Aims. Impaired fracture repair in patients with type 2 diabetes mellitus (T2DM) is not fully understood. In this study, we aimed to characterize the local changes in gene expression (GE) associated with diabetic fracture. We used an unbiased approach to compare GE in the fracture callus of Zucker diabetic fatty (ZDF) rats relative to wild-type (WT) littermates at three weeks following femoral osteotomy. Methods. Zucker rats, WT and homozygous for leptin receptor mutation (ZDF), were fed a moderately high-fat diet to induce T2DM only in the ZDF animals. At ten weeks of age, open femoral fractures were simulated using a unilateral osteotomy stabilized with an external fixator. At three weeks post-surgery, the fractured femur from each animal was retrieved for analysis. Callus formation and the extent of healing were assessed by radiograph and histology. Bone tissue was processed for total RNA extraction and messenger RNA (mRNA) sequencing (mRNA-Seq). Results. Radiographs and histology demonstrated impaired fracture healing in ZDF rats with incomplete bony bridge formation and an influx of intramedullary inflammatory tissue. In comparison, near-complete bridging between cortices was observed in Sham WT animals. Of 13,160 genes, mRNA-Seq analysis identified 13 that were differentially expressed in ZDF rat callus, using a false discovery rate (FDR) threshold of 10%. Seven genes were upregulated with high confidence (FDR = 0.05) in ZDF fracture callus, most with known roles in inflammation. Conclusion. These findings suggest that elevated or prolonged inflammation contributes to delayed fracture healing in T2DM. The identified genes may be used as biomarkers to monitor and treat delayed fracture healing in diabetic patients. Cite this article: Bone Joint Res 2023;12(10):657–666

Aims. Diabetes mellitus is the most common co-morbidity associated with necrotising fasciitis. This study aims to compare the clinical presentation, investigations, Laboratory Risk Indicator for Necrotising Fasciitis (LRINEC) score, microbiology and outcome of management of this condition in diabetic and non-diabetic patients. Patients and Methods. The medical records of all patients with surgically proven necrotising fasciitis treated at our institution between 2005 and 2014 were reviewed. Diagnosis of necrotising fasciitis was made on findings of ‘dishwater’ fluid, presence of greyish necrotic deep fascia and lack of bleeding on muscle dissection found intra-operatively. Information on patients’ demographics, presenting symptoms, clinical signs, investigations, treatment and outcome were recorded and analysed. Results. A total of 127 patients with surgically proven necrotising fasciitis were included in this study. In all, 78 (61.4%) were diabetic and 49 (38.6%) were non-diabetic. Diabetics tended to have polymicrobial infections (p = 0.03), renal impairment (p < 0.001), end-stage renal disease (p = 0.001) and multiple co-morbidities (p < 0.001). They presented atypically, with less tenderness (p = 0.042) and less hypotension (p = 0.034). This resulted in higher rates of misdiagnosis (p = 0.038) and a longer time to surgery (p = 0.05) leading to longer hospital stays (p = 0.043) and higher rates of amputation (p = 0.045). However, the rate of mortality is comparable (p = 0.525). A LRINEC score of > 8 appears to be more sensitive in diabetic patients (p < 0.001). However, the increased sensitivity in diabetic patients may be related to hyperglycemia and electrolyte abnormalities associated with renal impairment in these patients. Conclusion. The LRINEC score must be used with caution in diagnosing necrotising fasciitis in diabetic patients. A high index of suspicion is key to the early diagnosis and subsequent management of these patients. Cite this article: Bone Joint J 2016;98-B:1563–8

Aims. The antidiabetic agent metformin inhibits fibrosis in various organs. This study aims to elucidate the effects of hyperglycaemia and metformin on knee joint capsule fibrosis in mice. Methods. Eight-week-old wild-type (WT) and type 2 diabetic (db/db) mice were divided into four groups without or with metformin treatment (WT met(-/+), Db met(-/+)). Mice received daily intraperitoneal administration of metformin and were killed at 12 and 14 weeks of age. Fibrosis morphology and its related genes and proteins were evaluated. Fibroblasts were extracted from the capsules of 14-week-old mice, and the expression of fibrosis-related genes in response to glucose and metformin was evaluated in vitro. Results. The expression of all fibrosis-related genes was higher in Db met(-) than in WT met(-) and was suppressed by metformin. Increased levels of fibrosis-related genes, posterior capsule thickness, and collagen density were observed in the capsules of db/db mice compared with those in WT mice; these effects were suppressed by metformin. Glucose addition increased fibrosis-related gene expression in both groups of mice in vitro. When glucose was added, metformin inhibited the expression of fibrosis-related genes other than cellular communication network factor 2 (Ccn2) in WT mouse cells. Conclusion. Hyperglycaemia promotes fibrosis in the mouse knee joint capsule, which is inhibited by metformin. These findings can help inform the development of novel strategies for treating knee joint capsule fibrosis. Cite this article: Bone Joint Res 2024;13(7):321–331

