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The Journal of Bone & Joint Surgery British Volume
Vol. 82-B, Issue 1 | Pages 126 - 130
1 Jan 2000
Kurth AHA Kim S Sedlmeyer I Hovy L Bauss F

Cancer-induced bone diseases are often associated with increased bone resorption and pathological fractures. In recent years, osteoprotective agents such as bisphosphonates have been studied extensively and have been shown to inhibit cancer-related bone resorption in experimental and clinical studies. The third-generation bisphosphonate, ibandronate (BM 21.0955), is a potent compound for controlling tumour osteolysis and hypercalcaemia in rats bearing Walker 256 carcinosarcoma. We have studied the effect of ibandronate given as an interventional treatment on bone strength and bone loss after the onset of tumour growth in bone. Our results suggest that it is capable of preserving bone quality in rats bearing Walker 256 carcinosarcoma cells. Since other bisphosphonates have produced comparable results in man after their success in the Walker 256 animal models our findings suggest that ibandronate may be a powerful treatment for maintaining skeletal integrity in patients with metastatic bone disease


The Journal of Bone & Joint Surgery British Volume
Vol. 73-B, Issue 5 | Pages 774 - 778
1 Sep 1991
McCarthy C Steinberg G Agren M Leahey D Wyman E Baran D

To define the natural history of bone loss around a femoral prosthesis, the bone mineral content and bone mineral density were measured for each femur in 28 patients with unilateral total hip arthroplasty, 18 age-matched controls, and seven patients with unilateral osteoarthritis. The areas measured were inside the lesser trochanter and 4.8 cm distal to it. The contralateral hip served as the control. Three years after arthroplasty there was 40% loss in average bone mineral content inside the lesser trochanter, and 28% loss in average bone mineral content 4.8 cm distally in the medial cortex. At seven to 14 years after operation, patients had lost 40% of bone proximally and 49% distally. The data suggest that this may progress in a proximal-to-distal fashion, and could account for a 50% decrease in bone mass seven to 14 years after surgery


The Journal of Bone & Joint Surgery British Volume
Vol. 91-B, Issue 7 | Pages 870 - 876
1 Jul 2009
Kosashvili Y Backstein D Safir O Lakstein D Gross AE

Pelvic discontinuity with associated bone loss is a complex challenge in acetabular revision surgery. Reconstruction using ilio-ischial cages combined with trabecular metal acetabular components and morsellised bone (the component-cage technique) is a relatively new method of treatment. We reviewed a consecutive series of 26 cases of acetabular revision reconstructions in 24 patients with pelvic discontinuity who had been treated by the component-cage technique. The mean follow-up was 44.6 months (24 to 68). Failure was defined as migration of a component of > 5 mm. In 23 hips (88.5%) there was no clinical or radiological evidence of loosening at the last follow-up. The mean Harris hip score improved significantly from 46.6 points (29.5 to 68.5) to 76.6 points (55.5 to 92.0) at two years (p < 0.001). In three hips (11.5%) the construct had migrated at one year after operation. The complications included two dislocations, one infection and one partial palsy of the peroneal nerve. Our findings indicate that treatment of pelvic discontinuity using the component-cage construct is a reliable option


The Journal of Bone & Joint Surgery British Volume
Vol. 77-B, Issue 3 | Pages 429 - 434
1 May 1995
Saleh M Rees A

We report the results in the first 16 patients treated in Sheffield using bifocal techniques for diaphyseal bone loss and deformity secondary to trauma. Eight patients had bone-transport and eight had compression-distraction methods. At a mean follow-up of 24 months all 16 had excellent or good results with union of the fracture, correction of deformity and normal or near normal leg length. There were no major complications. Mean treatment times were 16 months for bone transport and 9.8 months for compression-distraction. Bone transport was more complicated requiring an average of 2.2 additional operations compared with only one for compression-distraction. Femoral cases had shorter treatment indices than tibial cases but had less favourable outcomes


The Journal of Bone & Joint Surgery British Volume
Vol. 87-B, Issue 2 | Pages 142 - 150
1 Feb 2005
Keating JF Simpson AHRW Robinson CM


The Journal of Bone & Joint Surgery British Volume
Vol. 93-B, Issue 7 | Pages 932 - 936
1 Jul 2011
Mahmoud M Koptan W

Ununited fractures of the scaphoid with extensive bone resorption are usually treated by bone grafting and internal fixation, using either an open or a minimally invasive technique. We studied the feasibility of percutaneous fixation without bone grafting in a consecutive series of 27 patients with established nonunion of an undisplaced fracture of the scaphoid and extensive local resorption of bone. They were treated by a single surgeon with rigid fixation alone, using a headless cannulated screw inserted through a volar percutaneous technique. Clinical examination, standard radiographs and CT confirmed that the fracture had united in all patients at a mean of 11.6 weeks (8 to 16), and that their functional scores had improved.

