Musculoskeletal involvement in cystic fibrosis.

The purpose of this study was to review the published evidence of the effects of cystic fibrosis (CF) on the musculoskeletal system, and their implications on the quality of life of these patients. With increasing longevity of CF patients, musculoskeletal manifestations have become important. Decreased bone mineral density (BMD) and bone mineral content (BMC) are common at all ages in CF patients, and its cause is probably multifactorial. Risk factors contributing to decreased BMC include age of the patient, imbalance between bone accretion and degradation, body mass, nutrition, activity, exposure to glucocorticoid therapy, and gonadal dysfunction. BMC correlates strongly to fat-free mass in CF patients. Lung transplant, while increasing life span, can worsen osteoporosis. Twenty-nine percent of patients are below the 10th percentile for height. Fracture rates are approximately twofold greater in females aged 16 to 32 years and males aged 25 to 34 years. Female patients aged 6 to 16 have a higher than normal fracture rate and a higher rate than their male counterparts. Spinal consequences of osteoporosis include excessive kyphosis in up to 62% of patients. Back pain was noted in 94% of patients. Arthritis in CF, although less common, can be very incapacitating, and it is mainly of three types: CF arthritis, hypertrophic osteoarthropathy, and arthritis due to co-existent conditions and drug reactions. The treatment of arthritis is mainly symptomatic in the majority of cases.     

Abnormal Bone Turnover in Cystic Fibrosis Adults

Cystic fibrosis (CF) patients often have low bone mineral density (BMD) and may suffer from fractures and kyphosis. The pathogenesis of low BMD in CF is multifactorial. To study bone metabolism, we collected fasting serum and urine from 50 clinically stable CF adults (mean age 28 years) and 53 matched controls to measure markers of bone formation and bone resorption. The CF subjects had moderate lung disease (FEV₁: 46.1 ± 18.6% predicted) and malnutrition (BMI: 20.0 ± 3.3 kg/m²). Only 3 subjects had normal BMD. CF subjects had higher urinary N-telopeptides of type I collagen (81.0 ± 60.0 vs 49.0 ± 24.2 nm BCE/mmol creatinine, p= 0.0006) and free deoxypyridinoline (7.3 ± 5.0 vs 5.3 ± 1.9 nM/mM, p= 0.004) levels than controls. Serum osteocalcin levels were similar in the two groups, a result confirmed by two immunoassays that recognize different epitopes on osteocalcin. Serum bone-specific alkaline phosphatase levels were elevated in CF patients (32.0 ± 11.3 vs 21.8 ± 7.0 U/l, p<0.0001), but were much more closely associated with serum total alkaline phosphatase levels (r = 0.51, p = 0.001) than with age or gender. Parathyroid hormone levels were elevated (p= 0.007) and 25-hydroxyvitamin D levels were depressed (p= 0.0002) in the CF patients in comparison with controls. These results indicate that adults with CF have increased bone resorption with little change in bone formation. Medications that decrease bone resorption or improve calcium homeostasis may be effective therapies for CF bone disease. Received: 22 June 2001 / Accepted: 1 August 2001     

Proposal for biologic drugs therapy in rheumatoid arthritis

Rheumatoid arthritis is a chronic, inflammatory disease with the prevalence about 1%. Rheumatoid arthritis is characterized with synovitis, often evolve erosions of the joints, pain and functional deficit. Etiology is unknown, but the development of such autoimmune disease is due to genetic and environmental factors. Most of the patients with diagnosis of rheumatoid arthritis use nonbiologic disease modifying antirheumatic drugs. Advances in the undersstanding of the disease process have led to the development of biological agents to treat rheumatoid arthritis. With the use of biologic agents we wish to evolve the goal of therapy from that of symptomatiic relief to clinical remission. Biologic drugs have documented, fast and continuous efficacy with generaly well accepted safety profile. On behalf of Croatian Society for Rheumatology we propose recommendations for the biologic therapy in rheumatoid arthritis.     