We reviewed 27 diabetic patients who sustained a tibial fracture treated with a reamed intramedullary nail and compared them with a control group who did not have diabetes. There were 23 closed fractures and four were open. Union was delayed until after six months in 12 of the 23 (52%) diabetic patients with closed fractures and ten of the 23 (43%) control patients (p = 0.768). In two patients with diabetes (9%), closed tibial fractures failed to unite and required exchange nailing, whereas all closed fractures in the control group healed without further surgery (p = 0.489). In both the diabetic and control groups with closed fractures two patients (9%) developed superficial infections. There were two (9%) deep infections in diabetic patients with closed fractures, but none in the control group (p = 0.489). Overall, there was no significant difference in the rate of complications between the diabetic patients and the control group, but there was a tendency for more severe infections in patients with diabetes

Objectives. Diabetes mellitus (DM) is known to impair fracture healing. Increasing evidence suggests that some microRNA (miRNA) is involved in the pathophysiology of diabetes and its complications. We hypothesized that the functions of miRNA and changes to their patterns of expression may be implicated in the pathogenesis of impaired fracture healing in DM. Methods. Closed transverse fractures were created in the femurs of 116 rats, with half assigned to the DM group and half assigned to the control group. Rats with DM were induced by a single intraperitoneal injection of streptozotocin. At post-fracture days five, seven, 11, 14, 21, and 28, miRNA was extracted from the newly generated tissue at the fracture site. Microarray analysis was performed with miRNA samples from each group on post-fracture days five and 11. For further analysis, real-time polymerase chain reaction (PCR) analysis was performed at each timepoint. Results. Microarray analysis showed that there were 14 miRNAs at day five and 17 miRNAs at day 11, with a greater than twofold change in the DM group compared with the control group. Among these types of miRNA, five were selected based on a comparative and extended literature review. Real-time PCR analysis revealed that five types of miRNA (miR-140-3p, miR-140-5p, miR-181a-1-3p, miR-210-3p, and miR-222-3p) were differentially expressed with changing patterns of expression during fracture healing in diabetic rats compared with controls. Conclusions. Our findings provide information to further understand the pathology of impaired fracture healing in a diabetic rat model. These results may allow the potential development of molecular therapy using miRNA for the treatment of impaired fracture healing in patients with DM. Cite this article: S. Takahara, S. Y. Lee, T. Iwakura, K. Oe, T. Fukui, E. Okumachi, T. Waki, M. Arakura, Y. Sakai, K. Nishida, R. Kuroda, T. Niikura. Altered expression of microRNA during fracture healing in diabetic rats. Bone Joint Res 2018;7:139–147. DOI: 10.1302/2046-3758.72.BJR-2017-0082.R1

To determine the relative risk of complications in treating ankle fractures in patients with diabetes, we compared the results of the management of displaced malleolar fractures in 26 patients with those of a matched group of non-diabetic patients, using a case-controlled study. The groups were matched for patient age, fracture type and treating surgeon. The incidence of significant complications in diabetic patients was 42.3%. By contrast, there were no complications in the matched group of non-diabetic patients. Of 19 diabetic patients treated surgically, six developed major complications including one case of malunion, one of necrosis of the wound edge requiring a flap, and two of deep sepsis. Two patients required amputation and both died. Diabetic patients with displaced ankle fractures treated non-operatively had a high incidence of loss of reduction and malunion but these caused few symptoms. In these patients, non-operative management may be preferable in view of the high risks of major complications after surgery and the acceptance of malunion by the older patient with lower demands