We concluded that extensive resorption at the fracture site is not an absolute indication for bone grafting, and that percutaneous fixation alone will eventually produce healing of ununited undisplaced fractures of the scaphoid regardless of the size of the gap.


The Journal of Bone & Joint Surgery British Volume
Vol. 73-B, Issue 2 | Pages 316 - 321
1 Mar 1991
Dagher F Roukoz S

We report our experience of the use of the Ilizarov technique to treat nine patients with severe compound tibial fractures. The mean defect in bone was 6.3 cm, and four cases were infected. All nine patients had satisfactory union and function without the use of bone grafts or antibiotics. The Ilizarov technique was very satisfactory; there were no major complications.


The Journal of Bone & Joint Surgery British Volume
Vol. 62-B, Issue 1 | Pages 104 - 110
1 Feb 1980
Jaworski Z Liskova-Kiar M Uhthoff H


The Journal of Bone & Joint Surgery British Volume
Vol. 83-B, Issue 3 | Pages 461 - 461
1 Apr 2001
FURLONG R


Bone & Joint Open
Vol. 4, Issue 7 | Pages 478 - 489
1 Jul 2023
Tennent D Antonios T Arnander M Ejindu V Papadakos N Rastogi A Pearse Y

Aims. Glenoid bone loss is a significant problem in the management of shoulder instability. The threshold at which the bone loss is considered “critical” requiring bony reconstruction has steadily dropped and is now approximately 15%. This necessitates accurate measurement in order that the correct operation is performed. CT scanning is the most commonly used modality and there are a number of techniques described to measure the bone loss however few have been validated. The aim of this study was to assess the accuracy of the most commonly used techniques for measuring glenoid bone loss on CT. Methods. Anatomically accurate models with known glenoid diameter and degree of bone loss were used to determine the mathematical and statistical accuracy of six of the most commonly described techniques (relative diameter, linear ipsilateral circle of best fit (COBF), linear contralateral COBF, Pico, Sugaya, and circle line methods). The models were prepared at 13.8%, 17.6%, and 22.9% bone loss. Sequential CT scans were taken and randomized. Blinded reviewers made repeated measurements using the different techniques with a threshold for theoretical bone grafting set at 15%. Results. At 13.8%, only the Pico technique measured under the threshold. At 17.6% and 22.9% bone loss all techniques measured above the threshold. The Pico technique was 97.1% accurate, but had a high false-negative rate and poor sensitivity underestimating the need for grafting. The Sugaya technique had 100% specificity but 25% of the measurements were incorrectly above the threshold. A contralateral COBF underestimates the area by 16% and the diameter by 5 to 7%. Conclusion. No one method stands out as being truly accurate and clinicians need to be aware of the limitations of their chosen technique. They are not interchangeable, and caution must be used when reading the literature as comparisons are not reliable. Cite this article: Bone Jt Open 2023;4(7):478–489


The Bone & Joint Journal
Vol. 105-B, Issue 5 | Pages 496 - 503
1 May 2023
Mills ES Talehakimi A Urness M Wang JC Piple AS Chung BC Tezuka T Heckmann ND

