Aims. Insufficient treatment response in rheumatoid arthritis (RA) patients requires novel treatment strategies to halt disease progression. The potential benefit of combination of cytokine-inhibitors in RA is still unclear and needs further investigation. To explore the impact of combined deficiency of two major cytokines, namely interleukin (IL)-1 and IL-6, in this study double deficient mice for IL-1αβ and IL-6 were investigated in different tumour necrosis factor (TNF)-driven inflammatory bone disorders, namely peripheral arthritis and sacroiliitis, as well as systemic bone loss. Methods. Disease course, histopathological features of arthritis, and micro-CT (µCT) bone analysis of local and systemic bone loss were assessed in 15-week-old IL1-/-IL6-/-hTNFtg in comparison to IL1-/-hTNFtg, IL6-/-hTNFtg, and hTNFtg mice. µCT bone analysis of single deficient and wild-type mice was also performed. Results. Combined deficiency of IL-1/IL-6 markedly ameliorated TNF-mediated arthritis and bilateral sacroiliitis, but without additive benefits compared to single IL-1 deficiency. This finding confirms the important role of IL-1 and the marginal role of IL-6 in TNF-driven pathways of local joint damage, but questions the efficacy of potential combinatorial therapies of IL-1 and IL-6 in treatment of RA. In contrast, combined deficiency of IL-1/IL-6 led to an additive protective effect on TNF-driven systemic bone loss compared to single IL-1 and IL-6 deficiency. This finding clearly indicates a common contribution of both IL-1 and IL-6 in TNF-driven systemic bone loss, and points to a discrepancy of cytokine dependency in local and systemic TNF-driven mechanisms of inflammatory arthritis. Conclusion. Combinatorial treatments in RA might provide different benefits to inflammatory local arthritis and systemic comorbidities. Cite this article: Bone Joint Res 2022;11(7):484–493

Aims. The purpose of this study was to determine whether there were long-term differences in outcomes of reverse shoulder arthroplasty (RSA) undertaken for acute proximal humeral fracture versus rotator cuff deficiency with a minimum follow-up of five years. Methods. This was a prospective cohort study comparing 67 patients with acute complex proximal humeral fracture and 64 patients with irreparable rotator cuff deficiency who underwent primary RSA. In the fracture group, there were 52 (77.6%) females and 15 (22.4%) males, with a mean age of 73.5 years (51 to 85), while in the arthropathy group, there were 43 (67.1%) females and 21 (32.9%) males, with a mean age of 70.6 years (50 to 84). Patients were assessed by the Constant score, University of California Los Angeles shoulder score (UCLA), short version of the Disability of the Arm Shoulder and Hand score (QuickDASH), and visual analogue scales (VAS) for pain and satisfaction. Radiological evaluation was also performed. Results. Mean follow-up was 8.4 years (5 to 11). There were no significant differences in mean absolute (p = 0.125) or adjusted (p = 0.569) Constant, UCLA (p = 0.088), QuickDASH (p = 0.135), VAS-pain (p = 0.062), or range of movement at the final follow-up. However, patient satisfaction was significantly lower in the fracture group (p = 0.002). The complication rate was 1.5% (one patient) versus 9.3% (six patients), and the revision rate was 1.5% (one patient) versus 7.8% (five patients) in the fracture and arthropathy groups, respectively. The ten-year arthroplasty survival was not significantly different (p = 0.221). Conclusion. RSA may be used not only for patients with irreparable rotator cuff deficiencies, but also for those with acute complex proximal humeral fractures. We found that RSA provided similar functional outcomes and a low revision rate for both indications at long-term. However, satisfaction is lower in patients with an acute fracture. Cite this article: Bone Joint J 2020;102-B(11):1555–1559

Deficiency of the abductor mechanism is a well-recognised cause of pain and limping after total hip replacement (THR). This can be found incidentally at the time of surgery, or it may arise as a result of damage to the superior gluteal nerve intra-operatively, or after surgery owing to mechanical failure of the abductor muscle repair or its detachment from the greater trochanter. The incidence of abductor failure has been reported as high as 20% in some studies. The management of this condition remains a dilemma for the treating surgeon. We review the current state of knowledge concerning post-THR abductor deficiency, including the aetiology, diagnosis and management, and the outcomes of surgery for this condition. Cite this article: Bone Joint J 2013;95-B:343–7

