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Bone & Joint Research
Vol. 11, Issue 11 | Pages 787 - 802
1 Nov 2022
Sebastian S Tandberg F Liu Y Raina DB Tägil M Collin M Lidgren L


There is a lack of biomaterial-based carriers for the local delivery of rifampicin (RIF), one of the cornerstone second defence antibiotics for bone infections. RIF is also known for causing rapid development of antibiotic resistance when given as monotherapy. This in vitro study evaluated a clinically used biphasic calcium sulphate/hydroxyapatite (CaS/HA) biomaterial as a carrier for dual delivery of RIF with vancomycin (VAN) or gentamicin (GEN).


The CaS/HA composites containing RIF/GEN/VAN, either alone or in combination, were first prepared and their injectability, setting time, and antibiotic elution profiles were assessed. Using a continuous disk diffusion assay, the antibacterial behaviour of the material was tested on both planktonic and biofilm-embedded forms of standard and clinical strains of Staphylococcus aureus for 28 days. Development of bacterial resistance to RIF was determined by exposing the biofilm-embedded bacteria continuously to released fractions of antibiotics from CaS/HA-antibiotic composites.

Bone & Joint Research
Vol. 9, Issue 10 | Pages 709 - 718
1 Oct 2020
Raina DB Liu Y Jacobson OLP Tanner KE Tägil M Lidgren L

Bone is a dynamic tissue with a quarter of the trabecular and a fifth of the cortical bone being replaced continuously each year in a complex process that continues throughout an individual’s lifetime. Bone has an important role in homeostasis of minerals with non-stoichiometric hydroxyapatite bone mineral forming the inorganic phase of bone. Due to its crystal structure and chemistry, hydroxyapatite (HA) and related apatites have a remarkable ability to bind molecules. This review article describes the accretion of trace elements in bone mineral giving a historical perspective. Implanted HA particles of synthetic origin have proved to be an efficient recruiting moiety for systemically circulating drugs which can locally biomodulate the material and lead to a therapeutic effect. Bone mineral and apatite however also act as a waste dump for trace elements and drugs, which significantly affects the environment and human health.

Cite this article: Bone Joint Res 2020;9(10):709–718.

Bone & Joint Research
Vol. 8, Issue 2 | Pages 49 - 54
1 Feb 2019
Stravinskas M Nilsson M Vitkauskiene A Tarasevicius S Lidgren L


The aim of this study was to analyze drain fluid, blood, and urine simultaneously to follow the long-term release of vancomycin from a biphasic ceramic carrier in major hip surgery. Our hypothesis was that there would be high local vancomycin concentrations during the first week with safe low systemic trough levels and a complete antibiotic release during the first month.


Nine patients (six female, three male; mean age 75.3 years (sd 12.3; 44 to 84)) with trochanteric hip fractures had internal fixations. An injectable ceramic bone substitute, with hydroxyapatite in a calcium sulphate matrix, containing 66 mg of vancomycin per millilitre, was inserted to augment the fixation. The vancomycin elution was followed by simultaneously collecting drain fluid, blood, and urine.

Bone & Joint Research
Vol. 7, Issue 10 | Pages 548 - 560
1 Oct 2018
Qayoom I Raina DB Širka A Tarasevičius Š Tägil M Kumar A Lidgren L

During the last decades, several research groups have used bisphosphonates for local application to counteract secondary bone resorption after bone grafting, to improve implant fixation or to control bone resorption caused by bone morphogenetic proteins (BMPs). We focused on zoledronate (a bisphosphonate) due to its greater antiresorptive potential over other bisphosphonates. Recently, it has become obvious that the carrier is of importance to modulate the concentration and elution profile of the zoledronic acid locally. Incorporating one fifth of the recommended systemic dose of zoledronate with different apatite matrices and types of bone defects has been shown to enhance bone regeneration significantly in vivo. We expect the local delivery of zoledronate to overcome the limitations and side effects associated with systemic usage; however, we need to know more about the bioavailability and the biological effects. The local use of BMP-2 and zoledronate as a combination has a proven additional effect on bone regeneration. This review focuses primarily on the local use of zoledronate alone, or in combination with bone anabolic factors, in various preclinical models mimicking different orthopaedic conditions.

Cite this article: I. Qayoom, D. B. Raina, A. Širka, Š. Tarasevičius, M. Tägil, A. Kumar, L. Lidgren. Anabolic and antiresorptive actions of locally delivered bisphosphonates for bone repair: A review. Bone Joint Res 2018;7:548–560. DOI: 10.1302/2046-3758.710.BJR-2018-0015.R2.

