Glycogen storage disease type 1a is associated with disturbed vitamin A metabolism and elevated serum retinol levels.

Glycogen storage disease type 1a (GSD Ia) is an inborn error of metabolism caused by mutations in the G6PC gene, encoding the catalytic subunit of glucose-6-phosphatase. Early symptoms include severe fasting intolerance, failure to thrive and hepatomegaly, biochemically associated with nonketotic hypoglycemia, fasting hyperlactidemia, hyperuricemia and hyperlipidemia. Dietary management is the cornerstone of treatment aiming at maintaining euglycemia, prevention of secondary metabolic perturbations and long-term complications, including liver (hepatocellular adenomas and carcinomas), kidney and bone disease (hypovitaminosis D and osteoporosis). As impaired vitamin A homeostasis also associates with similar symptoms and is coordinated by the liver, we here analysed whether vitamin A metabolism is affected in GSD Ia patients and liver-specific G6pc-/- knock-out mice. Serum levels of retinol and retinol binding protein 4 (RBP4) were significantly increased in both GSD Ia patients and L-G6pc-/- mice. In contrast, hepatic retinol levels were significantly reduced in L-G6pc-/- mice, while hepatic retinyl palmitate (vitamin A storage form) and RBP4 levels were not altered. Transcript and protein analyses indicate an enhanced production of retinol and reduced conversion the retinoic acids (unchanged LRAT, Pnpla2/ATGL and Pnpla3 up, Cyp26a1 down) in L-G6pc-/- mice. Aberrant expression of genes involved in vitamin A metabolism was associated with reduced basal messenger RNA levels of markers of inflammation (Cd68, Tnfα, Nos2, Il-6) and fibrosis (Col1a1, Acta2, Tgfß, Timp1) in livers of L-G6pc-/- mice. In conclusion, GSD Ia is associated with elevated serum retinol and RBP4 levels, which may contribute to disease symptoms, including osteoporosis and hepatic steatosis.

Bone mineral density improves during 2 years of treatment with bisphosphonates in patients with ankylosing spondylitis.

AIMS: To evaluate whether 2 years of treatment with bisphosphonates in combination with calcium/vitamin D supplements has an effect on lumbar spine and hip bone mineral density (BMD) in ankylosing spondylitis (AS) patients starting tumour necrosis factor-α inhibitors or receiving conventional treatment. Secondly, to explore the development of radiographic vertebral fractures. METHODS: Patients from the Groningen Leeuwarden AS cohort receiving bisphosphonates based on clinical indication and available 2-year follow-up BMD measurements were included. BMD of lumbar spine (L1-L4) and hip (total proximal femur) were measured using dual-energy X-ray absorptiometry. Spinal radiographs (Th4-L4) were scored for vertebral fractures according to the Genant method. RESULTS: In the 20 included patients (median 52 years, 14 males), lumbar spine and hip BMD Z-scores increased significantly; median from -1.5 (interquartile range [IQR] -2.2 to 0.4) to 0.1 (IQR -1.5 to 1.0); P < .001 and median from -1.0 (IQR -1.6 to -0.7) to -0.8 (IQR -1.2 to 0.0); P = .006 over 2 years, respectively. In patients also treated with tumour necrosis factor-α inhibitors (n = 11), lumbar spine and hip BMD increased significantly (median 2-year change +8.6% [IQR 2.4 to 19.6; P = .009] and +3.6% [IQR 0.7-9.0; P = .007]). In patients on conventional treatment (n = 9), lumbar spine BMD increased significantly (median 2-year change +3.6%; IQR 0.7 to 9.0; P = .011) and no improvement was seen in hip BMD (median -0.6%; IQR -3.1 to 5.1; P = .61). Overall, younger AS males with limited spinal radiographic damage showed most improvement in lumbar spine BMD. Four mild radiographic vertebral fractures developed in 3 patients and 1 fracture increased from mild to moderate over 2 years in postmenopausal women and middle-aged men. CONCLUSION: This explorative observational cohort study in AS showed that 2 years of treatment with bisphosphonates in combination with calcium/vitamin D supplements significantly improves lumbar spine BMD. Mild radiographic vertebral fractures still occurred.