Reverse total shoulder replacement (RTSR) depends on adequate deltoid function for a successful outcome. However, the anterior deltoid and/or axillary nerve may be damaged due to prior procedures or injury. The purpose of this study was to determine the compensatory muscle forces required for scapular plane elevation following RTSR when the anterior deltoid is deficient. The soft tissues were removed from six cadaver shoulders, except for tendon attachments. After implantation of the RTSR, the shoulders were mounted on a custom-made shoulder simulator to determine the mean force in each muscle required to achieve 30° and 60° of scapular plane elevation. Two conditions were tested: 1) Control with an absent supraspinatus and infraspinatus; and 2) Control with anterior deltoid deficiency. Anterior deltoid deficiency resulted in a mean increase of 195% in subscapularis force at 30° when compared with the control (p = 0.02). At 60°, the subscapularis force increased a mean of 82% (p < 0.001) and the middle deltoid force increased a mean of 26% (p = 0.04). Scapular plane elevation may still be possible following an RTSR in the setting of anterior deltoid deficiency. When the anterior deltoid is deficient, there is a compensatory increase in the force required by the subscapularis and middle deltoid. Attempts to preserve the subscapularis, if present, might maximise post-operative function

Aims. This study investigated the effects of β-caryophyllene (BCP) on protecting bone from vitamin D deficiency in mice fed on a diet either lacking (D-) or containing (D+) vitamin D. Methods. A total of 40 female mice were assigned to four treatment groups (n = 10/group): D+ diet with propylene glycol control, D+ diet with BCP, D-deficient diet with control, and D-deficient diet with BCP. The D+ diet is a commercial basal diet, while the D-deficient diet contains 0.47% calcium, 0.3% phosphorus, and no vitamin D. All the mice were housed in conditions without ultraviolet light. Bone properties were evaluated by X-ray micro-CT. Serum levels of klotho were measured by enzyme-linked immunosorbent assay. Results. Under these conditions, the D-deficient diet enhanced the length of femur and tibia bones (p < 0.050), and increased bone volume (BV; p < 0.010) and trabecular bone volume fraction (BV/TV; p < 0.010) compared to D+ diet. With a diet containing BCP, the mice exhibited higher BV and bone mineral density (BMD; p < 0.050) than control group. The trabecular and cortical bone were also affected by vitamin D and BCP. In addition, inclusion of dietary BCP improved the serum concentrations of klotho (p < 0.050). In mice, klotho regulates the expression level of cannabinoid type 2 receptor (Cnr2) and fibroblast growth factor 23 (Fgf23) through CD300a. In humans, data suggest that klotho is connected to BMD. The expression of klotho is also associated with bone markers. Conclusion. These data indicate that BCP enhances the serum level of klotho, leading to improved bone properties and mineralization in an experimental mouse model. Cite this article: Bone Joint Res 2022;11(8):528–540

We measured the plasma 25-hydroxyvitamin D. 3. (25(OH)D. 3. ) levels in 62 consecutive Caucasian patients undergoing total hip replacement for osteoarthritis. The patients were divided into two groups based on whether they were vitamin D sufficient or deficient. The groups were matched for age, gender and the American Society of Anaesthesiologists (ASA) grade. The prevalence of vitamin D deficiency in our patients was comparable with recent population-based studies performed in the United Kingdom. Patients with vitamin D deficiency had lower pre-operative Harris hip scores (Mann-Whitney test, p = 0.018) and were significantly less likely to attain an excellent outcome from total hip replacement (chi-squared test, p = 0.038). Vitamin D levels were found to positively correlate with both pre- and post-operative Harris hip scores. These results warrant further study of vitamin D deficiency in patients undergoing joint replacement as it is a risk factor for a suboptimal outcome which is relatively simple and cheap to correct