Bone & Joint Research
Vol. 5, Issue 10 | Pages 500 - 511
1 Oct 2016
Raina DB Gupta A Petersen MM Hettwer W McNally M Tägil M Zheng M Kumar A Lidgren L


We have observed clinical cases where bone is formed in the overlaying muscle covering surgically created bone defects treated with a hydroxyapatite/calcium sulphate biomaterial. Our objective was to investigate the osteoinductive potential of the biomaterial and to determine if growth factors secreted from local bone cells induce osteoblastic differentiation of muscle cells.

Materials and Methods

We seeded mouse skeletal muscle cells C2C12 on the hydroxyapatite/calcium sulphate biomaterial and the phenotype of the cells was analysed. To mimic surgical conditions with leakage of extra cellular matrix (ECM) proteins and growth factors, we cultured rat bone cells ROS 17/2.8 in a bioreactor and harvested the secreted proteins. The secretome was added to rat muscle cells L6. The phenotype of the muscle cells after treatment with the media was assessed using immunostaining and light microscopy.

Bone & Joint Research
Vol. 5, Issue 9 | Pages 427 - 435
1 Sep 2016
Stravinskas M Horstmann P Ferguson J Hettwer W Nilsson M Tarasevicius S Petersen MM McNally MA Lidgren L


Deep bone and joint infections (DBJI) are directly intertwined with health, demographic change towards an elderly population, and wellbeing.

The elderly human population is more prone to acquire infections, and the consequences such as pain, reduced quality of life, morbidity, absence from work and premature retirement due to disability place significant burdens on already strained healthcare systems and societal budgets.

DBJIs are less responsive to systemic antibiotics because of poor vascular perfusion in necrotic bone, large bone defects and persistent biofilm-based infection. Emerging bacterial resistance poses a major threat and new innovative treatment modalities are urgently needed to curb its current trajectory.

Materials and Methods

We present a new biphasic ceramic bone substitute consisting of hydroxyapatite and calcium sulphate for local antibiotic delivery in combination with bone regeneration. Gentamicin release was measured in four setups: 1) in vitro elution in Ringer’s solution; 2) local elution in patients treated for trochanteric hip fractures or uncemented hip revisions; 3) local elution in patients treated with a bone tumour resection; and 4) local elution in patients treated surgically for chronic corticomedullary osteomyelitis.

The Bone & Joint Journal
Vol. 96-B, Issue 9 | Pages 1222 - 1226
1 Sep 2014
W-Dahl A Sundberg M Lidgren L Ranstam J Robertsson O

We identified a group of patients from the Swedish Arthroplasty Register who reported no relief of pain or worse pain one year after a total knee replacement (TKR). A total of two different patient-reported pain scores were used during this process. We then evaluated how the instruments used to measure pain affected the number of patients who reported no relief of pain or worse pain, and the relative effect of potential risk factors.

Between 2008 and 2010, 2883 TKRs were performed for osteoarthritis in two Swedish arthroplasty units. After applying exclusion criteria, 2123 primary TKRs (2123 patients) were included in the study. The Knee injury and Osteoarthritis Outcome Score (KOOS) and a Visual Analogue Scale (VAS) for knee pain were used to assess patients pre-operatively and one year post-operatively.

Only 50 of the 220 patients (23%) who reported no pain relief on either the KOOS pain subscale or the VAS for knee pain did so with both of these instruments. Patients who reported no pain relief on either measure tended to have less pain pre-operatively but a higher degree of anxiety. Charnley category C was a predictor for not gaining pain relief as measured on a VAS for knee pain.

The number of patients who are not relieved of pain after a TKR differs considerably depending on the instrument used to measure pain.

Cite this article: Bone Joint J 2014;96-B:1222–6.

Bone & Joint Research
Vol. 3, Issue 7 | Pages 217 - 222
1 Jul 2014
Robertsson O Ranstam J Sundberg M W-Dahl A Lidgren L

We are entering a new era with governmental bodies taking an increasingly guiding role, gaining control of registries, demanding direct access with release of open public information for quality comparisons between hospitals. This review is written by physicians and scientists who have worked with the Swedish Knee Arthroplasty Register (SKAR) periodically since it began. It reviews the history of the register and describes the methods used and lessons learned.

Cite this article: Bone Joint Res 2014;3:217–22.

