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Bone & Joint Research
Vol. 7, Issue 2 | Pages 157 - 165
1 Feb 2018
Sun Y Kiraly AJ Sun AR Cox M Mauerhan DR Hanley EN

Objectives

The objectives of this study were: 1) to examine osteophyte formation, subchondral bone advance, and bone marrow lesions (BMLs) in osteoarthritis (OA)-prone Hartley guinea pigs; and 2) to assess the disease-modifying activity of an orally administered phosphocitrate ‘analogue’, Carolinas Molecule-01 (CM-01).

Methods

Young Hartley guinea pigs were divided into two groups. The first group (n = 12) had drinking water and the second group (n = 9) had drinking water containing CM-01. Three guinea pigs in each group were euthanized at age six, 12, and 18 months, respectively. Three guinea pigs in the first group were euthanized aged three months as baseline control. Radiological, histological, and immunochemical examinations were performed to assess cartilage degeneration, osteophyte formation, subchondral bone advance, BMLs, and the levels of matrix metalloproteinse-13 (MMP13) protein expression in the knee joints of hind limbs.


Bone & Joint Research
Vol. 6, Issue 1 | Pages 14 - 21
1 Jan 2017
Osagie-Clouard L Sanghani A Coathup M Briggs T Bostrom M Blunn G

Intermittently administered parathyroid hormone (PTH 1-34) has been shown to promote bone formation in both human and animal studies. The hormone and its analogues stimulate both bone formation and resorption, and as such at low doses are now in clinical use for the treatment of severe osteoporosis. By varying the duration of exposure, parathyroid hormone can modulate genes leading to increased bone formation within a so-called ‘anabolic window’. The osteogenic mechanisms involved are multiple, affecting the stimulation of osteoprogenitor cells, osteoblasts, osteocytes and the stem cell niche, and ultimately leading to increased osteoblast activation, reduced osteoblast apoptosis, upregulation of Wnt/β-catenin signalling, increased stem cell mobilisation, and mediation of the RANKL/OPG pathway. Ongoing investigation into their effect on bone formation through ‘coupled’ and ‘uncoupled’ mechanisms further underlines the impact of intermittent PTH on both cortical and cancellous bone. Given the principally catabolic actions of continuous PTH, this article reviews the skeletal actions of intermittent PTH 1-34 and the mechanisms underlying its effect.

Cite this article: L. Osagie-Clouard, A. Sanghani, M. Coathup, T. Briggs, M. Bostrom, G. Blunn. Parathyroid hormone 1-34 and skeletal anabolic action: The use of parathyroid hormone in bone formation. Bone Joint Res 2017;6:14–21. DOI: 10.1302/2046-3758.61.BJR-2016-0085.R1.


Bone & Joint Research
Vol. 7, Issue 1 | Pages 58 - 68
1 Jan 2018
Portal-Núñez S Ardura JA Lozano D Martínez de Toda I De la Fuente M Herrero-Beaumont G Largo R Esbrit P

Objectives

Oxidative stress plays a major role in the onset and progression of involutional osteoporosis. However, classical antioxidants fail to restore osteoblast function. Interestingly, the bone anabolism of parathyroid hormone (PTH) has been shown to be associated with its ability to counteract oxidative stress in osteoblasts. The PTH counterpart in bone, which is the PTH-related protein (PTHrP), displays osteogenic actions through both its N-terminal PTH-like region and the C-terminal domain.

Methods

We examined and compared the antioxidant capacity of PTHrP (1-37) with the C-terminal PTHrP domain comprising the 107-111 epitope (osteostatin) in both murine osteoblastic MC3T3-E1 cells and primary human osteoblastic cells.