This annotation considers the place of extra-articular reconstruction in the treatment of anterior cruciate ligament (ACL) deficiency. Extra-articular reconstruction has been employed over the last century to address ACL deficiency. However, the technique has not gained favour, primarily due to residual instability and the subsequent development of degenerative changes in the lateral compartment of the knee. Thus intra-articular reconstruction has become the technique of choice. However, intra-articular reconstruction does not restore normal knee kinematics. Some authors have recommended extra-articular reconstruction in conjunction with an intra-articular technique. . The anatomy and biomechanics of the anterolateral structures of the knee remain largely undetermined. Further studies to establish the structure and function of the anterolateral structures may lead to more anatomical extra-articular reconstruction techniques that supplement intra-articular reconstruction. This might reduce residual pivot shift after an intra-articular reconstruction and thus improve the post-operative kinematics of the knee.

Slipped capital femoral epiphysis (SCFE) is uncommon in India and we routinely look for associated metabolic or endocrine abnormalities. In this study we investigated a possible association between vitamin D deficiency and SCFE. All children presenting with SCFE during the study period had their 25-hydroxyvitamin D levels measured as part of an overall metabolic, renal and endocrine status evaluation, which included measurement of body mass index (BMI). Vitamin D status was compared with age-, gender- and habitat-matched controls with acute trauma or sepsis presenting to our emergency department. A total of 15 children (12 boys and three girls) with a mean age of 13 years (. sd. 1.81; 10 to 16) presented for treatment for SCFE during a two-year period beginning in January 2010. Renal and thyroid function was within the normal range in all cases. The mean BMI was 24.9 kg/m. 2. (17.0 to 33.8), which was significantly higher than that of the controls (p = 0.006). There was a statistically significant difference between the mean values of 25-hydroxyvitamin D in the children with SCFE and the controls (11.78 ng/ml (. sd. 5.4) versus 27.06 ng/ml (. sd. 5.53), respectively; p < 0.001). We concluded that, along with high BMI, there is a significant association of vitamin D deficiency and SCFE in India. Cite this article: Bone Joint J 2013;95-B:851–4

The late results of treatment of 24 legs in 21 children with congenital deficiency of the tibia are presented. A new classification is proposed which correlates well with recommendations for treatment and with the final functional result. Three types of deficiency were recognised: Type I, total absence of the tibia; Type II, distal absence; Type III, distal deficiency with tibiofibular diastasis. The early radiographic appearances, the functional status of the quadriceps and the severity of flexion contracture of the knee were important factors in the selection of the operations likely to give the best function

Ninety-seven limbs, in eighty-one patients, with a diagnosis of congenital deficiency of the fibula have been reviewed. A classification was devised to distinguish the minimal hypoplasia of the fibula (Type I) from the well-known complete absence (Type II). Congenital anomalies of the femur were present in 76 per cent of patients with Type I deficiency and in 59 per cent with Type II. The shortening of the limb was by 13 per cent in Type I and by 19 per cent in Type II, and the percentage shortening was fairly constant during growth. A detailed description of the spectrum of other congenital anomalies was found to be characteristic: for example, the ball and socket formation of the ankle, tarsal coalition and anomalies of the foot. The treatment aimed simply to equalise leg length in Type I deficiency, while amputation of the foot and the fitting of a prosthesis were necessary in Type II to obtain satisfactory function

Children with congenital focal deficiency of the proximal femur present many problems that are but rarely encountered by the individual surgeon who is thus unable to accumulate a wide experience. This paper reviews the literature and analyses the treatment of twenty-three cases at the Royal Children's Hospital, Melbourne, with the object of producing a rational plan of treatment. The management of instability of the hip, malrotation, inadequate proximal musculature and leg length inequality are separately considered for five grades of deficiency. Milder forms are amenable to subtrochanteric osteotomy to correct varus deformity. Exploration and grafting of the pseudarthrosis is indicated where progressive deformity develops. In the more severe deficiency, conservative management of the proximal bony defect provides a better result with an operation only rarely indicated. The gross leg length inequality may be most successfully overcome by Syme's amputation with subsequent fusion of the knee to create an above-knee amputee with an end-bearing stump allowing ready fitting of a prosthesis