Rheumatoid necroses in the forefoot

BACKGROUND: The incidence and morphological features of rheumatoid necroses (RN) in the forefoot are unknown. METHODS: Biopsy material from 223 patients with seropositive rheumatoid arthritis (RA) was examined morphologically. The incidence and morphological features of RN in the forefoot were evaluated. RESULTS: RN was found in 65% of cases, which had not been suspected clinically. It was correlated with pain in 69% of cases. CONCLUSIONS: Rheumatoid necrosis contributes to the development of pain and foot deformation. It can be a significant factor worsening the clinical behavior in seropositive RA patients.     

The Effect of Pregabalin on Bone Metabolism

The aim of the study was to determine the effect of pregabalin as monotherapy on biochemical markers and bone mineral density. 40 patients diagnosed with neuropathic pain or fibromyalgia syndrome who were using pregabalin for at least 6 months and age and sex matched 40 healthy individuals were recruited for this cross-sectional study. Bone mineral density of both groups were measured by dual energy x ray absorbsiometry(DXA), bone biochemical markers, serum calcium, and vitamin D levels were investigated. Association between pregabalin use and bone biochemical markers, serum calcium, vitamin D levels were evaluated. The mean age of 40 patients (27 females, 13 males) was 40.6 ± 7.1 years and the mean age of 40 healthy individuals (27 females, 13 males) was 40.4 ± 7.3 years. The other demographic data were similar. There were no significant differences in lumbar and femur neck BMD scores between 2 groups. Also, there were no associations neither between pregabalin use and biochemical markers including serum calcium levels nor between pregabalin use and vitamin D levels. However, the patients who had been used pregabalin less than 24 months had low lumbar t and z scores than patients who had been used pregabalin more than 24 months. This effect was more prominent in male patients. Although no negative effect of pregabalin was found on bone metabolism in these group of patients, we have suggested that further prospective controlled studies with large sample size in different age groups could provide new data about the effects of pregabalin on bone metabolism. We suggest to investigate the bone metabolism especially in male patients on pregabalin treatment who had been used pregabalin treatment less than 24 months.     

Role of bisphosphonates in the management of acute Charcot foot

Diabetes mellitus is the most common cause of Charcot neuropathy affecting foot and ankle. Acute Charcot foot(CF) presents with a red and swollen foot in co-ntrast to the painless deformed one of chronic CF. En-hanced osteoclastogenesis plays a central role in the pathogenesis of acute CF. Many studies have shown elevated levels of bone turnover markers in patients with acute CF confirming it. These findings have led cl-inicians to use anti-resorptive agents [bisphosphonates(BP), calcitonin, and denosumab] along with immobi-lization and offloading in acute CF patients. The ma-ximum evidence among all anti-resorptive agents is available for BPs, although its quality is low. Pamidronate has been shown to reduce the markers of activity of CF like raised skin temperature, pain, edema, and bone turnover markers in the majority of studies. Intravenous BPs are known to cause acute phase reactions leading to flu-like illness following their first infusion, which can be ameliorated by oral acetaminophen. Alendronate is the only oral BP used in these patients. It needs to be taken on an empty stomach with a full glass of water to avoid esophagitis. The side-effects and contraindications to BPs should be kept in mind while treating acute CF patients with them.     

Conduiturinary diversion and urinary-tract infection. I. Serum antibody titers against Escherichia coli and Proteus mirabilis in relation to urographic findings.

The serum antibody titers against Escherichia coli and/or Proteus mirabilis were elevated in 26 of 80 patients (33%) with a conduit urinary diversion. Urographic findings were abnormal in 44 of these 80 patients (55%). Urography was normal in 59% of the patients with normal antibody titers, but in only 15% of those with elevated titers. Raised antibody levels against E. coli O antigen (greater than 256 before and/or greater than 32 after mercaptoethanol treatment of serum) were associated with wide upper urinary tract or calculi more often than were normal E. coli antibody titers. Raised titers against P. mirabilis (greater than 256 before and/or greater than 32 after mercaptoethanol treatment of serum) were associated with scarring of the renal parenchyma more frequently than were normal titers. A statistically significant association was found between "small" kidney area and raised serum antibody titers against E. coli or P. mirabilis. The frequency of "small" kidney increased with the time lapse after urinary diversion. At 3 to 11 months postoperatively it was 29%, but among the patients with urinary diversion for more than five years the corresponding frequency was 82%. When at least one kidney was "small", the serum creatinine was higher than when both kidneys were of normal size. Patients with raised antibody titers tended also to have high serum creatinine (greater than or equal to 124 mumol/l) more often than those with normal titers (23 vs. 10%). These observations imply a connection between elevation of the antibody titers and destruction of the renal parenchyma in patients with conduit urinary diversion. They illustrate the value of antibody titration in the follow-up of patients with urinary diversion.     