Aims. It has been well documented in the arthroplasty literature that lumbar degenerative disc disease (DDD) contributes to abnormal spinopelvic motion. However, the relationship between the severity or pattern of hip osteoarthritis (OA) as measured on an anteroposterior (AP) pelvic view and spinopelvic biomechanics has not been well investigated. Therefore, the aim of the study is to examine the association between the severity and pattern of hip OA and spinopelvic motion. Methods. A retrospective chart review was conducted to identify patients undergoing primary total hip arthroplasty (THA). Plain AP pelvic radiographs were reviewed to document the morphological characteristic of osteoarthritic hips. Lateral spine-pelvis-hip sitting and standing plain radiographs were used to measure sacral slope (SS) and pelvic femoral angle (PFA) in each position. Lumbar disc spaces were measured to determine the presence of DDD. The difference between sitting and standing SS and PFA were calculated to quantify spinopelvic motion (ΔSS) and hip motion (ΔPFA), respectively. Univariate analysis and Pearson correlation were used to identify morphological hip characteristics associated with changes in spinopelvic motion. Results. In total, 139 patients were included. Increased spinopelvic motion was observed in patients with loss of femoral head contour, cam deformity, and acetabular bone loss (all p < 0.05). Loss of hip motion was observed in patients with loss of femoral head contour, cam deformity, and acetabular bone loss (all p < 0.001). A decreased joint space was associated with a decreased ΔPFA (p = 0.040). The presence of disc space narrowing, disc space narrowing > two levels, and disc narrowing involving the L5–S1 segment were associated with decreased spinopelvic motion (all p < 0.05). Conclusion. Preoperative hip OA as assessed on an AP pelvic radiograph predicts spinopelvic motion. These data suggest that specific hip osteoarthritic morphological characteristics listed above alter spinopelvic motion to a greater extent than others. Cite this article: Bone Joint J 2023;105-B(5):496–503


The Bone & Joint Journal
Vol. 104-B, Issue 10 | Pages 1110 - 1117
12 Oct 2022
Wessling M Gebert C Hakenes T Dudda M Hardes J Frieler S Jeys LM Hanusrichter Y

Aims. The aim of this study was to examine the implant accuracy of custom-made partial pelvis replacements (PPRs) in revision total hip arthroplasty (rTHA). Custom-made implants offer an option to achieve a reconstruction in cases with severe acetabular bone loss. By analyzing implant deviation in CT and radiograph imaging and correlating early clinical complications, we aimed to optimize the usage of custom-made implants. Methods. A consecutive series of 45 (2014 to 2019) PPRs for Paprosky III defects at rTHA were analyzed comparing the preoperative planning CT scans used to manufacture the implants with postoperative CT scans and radiographs. The anteversion (AV), inclination (IC), deviation from the preoperatively planned implant position, and deviation of the centre of rotation (COR) were explored. Early postoperative complications were recorded, and factors for malpositioning were sought. The mean follow-up was 30 months (SD 19; 6 to 74), with four patients lost to follow-up. Results. Mean CT defined discrepancy (Δ) between planned and achieved AV and IC was 4.5° (SD 3°; 0° to 12°) and 4° (SD 3.5°; 1° to 12°), respectively. Malpositioning (Δ > 10°) occurred in five hips (10.6%). Native COR reconstruction was planned in 42 cases (93%), and the mean 3D deviation vector was 15.5 mm (SD 8.5; 4 to 35). There was no significant influence in malpositioning found for femoral stem retention, surgical approach, or fixation method. Conclusion. At short-term follow-up, we found that PPR offers a viable solution for rTHA in cases with massive acetabular bone loss, as highly accurate positioning can be accomplished with meticulous planning, achieving anatomical reconstruction. Accuracy of achieved placement contributed to reduced complications with no injury to vital structures by screw fixation. Cite this article: Bone Joint J 2022;104-B(10):1110–1117


Bone & Joint Research
Vol. 11, Issue 7 | Pages 413 - 425
1 Jul 2022
Tu C Lai S Huang Z Cai G Zhao K Gao J Wu Z Zhong Z

