Effects of live music during chemotherapy in lymphoma patients: a randomized, controlled, multi-center trial.

PURPOSE: Chemotherapy is associated with both somatic and psychological side effects. Music might ease these problems. Several randomized controlled trials have investigated the effect of music, but the results are inconclusive. We aimed to examine whether live or pre-recorded music listening decreases anxiety during chemotherapy in newly diagnosed lymphoma patients. METHODS: A total of 143 patients with non-Hodgkin and Hodgkin lymphomas were randomly assigned into three groups receiving either 30 min of patient-preferred live music (n = 47), 30 min of patient-preferred pre-recorded music (n = 47), or standard care (n = 49) during up to five outpatient chemotherapy sessions. The primary endpoint was anxiety measured by the Spielberger's State Anxiety Inventory. Secondary endpoints included blood pressure, pulse rate, nausea and vomiting, serum catecholamine levels pre- and post-intervention to measure arousal levels, and health-related quality of life. The Musical Ability Test was used to link musical ability to the primary endpoint. RESULTS: When adjusting for age, sex, diagnosis, number of sessions, and baseline anxiety, the linear mixed model showed a borderline statistically significant reduction in the primary outcome anxiety in the live music group compared to standard care (7% (95% CI, - 14% to 0%, p = 0.05), while the effect of pre-recorded music was non-significant (5% (95% CI, - 12% to + 3%, p = 0.18). No intervention effects were seen in secondary outcomes. CONCLUSION: Our findings suggest that patient-preferred live music reduces anxiety among patients with malignant lymphomas undergoing chemotherapy. Musical ability among this group of cancer patients seems not to be a determining factor for effect of music intervention.

Cardiovascular safety of oral semaglutide in patients with type 2 diabetes: Rationale, design and patient baseline characteristics for the PIONEER 6 trial.

AIMS: To assess the cardiovascular (CV) safety of oral semaglutide, the first tablet formulation of a glucagon-like peptide-1 receptor agonist. MATERIALS AND METHODS: PIONEER 6 is a multinational, randomized, placebo-controlled, double-blind trial in patients with type 2 diabetes at high risk of CV events (defined as being aged ≥50 years and having established CV disease [CVD] or moderate [stage 3] chronic kidney disease [CKD], or being aged ≥60 years with ≥1 other CV risk factor). Patients were randomized to once-daily oral semaglutide (up to 14 mg) or placebo added to standard of care. The primary composite endpoint is time to first occurrence of CV death or non-fatal myocardial infarction or non-fatal stroke. The primary hypothesis was to exclude an excess in CV risk with oral semaglutide by assessing non-inferiority versus placebo for the primary endpoint (non-inferiority margin of 1.8 for the upper boundary of the 95% confidence interval of the hazard ratio). PIONEER 6 is event-driven, with follow-up continuing until accrual of at least 122 primary outcome events. There is no pre-defined minimal duration. RESULTS: Overall, 3183 patients have been enrolled (mean age 66.1 years, 31.6% females) in 214 sites across 21 countries. At baseline, the mean duration of diabetes was 14.9 years, mean glycated haemoglobin concentration was 66 mmol/mol (8.2%), and 84.6% of patients had established CVD/moderate CKD. CONCLUSIONS: PIONEER 6 will provide evidence regarding the CV safety of oral semaglutide in patients with type 2 diabetes and high CV risk.

Effects of metformin, rosiglitazone and insulin on bone metabolism in patients with type 2 diabetes.