Long-term drug survival and clinical effectiveness of etanercept treatment in patients with ankylosing spondylitis in daily clinical practice.

OBJECTIVES: Randomised controlled trials and open-label extension studies have demonstrated the clinical efficacy and safety of tumour necrosis factor-alpha (TNF-α) blocking therapy in pre-selected study patients with ankylosing spondylitis (AS). Our aim was to investigate the 7-year drug survival and clinical effectiveness of etanercept treatment in AS patients in daily clinical practice. METHODS: Consecutive AS patients from the prospective observational GLAS cohort who started etanercept because of active disease were included and evaluated over 7 years according to a fixed protocol. Continuation of treatment was based on BASDAI improvement and/or expert opinion. RESULTS: Of the 89 included AS patients, 45 (51%) were still using etanercept at 7 years of follow-up. Reasons for treatment discontinuation were adverse events (n=22), inefficacy (n=13), or other reasons although good clinical response (n=9). Etanercept treatment resulted in a rapid (after 6 weeks) and sustained improvement in disease activity (BASDAI, ASDAS, CRP, physician GDA), spinal mobility, physical function (BASFI), quality of life (ASQoL), and extra-spinal manifestations (swollen joints, tender joints and tender entheses). Furthermore, concomitant NSAID or DMARD use decreased significantly during follow-up. At 7 years, low disease activity and remission were present in 67-73% and 29-30% of the 45 patients, respectively. Of the patients who discontinued etanercept, 18 switched successfully to a second or third TNF-α blocker during follow-up. CONCLUSIONS: In a large cohort of AS patients treated with etanercept, approximately 50% continued this treatment for 7 years. Our broad evaluation of clinical endpoints proves the long-term effectiveness of etanercept treatment in daily clinical practice.

Radiographic vertebral fractures develop in patients with ankylosing spondylitis during 4 years of TNF-α blocking therapy.

OBJECTIVES: To determine the prevalence and incidence of radiographic vertebral fractures in ankylosing spondylitis (AS) patients treated with TNF-α blocking therapy for 4 years and to explore the relationship with patient characteristics, clinical assessments, radiographic damage, and bone mineral density (BMD). METHODS: This study included consecutive AS patients with active disease from the Groningen Leeuwarden AS (GLAS) cohort treated with TNF-α blocking therapy for 4 years and with available thoracic and lumbar radiographs at baseline and at 4 years. Vertebral fractures were assessed by two readers (mild: ≥20-<25%, moderate: ≥25-<40%, severe: ≥40% reduction in vertebral height). RESULTS: In 27 of 105 (26%) AS patients, radiographic vertebral fractures were observed at baseline. These patients were significantly older, had larger occiput-to-wall distance, and more spinal radiographic damage. During 4 years of TNF-α blocking therapy, 21 (20%) patients developed at least one new fracture. Older age, smoking, higher BASFI, low lumbar spine BMD (Z-score ≤-2), presence of moderate vertebral fractures, and use of anti-osteoporotic treatment at baseline were associated with the development of new fractures. Most fractures were mild and occurred in the thoracic spine. The improvement in lateral spinal mobility and lumbar spine BMD during treatment was significantly less in patients with new fractures (median change of 0.8 vs. 2.8 cm and 0.3 vs. 0.8 Z-score, respectively). CONCLUSIONS: The prevalence of radiographic vertebral fractures was high in AS patients with active disease. Although clinical assessments and BMD improved significantly, new vertebral fractures still developed during 4 years of TNF-α blocking therapy.

Diminished reliability of tryptase as risk indicator of mastocytosis in older overweight subjects.