Distribution of ABO Blood Group Antibody Titers in Pediatric Patients Awaiting Renal Transplantation: Implications for Organ Allocation Policy

BACKGROUND: Blood group-incompatible transplantation is one strategy used when a potential recipient does not have a compatible living donor. Current practice includes desensitization strategies to reduce antibody titers. However, when antibodies are low, in cardiac transplantation in neonates for example, no desensitization is required. This study is the first to examine the distribution of ABO blood group antibody titers in a population of pediatric patients on the deceased-donor renal transplantation waiting list. METHODS: All patients from two pediatric nephrology centers active on the national deceased-donor waiting list had antibody titers (total immunoglobulin load) measured. A simulation modeling the effect of allocating blood group-incompatible deceased-donor kidneys to those patients with titers of 16 or lower was developed. RESULTS: Twenty-four children were screened; eight (33.3%) had titers of either anti-A or anti-B antibodies of 8 or lower. A further three (12.5%) had either an anti-A or anti-B antibody titer of 16. Blood group A or B patients had lower antibody levels than blood group O patients. In blood group O patients, levels of anti-A antibodies were higher than anti-B antibodies (Wilcoxon signed rank test, P=0.028). The simulation model showed that a change in organ allocation policy would increase pediatric transplant activity by 2.2% and reduce the median waiting time for a transplant. CONCLUSION: This allocation strategy may be of particular benefit to those pediatric patients who have been on the deceased-donor waiting list for a long time or those with a high calculated reaction frequency.     

Emerging anti-osteoclast therapy for rheumatoid arthritis

Rheumatoid arthritis (RA) is an autoimmune inflammatory disorder characterized by progressive destruction of affected synovial joints. Recently, it was demonstrated that osteoclasts play critical roles in bone destruction in RA. Receptor activator of NF-κB ligand (RANKL), which belongs to the tumor necrosis factor superfamily, is indispensable for osteoclast differentiation and bone destruction in RA. Denosumab, a monoclonal antibody against human RANKL, not only increased bone mineral density, but also efficiently suppressed the progression of bone erosion in RA patients in a randomized controlled study. However, denosumab did not reduce the cartilage destruction or disease activity in RA, and further investigation is required to establish the appropriate positioning of denosumab in the treatment strategy of RA.     

Assessment of hand trabecular bone texture with high resolution direct digital radiograph in rheumatoid arthritis: a case control study

ObjectivesRheumatoid arthritis is characterized by an early inflammatory related periarticular osteopenia. A new high resolution direct digital X-ray device has been recently developed to provide bone texture analysis which is designed to assess changes in trabecular bone architecture. For the first time, we have evaluated trabecular bone texture impairment in rheumatoid arthritis patients compared to healthy controls.MethodsIn this cross-sectional study, the reproducibility was assessed by three separate digital X-rays of the right hand, with repositioning in 14 late rheumatoid arthritis patients and 14 healthy subjects. Then, trabecular bone texture of the MCP2 and MCP3 from patients enrolled in a prospective cohort of 78 rheumatoid arthritis patients was compared with that of 50 healthy subjects, using three texture parameters: Hmean, co-occurrence and run-length.ResultsThe coefficients of variation of the high resolution direct digital X-ray measurements ranged from 0.5 to 1.8%. Only the Hmean parameter was significantly decreased in rheumatoid arthritis patients compared to healthy subjects at MCP2 (0.637 ± 0.040 vs 0.654 ± 0.032, P < 0.05) and at MCP3 (0.646 ± 0.044 vs 0.665 ± 0.037, P < 0.05). This reduction was significantly correlated to disease activity.ConclusionsThis study demonstrated both the good reproducibility of the high resolution digital X-ray measurements and the trabecular bone texture impairment at MCP joints in rheumatoid arthritis patients. In addition to provide a high resolution hand radiograph, this technique may represent an interesting tool to easily quantify periarticular osteopenia with a low radiation dose.     