BACKGROUND: Fracture risk is increased in individuals with type 2 diabetes (T2D). The pathophysiological mechanisms accentuating fracture risk in T2D are convoluted, incorporating factors such as hyperglycaemia, insulinopenia, and antidiabetic drugs. The objectives of this study were to assess whether different insulin regimens, metformin and rosiglitazone influence bone metabolism. We explored if the concentration of metformin and rosiglitazone in blood or improved glycaemic control altered bone turnover. METHODS: Two-year clinical trial designed to investigate effects of antidiabetic treatment in 371 T2D patients. Participants were randomized to short or long-acting human insulin (non-blinded) and then further randomized to metformin + placebo, rosiglitazone + placebo, metformin + rosiglitazone or placebo + placebo (blinded). Fasting bone turnover markers (BTM) representing bone resorption (CTX) and formation (PINP) including HbA1c were measured at baseline and after 3, 12 and 24 months. Trough steady-state plasma concentrations of metformin and rosiglitazone were measured after 3, 6 and 9 months of treatment. Associations between treatments and BTMs during the follow-up of the trial were analysed in mixed-effects models that included adjustments for age, gender, BMI, renal function and repeated measures of HbA1c. RESULTS: BTMs increased from baseline to month 12 and remained higher at month 24, with CTX and PINP increasing 28.5% and 23.0% (all: p < 0.001), respectively. Allocation of insulin regimens was not associated with different levels of BTMs. Metformin and metformin + rosiglitazone but not rosiglitazone alone were associated with lower bone formation (PINP). Neither metformin nor rosiglitazone plasma concentrations was associated with BTMs. HbA1c was inversely associated with CTX but not P1NP. CONCLUSIONS: The choice of insulin treatment is not influencing BTMs, metformin treatment may decrease BTMs, and improvement of glycaemic control may influence bone resorption activity.

Sleep apnoea in patients undergoing bariatric surgery
.

INTRODUCTION: The objective of this study was to investigate the presence of obstructive sleep apnoea (OSA) among patients awaiting bariatric surgery and to evaluate if a change in symptoms and clinical measurements of OSA was seen one year after bariatric surgery.
 Methods: Patients awaiting bariatric surgery in the Region of Southern Denmark were invited to participate in an OSA examination during a 15-month period (2012-2013) using the Embletta device for cardiorespiratory monitoring before and one year after bariatric surgery. The Apnoea-Hypopnoea Index (AHI), weight, BMI and the Epworth Sleepiness Score (ESS) were measured prior to and one year after surgery. 
Results: A total of 56 patients were enrolled in the study, and 59% were found with OSA (AHI ≥ 5). Thirty-six patients were eligible for examination one year post-operatively. Twelve of these patients did not have OSA (AHI < 5) either at inclusion or at re-examination. In the remaining 24 patients with OSA, the BMI dropped from 44.4 prior to surgery to 30.8 kg/m2 one year after surgery (p < 0.01). Mean AHI decreased from 12.8 prior to surgery to 3.7 one year after surgery (p < 0.01). There was no effect of weight reduction on the ESS.
 Conclusions: A statistically significant reduction in AHI was seen in patients with OSA one year after surgery. No statistical differences were observed for ESS. 
Funding: This study was funded by "Fonden for Læge-videnskabelig Forskning m.v. ved sygehusene i Region Syd" and by "Edith og Vagn Hedegaard Jensen fond".
Trial registration: ClinGov (ID: S-20120004jln).

Kind of blue: A systematic review and meta-analysis of music interventions in cancer treatment.

OBJECTIVES: Music may be a valuable and low-cost coping strategy for cancer patients. We conducted a systematic review and meta-analysis to identify the psychological and physical effects of music interventions in cancer treatment. METHODS: We included randomized, controlled trials with adult patients in active cancer treatment exposed to different music interventions versus control conditions. Qualitative studies and systematic reviews were excluded. We identified a total of 2624 records through 2 systematic searches (June 2015 and September 2016) in PubMed, Scopus, EMBASE, Cinahl, Web of Science, Cochrane, and PsycINFO and used Risk of Bias Assessment, GRADE and Checklist for Reporting Music-Based Interventions to evaluate the music applied and quality of the studies. We conducted meta-analyses using Review Manager (version 5.3). PROSPERO reg. no. CRD42015026024. RESULTS: We included 25 RCT's (N = 1784) of which 20 were eligible for the meta-analysis (N = 1565). Music reduced anxiety (SMD -0·80 [95% CI, -1.35 to -0.25]), pain (SMD -0.88 [95% CI -1.45 to -0.32]), and improved mood (SMD -0.55 [95% CI, -0.98 to -0.13]). However, studies were hampered by heterogeneity with I2 varying between 54% and 96%. Quality of the studies ranged from very low to low. The most effective mode of music intervention appeared to be passive listening to self-selected, recorded music in a single session design. CONCLUSIONS: Music may be a tool in reducing anxiety, pain, and improving mood among patients with cancer in active treatment. However, methodological limitations in the studies conducted so far prevent firm conclusions.