We evaluated the use of a stemmed acetabular component in the treatment of severe acetabular deficiency during revision and complex primary total hip arthroplasty. There were 31 hips of which 24 were revisions (20 for aseptic loosening, four for infection) and the remainder were complex primary arthroplasties. At a mean follow-up of 10.7 years (6 to 12.8), no component had been revised for aseptic loosening; one patient had undergone a revision of the polyethylene liner for wear. There was one failure because of infection. At the latest follow-up, the cumulative survival rate for aseptic loosening, with revision being the end-point, was 100%; for radiographic loosening it was 92% and for infection and radiographic loosening it was 88%. These results justify the continued use of this stemmed component for the reconstruction of severe acetabular deficiency

This study reports the clinical outcome of reconstruction of deficient abductor muscles following revision total hip arthroplasty (THA), using a fresh–frozen allograft of the extensor mechanism of the knee. A retrospective analysis was conducted of 11 consecutive patients with a severe limp because of abductor deficiency which was confirmed on MRI scans. The mean age of the patients (three men and eight women) was 66.7 years (52 to 84), with a mean follow-up of 33 months (24 to 41). . Following surgery, two patients had no limp, seven had a mild limp, and two had a persistent severe limp (p = 0.004). The mean power of the abductors improved on the Medical Research Council scale from 2.15 to 3.8 (p < 0.001). Pre-operatively, all patients required a stick or walking frame; post-operatively, four patients were able to walk without an aid. Overall, nine patients had severe or moderate pain pre-operatively; ten patients had no or mild pain post-operatively. . At final review, the Harris hip score was good in five patients, fair in two and poor in four. . We conclude that using an extensor mechanism allograft is relatively effective in the treatment of chronic abductor deficiency of the hip after THA when techniques such as local tissue transfer are not possible. . Longer-term follow-up is necessary before the technique can be broadly applied. Cite this article: Bone Joint J 2015;97-B:1050–5

After establishing anatomical feasibility, functional reconstruction to replace the anterolateral part of the deltoid was performed in 20 consecutive patients with irreversible deltoid paralysis using the sternoclavicular portion of the pectoralis major muscle. The indication for reconstruction was deltoid deficiency combined with massive rotator cuff tear in 11 patients, brachial plexus palsy in seven, and an isolated axillary nerve lesion in two. All patients were followed clinically and radiologically for a mean of 70 months (24 to 125). The mean gender-adjusted Constant score increased from 28% (15% to 54%) to 51% (19% to 83%). Forward elevation improved by a mean of 37°, abduction by 30° and external rotation by 9°. The pectoralis inverse plasty may be used as a salvage procedure in irreversible deltoid deficiency, providing subjectively satisfying results. Active forward elevation and abduction can be significantly improved

In a prospective seven-year study, we treated 32 patients with partial ruptures of the anterior cruciate ligament (ACL) verified by arthroscopy. Twelve knees (38%) progressed to complete ACL deficiency with positive pivot shift tests and increased anteroposterior translation on tests with the KT-1000 arthrometer. Patients with partial ACL tears frequently had limitation for strenuous sports, while those developing ACL deficiency had additional functional limitations involving recreational activities. Three factors were statistically significant in predicting which partial tears would develop complete ACL deficiency: the amount of ligament tearing--one-fourth tears infrequently progressed, one-half tears progressed in 50% and three-fourth tears in 86%; a subtle increase in initial anterior translation; and the occurrence of a subsequent re-injury with giving-way

We studied the possible role of melatonin deficiency in experimentally-induced scoliosis. A total of 90 chickens underwent pinealectomy on the third day after hatching: 30 were treated with serotonin, 30 with melatonin and 30 received no therapy (control group). Scoliosis developed in all the control group, in 22 of the serotonin group, and in only 6 of the melatonin group. The six melatonin-treated chickens with scoliosis had less severe spinal deformities than those in the serotonin-treated group. There were lower blood melatonin concentrations in chickens with scoliosis than in those without. Our findings suggest that melatonin deficiency contributes to the aetiology of this experimental scoliosis, probably by interfering with the normally symmetrical growth of the proprioceptive system involving the paraspinal muscles and the spine