Bone & Joint Research
Vol. 3, Issue 3 | Pages 48 - 50
1 Mar 2014
Lidgren L Gomez-Barrena E N. Duda G Puhl W Carr A

The Journal of Bone & Joint Surgery British Volume
Vol. 90-B, Issue 12 | Pages 1558 - 1561
1 Dec 2008
Ranstam J Wagner P Robertsson O Lidgren L

Public disclosure of outcome-orientated ranking of hospitals is becoming increasingly popular and is routinely used by Swedish health-care authorities. Whereas uncertainty about an outcome is usually presented with 95% confidence intervals, ranking’s based on the same outcome are typically presented without any concern for bias or statistical precision. In order to study the effect of incomplete registration of re-operation on hospital ranking we performed a simulation study using published data on the two-year risk of re-operation after total hip replacement.

This showed that whereas minor registration incompleteness has little effect on the observed risk of revision, it can lead to major errors in the ranking of hospitals. We doubt whether a level of data entry sufficient to generate a correct ranking can be achieved, and recommend that when ranking hospitals, the uncertainties about data quality and random events should be clearly described as an integral part of the results.

The Journal of Bone & Joint Surgery British Volume
Vol. 90-B, Issue 1 | Pages 7 - 10
1 Jan 2008
Lidgren L

This paper considers the increased risk of the development of lymphoma in patients with chronic inflammatory disease who undergo metal-on-metal arthroplasty.

The Journal of Bone & Joint Surgery British Volume
Vol. 89-B, Issue 5 | Pages 599 - 603
1 May 2007
Robertsson O Stefánsdòttir A Lidgren L Ranstam J

Patients with osteoarthritis undergoing knee replacement have been reported to have an overall reduced mortality compared with that of the general population. This has been attributed to the selection of healthier patients for surgery. However, previous studies have had a maximum follow-up time of ten years. We have used information from the Swedish Knee Arthroplasty Register to study the mortality of a large national series of patients with total knee replacement for up to 28 years after surgery and compared their mortality with that of the normal population. In addition, for a subgroup of patients operated on between 1980 and 2002 we analysed their registered causes of death to determine if they differed from those expected.

We found a reduced overall mortality during the first 12 post-operative years after which it increased and became significantly higher than that of the general population. Age-specific analysis indicated an inverse correlation between age and mortality, where the younger the patients were, the higher their mortality. The shift at 12 years was caused by a relative over-representation of younger patients with a longer follow-up. Analysis of specific causes of death showed a higher mortality for cardiovascular, gastrointestinal and urogenital diseases. The observation that early onset of osteoarthritis of the knee which has been treated by total knee replacement is linked to an increased mortality should be a reason for increased general awareness of health problems in these patients.

The Journal of Bone & Joint Surgery British Volume
Vol. 86-B, Issue 7 | Pages 958 - 961
1 Sep 2004
Dreinhöfer KE Féron J Herrera A Hube R Johnell O Lidgren L Miles K Panarella L Simpson H Wallace WA

The Journal of Bone & Joint Surgery British Volume
Vol. 86-B, Issue 1 | Pages 120 - 125
1 Jan 2004
Nilsson M Wang J Wielanek L Tanner KE Lidgren L

An injectable material consisting of calcium sulphate mixed with hydroxyapatite was investigated as a possible alternative to autograft in the restoration of bone defects. The material was studied both in vitro in simulated body fluid (SBF) and in vivo when implanted in rat muscles and into the proximal tibiae of rabbits. Variation in the strength and weight of the material during ageing in SBF was measured. Tissue response, material resorption and bone ingrowth were studied in the animal models.

A good tissue response was observed in both the rat muscles and rabbit tibiae without inflammatory reactions or the presence of fibrous tissue. Ageing in SBF showed that during the first week carbonated hydroxyapatite precipitated on the surfaces of the material and this may enhance bone ingrowth.

The Journal of Bone & Joint Surgery British Volume
Vol. 84-B, Issue 6 | Pages 908 - 914
1 Aug 2002
Yuan X Ryd L Tanner KE Lidgren L

We present a new approach for the accurate reconstruction of three-dimensional skeletal positions using roentgen single-plane photogrammetric analysis (RSPA). This technique uses a minimum of three markers embedded in each segment which allow continuous, real-time, internal skeletal movement to be measured from single-plane images, provided that the precise distance between the markers is known.

A simulation study indicated that the error propagation in this approach is influenced by focus position, object position, the number of control points, the accuracy of the previous measurement of the distance between markers and the accuracy of image measurement. For reconstruction of normal movement of the knee with an input measurement error of sd = 0.02 mm, the rotational and translational differences between reconstructed and original movement were less than 0.27° and 0.9 mm, respectively.