BACKGROUND: Currently, measurement of serum tryptase level is the most commonly used test to estimate the need for bone marrow biopsy in patients suspected to have indolent systemic mastocytosis (ISM). Yet tryptase levels do not solely reflect the mast cell load and can be elevated by overweight, older age, and impaired renal function. The influence of these factors on urinary methylhistamine (MH) and methylimidazole acetic acid (MIMA) is still unknown. OBJECTIVE: We investigated the impact of age, body mass index (BMI), and kidney function on the diagnostic accuracy of tryptase, MH, and MIMA to select the most optimal test indicating the necessity of a bone marrow biopsy in ISM-suspected patients. METHODS: Retrospective data analysis of all adults in whom bone marrow investigations were performed because of high clinical suspicion and/or elevated tryptase, MH, or MIMA. RESULTS: 194 subjects were included. ISM was present in 112 and absent in 82 subjects (non-ISM). Tryptase was elevated by age and body weight in non-ISM subjects and by BMI in ISM subjects; however, these factors did not influence MH or MIMA. In the total study population, the diagnostic accuracy of tryptase, MH, and MIMA were comparable (area under the curve 0.80, 0.80, and 0.83). In subjects >50 years with a BMI >25 kg/m(2), the diagnostic accuracy of MIMA was higher compared with that of tryptase (area under the curve 0.93 vs 0.74; P = .011). CONCLUSION: In ISM-suspected patients >50 years with a BMI of >25 kg/m(2), MIMA has a greater value compared with tryptase in estimating the need for bone marrow biopsy.

Patient-tailored dose reduction of TNF-α blocking agents in ankylosing spondylitis patients with stable low disease activity in daily clinical practice.

OBJECTIVES: Tumour necrosis factor-alpha (TNF-α) blocking agents are very effective in controlling systemic inflammation and improving clinical assessments in ankylosing spondylitis (AS). In view of potential side effects and high costs of long-term treatment, our aim was to investigate whether dose reduction of TNF-α blocking agents is possible without loss of effectiveness in AS patients in daily clinical practice. METHODS: Patients from the prospective observational GLAS cohort, fulfilling the modified New York criteria for AS, with active disease before start of TNF-α blocking therapy and stable (≥6 months) low disease activity on the conventional dose regimen, who started with dose reduction of TNF-α blocking therapy before June 2011 were studied. Dose reduction was patient-tailored (step-by-step approach) and consisted of lowering the dose and/or extending the interval between doses. RESULTS: Between June 2005 and March 2011, 58 AS patients started dose reduction of etanercept (n=39), infliximab (n=10), or adalimumab (n=9). Of all patients, 74%, 62%, and 53% maintained their reduced dose or dosing frequency after 6, 12, and 24 months, respectively. The mean dose of TNF-α blocking therapy over time corresponded to 62% of the standard dose regimen. Disease activity remained low in the majority of patients who maintained dose reduction after 24 months (94% had BASDAI<4). If there was recurrence of disease symptoms, patients achieved good clinical response after returning to the conventional regimen (88% reached BASDAI<4). CONCLUSIONS: In this observational cohort, patient-tailored dose reduction of TNF-α blocking agents was successful preserving stable low disease activity over 24 months in approximately half of the AS patients.

Predictors of new fragility fractures after diagnosis of indolent systemic mastocytosis.

BACKGROUND: Fragility fractures (FFxs) and osteoporosis occur frequently in patients with indolent systemic mastocytosis (ISM), even before 50 years of age. OBJECTIVE: We sought to develop a prediction model to identify individual patients with ISM at risk of new FFxs. METHODS: Data on lifetime fractures and trauma circumstances were collected from vertebral morphometry, patients' records, and questionnaires. Clinical, lifestyle, and bone characteristics were measured. Patients receiving treatment for osteoporosis before ISM diagnosis or with missing bone data were excluded from FFx risk assessment. RESULTS: In total, 389 lifetime fractures occurred in 127 of the 221 patients with ISM (age, 19-77 years), including 90 patients with 264 FFxs. Median follow-up after diagnosis was 5.4 years (range, 0.4-15.3 years), with 5- and 10-year FFx risks of 23% ± 3% and 31% ± 4%, respectively. Male sex, high levels of bone resorption (serum type I collagen C-telopeptide), low hip bone mineral density, absence of urticaria pigmentosa, and alcohol intake at the time of ISM diagnosis were independent predictors of future FFxs. The MastFx score, a prediction model using these 5 characteristics, showed good accuracy (area under the curve, 0.80) to determine the risk of new FFxs. QFracture, a validated risk scoring tool for persons aged 30 to 99 years, was not useful in patients with ISM. CONCLUSION: The MastFx score distinguishes patients with ISM at high, intermediate, and low risk of new FFxs. The included characteristics sex, serum type I collagen C-telopeptide, hip bone mineral density, urticaria pigmentosa, and alcohol intake are easy to collect in clinical practice. The high occurrence of FFxs in patients with ISM underlines the importance of optimizing bone quality and early start of therapeutic prevention in patients at risk.

