10 Frakturen in 21 Jahren

A 78 year old woman had suffered ten spontaneous bone fractures, the first occurring when she was 57 years old. She is now wheel-chair bound. After 21 years, the underlying osteomalacia due to oligosymptomatic celiac disease with malabsorption was diagnosed. The treatment consists of a gluten free diet and substitution of calcium and vitamin D until there is a normalisation of calcium, vitamin D and alkaline phosphatase. Any spontaneous fracture deserves a careful search for metabolic bone disease. An elevation of alkaline phosphatase indicates osteomalacia rather than osteoporosis.     

Coeliac disease and risk of tuberculosis: a population based cohort study

BACKGROUND: Coeliac disease (CD) is an autoimmune disease often characterised by malnutrition and linked to a number of complications such as an increased risk of lymphoma, adverse pregnancy outcome, and other autoimmune diseases. Tuberculosis (TB) affects a large proportion of the world population and is more common in individuals with malnutrition. We investigated the risk of TB in 14 335 individuals with CD and 69 888 matched reference individuals in a general population based cohort study. METHODS: Cox proportional hazards method was used to calculate the risk of subsequent TB in individuals with CD. In a separate analysis, the risk of CD in individuals with prior TB was calculated using conditional logistic regression. RESULTS: CD was associated with an increased risk of subsequent TB (hazard ratio (HR) 3.74, 95% CI 2.14 to 6.53; p < 0.001). Similar risk estimates were seen when the population was stratified for sex and age at CD diagnosis. Individuals with CD were also at increased risk of TB diagnosed in departments of pulmonary medicine, infectious diseases, paediatrics, or thoracic medicine (HR 4.76, 95% CI 2.23 to 10.16; p < 0.001). The odds ratio for CD in individuals with prior TB was 2.50 (95% CI 1.75 to 3.55; p < 0.001). CONCLUSIONS: CD is associated with TB. This may be due to malabsorption and lack of vitamin D in persons with CD. Individuals with TB and gastrointestinal symptoms should be investigated for CD.     

Bone in celiac disease

Summary  Chronic inflammation and malabsorption in celiac disease (CD) can cause bone metabolism alterations and bone mineral loss in children and adults. Bone status before and after gluten-free diet, epidemiology of fractures, and possible treatment options for CD-related osteoporosis are presented. Controversial aspects of this complication of CD are discussed. The relationship between bone derangements and celiac disease (CD) was recognized almost 50 years ago, but many questions are still open. We are now aware that osteoporosis is a relatively frequent atypical presentation of CD, especially in adults, and that undiagnosed CD can be the cause of osteoporosis and related fractures. Chronic inflammatory intestinal diseases, including CD, can affect bone and mineral metabolism because of alterations in both systemic and local regulatory factors. The pathogenetic processes are still controversial, but two main mechanisms seem to be involved: intestinal malabsorption and the presence of chronic inflammation. This review analyzes the published data on bone involvement in children, adolescents, and adults either before or after a gluten-free diet. Special attention is paid to the epidemiology of fractures in celiac patients, considering that fractures are a major complication of osteoporosis and an important problem in the management of a chronic disease like CD. The usefulness of screening osteoporotic patients systematically for CD is still an open question, but some rules can be given. Finally, the current treatment options for children and adults are discussed. Recommendations for future clinical research are proposed.

Measurement of total resorption surface in iliac crest trabecular bone in man

Total resorption surface has been measured under ordinary light and polarized light in trabecular iliac crest bone from 57 healthy subjects and 40 patients with privational or malabsorption metabolic bone disease. Results obtained with the two methods were similar, although values for total resorption surface measured under polarized light were usually lower than those obtained under ordinary light in both groups of subjects studied. This most likely reflects the greater accuracy in the microscopic identification of resorption surface under polarized light.     

Celiac Disease and Metabolic Bone Disease

Celiac disease is a common autoimmune gastrointestinal disorder affecting multiple organs, precipitated in genetically vulnerable persons by the ingestion of gluten. Gluten is poorly digested and is presented to the intestinal mucosa as a large polypeptide. Binding to human leukocyte antigen-DQ2 and human leukocyte antigen-DQ8 molecules on antigen-presenting cells stimulates cellular and humeral immune reactions. Although common serological tests are available to diagnose celiac disease, the diagnosis of celiac disease is often delayed or missed because of lack of recognition as the disease presentation in adults is highly variable and may be asymptomatic. Celiac disease is a common secondary cause of metabolic bone disease and delayed treatment with gluten-free diet affects bone mineral density and fracture risk, so it is crucial to diagnose and treat celiac disease promptly. In this article, we will review recent studies of celiac disease in adults and provide practical, easily accessible information for busy clinicians.     