High burden of coronary atherosclerosis in patients with a new diagnosis of type 2 diabetes.

PURPOSE: The purposes of this study were to compare the presence, extent and composition of coronary plaques in asymptomatic patients with newly diagnosed type 2 diabetes to age- and sex-matched controls. METHODS: Patients with newly diagnosed (<1 year) type 2 diabetes ( n = 44) and controls ( n = 44) underwent contrast-enhanced coronary computed tomography angiography. Advanced plaque analysis including total plaque volume and volumes of plaque components (calcified plaque and non-calcified plaque, including low-attenuation [low-density non-calcified plaque]) was performed using validated semi-automated software. RESULTS: Coronary artery calcification was more often seen in patients with type 2 diabetes (66%) versus controls (48%), p < 0.05. Both the absolute volume (median; interquartile range) of low-density non-calcified plaque (7.9 mm3; 0-50.5 mm3 vs 0; 0-34.3 mm3, p < 0.05) and the increase in low-density non-calcified plaque ratio in relation to total plaque volume ( τ = 0.5, p < 0.001) were significantly higher in patients with type 2 diabetes. More patients with type 2 diabetes had spotty calcification (31% vs 0%, p < 0.05). By multivariate analysis, the presence of any low-density non-calcified plaque was higher in males (odds ratio: 4.06, p < 0.05), who also demonstrated a larger low-density non-calcified plaque volume ( p < 0.001). The presence and extent of low-density non-calcified plaque increased with age, smoking, hypertension and hyperglycaemia, all p < 0.05. CONCLUSION: Asymptomatic patients with newly diagnosed type 2 diabetes had plaque features associated with increased vulnerability as compared with age- and sex-matched controls.

Bone structural changes after gastric bypass surgery evaluated by HR-pQCT: a two-year longitudinal study.

OBJECTIVE, DESIGN AND METHODS: Roux-en-Y gastric bypass (RYGB) has proved successful in attaining sustained weight loss but may lead to metabolic bone disease. To assess impact on bone mass and structure, we measured a real bone mineral density at the hip and spine by dual-energy X-ray absorptiometry, and volumetric BMD (vBMD) and bone microarchitecture at the distal radius and tibia by high-resolution peripheral quantitative CT in 25 morbidly obese subjects (15 females, 10 males) at 0, 12 and 24 months after RYGB. Bone turnover markers (BTMs), calciotropic and gut hormones and adipokines were measured at the same time points. RESULTS: After a 24.1% mean weight loss from baseline to month 12 (P < 0.001), body weight plateaued from month 12 to 24 (-0.9%, P = 0.50). However, cortical and trabecular vBMD and microarchitecture deteriorated through the 24 months, such that there was a 5 and 7% reduction in estimated bone strength at the radius and tibia respectively (both P < 0.001). The declines observed in the first 12 months were matched or exceeded by declines in the 12- to 24-month period. While a significant increase in BTMs and decrease in leptin and insulin were seen at 24 months, these changes were maximal at month 12 and stabilized from month 12 to 24. CONCLUSIONS: Despite weight stabilization and maintenance of metabolic parameters, bone loss and deterioration in bone strength continued and were substantial in the second year. The clinical importance of these changes in terms of increased risk of developing osteoporosis and fragility fractures remain an important concern.

Bone Structural Changes and Estimated Strength After Gastric Bypass Surgery Evaluated by HR-pQCT.

Roux-en-Y gastric bypass surgery (RYGB) is an effective treatment of morbid obesity, with positive effects on obesity-related complications. The treatment is associated with bone loss, which in turn might increase fracture risk. The aim of this study was to evaluate changes in bone mineral density (BMD) and bone architecture assessed using dual-energy X-ray absorptiometry (DXA) and high-resolution peripheral quantitative computed tomography (HR-pQCT), 6 and 12 months after RYGB, and correlate them to changes in selected biochemical markers. A prospective cohort study included 25 morbidly obese patients (10 males, 15 females). Patients were examined with DXA of the hip and spine, HR-pQCT of radius and tibia, and blood sampling before and 6 and 12 months after RYGB. Patients lost in average 33.5 ± 12.1 kg (25.8 ± 8.5 %) in 12 months. In tibia, we found significant loss of total, cortical and trabecular volumetric BMD after 12 months (all p < 0.001). Microarchitectural changes involved lower trabecular number, increased trabecular separation, and network inhomogeneity along with thinning of the cortex. Estimated bone failure load was decreased after 12 months (p = 0.005). We found only minor changes in radius. Results demonstrate significant alterations of bone microarchitecture suggesting an accelerated endosteal resorption along with disintegration of the trabecular structure which resulted in a loss of estimated bone strength in tibia. Such changes may underlie the recently reported increased risk of fracture in bariatric patients after surgery. We only observed bone structural changes in the weight-bearing bone, which indicates that mechanical un-loading is the primary mediator.