The Bone & Joint Journal
Vol. 98-B, Issue 1 | Pages 75 - 80
1 Jan 2016
Merolla G Chin P Sasyniuk TM Paladini P Porcellini G

Aims

We evaluated clinical and radiographic outcomes of total shoulder arthroplasty (TSA) using the second-generation Trabecular Metal (TM) Glenoid component. The first generation component was withdrawn in 2005 after a series of failures were reported. Between 2009 and 2012, 40 consecutive patients with unilateral TSA using the second-generation component were enrolled in this clinical study. The mean age of the patients was 63.8 years (40 to 75) and the mean follow-up was 38 months (24 to 42).

Methods

Patients were evaluated using the Constant score (CS), the American Shoulder and Elbow Surgeons (ASES) score and routine radiographs.


Objectives

This investigation sought to advance the work published in our prior biomechanical study (Journal of Orthopaedic Research, 2016). We specifically sought to determine whether there are additional easy-to-measure parameters on plain radiographs of the proximal humerus that correlate more strongly with ultimate fracture load, and whether a parameter resembling the Dorr strength/quality characterisation of proximal femurs can be applied to humeri.

Materials and Methods

A total of 33 adult humeri were used from a previous study where we quantified bone mineral density of the proximal humerus using radiographs and dual-energy x-ray absorptiometry (DEXA), and regional mean cortical thickness and cortical index using radiographs. The bones were fractured in a simulated backwards fall with the humeral head loaded at 2 mm/second via a frustum angled at 30° from the long axis of the bone. Correlations were assessed with ultimate fracture load and these new parameters: cortical index expressed in areas (“areal cortical index”) of larger regions of the diaphysis; the canal-to-calcar ratio used analogous to its application in proximal femurs; and the recently described medial cortical ratio.


Bone & Joint Research
Vol. 2, Issue 5 | Pages 79 - 83
1 May 2013
Goffin JM Pankaj P Simpson AHRW Seil R Gerich TG

Objectives

Because of the contradictory body of evidence related to the potential benefits of helical blades in trochanteric fracture fixation, we studied the effect of bone compaction resulting from the insertion of a proximal femoral nail anti-rotation (PFNA).

Methods

We developed a subject-specific computational model of a trochanteric fracture (31-A2 in the AO classification) with lack of medial support and varied the bone density to account for variability in bone properties among hip fracture patients.


Bone & Joint Research
Vol. 3, Issue 7 | Pages 230 - 235
1 Jul 2014
van der Jagt OP van der Linden JC Waarsing JH Verhaar JAN Weinans H

Objectives

Electromagnetic fields (EMF) are widely used in musculoskeletal disorders. There are indications that EMF might also be effective in the treatment of osteoporosis. To justify clinical follow-up experiments, we examined the effects of EMF on bone micro-architectural changes in osteoporotic and healthy rats. Moreover, we tested the effects of EMF on fracture healing.

Methods

EMF (20 Gauss) was examined in rats (aged 20 weeks), which underwent an ovariectomy (OVX; n = 8) or sham-ovariectomy (sham-OVX; n = 8). As a putative positive control, all rats received bilateral fibular osteotomies to examine the effects on fracture healing. Treatment was applied to one proximal lower leg (three hours a day, five days a week); the lower leg was not treated and served as a control. Bone architectural changes of the proximal tibia and bone formation around the osteotomy were evaluated using in vivo microCT scans at start of treatment and after three and six weeks.


Bone & Joint Research
Vol. 1, Issue 2 | Pages 13 - 19
1 Feb 2012
Smith MD Baldassarri S Anez-Bustillos L Tseng A Entezari V Zurakowski D Snyder BD Nazarian A

Objectives

This study aims to assess the correlation of CT-based structural rigidity analysis with mechanically determined axial rigidity in normal and metabolically diseased rat bone.

Methods

A total of 30 rats were divided equally into normal, ovariectomized, and partially nephrectomized groups. Cortical and trabecular bone segments from each animal underwent micro-CT to assess their average and minimum axial rigidities using structural rigidity analysis. Following imaging, all specimens were subjected to uniaxial compression and assessment of mechanically-derived axial rigidity.