Bone and Celiac Disease

More than 50 % of untreated patients with celiac disease (CD) have bone loss detected by bone densitometry (dual-energy X-ray absorptiometry:DXA). Moreover, patients with CD are more likely to have osteoporosis and fragility fractures, especially of the distal radius. Although still controversial, we recommend DXA screening in all celiac disease patients, particularly in those with symptomatic CD at diagnosis and in those who present risk factors for fracture such as older age, menopausal status, previous fracture history, and familial hip fracture history. Bone microarchitecture, especially the trabecular network, may be deteriorated, explaining the higher fracture risk in these patients. Adequate calcium and vitamin D supplementation are also recommended to optimize bone recovery, especially during the first years of gluten free diet (GFD). If higher fracture risk persists after 1 or 2 years of GFD, specific osteoactive treatment may be necessary to improve bone health.     

Cellular immunodeficiency in Paget's disease of bone: Changes induced by treatment with elcatonin

Summary We have found a cellular immune defect (low CD4 T lymphocyte count, high CD8 T lymphocyte count and a low CD4/CD8 ratio) in 39 PDB patients. This finding is not correlated with the bone metabolic activity of the disease. There was an improvement in the cellular immune defect in fifteen patients after treatment with elcatonin. These changes could be related to the improvement in the metabolic derangement or else could be the consequence of an effect on altered immunity.     

Bone loss in celiac disease is related to secondary hyperparathyroidism.

Celiac disease is a major cause of intestinal malabsorption. Previous studies have demonstrated that celiac disease is associated with significant osteoporotic bone loss. These studies have suggested that successful treatment of the malabsorption is associated with amelioration of the bone loss. Such studies have failed to examine bone mass at peripheral skeletal sites which is more likely to be responsive to changes in parathyroid hormone (PTH) in response to calcium malabsorption. We have examined bone density in the lumbar spine, femoral neck, and distal forearm in 35 patients with celiac disease who had been established on gluten-free diet. In addition, the concentrations of PTH and 1,25-dihydroxyvitamin D (1,25(OH)2D) were measured. Bone density was below that expected for the subject's age and gender at all sites. This was most marked in the distal forearm where the bone density was 1.40 SD below expected (p < 0.0001). In the forearm, there was a negative relationship between bone density and PTH concentration (r = -0.49, p = 0.009). In the forearm and lumbar spine, there was a negative relationship between 1,25(OH)2D concentration and bone density. Bone mass was not related to the concentration of 25-hydroxyvitamin D at any of the skeletal sites measured. Bone density is reduced in the peripheral skeleton in celiac disease and this deficit persists despite treatment with apparent normalization at axial skeletal sites. This reduction in bone mass is related to the presence of secondary hyperparathyroidism which should be sought in all patients with treated celiac disease.     

PET-MRI for the Study of Metabolic Bone Disease

Purpose of Review

This review article attempts to summarize the current state and applications of the hybrid imaging modality of PET-MRI to metabolic bone diseases. The advances of PET and MRI are also discussed for metabolic bone diseases as potentially applied via PET-MRI.

Recent Findings

Etiologies and mechanisms of metabolic bone disease can be complex where molecular changes precede structural changes. Although PET-MRI has yet to be applied directly to metabolic bone disease, possible applications exist since PET, specifically ¹⁸F-NaF PET, can quantitatively track changes in bone metabolism and is useful for assessing treatment, while MRI can give detailed information on bone water concentration, porosity, and architecture through novel techniques such as UTE and ZTE MRI.

Summary

Earlier detection and further understanding of metabolic bone disease via PET and MRI could lead to better treatment and prevention. More research using this modality is needed to further understand how it can be implemented in this realm.