Prevalence of pain in adults with cystic fibrosis.

BACKGROUND: Cystic fibrosis (CF) may strongly condition the life of affected people. CF may be associated with relevant painful conditions caused by complications of the illness and also by therapy itself, which may represent an additional load of suffering. This study was aimed at evaluating the prevalence of pain symptoms in adult CF patients, if they are noticed and treated, and the influence of pain symptoms on patients' life. METHOD: Using a questionnaire, we examined 239 adults with CF (17% of the whole Italian adult CF population). RESULTS: We found a high prevalence of painful episodes among CF adult patients, as for both intensity and frequency. In a 2 months period 32.6% of patients experienced episodes of pain described as intense to severe, and 29.7% had more than 10 occurrences of pain in the same location. Headache, gastric pain and backache were the most frequently reported kind of pain. 59.8% of subjects perceived pain episodes as the cause of unfavorable effects on their life. Only 42.6% of those with pain asked a CF center physician for help and another 3.5% a general practitioner. CONCLUSION: Painful symptoms can be the cause of a worsening of the quality of life for adults with CF; the relevance of pain in CF adult patients may often be underestimated; the assessment of pain should be routinely performed as a part of care in CF centers.     

Atlantoaxial laxity in rheumatoid arthritis

We found that 14 of 162 rheumatoid arthritis patients with chronic occipitocervical pain had anterior atlantoaxial instability in the absence of any corresponding radiographic changes in the joint cartilage or subchondral bone. Our findings suggest that ligamentous instability is a prerequisite for this type of change. At the time of the detection of the instability, the median duration of disease was 12 (6-28) years. Rheumatoid occipitocervical pain may be initially caused by facet-joint arthritis or inflammation in the ligaments, and at a later stage also by irritation of the C2 nerve roots.     

Atlantoaxial laxity in rheumatoid arthritis

We found that 14 of 162 rheumatoid arthritis patients with chronic occipitocervical pain had anterior atlantoaxial instability in the absence of any corresponding radiographic changes in the joint cartilage or subchondral bone. Our findings suggest that ligamentous instability is a prerequisite for this type of change. At the time of the detection of the instability, the median duration of disease was 12 (6-28) years. Rheumatoid occipitocervical pain may be initially caused by facet -joint arthritis or inflammation in the ligaments, and at a later stage also by irritation of the C2 nerve roots.     

Weekly risedronate in kidney transplant patients with osteopenia

Daily bisphosphonate is effective in preventing and treating corticosteroid-induced osteoporosis in renal transplant recipients, although it frequently has gastrointestinal side effects. The aim was to assess efficacy and side effect profile of weekly oral risedronate. Eighty-four renal transplant patients, receiving either cyclosporin A or tacrolimus and steroids were prospectively included. The study group (39 patients) received 35 mg risedronate weekly, vitamin D and calcium, while control group (45 patients) only vitamin D and calcium. At baseline, 6 and 12 months, creatinine, calcium, phosphorus, alkaline phosphatase and iPTH were determined. Fractures and bone mineral densities were assessed by X-rays and dual-energy X-ray absorptiometry, respectively. Pain was assessed by clinical interview. Mineral bone density score increased significantly in risedronate group after 1 year. There were no differences in the incidence of fractures, although, anamnestic pain assessment revealed that 3% of treatment group reported to have bone pain compared with 18% in nontreatment group (P < 0.05). Follow-up calcium, phosphorus, alkaline phosphatases, and iPTH levels showed no differences from basal measures. Risedronate was well tolerated with no major side effects. Weekly oral risedronate in renal transplanted patients reduces bone mineral loss and bone pain and has an excellent side effect profile.     