Our results showed that the accuracy of RSPA is sufficient for the analysis of most movement of joints. This approach can be applied in combination with force measurements for dynamic studies of the musculoskeletal system.

The Journal of Bone & Joint Surgery British Volume
Vol. 83-B, Issue 3 | Pages 339 -
1 Apr 2001
Dunbar MJ Robertsson O Ryd L Lidgren L

The Swedish Knee Arthroplasty Registry (SKAR) has recorded knee arthroplasties prospectively in Sweden since 1975. The only outcome measure available to date has been revision status. While questionnaires on health outcome may function as more comprehensive endpoints, it is unclear which are the most appropriate. We tested various outcome questionnaires in order to determine which is the best for patients who have had knee arthroplasty as applied in a cross-sectional, discriminative, postal survey.

Four general health questionnaires (NHP, SF-12, SF-36 and SIP) and three disease/site-specific questionnaires (Lequesne, Oxford-12, and WOMAC) were tested on 3600 patients randomly selected from the SKAR. Differences were found between questionnaires in response rate, time required for completion, the need for assistance, the efficiency of completion, the validity of the content and the reliability. The mean overall ranks for each questionnaire were generated. The SF-12 ranked the best for the general health, and the Oxford-12 for the disease/site-specific questionnaires. These two questionnaires could therefore be recommended as the most appropriate for use with a large knee arthroplasty database in a cross-sectional population.

The Journal of Bone & Joint Surgery British Volume
Vol. 83-B, Issue 1 | Pages 45 - 49
1 Jan 2001
Robertsson O Knutson K Lewold S Lidgren L

A total of 10474 unicompartmental knee arthroplasties was performed for medial osteoarthritis in Sweden between 1986 and 1995. We sought to establish whether the number of operations performed in an orthopaedic unit affected the incidence of revision. Three different implants were analysed: one with a high revision rate, known to have unfavourable mechanical and design properties; a prosthesis which is technically demanding with a known increased rate of revision; and the most commonly used unicompartmental device.

Most of the units performed relatively few unicompartmental knee arthroplasties per year and there was an association between the mean number carried out and the risk of later revision. The effect of the mean number of operations per year on the risk of revision varied. The technically demanding implant was most affected, that most commonly used less so, and the outcome of the unfavourable design was not influenced by the number of operations performed.

For unicompartmental arthroplasty, the long-term results are related to the number performed by the unit, probably expressing the standards of management in selecting the patients and performing the operation.

The Journal of Bone & Joint Surgery British Volume
Vol. 78-B, Issue 6 | Pages 861 - 862
1 Nov 1996
Fulford P Lidgren L

The Journal of Bone & Joint Surgery British Volume
Vol. 77-B, Issue 6 | Pages 862 - 864
1 Nov 1995
Franzen H Toksvig-Larsen S Lidgren L Onnerfalt R

We report the preliminary findings of the use of roentgen stereophotogrammetric analysis to evaluate the early migration of five femoral components after revision for mechanical loosening using impacted cancellous allograft and cement. All hips were examined at one week, four to six months and one year after surgery. All the components subsided by 0.4 to 4.9 mm during the first year. In four hips the prosthetic head was displaced 1.1 to 6.9 mm posteriorly. Fixation of the femoral components was less secure than after primary arthroplasty but the incidence and magnitude of early migration were similar to those after revision with cement alone.

The Journal of Bone & Joint Surgery British Volume
Vol. 68-B, Issue 5 | Pages 795 - 803
1 Nov 1986
Knutson K Lindstrand A Lidgren L

A prospective nation-wide study of knee arthroplasty has been under way in Sweden since October 1975. By the end of 1983, 4505 arthroplasties for osteoarthritis and 3495 for rheumatoid arthritis had been recorded and reviewed one, three and six years after the operation. Using actuarial methods, the probability of the prosthesis remaining in situ after six years was calculated. In osteoarthritis this probability ranged from 65% for hinged prostheses to 90% for medial compartment prostheses. Two-and three-compartment prostheses produced intermediate results with 87% survival. In rheumatoid arthritis the probability varied from 72% for medial compartment prostheses to 90% for two- and three-compartment prostheses. The main reason for failure was loosening of the components, the second most common was infection. The probability of revision for infection by six years was 2% in osteoarthritis and 3% in rheumatoid arthritis. Most revisions were to a three-compartment prosthesis. Knee fusion at primary revision was required in 2% of the cases at six years.