A retrospective study of 44 diabetic patients who, between them, had 62 Charnley low-friction arthroplasties, showed a superficial-infection rate of 9.7 per cent and a deep-infection rate of 5.6 per cent. All the operations were carried out in the Charnley clear-air enclosure and prophylactic antibiotics were not used. A statistically significant increase in the overall rate of infection was found in diabetic patients when compared with non-diabetic osteoarthritic patients (P less than 0.001) and rheumatoid patients (P less than 0.01). Hence it is suggested that in diabetic patients there may well be a place for prophylactic antibiotics in hip replacement surgery in addition to the use of the clean-air enclosure

Between 2000 and 2006 we performed salvage tibiotalar arthrodesis in 17 diabetic patients (17 ankles) with grossly unstable ankles caused by bimalleolar fractures complicated by Charcot neuro-arthropathy. There were ten women and seven men with a mean age of 61.6 years (57 to 69). A crossed-screw technique was used. Two screws were used in eight patients and three screws in nine. Additional graft from the malleoli was used in all patients. The mean follow-up was 26 months (12 to 48) and the mean time to union was 5.8 months (4 to 8). A stable ankle was achieved in 14 patients (82.4%), nine of whom had bony fusion and five had a stiff fibrous union. The results were significantly better in underweight patients, in those in whom surgery had been performed three to six months after the onset of acute Charcot arthropathy, in those who had received anti-resorptive medication during the acute stage, in those without extensive peripheral neuropathy, and in those with adequate peripheral oxygen saturation (> 95%). The arthrodesis failed because of avascular necrosis of the talus in only three patients (17.6%), who developed grossly unstable, ulcerated hindfeet, and required below-knee amputation

We studied a cohort of 26 diabetic patients with chronic ulceration under the first metatarsal head treated by a modified Jones extensor hallucis longus and a flexor hallucis longus transfer. If the first metatarsal was still plantar flexed following these two transfers, a peroneus longus to the peroneus brevis tendon transfer was also performed. Finally, if ankle dorsiflexion was < 5° with the knee extended, a Strayer-type gastrocnemius recession was performed. The mean duration of chronic ulceration despite a minimum of six months’ conservative care was 16.2 months (6 to 31). A total of 23 of the 26 patients were available for follow-up at a mean of 39.6 months (12 to 61) after surgery. All except one achieved complete ulcer healing at a mean of 4.4 weeks (2 to 8) after surgery, and there was no recurrence of ulceration under the first metatarsal. We believe that tendon balancing using modified Jones extensor hallucis longus and flexor hallucis longus transfers, associated in selected cases with a peroneus longus to brevis transfer and/or Strayer procedure, can promote rapid and sustained healing of chronic diabetic ulcers under the first metatarsal head

Aims. Local antibiotics are used in the surgical management of foot infection in diabetic patients. This systematic review analyzes the available evidence of the use of local antibiotic delivery systems as an adjunct to surgery. Materials and Methods. Databases were searched to identify eligible studies and 13 were identified for inclusion. Results. Overall, the quality of the studies was poor. A single trial suggested that wound healing is quicker when a gentamicin-impregnated collagen sponge was implanted at time of surgery, with no difference in length of stay or rate of amputation. Results from studies with high risk of bias indicated no change in wound healing when a gentamicin-impregnated sponge was implanted during transmetatarsal amputation, but a reduction in the incidence of wound breakdown (8% vs 25%, not statistically significant) was identified. A significant cost reduction was identified when using an antimicrobial gel to deliver antibiotics and anti-biofilm agents (quorum-sensing inhibitors) compared with routine dressings and systemic antibiotics. Analyses of case series identified 485 patients who were treated using local antibiotic delivery devices. The rates of wound healing, re-operation, and mortality were comparable to those that have been previously reported for the routine management of these infections. Conclusion. There is a lack of good-quality evidence to support the use of local antibiotic delivery devices in the treatment of foot infections in patients with diabetes. Cite this article: Bone Joint J 2018;100-B:1409–15