Clinical studies on bone-related outcome and the effect of TNF-α blocking therapy in ankylosing spondylitis.

PURPOSE OF REVIEW: To provide an overview of clinical trials and observational studies investigating the effect of tumor necrosis factor-alpha (TNF-α) blocking therapy on bone formation and bone loss in patients with ankylosing spondylitis (AS). RECENT FINDINGS: The effect of TNF-α blocking therapy on excessive bone formation or osteoproliferation remains inconclusive. Radiographic assessment of spinal osteoproliferation is complicated by the overall slow rate of progression and the high variability between individual AS patients. Multiple studies demonstrated that TNF-α blocking therapy results in a significant increase in bone mineral density (BMD) at the lumbar spine and hip. Based on bone turnover marker (BTM) analysis, this can mainly be explained by an increase in mineralization and decrease in bone resorption. SUMMARY: Both osteoproliferation (e.g. syndesmophytes and ankylosis of vertebrae) and excessive bone loss resulting in osteoporosis and vertebral fractures are frequently present in AS. Previous studies showed that BMD increases during TNF-α blocking therapy. Long-term follow-up in a large cohort of patients is needed to investigate whether TNF-α blockers can consolidate or stop spinal osteoproliferation and prevent vertebral fractures. Future studies should focus on the effect of these agents on bone-related outcome in AS patients with early vs. advanced disease.

Procollagen type I N-terminal peptide in preterm infants is associated with growth during the first six months post-term.

OBJECTIVE: To identify growth-related collagen and bone parameters in small-for-gestational-age (SGA) and appropriate-for-gestational-age (AGA) preterm infants during the first six months post-term. In SGA preterm infants, increased growth and decreased bone acquisition, which we demonstrated previously, may be reflected by these markers. DESIGN: Observational study within a randomized controlled trial. PATIENTS: Thirty-three SGA (weight, length or both at birth <-2 SDS) and 98 AGA preterm infants (gestational age [median (IQR)]: 31·1 (1·6) vs 30·3 (2·0) weeks; 72·7% vs 42·9% boys). MEASUREMENTS: Weight (g), length (cm), procollagen type I N-terminal peptide (PINP; µg/l), urinary helical peptide (UHP; µg/mmol creatinine) and alkaline phosphatase (ALP; U/l) expressed as standard deviation scores (SDS) at term age, three and six months post-term. RESULTS: Weight and length gain during the first six months post-term and PINP SDS at term age, three months and six months post-term were higher in SGA compared with AGA infants. UHP SDS and ALP SDS were similar in SGA and AGA infants. PINP SDS and UHP SDS at term age and PINP SDS at three months were associated with subsequent weight and length gain until six months post-term. CONCLUSIONS: Increased growth in SGA compared with AGA preterm infants is reflected by increased collagen type I synthesis during the first six months post-term, suggesting that PINP and UHP correspond with growth in preterm infants. An explanation for decreased bone acquisition of SGA preterm infants may be that increased collagen type I synthesis is not directly followed by increased bone mineralization.

Higher mast cell load decreases the risk of Hymenoptera venom-induced anaphylaxis in patients with mastocytosis.