     

How Activity of Inflammatory Bowel Disease Influences Bone Loss

Bone loss is a common problem for individuals with inflammatory bowel disease (IBD). The aim of our study was to assess bone mineral density (BMD) in patients with IBD and to investigate the role of corticosteroid (CS) use and duration and activity of disease on BMD. Ninety-two patients (56 men and 36 women) with IBD, of whom 32 had ulcerative colitis (UC) and 60 had Crohn's disease (CD), underwent clinical assessment. Lumbar and femoral neck BMDs were measured by dual-energy X-ray absorptiometry. Osteopenia was observed in 14 patients (43%) with UC and in 24 patients (40%) with CD (p = 0.187). Four patients (12%) with UC and 7 patients (11%) with CD had osteoporosis (p = 0.308). Femoral BMD decreased in patients with long duration of CS use and correlated inversely with disease activity. Multiple regression analysis of BMD showed that statistically significant risk factors were duration of active disease and body mass index as well. Based on our results, it is necessary to take into account the risk of decreased BMD in patients with IBD. It is most important to achieve disease remission as soon as possible in addition to nutritional support.     

The Second Most Common Bone Disease: A Review on Paget’s Disease of Bone

Paget disease of bone (PDB) is the second most common metabolic bone disease. It is a chronic disease with a mono- or polyostotic appearance that is characterized by an increased bone turnover. The orthopedic surgeon is often confronted with such symptoms and complications as bone pain, skeletal deformities, and pathologic fractures caused by the “out-of-balance bone remodeling process”. Careful evaluation of the clinical and radiographic findings is necessary to determine whether treatment of PDB is indicated. The mode of action of effective pharmacological treatments consists of reducing the increase in osteoclast-mediated bone resorption that characterizes the disease. Bisphosphonates are the compounds of choice for PDB therapy; these are readily available and have received approval. Patients with PDB are at increased risk for surgical complications, such as blood loss and heterotopic bone formation, if operative treatment is necessary. However, advances in surgical techniques and accompanying medical treatment could potentially improve the overall outcome of these patients. To achieve that goal, careful perioperative interdisciplinary management and monitoring are essential. S. Seitz and M. Priemel have contributed equally to this work.     

Calcium Intake and Metabolic Bone Disease after Eight Years of Roux-en-Y Gastric Bypass

Background Roux-en-Y gastric bypass (RYGBP) has been found to be the most efficient way to lose weight and maintain the weight loss in morbid obesity. However, with the formation of a new stomach and the modification of intestinal anatomy, there are significant changes on physiological properties of these organs that lead to nutrient deficiency, including calcium. The objectives of this study were to evaluate calcium intake, bone metabolism, and prevalence of metabolic bone disease in women subjected to RYGBP after 8 years. Methods Food frequency questionnaire and 3-day dietary recall, laboratory tests of bone metabolism and bone mineral density were accessed. Results Calcium intake was below the recommendation in all women. Serum PTH and alkaline phosphatase were elevated, whereas vitamin D and urinary calcium were significantly lower. Also, a higher prevalence of metabolic bone disease than the one expected for the normal population at the same age was noted. Conclusion These data suggest that metabolic bone disease could be a complication of this type of surgery.     

Recognition of Chronic Kidney Disease in a General Medicine Outpatient Clinic

Abstract

Chronic kidney disease (CKD) is a major health problem. Recent emphasis has been to prevent the progression of CKD. We used chart audits to see if CKD was an under-recognized condition in a general medicine resident clinic. Data focused on recognition of CKD, 3 or 4, evaluation of metabolic bone disease, and anemia. A multifaceted educational initiative was developed and occurred between 2005 and 2010. Three retrospective chart audits were performed, in 2005 prior to the education and again in 2007 and 2010. In 2005, less than one-fifth of patients were identified as CKD, 3 or 4. Evaluation of bone disease and anemia is similar. Initial results were reviewed with the residents and handouts for metabolic bone monitoring were developed. Wall charts of the handouts were also posted. In 2007, CKD recognition increased slightly, but more patients had bone disease and anemia evaluations. After 2007, the only educational intervention was a CKD lecture given yearly. In 2010, the audit saw decreased recognition of CKD and a decline in metabolic bone monitoring. Although complete blood count (CBC) monitoring decreased, iron studies increased to 50% of patients. We conclude that despite educational initiatives and re-enforcement efforts with the internal medicine residents and attending staff, major issues related to CKD are not being recognized or addressed. With an increasing CKD population, attempts must be made to improve recognition and management. Novel strategies need to be developed.     

