Treatment Effect of Zoledronic Acid in Chronic Non-bacterial Osteomyelitis of the Jaw: A Case Series.

Chronic non-bacterial osteomyelitis (CNO) is an autoinflammatory, osteolytic bone disorder sometimes localized to a unifocal site in the jaw, causing long-term pain and reduced function. The aim of this study was to describe the patients with CNO of the jaw, focusing on treatment with zoledronic acid for pain relief. An analysis of medical records of 24 patients with CNO of the jaw, including treatment with zoledronic acid and effects on pain relief. Descriptive statistics and nonparametric tests were used to describe the population and compare treatment effects, respectively. The average treatment period was 33.4 months (median 23; Q1 11.5; Q3 42.0) with an average of 4.1 infusions (median 3; Q1 2; Q3 5) of zoledronic acid. The average pain VAS score (visual analogue scale) was significantly reduced from 7.7 (median 8; Q1 6.5; Q3 8.5) to 2.5 points (median 2; Q1 0.5; Q3 4.5) (p < 0.001). At final visit, 46% of patients reported no pain and 38% reported a reduction of pain. At least 67% of patients had at least one episode of pain recurrence, and most patients experienced the first recurrence within a year of initial treatment. Four patients (16%) had no pain relief from the treatment. In this group of patients with CNO of the jaw, there was a positive response to treatment with zoledronic acid on pain relief, averaging 5.2 points on a pain VAS score, with 84% of patients treated experiencing either a partial or a total reduction in pain after about 2.5 years.

Long-Term Changes in Sarcopenia and Body Composition in Diabetes Patients with and without Charcot Osteoarthropathy.

BACKGROUND: Charcot osteoarthropathy of the foot (COA) can currently only be treated using prolonged periods of immobilization of the affected extremity. Therefore, the hypothesis is that COA leads to altered body composition and increased sarcopenia. OBJECTIVE: To investigate the changes over several years in sarcopenia, body composition, and fat distribution in diabetes patients with previous COA compared to diabetes patients without previous COA. METHODS: Prospective observational clinical study. Twenty-one subjects were included and had two DXA scans done with mean 8.6-year intervals to compare changes in lean mass and fat distribution. The lean mass of limbs was used as an estimate of appendicular lean mass (aLM). Fat mass and aLM were then used to detect sarcopenic individuals using different methods. Results and Conclusions. As compared to baseline, both groups had significant loss of lean mass, and diabetics without COA had significant gain of total fat percentage. No statistically different prevalence of sarcopenia between the groups could be established. Likewise, no difference was found in total lean and fat mass changes. None of the groups had statistically significant changes of android fat distribution. As compared with published data on sarcopenia, people with diabetes might be more prone to sarcopenia than healthy individuals.

Risk factors for development of nephropathy in patients with a diabetic Charcot foot.

OBJECTIVE: Charcot foot is a rare complication to neuropathy and can cause severe foot deformities and ulcerations, which often require prolonged antibiotical treatment. The objective of this retrospective study was to investigate whether this treatment is associated to impaired renal function. RESULTS: In total, 163 patients were included, of whom 105 (64%) had received ß-lactam antibiotics for a mean total duration of 13.0 months. There was a significant increase in the urine albumin/creatinine ratio in the group that received antibiotics (p = 0.017), and the use of antibiotics was associated to a subsequent diagnosis of nephropathy (p = 0.01). Patients treated with antibiotics had a 21.9% risk of developing subsequent nephropathy versus 5.2% for patients not treated with antibiotics. We suggest increased awareness on signs of nephropathy in patients with severe Charcot foot.

Healing of Diabetic Foot Ulcers in Patients Treated at the Copenhagen Wound Healing Center in 1999/2000 and in 2011/2012.