The chronic autoimmune thyroiditis quality of life selenium trial (CATALYST): study protocol for a randomized controlled trial.

BACKGROUND: Patients with chronic autoimmune thyroiditis have impaired health-related quality of life. The thyroid gland has a high selenium concentration, and specific selenoprotein enzyme families are crucial to immune function, and catalyze thyroid hormone metabolism and redox processes in thyroid cells. Previous randomized controlled trials have found that selenium supplementation decreases thyroid-disease-specific antibody levels. We hypothesize that selenium might be beneficial in the treatment of chronic autoimmune thyroiditis. METHODS/DESIGN: The CATALYST trial is an investigator-initiated randomized, blinded, multicentre clinical trial of selenium supplementation versus placebo in patients with chronic autoimmune thyroiditis. INCLUSION CRITERIA: age ≥18 years; serum thyroid peroxidase antibody level ≥100 IU/ml within the previous 12 months; treatment with levothyroxine and written informed consent. EXCLUSION CRITERIA: previous diagnosis of toxic nodular goitre, Graves' hyperthyroidism, postpartum thyroiditis, Graves' orbitopathy; previous antithyroid drug treatment, radioiodine therapy or thyroid surgery; immune-modulatory or other medication affecting thyroid function; pregnancy, planned pregnancy or breastfeeding; allergy towards any intervention or placebo component; intake of selenium supplementation >55 µg/day; inability to read or understand Danish or lack of informed consent. The trial will include 2 × 236 participants. The experimental intervention and control groups will receive 200 µg selenium-enriched yeast or matching placebo tablets daily for 12 months. The experimental supplement will be SelenoPrecise®. The primary outcome is thyroid-related quality of life assessed by the Thyroid Patient-Reported Outcome (ThyPRO) questionnaire. Secondary outcomes include serum thyroid peroxidase antibody concentration; serum triiodothyronine/thyroxine ratio; levothyroxine dosage; adverse reactions and serious adverse reactions and events. DISCUSSION: In this pragmatic trial, participating patients follow their usual treatment at their usual hospitals. In order to collect high-quality data on the clinical course and quality of life, and to minimize missing data, an elaborate trial management system has been designed. 12 months intervention duration was selected in consideration of the primary outcome, thyroid-related quality of life. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT02013479.

Low dose spironolactone reduces blood pressure in patients with resistant hypertension and type 2 diabetes mellitus: a double blind randomized clinical trial.

BACKGROUND: The increased risk of cardiovascular morbidity and mortality associated with arterial hypertension is particularly pronounced in patients with type 2 diabetes mellitus. Blood pressure control is, therefore, decisively important but often not sufficiently achieved. OBJECTIVE: The primary objective of this study was to evaluate the antihypertensive effect of low dose spironolactone added to triple therapy for resistant hypertension in patients with type 2 diabetes measured by ambulatory monitoring. Secondary objectives were to evaluate the effects on glycaemic control and urinary albumin excretion as well as adverse effects. METHODS: In a multicentre, double-blind, randomized, placebo-controlled study 119 patients with blood pressure at or above 130/80 mmHg despite triple antihypertensive therapy were included. One tablet of 25 mg spironolactone or placebo was added to previous treatment and increased to two if blood pressure below 130/80 mmHg was not achieved after 4 weeks. Blood pressure was measured by ambulatory monitoring at baseline and after 16 weeks. RESULTS: The study was completed by 112 patients, 57 randomized to spironolactone and 55 to placebo. Average daytime placebo-corrected blood pressure was reduced by 8.9 (4.7-13.2)/3.7 (1.5-5.8) mmHg. Also office blood pressure, night-time, 24-h and pulse pressures were reduced significantly. Urinary albumin/creatinine ratio was significantly reduced in the spironolactone group. Glycaemic control remained unchanged. Hyperkalemia was the most frequent adverse event leading to dose reduction in three cases and discontinuation in one, whereas gynaecomastia was not reported. CONCLUSION: Low dose spironolactone exerts significant BP and urinary albumin creatinine ratio lowering effects in high-risk patients with resistant hypertension and type 2 diabetes mellitus.