Aims. Gap junction intercellular communication (GJIC) in osteocytes is impaired by oxidative stress, which is associated with age-related bone loss. Ageing is accompanied by the accumulation of advanced oxidation protein products (AOPPs). However, it is still unknown whether AOPP accumulation is involved in the impairment of osteocytes’ GJIC. This study aims to investigate the effect of AOPP accumulation on osteocytes’ GJIC in aged male mice and its mechanism. Methods. Changes in AOPP levels, expression of connexin43 (Cx43), osteocyte network, and bone mass were detected in 18-month-old and three-month-old male mice. Cx43 expression, GJIC function, mitochondria membrane potential, reactive oxygen species (ROS) levels, and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activation were detected in murine osteocyte-like cells (MLOY4 cells) treated with AOPPs. The Cx43 expression, osteocyte network, bone mass, and mechanical properties were detected in three-month-old mice treated with AOPPs for 12 weeks. Results. The AOPP levels were increased in aged mice and correlated with degeneration of osteocyte network, loss of bone mass, and decreased Cx43 expression. AOPP intervention induced NADPH oxidase activation and mitochondrial dysfunction, triggered ROS generation, reduced Cx43 expression, and ultimately impaired osteocytes’ GJIC, which were ameliorated by NADPH oxidase inhibitor apocynin, mitochondria-targeted superoxide dismutase mimetic (mito-TEMPO), and ROS scavenger N-acetyl cysteine. Chronic AOPP loading accelerated the degradation of osteocyte networks and decreased Cx43 expression, resulting in deterioration of bone mass and mechanical properties in vivo. Conclusion. Our study suggests that AOPP accumulation contributes to age-related impairment of GJIC in osteocytes of male mice, which may be part of the pathogenic mechanism responsible for bone loss during ageing. Cite this article: Bone Joint Res 2022;11(7):413–425


The Bone & Joint Journal
Vol. 104-B, Issue 9 | Pages 1039 - 1046
1 Sep 2022
Özdemir E Kuijpers MFL Visser J Schreurs BW Rijnen WHC

Aims. The aim of this study is to report the long-term outcomes of instrumented femoral revisions with impaction allograft bone grafting (IBG) using the X-change femoral revision system at 30 years after introduction of the technique. Methods. We updated the outcomes of our previous study, based on 208 consecutive revisions using IBG and the X-change femoral revision system in combination with a cemented polished stem, performed in our tertiary care institute between 1991 and 2007. Kaplan-Meier survival analyses were used to determine the survival rate of the revisions with endpoint revision for any reason and aseptic loosening. Secondary outcomes were radiological loosening and patient-reported outcome measures. Results. Mean age at revision total hip arthroplasty (THA) was 64.9 years (30 to 86). The most prevalent diagnosis for the femoral revision was aseptic loosening. At review in May 2021, 81 patients (85 hips) were still alive and 118 patients (120 hips; 58%) had died. Three patients (3 hips; 1%) were lost to follow-up at 11, 15, and 16 years after surgery, respectively. Data of all deceased and lost patients were included until final follow-up. The mean follow-up was 13.4 years (0 to 28). During the follow-up, 22 re-revisions were performed. The most common reason for re-revision was infection (n = 12; 54%). The survival with endpoint re-revision for any reason was 86% (95% confidence interval (CI) 79 to 91) at 20 years and 74% (95% CI 43 to 89) at 25 years after surgery. The survival for endpoint re-revision for aseptic loosening was 97% (95% CI 91 to 99) after both 20 and 25 years. Conclusion. We conclude that femoral IBG is a valuable technique that can reconstitute femoral bone loss in the long term. After 25 years of follow-up, few re-revisions for aseptic loosening were required. Also, the overall revision rate is very acceptable at a long follow-up. This technique is especially attractive for younger patients facing femoral revisions with extensive bone loss. Cite this article: Bone Joint J 2022;104-B(9):1039–1046


The Bone & Joint Journal
Vol. 105-B, Issue 8 | Pages 888 - 894
1 Aug 2023
Murray J Jeyapalan R Davies M Sheehan C Petrie M Harrison T

Aims. Total femoral arthroplasty (TFA) is a rare procedure used in cases of significant femoral bone loss, commonly from cancer, infection, and trauma. Low patient numbers have resulted in limited published work on long-term outcomes, and even less regarding TFA undertaken for non-oncological indications. The aim of this study was to evaluate the long-term clinical outcomes of all TFAs in our unit. Methods. Data were collected retrospectively from a large tertiary referral revision arthroplasty unit’s database. Inclusion criteria included all patients who underwent TFA in our unit. Preoperative demographics, operative factors, and short- and long-term outcomes were collected for analysis. Outcome was defined using the Musculoskeletal Infection Society (MSIS) outcome reporting tool. Results. Overall, 38 TFAs were identified. The mean age was 73 years (42 to 80). All patients underwent TFA for non-oncological indications, most commonly as a consequence of infection (53%) and periprosthetic fracture (26%). The mean follow-up time was ten years (0 to 26); 63% of TFAs were considered a success based upon the MSIS outcome reporting tool. The mean time between TFA and death was 8.5 years (0.2 to 19.2), with two patients dying within one year of surgery. Within the cohort, 66% suffered at least one complication, dislocation being most common (37%); 55% of the total cohort required at least one subsequent operation. In total, 70% of TFAs undertaken for infection were considered infection-free at time of final follow-up. The percentage of mobile patients improved from 52% to 65% between pre- and postoperation, with all patients being able to at least transfer from bed to chair at time of final review. Conclusion. This study is the largest in the UK assessing the use of TFA in patients with bone loss secondary to non-oncological conditions. It demonstrates that TFA has a significant complication profile, however it is favourable in terms of mortality and rehabilitation when compared to amputation and disarticulation. Cite this article: Bone Joint J 2023;105-B(8):888–894