Bladder,bowel and bones—skeletal changes after intestinal urinary diversion

Impaired bone metabolism following urinary diversion through intestinal segments has always been a controversial subject of unclear clinical relevance. Whereas the perpetuated pathophysiological considerations seem conclusive in theory, the role of acidosis and malabsorption is less clear in animal experimentation and, even more so, in the clinical reality of modern continent diversion. In hardly any of the available contemporary case series was overt derangement of the acid-base balance, rickets or osteomalacia encountered. No consistent changes in osteotropic serum parameters could be found with normal calcium and phosphate in all patients. The assumption that colonic reservoirs have a higher risk of developing metabolic bone disease could not be confirmed by clinical data. As early correction of base excess is easy and probably a common policy in patients with intestinal urinary reservoirs, it will be virtually impossible to further study the natural history of bone metabolism after urinary diversion. While there is no need for a bone specific follow-up in asymptomatic adults with a normal acid-base balance, particular attention should be paid to children and to all patients with impaired renal function.     

New approaches to the problems of osteoporosis

Professor Urist's contributions to the understanding of osteoporosis are worthy of reevaluation at this time, when interest in the field has reached unprecedented heights. Recent advances in technology have greatly increased our understanding of osteoporosis by showing that there is no loss of bone in normal premenopausal women, and that the loss which starts at the menopause can be attributed to an increase in bone resorption. It is suggested that the primary event is a rise in plasma calcium that leads to a rise in obligatory urinary calcium loss, which in turn increases the calcium requirement. The subset of the postmenopausal population who develop fractures (particularly in the spine) show additional risk factors, which include malabsorption of calcium (which further increases bone resorption) and reduced adrenal androgen production (which may produce a fall in bone formation). The treatment of established cases requires control of bone resorption by calcium supplementation and/or hormone therapy, with the addition of calcitriol if malabsorption of calcium is present. Stimulation of bone formation is more difficult, but there is a suggestion that this may be possible with the use of anabolic steroids.     

Gene expression profile of the bone microenvironment in human fragility fracture bone

Osteoporosis (OP) is a common age-related systemic skeletal disease, with a strong genetic component, characterised by loss of bone mass and strength, which leads to increased bone fragility and susceptibility to fracture. Although some progress has been made in identifying genes that may contribute to OP disease, much of the genetic component of OP has yet to be accounted for. Therefore, to investigate the molecular basis for the changes in bone causally involved in OP and fragility fracture, we have used a microarray approach. We have analysed altered gene expression in human OP fracture bone by comparing mRNA in bone from individuals with fracture of the neck of the proximal femur (OP) with that from age-matched individuals with osteoarthritis (OA), and control (CTL) individuals with no known bone pathology. The OA sample set was included because an inverse association, with respect to bone density, has been reported between OA and the OP individuals. Compugen H19K oligo human microarray slides were used to compare the gene expression profiles of three sets of female samples comprising, 10 OP-CTL, 10 OP-OA, and 10 OA-CTL sample pairs. Using linear models for microarray analysis (Limma), 150 differentially expressed genes in OP bone with t scores >5 were identified. Differential expression of 32 genes in OP bone was confirmed by real time PCR analysis (p<0.01). Many of the genes identified have known or suspected roles in bone metabolism and in some cases have been implicated previously in OP pathogenesis. Three major sets of differentially expressed genes in OP bone were identified with known or suspected roles in either osteoblast maturation (PRRX1, ANXA2, ST14, CTSB, SPARC, FST, LGALS1, SPP1, ADM, and COL4A1), myelomonocytic differentiation and osteoclastogenesis (TREM2, ANXA2, IL10, CD14, CCR1, ADAM9, CCL2, CTGF, and KLF10), or adipogenesis, lipid and/or glucose metabolism (IL10, MARCO, CD14, AEBP1, FST, CCL2, CTGF, SLC14A1, ANGPTL4, ADM, TAZ, PEA15, and DOK4). Altered expression of these genes and others in these groups is consistent with previously suggested underlying molecular mechanisms for OP that include altered osteoblast and osteoclast differentiation and function, and an imbalance between osteoblastogenesis and adipogenesis.     