Rosiglitazone decreases plasma levels of osteoprotegerin in a randomized clinical trial with type 2 diabetes patients.

Cardiovascular disease is the leading cause of death in patients with type 2 diabetes mellitus (T2DM). We suggested that plasma osteoprotegerin (OPG), a strong, independent predictor of cardiovascular disease, could discriminate between anti-diabetic treatments depending on their benefits regarding cardiovascular disease. The South Danish Diabetes Study, an investigator-driven, randomized, controlled clinical trial lasting 2 years, was used to test this hypothesis in patient groups with different medication strategies (insulin aspart or NPH insulin, added either metformin/placebo or rosiglitazone/placebo). A total of 371 individuals were eligible for the study. Basic variables were analysed along with measurement of plasma OPG and HbA(1c) at the beginning and end of the study. Only rosiglitazone treatment caused a significant decrease in plasma OPG concentrations (p = 0.003), while no significant change was seen in the other treatment groups. The effect of rosiglitazone on plasma OPG remained significant in a univariate analysis adjusted for change in HbA(1c) (p = 0.013). Of note, the change in plasma OPG significantly correlated with HbA(1c) improvement in rosiglitazone-treated patients (R = 0.29, p = 0.0002), while this correlation was poor in those not receiving rosiglitazone (R = 0.06, p =0.48). Treatment with rosiglitazone among patients with T2DM reduces the concentration of plasma OPG. This is not seen with metformin despite similar reductions in HbA(1c) . Alteration in the OPG/RANKL pathway by glitazones may have implications for the understanding of both cardiovascular effects and bone side effects of the drug.

Phenotype presentation of hypophosphatemic rickets in adults.

Hypophosphatemic rickets (HR) is a group of rare disorders caused by excessive renal phosphate wasting. The purpose of this cross-sectional study of 38 HR patients was to characterize the phenotype of adult HR patients. Moreover, skeletal and endodontic severity scores were defined to assess possible gender differences in disease severity in patients with genetically verified X-linked HR. Compared to normal reference data, i.e., z = 0, HR patients had significantly lower final height, with a mean difference in z-score of -1.9 (95% CI -2.4 to -1.4, P < 0.001). Compared to paired z-scores of final height, z-scores of leg length were significantly lower and those of sitting height were significantly higher (P < 0.001), resulting in disproportion as indicated by the significantly elevated sitting height ratio, mean difference in z-score of 2.6 (95% CI 2.1-3.1, P < 0.001). Z-scores of head circumference (median 1.4, range -0.4 to 5.5, P < 0.001) and z-scores of bone mineral density (BMD) of the lumbar spine (median 1.9, range -1.5 to 8.6, P < 0.001) were significantly elevated compared to normal reference data. The relative risk (RR) of fracture was reduced (RR = 0.34, 95% CI 0.20-0.57, P < 0.001). The skeletal severity score tended to be higher in males compared to females (P = 0.07), and no gender difference in endodontic severity was found. In conclusion, adult HR patients were characterized by short stature and were disproportioned. They had elevated BMD of the lumbar spine and a reduced risk of fractures. We found a tendency for males to be more severely affected than females.

Degradation of the organic phase of bone by osteoclasts: a secondary role for lysosomal acidification.