AIM: To describe differences in healing time of diabetic foot ulcers for patients treated at the Copenhagen Wound Healing Center, Bispebjerg Hospital, between the years 1999/2000 and 2011/2012. The Center is highly specialized and receives diabetes patients with hard-to-heal foot ulcers. A further aim is to attempt to find predictors of healing time of diabetic foot ulcers. METHODS: A retrospective descriptive study of records from patients with diabetic foot ulcer treated at the Copenhagen Wound Healing Center in 1999, 2000, 2011, or 2012. Follow-up data was collected until the 3rd of August 2018. RESULTS: Median time (range) to healing was 6 (61.3) months in 1999/2000 and 6.6 (67.8) in 2011/2012 (p = 0.2). About 33% of ulcers were healed, 17% were minor or major amputated, and 1.5% were dead within one year in 1999/2000, whereas 30% of ulcers were healed (p = 0.6), 14% were amputated (p = 0.2), and 12.8% were dead within one year in 2011/2012 (p < 0.001). The single factor found significantly associated with longer ulcer duration was infection. Related to shorter ulcer duration were toe localization of the ulcer and good glycemic control. CONCLUSION: The median time to healing of a diabetic foot ulcer was long, around 6 months and with a high recurrence rate in 1999/2000 as well as in 2011/2012. Some factors were found to be significantly related to healing time, and intervention addressing these may improve the time to heal, although such interpretations must be taken with precaution from the present study and should be proven in randomized prospective intervention trials.

Mortality and complications after treatment of acute diabetic Charcot foot.

AIMS: Charcot foot is a rare but disabling complication to diabetic neuropathy, and can cause permanent, limb-threatening deformities. The aim of this study was to investigate a population of patients a Charcot foot on a case-by-case basis, in order to assess the consequences of an acute Charcot foot and its complications. METHODS: The study was conducted a retrospective study of patients admitted to the Copenhagen Wound Healing Center between 1996 and 2015 with the diagnosis of Charcot foot (DM14.6) and diabetes mellitus type 1 or 2 (DE10.X and DE11.X). Physical and electronic records were used, and compared to data from the Danish Diabetes Registry. RESULTS: In total 392 patients were identified of which 173 were included. There were 26% with type 1 diabetes (initial HbA1c 81.7 ±â€¯21.4 mmol/mol) and 74% with type 2 diabetes (initial HbA1c 66.5 ±â€¯20.3 mmol/mol). Primary off-loading was with a removable walker in 95% of the cases (average off-loading time 8.3 months). The 5-year mortality was 14% with a mean survival time of 12.7 years. There was an association between lack of compliance and occurrence of foot complications, as well as between having a Charcot foot and leaving the workforce. CONCLUSION: More patients had type 1 diabetes compared to the background population, and they had a higher HbA1c than the general population of diabetes patients. A total of 67% developed complications such as ulcers, while patients non-compliant to treatment did significantly worse than those being compliant. The 5-year mortality was low, 14%, and comparable to diabetes patients without Charcot foot.

Markers of Local Inflammation and Bone Resorption in the Acute Diabetic Charcot Foot.

OBJECTIVE: Due to the localized nature of Charcot foot, systemically altered levels of inflammation markers can be difficult to measure. The aim of this study was to investigate whether it is possible to detect an arteriovenous (A-V) flux in any locally produced inflammatory biomarkers from an acute Charcot foot by comparing local and systemic measurements. METHODS: We included patients with acute diabetic Charcot foot. Blood was sampled from the vena saphena magna on the distal part of the crus bilaterally as well as from the arteria radialis. To minimize the A-V shunting effect, the feet were externally cooled with ice water prior to resampling. RESULTS: Both before and after cooling, the A-V flux of interleukin-6 (IL-6) between the Charcot feet and the arterial level was significantly higher than the flux between the healthy feet and the arterial level (Δvaluebefore: 7.25 versus 0.41 pg/mL, resp., p = 0.008; Δvalueafter: 10.04 versus 1.68 pg/mL, resp., p = 0.032). There were no differences in the fluxes for other markers of inflammation. CONCLUSION: We have found an increased A-V flux of IL-6 in the acute diabetic Charcot foot compared to the healthy foot in the same patients.

A review of bone metabolism and developments in medical treatment of the diabetic Charcot foot.

Charcot foot is a rare but severe, and possibly limb-threatening, complication to neuropathy and diabetes mellitus. The current treatment consists of long-term off-loading, and has a large negative impact on the patient's life. Much research has gone into understanding the condition and its biochemical mechanisms, however, the underlying pathogenesis of a Charcot foot is not yet fully understood. In the recent decades several key advances in our understanding of the Charcot foot have been made, both in regards to the changes in bone metabolism and structure an acute Charcot foot can cause, and to the molecular pathways involved in this. This review summerizes the available research into the bone metabolism around a Charcot foot, with an emphasis on the biochemical profile. The existing data regarding attempts at medical treatment is also reviewed, including novel trials targetting specific inflammatory pathways upregulated in the acute diabetic Charcot foot.