Bone & Joint Research
Vol. 11, Issue 5 | Pages 304 - 316
17 May 2022
Kim MH Choi LY Chung JY Kim E Yang WM

Aims. The association of auraptene (AUR), a 7-geranyloxycoumarin, on osteoporosis and its potential pathway was predicted by network pharmacology and confirmed in experimental osteoporotic mice. Methods. The network of AUR was constructed and a potential pathway predicted by Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) terms enrichment. Female ovariectomized (OVX) Institute of Cancer Research mice were intraperitoneally injected with 0.01, 0.1, and 1 mM AUR for four weeks. The bone mineral density (BMD) level was measured by dual-energy X-ray absorptiometry. The bone microstructure was determined by histomorphological changes in the femora. In addition, biochemical analysis of the serum and assessment of the messenger RNA (mRNA) levels of osteoclastic markers were performed. Results. In total, 65.93% of the genes of the AUR network matched with osteoporosis-related genes. Osteoclast differentiation was predicted to be a potential pathway of AUR in osteoporosis. Based on the network pharmacology, the BMD and bone mineral content levels were significantly (p < 0.05) increased in the whole body, femur, tibia, and lumbar spine by AUR. AUR normalized the bone microstructure and the serum alkaline phosphatase (ALP), bone-specific alkaline phosphatase (bALP), osteocalcin, and calcium in comparison with the OVX group. In addition, AUR treatment reduced TRAP-positive osteoclasts and receptor activator of nuclear factor kappa-B ligand (RANKL). +. nuclear factor of activated T cells 1 (NFATc1). +. expression in the femoral body. Moreover, the expressions of initiators for osteoclastic resorption and bone matrix degradation were significantly (p < 0.05) regulated by AUR in the lumbar spine of the osteoporotic mice. Conclusion. AUR ameliorated bone loss by downregulating the RANKL/NFATc1 pathway, resulting in improvement of osteoporosis. In conclusion, AUR might be an ameliorative cure that alleviates bone loss in osteoporosis via inhibition of osteoclastic activity. Cite this article: Bone Joint Res 2022;11(5):304–316


Bone & Joint Open
Vol. 3, Issue 2 | Pages 114 - 122
1 Feb 2022
Green GL Arnander M Pearse E Tennent D

Aims. Recurrent dislocation is both a cause and consequence of glenoid bone loss, and the extent of the bony defect is an indicator guiding operative intervention. Literature suggests that loss greater than 25% requires glenoid reconstruction. Measuring bone loss is controversial; studies use different methods to determine this, with no clear evidence of reproducibility. A systematic review was performed to identify existing CT-based methods of quantifying glenoid bone loss and establish their reliability and reproducibility. Methods. A Preferred Reporting Items for Systematic reviews and Meta-Analyses-compliant systematic review of conventional and grey literature was performed. Results. A total of 25 studies were initially eligible. Following screening, nine papers were included for review. Main themes identified compared 2D and 3D imaging, as well as linear- compared with area-based techniques. Heterogenous data were acquired, and therefore no meta-analysis was performed. Conclusion. No ideal CT-based method is demonstrated in the current literature, however evidence suggests that surface area methods are more reproducible and lead to fewer over-estimations of bone loss, provided the views used are standardized. A prospective imaging trial is required to provide a more definitive answer to this research question. Cite this article: Bone Jt Open 2022;3(2):114–122