BACKGROUND: Increased basal serum tryptase (bsT) levels are a well-described risk factor for Hymenoptera venom-induced anaphylaxis (HVAn) in patients allergic to Hymenoptera venom. Increased bsT levels might also indicate the presence of mastocytosis. In this study we evaluated whether the risk of HVAn increases with increasing mast cell load in patients with mastocytosis. METHODS: Consecutive patients with different subtypes of mastocytosis (n = 329) admitted to the University Medical Center Groningen were retrospectively assessed. As markers for mast cell load, levels of both bsT and the urinary histamine metabolites methylhistamine and methylimidazole acetic acid (MIMA) were used. RESULTS: In the entire patient group, irrespective of disease subtype and Hymenoptera venom exposure, HVAn prevalence gradually increased with increasing marker levels to a maximum of 36% to 47% at a bsT level of 28.0 µg/L, a methylhistamine level of 231.0 µmol/mol creatinine, and a MIMA level of 2.7 mmol/mol creatinine but decreased thereafter with a further increase in these levels. In patients with indolent systemic mastocytosis with a history of Hymenoptera venom exposure after age 15 years or greater (n = 152), MIMA and age at the most recent Hymenoptera sting were independent predictors for HVAn (odds ratios of 0.723 [P = .001] and 1.062 [P < .001], respectively). CONCLUSIONS: In patients with mastocytosis, HVAn prevalence does not increase constantly with increasing levels of mast cell load parameters: after a gradual increase to a maximum of near 50%, it decreases with a further increase in these levels. In the indolent systemic mastocytosis population, all mast cell load markers were independent negative predictors of HVAn. These findings suggest a complex pathophysiologic association between mast cell load and HVAn risk in patients with mastocytosis.

After an initial balance favoring collagen formation and mineralization, bone turnover markers return to pre-treatment levels during long-term TNF-α inhibition in patients with ankylosing spondylitis.

BACKGROUND: Bone turnover balance favors bone formation, especially mineralization, during the first 3 years of treatment with TNF-α inhibitors (TNFi). Our aim was to evaluate the course of serum bone turnover markers (BTM) and to investigate if facilitation of mineralization reflected by BTM BALP continues to increase during 6 years of TNFi treatment in patients with ankylosing spondylitis (AS) in daily clinical practice. METHODS: Included were outpatients from the University Medical Center Groningen (UMCG) participating in the Groningen Leeuwarden Axial SpA (GLAS) cohort who were treated with TNFi for at least 6 years. Serum markers of collagen resorption, bone regulation, collagen formation and facilitator of bone mineralization (sCTX, OC, PINP and BALP, respectively) were measured at baseline, 3 and 6 months, 1, 2, 4 and 6 years. Z-scores were calculated to correct for age and gender. RESULTS: 53 AS patients were eligible for analyses (66% male, mean age 39±11 years). Disease activity showed rapid and sustained improvement after start of TNFi. Evaluating BTM, sCTX did not significantly change during 6 years of treatment. OC was only significantly increased at 3 months compared to baseline, with median change in Z-score of +0.5. PINP significantly increased at 3 and 6 months and 2 years of treatment, with maximum median change in Z-score of +0.3. Interestingly, BALP was significantly increased at all time points up to and including 2 years of TNFi treatment, with maximum change in median Z-score of +1.2, and decreased thereafter. CONCLUSION: In AS patients receiving long-term TNFi, bone turnover balance favored collagen formation and facilitation of mineralization during the first 2 years of treatment. Thereafter, at 4 and 6 years of follow-up, BTM Z-scores returned to pre-treatment levels.

Serum levels of bone turnover markers including calculation of Z-scores: Data from a Dutch healthy reference cohort.

Introduction: Bone turnover markers (BTM) are biochemical compounds reflecting different stages of bone metabolism. Their levels change with age and differ between males and females. This makes clinical interpretation and comparison more difficult. Therefore, our aim was to establish BTM reference values which can be used to calculate Z-scores for use in daily clinical practice. Methods: Serum markers of collagen resorption, bone formation/regulation, collagen formation and bone mineralization (sCTX, OC, PINP and BALP, respectively) were measured in non-fasting volunteers without bone-related abnormalities. Raw data was plotted and gender-specific age cohorts were established with their respective means and standard deviations (SD). Z-scores can be calculated using these reference values to correct for the influence of age and gender on BTM. Results: In total, 856 individuals were included of which 486 (57 %) were female. Individuals were aged between 7 and 70 years. Highest serum levels of BTM were found in childhood and puberty. Peak levels are higher in boys than girls and prevail at later ages. In adults, BTM levels decrease before reaching stable nadir levels. In adults, 10-year reference cohorts with means and SD were provided to calculate Z-scores. Conclusion: With our data, Z-scores of sCTX, OC, PINP and BALP can be calculated using reference categories (for age and gender) of Caucasian healthy volunteers. Clinicians can use BTM Z-scores to determine whether there are changes in bone turnover physiology beyond those expected during aging. BTM Z-scores facilitate harmonization of data interpretation in daily clinical practice and research.