High prevalence of vitamin K and D deficiency and decreased BMD in inflammatory bowel disease

Summary  Vitamin K and D deficiency and decreased bone mineral density (BMD) were highly prevalent in patients with inflammatory bowel disease (IBD), especially Crohn’s disease (CD). Dietary intakes of these vitamins, however, were above the Japanese adequate intakes in IBD patients, suggesting that malabsorption is the basis for hypovitaminosis K and D and decreased BMD. Introduction  We have studied the possible involvement of vitamin K and D deficiency in the pathogenesis of decreased BMD in IBD. Methods  Seventy patients with IBD were evaluated for their BMD; plasma levels of vitamin K; phylloquinone (PK), menaquinone-7 (MK-7), and 25OH-D; serum PTH, protein induced by vitamin K absence (PIVKA-II), and undercarboxylated osteocalcin (ucOC) levels; and their food intake. Results  Compared with ulcerative colitis (UC) patients, CD patients had significantly lower plasma vitamin K and 25OH-D concentrations; significantly higher serum levels of PTH, PIVKA-II, and ucOC; and significantly lower BMD scores at almost all measurement sites. More IBD patients were vitamin K deficient in bone than in liver. Multiple regression analyses revealed that low plasma concentrations of vitamin K and 25OH-D were independent risk factors for low BMD and that they were associated with the patients’ fat intake, but not with their intake of these vitamins. Conclusion  IBD patients have high prevalence of decreased BMD and vitamin K and D deficiency probably caused by malabsorption of these vitamins.     

Mineral and Bone Disease in Kidney Transplant Recipients

Purpose of Review

Despite metabolic improvements following kidney transplantation, transplant recipients still often suffer from complex mineral and bone disease after transplantation.

Recent Findings

The pathophysiology of post-transplant disease is unique, secondary to underlying pre-transplant mineral and bone disease, immunosuppression, and changing kidney function. Changes in modern immunosuppression regimens continue to alter the clinical picture. Modern management includes reducing cumulative steroid exposure and correcting the biochemical abnormalities in mineral metabolism. While bone mineral density screening appears to help predict fracture risk and anti-osteoporotic therapy appears to have a positive effect on bone mineral density, more data regarding specific treatment is necessary.

Summary

Patients with mineral and bone disease after kidney transplantation require special care in order to properly manage and mitigate their mineral and bone disease. Recent changes in clinical management of transplant patients may also be changing the implications on patients’ mineral and bone disease.

     

Familial Celiac Disease Remission as a Result of a Full Donor Immunologic Recovery After Sibling Cord Blood Transplantation for Chronic Granulomatous Disease: A Case Report

We present a case report of a boy diagnosed with both chronic granulomatous disease (CGD) and familial celiac disease (CD) who underwent cord blood transplantation from a partially matched sibling donor. The presentation of CD resembled Crohn-like enteropathy, which is a canonical manifestation of CGD. Nearly 1 year post-hematopoietic stem cell transplantation (HSCT), a gluten-containing diet was reintroduced, and no reappearance of clinical, serologic, or histologic markers of CD was observed. The relatively high incidence of rare genetic diseases in pediatric patients suggests the need for additional caution in the interpretation of symptoms mimicking already known hallmarks of more common conditions. In addition, the presented data confirm the previous rare observations that allogeneic HSCT leads to durable induction of gluten tolerance in patients with CD, which can warrant its use in patients with refractory subtypes of CD.     

Is There Any Association Between the Presence of Bone Disease and Cumulative Exposure to Lead?

There is evidence from cell culture experiments, animal studies, and from measurements in humans that lead may exert detrimental effects on bone mineral metabolism. In order to explore a possible association between lead and bone disease, both cortical and trabecular bone lead content as well as serum lead concentration was measured in 117 patients who attended a metabolic bone disease clinic (n = 92) or were undergoing dialysis for renal failure (n = 25). Cortical bone lead content was higher in patients suffering from Paget's disease than it was in controls, patients with osteoporosis, and patients on dialysis. Trabecular bone lead content was lowest in patients with Paget's disease or osteitis fibrosa. There was no association between bone lead content and serum alkaline phosphatase concentration in patients suffering from osteoporosis. No statistically significant differences in serum lead concentrations were found between groups. Our results do not distinguish between the two possibilities that increased bone turnover due to Paget's disease releases lead from trabecular bone which is then available for deposition into cortical bone or the alternative possibility that an increased lead content in cortical bone may cause increased turnover with release of lead from trabecular bone. Received: 29 April 1997 / Accepted: 26 January 1998