The Journal of Bone & Joint Surgery British Volume
Vol. 93-B, Issue 4 | Pages 558 - 565
1 Apr 2011
Xie X Wang X Zhang G Liu Z Yao D Hung L Hung VW Qin L

Corticosteroids are prescribed for the treatment of many medical conditions and their adverse effects on bone, including steroid-associated osteoporosis and osteonecrosis, are well documented. Core decompression is performed to treat osteonecrosis, but the results are variable. As steroids may affect bone turnover, this study was designed to investigate bone healing within a bone tunnel after core decompression in an experimental model of steroid-associated osteonecrosis. A total of five 28-week-old New Zealand rabbits were used to establish a model of steroid-induced osteonecrosis and another five rabbits served as controls. Two weeks after the induction of osteonecrosis, core decompression was performed by creating a bone tunnel 3 mm in diameter in both distal femora of each rabbit in both the experimental osteonecrosis and control groups. An in vivo micro-CT scanner was used to monitor healing within the bone tunnel at four, eight and 12 weeks postoperatively. At week 12, the animals were killed for histological and biomechanical analysis.

In the osteonecrosis group all measurements of bone healing and maturation were lower compared with the control group. Impaired osteogenesis and remodelling within the bone tunnel was demonstrated in the steroid-induced osteonecrosis, accompanied by inferior mechanical properties of the bone.

We have confirmed impaired bone healing in a model of bone defects in rabbits with pulsed administration of corticosteroids. This finding may be important in the development of strategies for treatment to improve the prognosis of fracture healing or the repair of bone defects in patients receiving steroid treatment.


The Bone & Joint Journal
Vol. 98-B, Issue 8 | Pages 1099 - 1105
1 Aug 2016
Weiser L Dreimann M Huber G Sellenschloh K Püschel K Morlock MM Rueger JM Lehmann W

Aims

Loosening of pedicle screws is a major complication of posterior spinal stabilisation, especially in the osteoporotic spine. Our aim was to evaluate the effect of cement augmentation compared with extended dorsal instrumentation on the stability of posterior spinal fixation.

Materials and Methods

A total of 12 osteoporotic human cadaveric spines (T11-L3) were randomised by bone mineral density into two groups and instrumented with pedicle screws: group I (SHORT) separated T12 or L2 and group II (EXTENDED) specimen consisting of T11/12 to L2/3. Screws were augmented with cement unilaterally in each vertebra. Fatigue testing was performed using a cranial-caudal sinusoidal, cyclic (1.0 Hz) load with stepwise increasing peak force.


Bone & Joint Research
Vol. 4, Issue 4 | Pages 56 - 64
1 Apr 2015
Lv YM Yu QS

Objectives

The major problem with repair of an articular cartilage injury is the extensive difference in the structure and function of regenerated, compared with normal cartilage. Our work investigates the feasibility of repairing articular osteochondral defects in the canine knee joint using a composite lamellar scaffold of nano-ß-tricalcium phosphate (ß-TCP)/collagen (col) I and II with bone marrow stromal stem cells (BMSCs) and assesses its biological compatibility.

Methods

The bone–cartilage scaffold was prepared as a laminated composite, using hydroxyapatite nanoparticles (nano-HAP)/collagen I/copolymer of polylactic acid–hydroxyacetic acid as the bony scaffold, and sodium hyaluronate/poly(lactic-co-glycolic acid) as the cartilaginous scaffold. Ten-to 12-month-old hybrid canines were randomly divided into an experimental group and a control group. BMSCs were obtained from the iliac crest of each animal, and only those of the third generation were used in experiments. An articular osteochondral defect was created in the right knee of dogs in both groups. Those in the experimental group were treated by implanting the composites consisting of the lamellar scaffold of ß-TCP/col I/col II/BMSCs. Those in the control group were left untreated.