Baseline predictors of response to TNF-α blocking therapy in ankylosing spondylitis.

PURPOSE OF REVIEW: Identifying the characteristics of patients with ankylosing spondylitis (AS) before start of treatment which are able to predict a beneficial response to tumor necrosis factor-alpha (TNF-α) blocking therapy is relevant, especially in view of the high costs and potential side-effects of these agents. This review provides an overview of clinical trials and observational studies investigating baseline predictors of response after 3-6 months of TNF-α blocking therapy and baseline predictors of long-term anti-TNF-α treatment continuation in AS. RECENT FINDINGS: In multiple studies, increased acute phase reactants, higher disease activity, higher functional status, younger age, and HLA-B27 positivity were identified as independent baseline predictors of achieving clinical response to TNF-α blocking therapy. Increased acute phase reactants, presence of peripheral arthritis, and male sex were repeatedly identified as independent baseline predictors of anti-TNF-α treatment continuation. SUMMARY: Several studies using multivariate analyses identified comparable baseline predictors of response and/or continuation of TNF-α blocking therapy. The single predictors identified have, at best, moderate capacity to predict treatment response in the individual patient. The development of a prediction model may lead to a more robust instrument to support physicians in decision making on TNF-α blocking therapy in AS in daily clinical practice.

Fracture Risk Reduction by Bisphosphonates in Mastocytosis?

BACKGROUND: Fragility fractures (FFxs) and osteoporosis are frequent manifestations of indolent systemic mastocytosis (ISM). So far, the effect of antiosteoporotic therapy on FFxs has scarcely been investigated. OBJECTIVE: This study evaluates the long-term effect of bisphosphonate treatment on FFxs, bone mineral density (BMD), and bone resorption in patients with ISM in daily clinical practice. METHODS: Patients with ISM who received bisphosphonates because of osteoporosis and/or FFxs were retrospectively analyzed (n = 58). Fractures were recorded by vertebral fracture assessment, X-rays of the thoracolumbar spine, medical records, and a questionnaire. Five-year analysis (n = 30) was made by comparing observed 5-year FFx risk with MastFx-predicted FFx risk for patients with ISM not treated with antiosteoporotic drugs and analyzing 5-year change in BMD and serum collagen C telopeptide (sCTx) Z-scores. RESULTS: During the median follow-up of 7.3 years, 14 of 58 patients suffered 40 FFxs. Five- and 10-year FFx-free survival were 81.9% (standard error [SE], 5.5%) and 67.0% (SE, 7.7%), respectively. FFx risk was significantly higher in patients with previous vertebral FFxs (P = .004), lower femoral BMD at baseline (P = .042), and history of anaphylaxis (P = .028). No 5-year FFx risk reduction could be proven, possibly due to the small sample size. The lumbar BMD Z-score significantly increased from median (interquartile range [IQR]) -2.20 (-2.80 to -1.50) to -1.50 (-2.30 to -0.60) (P < .001, n = 27). The sCTx Z-score decreased from median 0.71 (IQR, -0.59 to 2.39) to -0.95 (-1.30 to -0.16) (P = .008, n = 15). CONCLUSION: Bisphosphonates significantly increase BMD and decrease sCTx in patients with ISM. However, FFxs still frequently occur. Especially patients with previous FFxs remain at high risk of new FFxs.

Biochemical markers predictive for bone marrow involvement in systemic mastocytosis.

Systemic mastocytosis is characterized by bone marrow involvement, which requires a bone marrow biopsy for diagnostic work-up. We questioned whether bone marrow involvement could be predicted using biochemical markers. We selected patients with various symptoms suggestive of indolent systemic mastocytosis, of whom 63 ultimately had bone marrow involvement. Patients suspected of aggressive mastocytosis, or mastocytosis associated with other hematologic diseases were excluded. Evaluation of 115 patients and 15 patient controls demonstrated a test accuracy for serum tryptase, urinary N(-) methylhistamine and N(-) methylimidazole acetic acid of 96%, 88% and 95% respectively. These markers provide an excellent pre-test probability of indolent systemic mastocytosis.