Long-term effects on the progress of neuropathy after diabetic Charcot foot: an 8.5-year prospective case-control study.

OBJECTIVE: Charcot foot is a severe complication to diabetes mellitus, associated with diabetic neuropathy. Any long-term effects of a Charcot foot on the progress of neuropathy are still largely unexplored. The objective was to investigate whether a previous Charcot foot had any long-term effects on the progress of neuropathy. RESULTS: An 8.5-year follow-up case-control study of 49 individuals with diabetes mellitus, 24 of whom also had Charcot foot at baseline visit in 2005-2007. Neuropathy was assessed with a questionnaire, biothesiometry, heart rate variability and venous occlusion plethysmography. Of the 49 baseline participants, 22 were able to participate in the follow-up. Twelve had passed away in the meantime. Heart rate variability was unchanged in both groups; from 9.7 to 7.2 beats/min (p = 0.053) in the Charcot group, and 14.3 to 12.6 beats/min (p = 0.762) in the control group. Somato-sensoric neuropathy showed no difference between baseline and follow-up in the Charcot group (from 39.1 to 38.5 V) (p = 0.946), but a significantly worsened sensitivity in the control group (from 25.1 to 38.9 V) (p = 0.002). In conclusion, we found that any differences in somatic or cardial autonomic neuropathy present at baseline had disappeared at follow-up after 8.5 years.

Bone mineral density and markers of bone turnover and inflammation in diabetes patients with or without a Charcot foot: An 8.5-year prospective case-control study.

BACKGROUND AND AIMS: Charcot foot is a rare but severe complication to diabetes and peripheral neuropathy. It is still unclear if an acute Charcot foot has long-term effects on the bone metabolism. To investigate this, we conducted a follow-up study to examine if a previously acute Charcot foot has any long-term effects on bone mineral density (BMD) or local or systemic bone metabolism. METHODS: An 8.5-year follow-up case-control study of 44 individuals with diabetes mellitus, 24 of whom also had acute or chronic Charcot foot at the baseline visit in 2005-2007, who were followed up in 2015 with DXA scans and blood samples. RESULTS: 21 of the 44 baseline participants participated in the follow-up. There were no difference in the change in total hip BMD from baseline to follow-up in either the Charcot or the control group (p = 0.402 and 0.517), and no increased risk of osteoporosis in the previous Charcot feet either. From baseline to follow-up, there was a significant difference in the change in levels of fsRANK-L in the Charcot group, but not in the control group (p = 0.002 and 0.232, respectively). At follow-up, there were no differences in fsRANK-L between the groups. The fsRANK-L/OPG ratio also significantly decreased from baseline to follow-up in the Charcot group (3.4 versus 0.5) (p = 0.009), but not in the control group (1.3 versus 1.1) (p = 0.302). CONCLUSION: We found that diabetes patients with an acute Charcot foot have an elevated fsRANK-L/OPG ratio, and that the level decreased from baseline to follow-up to be comparable to the level in diabetes patients without previous or current Charcot foot. We found no permanent effect of an acute Charcot foot on hip or foot BMD.

Clinical management of acute diabetic Charcot foot in Denmark.

INTRODUCTION: Charcot foot is a severe complication to diabetes mellitus and treatment involves several different clinical specialities. Our objective was to describe the current awareness, knowledge and treatment practices of Charcot foot among doctors who handle diabetic foot disorders. METHODS: This study is based on a questionnaire survey sent out to healthcare professionals, primarily doctors, working with diabetic foot ulcers and Charcot feet in the public sector of the Danish healthcare system. RESULTS: The survey obtained a 52% response rate. A temperature difference of > 2 °C between the two feet was the most used method of diagnosing Charcot foot. Along with clinical inspection, temperature difference was also the measurement used for monitoring of healing. None of the suggested formalised classification systems were used to any extent. Most responders use detachable bandages for offloading (83%). All centres use some form of a multidisciplinary team, with the most common permanent members being orthopaedic surgeons (71%), wound specialist nurses (76%), podiatrists (65%), endocrinologists (47%) and diabetes specialist nurses (41%). CONCLUSION: We conducted a survey of the diagnosis and treatment practices of acute diabetic Charcot foot at diabetes foot clinics in Denmark. The responders seem to follow the international recommendations and guidelines on management of the acute diabetic Charcot foot, despite a lack of Danish guidelines. FUNDING: none. TRIAL REGISTRATION: not relevant.