Bone & Joint Research
Vol. 5, Issue 5 | Pages 191 - 197
1 May 2016
Kienast B Kowald B Seide K Aljudaibi M Faschingbauer M Juergens C Gille J

Objectives

The monitoring of fracture healing is a complex process. Typically, successive radiographs are performed and an emerging calcification of the fracture area is evaluated. The aim of this study was to investigate whether different bone healing patterns can be distinguished using a telemetric instrumented femoral internal plate fixator.

Materials and Methods

An electronic telemetric system was developed to assess bone healing mechanically. The system consists of a telemetry module which is applied to an internal locking plate fixator, an external reader device, a sensor for measuring externally applied load and a laptop computer with processing software. By correlation between externally applied load and load measured in the implant, the elasticity of the osteosynthesis is calculated. The elasticity decreases with ongoing consolidation of a fracture or nonunion and is an appropriate parameter for the course of bone healing. At our centre, clinical application has been performed in 56 patients suffering nonunion or fracture of the femur.


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

Objectives

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.


The Bone & Joint Journal
Vol. 98-B, Issue 7 | Pages 969 - 975
1 Jul 2016
Theivendran K Varghese M Large R Bateman M Morgan M Tambe A Espag M Cresswell T Clark DI

Aim

We present the medium-term clinical results of a reverse total shoulder arthroplasty with a trabecular metal glenoid base plate.

Patients and Methods

We reviewed 125 consecutive primary reverse total shoulder arthroplasties (RTSA) implanted in 124 patients for rotator cuff arthropathy. There were 100 women and 24 men in the study group with a mean age of 76 years (58 to 89). The mean follow-up was 32 months (24 to 60). No patient was lost to follow-up.


The Bone & Joint Journal
Vol. 98-B, Issue 7 | Pages 867 - 873
1 Jul 2016
Dalury DF

As the number of younger and more active patients treated with total knee arthroplasty (TKA) continues to increase, consideration of better fixation as a means of improving implant longevity is required. Cemented TKA remains the reference standard with the largest body of evidence and the longest follow-up to support its use. However, cementless TKA, may offer the opportunity of a more bone-sparing procedure with long lasting biological fixation to the bone. We undertook a review of the literature examining advances of cementless TKA and the reported results.

Cite this article: Bone Joint J 2016;98-B:867–73.


The Bone & Joint Journal
Vol. 98-B, Issue 4 | Pages 504 - 511
1 Apr 2016
Ajami S Blunn GW Lambert S Alexander S Foxall Smith M Coathup MJ

Aims

To assess the extent of osteointegration in two designs of shoulder resurfacing implants. Bony integration to the Copeland cylindrical central stem design and the Epoca RH conical-crown design were compared.

Patients and Methods

Implants retrieved from six patients in each group were pair-matched. Mean time to revision surgery of Copeland implants was 37 months (standard deviation (sd) 23; 14 to 72) and Epoca RH 38 months (sd 28; 12 to 84). The mean age of patients investigated was 66 years (sd 4; 59 to 71) and 58 years (sd 17; 31 to 73) in the Copeland and Epoca RH groups respectively. None of these implants were revised for loosening.


The Bone & Joint Journal
Vol. 98-B, Issue 3 | Pages 307 - 312
1 Mar 2016
Maggs JL Smeatham A Whitehouse SL Charity J Timperley AJ Gie GA

Aims

We report on the outcome of the Exeter Contemporary flanged cemented all-polyethylene acetabular component with a mean follow-up of 12 years (10 to 13.9). This study reviewed 203 hips in 194 patients. 129 hips in 122 patients are still in situ; 66 hips in 64 patients were in patients who died before ten years, and eight hips (eight patients) were revised. Clinical outcome scores were available for 108 hips (104 patients) and radiographs for 103 hips (100 patients).

Patients and Methods

A retrospective review was undertaken of a consecutive series of 203 routine primary cemented total hip arthroplasties (THA) in 194 patients.