Side effects of pharmacotherapy on bone with long-acting gonadorelin agonist triptorelin for paraphilia.

INTRODUCTION: There have been limited research studies concerning the use of libido inhibitors for the treatment of patients with a paraphilia. Observational studies suggest that agents that lower testosterone are an effective treatment for paraphilia. AIM: We report a case of hormonal treatment of paraphilia that was associated with side effects. METHOD: A 35-year-old man with a paraphilia was treated with long-acting gonadorelin. RESULTS: The desired result was reduced preoccupation with sexuality, but there were various side effects including a serious amount of bone loss. CONCLUSION: We believe that more attention should be given to the adverse effects of long-term treatment with triptorelin. In our view the drug regime needs to be revised.

High prevalence of morphometric vertebral deformities in patients with inflammatory bowel disease.

BACKGROUND: Earlier studies have documented that the prevalence of decreased bone mineral density (BMD) is elevated in patients with inflammatory bowel disease. The objective of this study was to investigate the prevalence of vertebral deformities in inflammatory bowel disease patients and their relation with BMD and bone turnover. METHODS: One hundred and nine patients with Crohn's disease (CD) and 72 with ulcerative colitis (UC) (age 44.5+/-14.2 years) were studied. BMD of the hip (by dual X-ray absorptiometry) was measured and a lateral single energy densitometry of the spine for assessment of vertebral deformities was performed. Serum markers of bone resorption (carboxy-terminal cross-linked telopeptide of type I collagen) and formation (procollagen type I amino-terminal propeptide) were measured, and determinants of prevalent vertebral deformities were assessed using logistic regression analysis. RESULTS: Vertebral deformities were found in 25% of both CD and UC patients. Comparing patients with and without vertebral deformities, no significant difference was found between Z-scores and T-scores of BMD, or levels of serum carboxy-terminal cross-linked telopeptide of type I collagen and serum procollagen type I amino-terminal propeptide. Using logistic regression analysis the only determinant of any morphometric vertebral deformity was sex. The presence of multiple vertebral deformities was associated with older age and glucocorticoid use. CONCLUSION: The prevalence of morphometric vertebral deformities is high in CD and UC. Male sex, but neither disease activity, bone turnover markers, clinical risk factors, nor BMD predicted their presence. The determinants for having more than one vertebral deformity were age and glucocorticoid use. This implies that in addition to screening for low BMD, morphometric assessment of vertebral deformities is warranted in CD and UC.

Ankylosing spondylitis disease activity score is related to NSAID use, especially in patients treated with TNF-α inhibitors.

BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) are regarded as the cornerstone of conventional treatment for AS. However little is known about concomitant NSAID use during treatment (with TNF-α inhibitors) in daily clinical practice. METHODS AND FINDINGS: Consecutive patients from the GLAS cohort were included. NSAID use and ASAS-NSAID index were evaluated at group level and at individual patient level during 52 weeks of follow-up. Analyses were stratified for treatment regimen. Generalized estimating equations (GEE) was used to evaluate NSAID use in relation to assessments of disease activity over time. In patients starting TNF-α inhibitors (n = 254), 79% used NSAIDs at baseline and this proportion decreased significantly to 38% at 52 weeks. ASAS-NSAID index also decreased significantly from median 65 to 0. In patients on conventional treatment (n = 139), 74% used NSAIDs at baseline with median ASAS-NSAID index of 50 and this remained stable during follow-up. At each follow-up visit, approximately half of the patients changed their type or dose of NSAIDs. GEE analysis over time showed that NSAID use was associated with AS disease activity score (p<0.05). This relation was more pronounced in patients treated with TNF-α inhibitors compared to conventional treatment (B = 0.825 vs. B = 0.250). CONCLUSIONS: In this observational cohort of established AS patients, there was no difference in baseline NSAID use between patients with and without indication for TNF-α inhibitors. NSAID use decreased significantly after starting TNF-α inhibitors. During conventional treatment, NSAID use remained stable at group level. However, NSAID use changed frequently at individual patient level and was significantly associated with disease activity.