Sarcopenia and body composition in diabetic Charcot osteoarthropathy.

BACKGROUND: Treatment of Charcot osteoarthropathy (COA) requires restricted walking and offloading for several months, which lead to fat re-distribution and increased sarcopenia. OBJECTIVES/AIM: To investigate whether subjects with COA have an altered body composition compared to controls. METHODS: Cross-sectional case-control study of people with diabetes with acute or chronic Charcot osteoarthropathy, matched with otherwise healthy people with diabetes. A total of 49 subjects (distribution ~1:1) had a total body DXA-scanning, measuring appendicular lean mass, android/gynoid and truncal/total body fat distribution ratios. RESULTS: Sarcopenia frequency was higher in the total population with diabetes overall (9-40%), compared to normal materials. Using two different models for correlating appendicular lean mass to sarcopenia, there were no differences in sarcopenia-rates between the groups (P=0.413 and 0.948 respectively). There was no significant difference in lean tissue mass between the affected and the unaffected leg in the immobilised subject group (P=0.830). The average fat percentage was (29.4-37.7%) in the population with diabetes, compared to a matching background population (24.5-31.9%), whereas there were no significant differences found between the groups (P=0.065). Neither truncal/total fat percent nor android/gynoid fat percent ratios showed differences between the groups. CONCLUSION: To our knowledge, this is the first published dataset investigating body composition in subjects with Charcot osteoarthropathy. The study population of diabetics were more fat and sarcopenic than normal subjects, whereas no statistically significant impact of Charcot osteoarthropathy was found.

The management of diabetic foot ulcers in Danish hospitals is not optimal.

INTRODUCTION: The diabetic foot is a complicated health issue which ideally involves several different specialists to ensure the most effective treatment. The Danish Health and Medicines Authority recently published a national guideline to address the implementation of multidisciplinary teams in the treatment. The objective of this study was to describe the treatment practices at the time the guidelines were launched. METHODS: A questionnaire-based survey was conducted among Danish hospital departments working with diabetic feet. All public departments were invited by e-mail to participate and the participant answering the questionnaire was identified as knowledgeable about the department's procedures on treatment of diabetic feet. Only one questionnaire per department was allowed. RESULTS: A total of 62 questionnaires were sent out. We achieved a response rate of ~37% (n = 23). Respondents (n = 13) were mostly orthopaedic surgeons. A classification system of the diabetic foot was rarely or never used, and eight respondents (42%) reported having a multidisciplinary team in accordance with the national guidelines. 73% of the respondents performed some form of surgical intervention on diabetic feet, mainly minor procedures. CONCLUSION: The study demonstrated that several areas of treatment practices relating to the diabetic foot had potential for improvement as they did not adhere to national Danish guidelines. A follow-up survey, allowing time for local implementation, seems warranted.

The effect of oral loading doses of cholecalciferol on the serum concentration of 25-OH-vitamin-D.

BACKGROUND/OBJECTIVES: Severe vitamin D deficiency can be treated with oral loading doses of cholecalciferol. Our objective was to develop an algorithm to accurately calculate the amount of cholecalciferol needed for a loading dose, and what factors should be taken into account. METHODS: Two studies were conducted on subjects with Vitamin D deficiency. Study 1 was observational, retrospective and included 88 subjects treated with a daily supplementation of cholecalciferol. 60 of these furthermore received a loading dose, calculated by an algorithm.Study 2 was prospective and included 29 subjects treated with a cholecalciferol loading dose, calculated by an algorithm developed based on data from study 1, which included BMI. RESULTS: Baseline 25OH-vit.D was below 25 nmol/L (study 1) and 23 nmol/L (study 2). Subjects were given a single loading dose of cholecalciferol, averaging 172,000 IU (study 1) and 212,000 IU (study 2), based on their baseline 25OH-vit.D level.25OH-vit.D increased by 35 nmol/L (study 1) and 56 nmol/L (study 2)(range 113.0, SD 29.79) respectively. In study 2 the increase lead to an end 25OH-vit.D of 79 nmol/L--not significantly different from the target value of 80 nmol/L (P=0.46). The increase in 25OH-vit.D in study 1 was significantly lower than in study 2 (P<0.001). CONCLUSION: When calculating loading doses of cholecalciferol, taking subject BMI into account gives a better estimate of the loading dose of vitamin D3 needed to treat vitamin D deficiency. It does not, however, remove the large interindividual variation in dose-response.