Bone & Joint Open
Vol. 3, Issue 3 | Pages 173 - 181
1 Mar 2022
Sobol KR Fram BR Strony JT Brown SA

Aims. Endoprosthetic reconstruction with a distal femoral arthroplasty (DFA) can be used to treat distal femoral bone loss from oncological and non-oncological causes. This study reports the short-term implant survivorship, complications, and risk factors for patients who underwent DFA for non-neoplastic indications. Methods. We performed a retrospective review of 75 patients from a single institution who underwent DFA for non-neoplastic indications, including aseptic loosening or mechanical failure of a previous prosthesis (n = 25), periprosthetic joint infection (PJI) (n = 23), and native or periprosthetic distal femur fracture or nonunion (n = 27). Patients with less than 24 months’ follow-up were excluded. We collected patient demographic data, complications, and reoperations. Reoperation for implant failure was used to calculate implant survivorship. Results. Overall one- and five-year implant survivorship was 87% and 76%, respectively. By indication for DFA, mechanical failure had one- and five-year implant survivorship of 92% and 68%, PJI of 91% and 72%, and distal femur fracture/nonunion of 78% and 70% (p = 0.618). A total of 37 patients (49%) experienced complications and 27 patients (36%) required one or more reoperation. PJI (n = 16, 21%), aseptic loosening (n = 9, 12%), and wound complications (n = 8, 11%) were the most common complications. Component revision (n = 10, 13.3%) and single-stage exchange for PJI (n = 9, 12.0 %) were the most common reoperations. Only younger age was significantly associated with increased complications (mean 67 years (SD 9.1)) with complication vs 71 years (SD 9.9) without complication; p = 0.048). Conclusion. DFA is a viable option for distal femoral bone loss from a range of non-oncological causes, demonstrating acceptable short-term survivorship but with high overall complication rates. Cite this article: Bone Jt Open 2022;3(3):173–181


Bone & Joint Research
Vol. 9, Issue 3 | Pages 139 - 145
1 Mar 2020
Guebeli A Platz EA Paller CJ McGlynn KA Rohrmann S

Aims. To examine the relationship of sex steroid hormones with osteopenia in a nationally representative sample of men in the USA. Methods. Data on bone mineral density (BMD), serum sex hormones, dairy consumption, smoking status, and body composition were available for 806 adult male participants of the cross-sectional National Health and Nutrition Examination Survey (NHANES, 1999-2004). We estimated associations between quartiles of total and estimated free oestradiol (E2) and testosterone (T) and osteopenia (defined as 1 to 2.5 SD below the mean BMD for healthy 20- to 29-year-old men) by applying sampling weights and using multivariate-adjusted logistic regression. We then estimated the association between serum hormone concentrations and osteopenia by percentage of body fat, frequency of dairy intake, cigarette smoking status, age, and race/ethnicity. Results. Men in the lowest quartile of total E2 concentrations (< 21.52 pg/ml) had greater odds of osteopenia compared with men in the highest quartile (odds ratio (OR) 2.29, 95% confidence interval (CI) 1.11 to 4.73; p-trend = 0.030). Total and free T were not associated with osteopenia. Low total E2 concentrations were associated with greater odds of osteopenia among non-daily dairy consumers (p-trend = 0.046), current or former smokers (p-trend = 0.032), and younger men (p-trend = 0.031). No differences were observed by race/ethnicity and obesity. Conclusion. In this nationally representative study of the USA, men with lower total E2 were more likely to have osteopenia, which was particularly evident among younger men, men with less-than-daily dairy consumption, and current or former smokers. Cite this article:Bone Joint Res. 2020;9(3):139–145


Bone & Joint 360
Vol. 12, Issue 3 | Pages 27 - 30
1 Jun 2023

The June 2023 Shoulder & Elbow Roundup. 360. looks at: Proximal humerus fractures: what does the literature say now?; Infection risk of steroid injections and subsequent reverse shoulder arthroplasty; Surgical versus non-surgical management of humeral shaft fractures; Core outcome set needed for elbow arthroplasty; Minimally invasive approaches to locating radial nerve in the posterior humeral approach; Predictors of bone loss in anterior glenohumeral instability; Does the addition of motor control or strengthening exercises improve rotator cuff-related shoulder pain?; Terminology and diagnostic criteria used in patients with subacromial pain syndrome