Rheumatoide Arthritis: Diagnostik und Therapie 2012

Rheumatoid Arthritis (RA) should be suspected if patients do not only complain of joint pain, but suffer from joint swelling, sensation of heat, hyperemia and warmth around the joints. An arthritic joint pain should be most prominent at night time or early in the morning and cause morning stiffness (>?30?min) of the joint, exercise will improve the symptoms. Diagnosis of RA will be even more likely if wrists, MCP- or PIP joints are affected. Serologic procedures will test for rheumatoid factor or anti-citrullinated antibodies (CCP Ab). One needs to keep in mind that positive results for rheumatoid factor or CCP Ab alone never proves the diagnosis of RA. After diagnosis therapy should be started immediately, recruiting physiotherapy, pain medication, corticosteroids and disease-modifying anti-rheumatic drugs (DMARDs), primarily methotrexate. At the latest after failure of two DMARDs biologics like TNF-α-blockers, an Interleukin-6-Receptor-antibody, a B-cell-specific antibody or a rather T-cell-specific biologic will be initiated. Aim of therapy is freedom of symptoms of an ongoing arthritis, low dosage of immunosuppressants (especially corticosteroids maximally 5?mg/day), stop of radiological progression and prevention of long term consequences of inflammation like myocardial infarction, stroke or lymphoma.     

Injectable form of calcium sulphate as treatment of aneurysmal bone cysts

Background: Aneurysmal bone cysts (ABC) are a rare condition in adolescents and teenagers but may result in pain, fracture and growth abnormalities. The gold standard of open curettage carries the risk of surgical complications and still a local recurrence rate of 20–30%. Percutaneous treatment of ABC have rarely been reported and a poor response the usual outcome. This study investigated a new technique of percutaneous aspiration and injection of ABC using an aqueous solution of calcium sulphate. Methods: A radiological diagnosis of a bone cyst was made in 15 consecutive patients and pathologically confirmed as ABC. Most had already sustained a fracture and/or had been previously unsuccessfully treated by minimally invasive techniques including embolization or methylprednisolone injection. The procedure of aspiration and injection with calcium sulphate was undertaken, and the patients were reviewed regularly both clinically and radiologically for a minimum of 2 years. Results: The calcium sulphate cement was reabsorbed completely within 8 weeks. The first osseous response was periosteal new bone formation circumferentially followed by gradual opacification of the cystic cavity. All except one patient that described pain before the procedure reported complete relief of symptoms by 4 weeks. Two patients developed a local recurrence of the cyst, and one subsequently developed a pathological fracture. Two patients sustained pathological fractures through healed cysts, 12 and 22 months after the procedure, respectively. Conclusions: This new technique has shown good early clinical and radiological responses and a low complication rate in a consecutive group of patients with ABC.     

Patient-reported pain and impaired sleep quality in adult patients with cystic fibrosis

BackgroundSleep impairment has been described in patients with cystic fibrosis (CF). Pain is a known cause of sleep disturbance and as pain is commonly reported in patients with CF, we sought to find an association between impaired sleep quality and pain.MethodsFifty adult CF patients completed surveys of pain and sleep quality. The results were analyzed with additional clinical data including age, sex, nutritional status, and lung function.ResultsThirty-two patients (64%) reported recent pain and 33 patients (66%) reported abnormal sleep quality. The patients with pain report worse sleep quality than those without pain (p = 0.006). There was a strong correlation between impaired sleep quality and pain (p < 0.0001).ConclusionsWe found that pain and poor sleep quality are reported in a majority of adult CF patients and there is a strong correlation between the two. This will have important clinical implications in the evaluation and treatment of adult patients.     

Yellow nail syndrome associated with thiol compound therapy for rheumatoid arthritis. Two case reports

Yellow nail syndrome is characterized by ungual dystrophy, lower limb lymphedema, and pleural effusions or bronchiectasis. Rheumatoid arthritis is the autoimmune disorder most often associated with yellow nail syndrome. We report two new cases of yellow nail syndrome in patents receiving thiol compound therapy for rheumatoid arthritis. Eight similar cases have been reported since 1979, suggesting a possible causative effect of this class of drugs.     

Anterior interosseous nerve entrapment: (Kiloh-Nevin syndrome) report of seven cases.

Pain may be the earliest symptom of anterior interosseous nerve entrapment (Kiloh-Nevin syndrome), and seems not to have been described before. The arcuate ligament of Fearn and Goodfellow may entrap the median as well as the anterior interosseous nerves, in which case a patient may have numbness as well as pain. Rheumatoid disease and gouty arthritis may be a predisposing factor in anterior interosseous nerve entrapment.