We report the use of the reverse shoulder prosthesis in the revision of a failed shoulder hemiarthroplasty in 19 shoulders in 18 patients (7 men, 11 women) with severe pain and loss of function. The primary procedure had been undertaken for glenohumeral arthritis associated with severe rotator cuff deficiency. Statistically significant improvements were seen in pain and functional outcome. After a mean follow-up of 44 months (24 to 89), mean forward flexion improved by 26.4° and mean abduction improved by 35°. There were six prosthesis-related complications in six shoulders (32%), five of which had severe bone loss of the glenoid, proximal humerus or both. Three shoulders (16%) had non-prosthesis related complications. The use of the reverse shoulder prosthesis provides improvement in pain and function for patients with failure of a hemiarthroplasty for glenohumeral arthritis and rotator cuff deficiency. However, high rates of complications were associated with glenoid and proximal humeral bone loss

A long-term review of 131 children fitted with upper limb prostheses at the Ontario Crippled Children's Centre between 1965 and 1975 is reported. There were 116 children with congenital deficiencies and 15 who had had amputations. Follow-up ranged from 7 to 17 years. A total of 42 children had abandoned their prostheses, 37 of whom had congenital deformities and five were amputees. The level of deficiency was of fundamental importance in determining whether the prosthesis would be accepted; in the forearm, the longer the stump, the more likely it was that the child would discard the prosthesis. Overall, 50 per cent of children fitted over the age of two years abandoned their prostheses compared with only 22 per cent of patients who had been fitted before the age of two years. The highest drop-out rate was at the age of 13 years when the children became more conscious of their cosmetic appearance. Suggestions for reducing the high drop-out rate in the early teens are put forward

Van Nes rotationplasty may be used for patients with congenital proximal focal femoral deficiency (PFFD). The lower limb is rotated to use the ankle and foot as a functional knee joint within a prosthesis. A small series of cases was investigated to determine the long-term outcome. At a mean of 21.5 years (11 to 45) after their rotationplasty, a total of 12 prosthetic patients completed the Short-Form (SF)-36, Faces Pain Scale-Revised, Harris hip score, Oswestry back pain score and Prosthetic Evaluation Questionnaires, as did 12 age- and gender-matched normal control participants. A physical examination and gait analysis, computerised dynamic posturography (CDP), and timed ‘Up & Go’ testing was also completed. Wilcoxon Signed rank test was used to compare each PFFD patient with a matched control participant with false discovery rate of 5%. There were no differences between the groups in overall health and well-being on the SF-36. Significant differences were seen in gait parameters in the PFFD group. Using CDP, the PFFD group had reduced symmetry in stance, and reduced end point and maximum excursions. Patients who had undergone Van Nes rotationplasty had a high level of function and quality of life at long-term follow-up, but presented with significant differences in gait and posture compared with the control group. Cite this article: Bone Joint J 2013;95-B:192–8

1. A child is described who presented with very severe rickets and gross myopathy. The clinical, biochemical and radiological signs were identical with those to be expected of a very chronic and severe vitamin D deficiency. The child's diet, however, had been normal. 2. All the pathological signs, except for residual dwarfism and leg bowing, disappeared on treatment with very large doses of vitamin D. 2. Ordinary anti-rachitic doses had no effect. 3. We suggest that this child demonstrates a true resistance to the action of vitamin D and that the defect is permanent. The findings in two similar patients that we have seen suggest that the condition is inherited as an autosomal recessive gene, and that it may be the same disease as that described in the continental literature as "hereditäre pseudo-mangelrachitis" and by other names. 4. The disease seems distinct clinically and biochemically from the disease originally described under the name "vitamin resistant rickets," which does not respond so well to massive vitamin D therapy and which is usually inherited as a sex-linked dominant gene