The systemic effects of diabetes mellitus are well recognised. The heart, kidney, central and peripheral nervous systems, and the distal parts of the limbs are often the site of end-organ damage resulting from ischaemia. Infarction of large muscle groups in the limb, not associated with gangrene, is uncommon. There have been few reported cases other than radiological descriptions of diabetic muscle infarcts. While previous reports have illustrated some of the clinical and radiological characteristics of this condition, the paucity of published cases makes it difficult to determine the most appropriate methods of diagnosis and treatment. During a five-year period we treated 14 patients with diabetes mellitus, aged from 32 to 59 years, who were referred to a musculoskeletal oncology service for suspected soft-tissue sarcoma, but were subsequently found to have a diabetic muscle infarct. Closed needle biopsy was performed in 13 without complications. In 12 patients, the symptoms resolved without surgical treatment

The relationship between the bone mineral density (BMD) and Charcot arthropathy is unclear. Prospectively, 55 consecutive diabetic patients presenting with a Charcot arthropathy of the foot or ankle were classified as having a fracture, dislocation, or a combination fracture-dislocation pattern of initial destruction. In these groups we used dual-energy x-ray absorptiometry to compare the peripheral bone of the affected and unaffected limbs. The clinical data relating to diabetes and related major comorbidities and the site of the arthropathy (ankle, hindfoot, midfoot, forefoot) were also compared. There were 23 patients with a fracture pattern, 23 with a dislocation pattern, and nine with a combination. The age-adjusted odds ratio for developing a Charcot joint with a fracture pattern as opposed to a dislocation pattern in patients with osteopenia was 9.5 (95% confidence interval 2.4 to 37.4; p = 0.0014). Groups also differed as to the site of the arthropathy. Fracture patterns predominated at the ankle and forefoot whereas dislocations did so in the midfoot. Diabetic Charcot arthropathy of the foot and ankle differs according to the pattern of the initial destruction. The fracture pattern is associated with peripheral deficiency of BMD. The dislocation pattern is associated with a normal BMD

The clinical details of six patients who developed spontaneous dislocations in the foot or ankle are presented. All were shown to have diabetic neuropathy. This previously unreported condition can occur with a short history of diabetes. Some cases can be managed without operation, though arthrodesis probably offers the best chance of obtaining a stable foot of satisfactory shape

Aims

Type 2 diabetes mellitus (T2DM) impairs bone strength and is a significant risk factor for hip fracture, yet currently there is no reliable tool to assess this risk. Most risk stratification methods rely on bone mineral density, which is not impaired by diabetes, rendering current tests ineffective. CT-based finite element analysis (CTFEA) calculates the mechanical response of bone to load and uses the yield strain, which is reduced in T2DM patients, to measure bone strength. The purpose of this feasibility study was to examine whether CTFEA could be used to assess the hip fracture risk for T2DM patients.

Charcot neuro-osteoarthropathy (CN) of the midfoot presents a major reconstructive challenge for the foot and ankle surgeon. The Synthes 6 mm Midfoot Fusion Bolt is both designed and recommended for patients who have a deformity of the medial column of the foot due to CN. We present the results from the first nine patients (ten feet) on which we attempted to perform fusion of the medial column using this bolt. Six feet had concurrent hindfoot fusion using a retrograde nail. Satisfactory correction of deformity of the medial column was achieved in all patients. The mean correction of calcaneal pitch was from 6° (-15° to +18°) pre-operatively to 16° (7° to 23°) post-operatively; the mean Meary angle from 26° (3° to 46°) to 1° (1° to 2°); and the mean talometatarsal angle on dorsoplantar radiographs from 27° (1° to 48°) to 1° (1° to 3°).

However, in all but two feet, at least one joint failed to fuse. The bolt migrated in six feet, all of which showed progressive radiographic osteolysis, which was considered to indicate loosening. Four of these feet have undergone a revision procedure, with good radiological evidence of fusion. The medial column bolt provided satisfactory correction of the deformity but failed to provide adequate fixation for fusion in CN deformities in the foot.

In its present form, we cannot recommend the routine use of this bolt.

Cite this article: Bone Joint J 2015; 97-B:809–13

Chronic infections and ulceration around the tendo Achillis are difficult to manage. Split-skin grafts do not survive even on healthy exposed tendon. Refractory cases may require plastic surgical intervention with the use of free flaps. Patients with significant vascular disease are not suitable for such techniques. Flexor hallucis longus tendon transfer is an established treatment for chronic ruptures of the tendo Achillis.

We report the successful treatment of an infected tendo Achillis with excision and reconstruction with flexor hallucis longus transfer. The muscle belly of this tendon allowed later skin grafting while the tendon transfer provided good functional recovery.