ratio, reduced cellularity, better vascular structure and higher GAGs content when compared with control. The finding may explain the clinical improvement observed in these patients at week 6 onwards. Linked in-vitro studies showed that autologous PRP with its cellular components, which include platelets, leukocytes and erythrocytes, has the ability to stimulate tendon cell migration to the injury site and stimulate proliferation in the injured human tendon. Additionally, it may maintain tissue viability in the hypoxic environment that follows tendon injury. Promoting migration and proliferation of cells and maintain tissue viability may play an important role to accelerate tendon healing. The findings of this project has informed the design of a phase II large multi-centre randomised controlled trial and helped secure major funding from the National Institute of Health Research (NIHR). This trial will set the scene for PRP use in tendon treatment.

O aparelho propulsor mandibular é utilizado na odontologia para modular o crescimento da cartilagem condilar, por meio de forças geradas pela alteração postural da musculatura. Neste estudo foi avaliado o papel de integrinas ligantes de fibronectina (FN) na transdução das forças mecânicas geradas pelo aparelho, em ratos. Por meio de imuno-histoquímica e PCR em tempo real verificou-se que, in vivo, o uso do aparelho modulou a expressão das subunidades <font face=\"symbol\">1, <font face=\"symbol\">5, e <font face=\"symbol\">v de integrinas, FN e PCNA, um marcador de proliferação celular. In vitro, forças distensivas cíclicas aplicadas sobre células da cartilagem condilar aumentaram a expressão de mRNA para FN, fatores de crescimento IGF-I e IGF-II e PCNA. A adição do peptídeo GRGDSP, que bloqueia a ligação de algumas integrinas à FN, inibiu todos os efeitos, exceto na expressão de IGF-II. Esses resultados sugerem que integrinas ligantes de FN desempenham papel importante na mecano-transdução neste sistema e contribuem para o entendimento das bases moleculares envolvidas na ortopedia funcional dos maxilares / The mandibular propulsor appliance is widely used in dentistry to modulate the growth of the condylar cartilage, through forces generated by postural changes in the orofacial musculature. The aim of this study was to evaluate the role of fibronectin (FN)-binding integrins in the transduction of mechanical forces generated by the appliance in rats. By immunohistochemistry and real time PCR it was observed that, in vivo, the appliance´s use modulated the expression of the integrin subunits <font face=\"symbol\">1, <font face=\"symbol>\"5, and <font face=\"symbol\">v, FN and PCNA, a cell proliferation marker. In vitro, the application of cyclic distension forces on condylar cartilage cells increased the expression of FN, IGF-I, IGF-II and PCNA mRNA. Addition of the peptide GRGDSP, which blocks the binding of some integrins to FN, inhibited all the effects except the increase in IGF-II mRNA. These results suggest that FN-binding integrins play an important role in mechanotransduction in this system, contributing to the understanding of the molecular basis involved in maxillary functional orthopedic therapy.

<p> </p><p>In orthopaedic practice, fractures are usually stabilised with metal screws or rods. This is done in order to keep the fracture parts in place during the rather slow healing process. The healing time can potentially be reduced by local- or systemic treatment with different bone promoting drugs. In later years, lithium, otherwise used to treat bipolar disease, has shown promise to be such a drug.</p><p> </p><p>The aim of this master thesis was to find a way to coat metal bone screws with lithium and to characterise the coating. The coating was to be designed in such a way that it could release lithium to the surrounding bone tissue.</p><p> </p><p>Lithium chloride was incorporated into a titanate sol-gel and attached to silicon wafers and stainless steel screws by dip coating. Wafers were used for initial <em>in vitro</em> studies of how lithium changed coating characteristics. This was studied using ellipsometry, AFM and SEM. Lithium is most probably physisorbed and not incorporated into the network building up the sol-gel. Coating structure is changed as more lithium is incorporated. For large amounts of lithium, the nanoparticles normally formed when curing the sol-gel are inhibited. One effect of this is reduced bioactivity, seen as a reduced ability for calcium phosphate crystals to nucleate on the coating when immersed in simulated body fluid.</p><p>Lithium release was investigated using AAS. Lithium is released from the coating, showing a burst effect. By changing the number of coating layers used, the release profile can be partly altered. The coating was also applied to screws, showing good attachment, and the lithium release profile was similar to the one seen from wafers.</p><p>Finally, a screw model was used in rats to assess the effect of local lithium treatment from screws and systemic lithium treatment on fracture healing. In the model, a screw was inserted in tibia, mimicking a fracture. When the bone around the screw was healed, a pullout test was performed, giving information about the strength of the bone surrounding the screw. No significant difference could be found for either local- or systemic lithium treatment compared to control. However, when evaluating the strength of intact bone in a similar way, a positive effect of systemic lithium treatment could be seen. Therefore, it is still likely that lithium has a positive effect on bone and further studies are needed to fully evaluate its role in fracture healing.</p><p> </p> / <p><p>Vid behandling av benbrott stabiliseras vanligtvis frakturen internt med metallskruvar och</p><p>metallstavar. Detta görs för att hålla brottbitarna på plats under den relativt långsamma läkprocessen. Det är möjligt att minska tiden för frakturläkning genom att lokalt eller systemiskt behandla med olika läkemedel som främjar bentillväxt. På senare år har det presenterats bevis för att litium, som annars används som psykofarmaka, fungerar som ett sådant läkemedel.</p><p> </p><p>Syftet med detta examensarbete var att hitta en metod för att fästa litium på benimplantat. Litium skulle fästas på ett sådant sätt att frisläppning till omgivande vävnad blev möjlig.</p><p> </p><p>Litiumklorid inkorporerades i en titanat-solgel och lager av detta lades på kiselytor och rostfria skruvar genom s.k. ”dip-coating”. Kiselytorna användes för initiala <em>in vitro</em>-studier av hur litium ändrade beläggningens egenskaper. Litium sitter antagligen fast på ytan av det tredimensionella nätverk som utgör solgelen, istället för att sitta inbundet i nätverket. Lagerstrukturen ändras ju mer litium som inkorporeras och vid stora mängder skapas inte de nanopartiklar som vanligtvis finns i en solgel-baserad beläggning. En följd av detta är reducerad bioaktivitet för beläggningen, dvs. en minskad förmåga för kalciumfosfatkristaller att bildas på ytan. Litium frisläpps från beläggningen, dock sker denna frisläppning snabbt. Genom att belägga ytan med flera lager av solgel kan frisläppningskinetiken delvis ändras. Solgelen kunde också med god vidhäftning appliceras på skruvar och frisläppningskinetiken från en skruv är liknande den från en kiselyta.</p>Slutligen användes en skruvmodell i råtta för att undersöka vilken effekt lokal respektive systemisk litiumbehandling har på frakturläkning. I modellen efterliknas ett benbrott genom att en skruv sätts in i skenbenet.  När benvävnaden runt skruven har läkt görs ett utdragstest på skruven vilket ger information om benets styrka. Ingen signifikant skillnad i skruvens utdragskraft kunde ses mellan de båda försöksgrupperna och kontrollgruppen. Däremot hade gruppen som fick systemisk litiumbehandling fått starkare ben totalt, vilket indikerar att litium har effekt på <em>intakt</em> ben. På grund av dessa resultat finns det fortfarande skäl att tro att litium har en positiv påverkan på ben, varför dess effekt på frakturläkning bör undersökas ytterligare. </p>