The Bone & Joint Journal
Vol. 97-B, Issue 12 | Pages 1608 - 1614
1 Dec 2015
Tice A Kim P Dinh† L Ryu JJ Beaulé PE

The primary purpose of this study of metal-on-metal (MoM) hip resurfacing was to compare the effect of using a cementless or cemented femoral component on the subsequent bone mineral density (BMD) of the femoral neck.

This was a single-centre, prospective, double-blinded control trial which randomised 120 patients (105 men and 15 women) with a mean age of 49.4 years (21 to 68) to receive either a cemented or cementless femoral component. Follow-up was to two years. Outcome measures included total and six-point region-of-interest BMD of the femoral neck, radiological measurements of acetabular inclination, neck-shaft and stem-shaft angles, and functional outcome scores including the Harris hip score, the Western Ontario and McMaster Universities Osteoarthritis Index and the University of California at Los Angeles activity scale.

In total, 17 patients were lost to follow-up leaving 103 patients at two years. There were no revisions in the cementless group and three revisions (5%) in the cemented group (two because of hip pain and one for pseudotumour).

The total BMD was significantly higher in the cementless group at six months (p < 0.001) and one year (p = 0.01) than in the cemented group, although there was a loss of statistical significance in the difference at two years (p = 0.155).

All patient outcomes improved significantly: there were no significant differences between the two groups.

The results show better preservation of femoral neck BMD with a cementless femoral component after two years of follow-up. Further investigation is needed to establish whether this translates into improved survivorship.

Cite this article: Bone Joint J 2015;97-B:1608–14.


The Journal of Bone & Joint Surgery British Volume
Vol. 93-B, Issue 12 | Pages 1638 - 1645
1 Dec 2011
Kanemura T Ishikawa Y Matsumoto A Yoshida G Sakai Y Itoh Z Imagama S Kawakami N

We evaluated the maturation of grafted bone in cases of successful fusion after a one- or two-level posterior lumbar interbody fusion (PLIF) using interbody carbon cages. We carried out a five-year prospective longitudinal radiological evaluation of patients using plain radiographs and CT scans. One year after surgery, 117 patients with an early successful fusion were selected for inclusion in the study. Radiological evaluation of interbody bone fusion was graded on a 4-point scale. The mean grades of all radiological and CT assessments increased in the five years after surgery, and differences compared to the previous time interval were statistically significant for three or four years after surgery. Because the grafted bone continues to mature for three years after surgery, the success of a fusion should not be assessed until at least three years have elapsed. There were no significant differences in the longitudinal patterns of grafted bone maturity between iliac bone and local bone. However, iliac bone grafting may remodel faster than local bone.


The Bone & Joint Journal
Vol. 97-B, Issue 4 | Pages 473 - 477
1 Apr 2015
Bone MC Dold P Flohr M Preuss R Joyce TJ Aspden RM Holland J Deehan D

Concerns have been raised that deformation of acetabular shells may disrupt the assembly process of modular prostheses. In this study we aimed to examine the effect that the strength of bone has on the amount of deformation of the acetabular shell. The hypothesis was that stronger bone would result in greater deformation. A total of 17 acetabular shells were inserted into the acetabula of eight cadavers, and deformation was measured using an optical measuring system. Cores of bone from the femoral head were taken from each cadaver and compressed using a materials testing machine. The highest peak modulus and yield stress for each cadaver were used to represent the strength of the bone and compared with the values for the deformation and the surgeon’s subjective assessment of the hardness of the bone. The mean deformation of the shell was 129 µm (3 to 340). No correlation was found between deformation and either the maximum peak modulus (r² = 0.011, t = 0.426, p = 0.676) or the yield stress (r² = 0.024, t = 0.614, p = 0.549) of the bone. Although no correlation was found between the strength of the bone and deformation, the values for the deformation observed could be sufficient to disrupt the assembly process of modular acetabular components.

Cite this article: Bone Joint J 2015; 97-B:473–7.