UNLABELLED: Osteoclasts degrade bone matrix by secretion of hydrochloric acid and proteases. We studied the processes involved in the degradation of the organic matrix of bone in detail and found that lysosomal acidification is involved in this process and that MMPs are capable of degrading the organic matrix in the absence of cathepsin K. INTRODUCTION: Osteoclasts resorb bone by secretion of acid by the vacuolar H+-adenosine triphosphatase (V-ATPase) and the chloride channel ClC-7, followed by degradation of the matrix, mainly collagen type I, by cathepsin K and possibly by matrix metalloproteinases (MMPs). However, the switch from acidification to proteolysis and the exact roles of both the ion transporters and the proteinases still remain to be studied. MATERIALS AND METHODS: We isolated CD14+ monocytes from human peripheral blood from either controls or patients with autosomal dominant osteopetrosis type II (ADOII) caused by defective ClC-7 function and cultured them in the presence of RANKL and macrophage-colony stimulating factor (M-CSF) to generate osteoclasts. We decalcified cortical bovine bone slices and studied the osteoclasts with respect to morphology, markers, and degradation of the decalcified matrix in the presence of various inhibitors of osteoclast acidification and proteolysis, using normal calcified bone as a reference. RESULTS: We found that ADOII osteoclasts not only have reduced resorption of the calcified matrix, but also 40% reduced degradation of the organic phase of bone. We found that both acidification inhibitors and cathepsin K inhibitors reduced degradation of the organic matrix by 40% in normal osteoclasts, but had no effect in the ADOII osteoclasts. Furthermore, we showed that inhibition of MMPs leads to a 70% reduction in the degradation of the organic bone matrix and that MMPs and cathepsin K have additive effects. Finally, we show that osteoclastic MMPs mediate release of the carboxyterminal telopeptide of type I collagen (ICTP) fragment in the absence of cathepsin K activity, and therefore, to some extent, are able to compensate for the loss of cathepsin K activity. CONCLUSIONS: These data clearly show that osteoclastic acidification of the lysosomes plays a hitherto nonrecognized role in degradation of the organic matrix. Furthermore, these data shed light on the complicated interplay between acidification dependent and independent proteolytic processes, mediated by cathepsin K and the MMPs, respectively.

Osteoclasts from patients with autosomal dominant osteopetrosis type I caused by a T253I mutation in low-density lipoprotein receptor-related protein 5 are normal in vitro, but have decreased resorption capacity in vivo.

Autosomal dominant osteopetrosis type I (ADOI) is presumably caused by gain-of-function mutations in the LRP5 gene. Patients with a T253I mutation in LRP5 have a high bone mass phenotype, characterized by increased mineralizing surface index but abnormally low numbers of small osteoclasts. To investigate the effect of the T253I mutation in LRP5 on osteoclasts, we isolated CD14+ monocytes from ADOI patients and assessed their ability to generate osteoclasts when treated with RANKL and M-CSF compared to that of age- and sex-matched control osteoclasts. We found normal osteoclastogenesis, expression of osteoclast markers, morphology, and localization of proteins involved in bone resorption, such as ClC-7 and cathepsin K. The ability to resorb bone was also normal. In vivo, we compared the bone resorption and bone formation response to T3 in ADOI patients and age- and sex-matched controls. We found attenuated resorptive response to T3 stimulation, despite a normal bone formation response, in alignment with the reduced number of osteoclasts in vivo. These data demonstrate that ADOI osteoclasts are normal with respect to all aspects investigated in vitro. We speculate that the mutations causing ADOI alter the osteoblastic phenotype toward a smaller potential for supporting osteoclastogenesis.

Acidification of the osteoclastic resorption compartment provides insight into the coupling of bone formation to bone resorption.

Patients with defective osteoclastic acidification have increased numbers of osteoclasts, with decreased resorption, but bone formation that remains unchanged. We demonstrate that osteoclast survival is increased when acidification is impaired, and that impairment of acidification results in inhibition of bone resorption without inhibition of bone formation. We investigated the role of acidification in human osteoclastic resorption and life span in vitro using inhibitors of chloride channels (NS5818/NS3696), the proton pump (bafilomycin) and cathepsin K. We found that bafilomycin and NS5818 dose dependently inhibited acidification of the osteoclastic resorption compartment and bone resorption. Inhibition of bone resorption by inhibition of acidification, but not cathepsin K inhibition, augmented osteoclast survival, which resulted in a 150 to 300% increase in osteoclasts compared to controls. We investigated the effect of inhibition of osteoclastic acidification in vivo by using the rat ovariectomy model with twice daily oral dosing of NS3696 at 50 mg/kg for 6 weeks. We observed a 60% decrease in resorption (DPYR), increased tartrate-resistant acid phosphatase levels, and no effect on bone formation evaluated by osteocalcin. We speculate that attenuated acidification inhibits dissolution of the inorganic phase of bone and results in an increased number of nonresorbing osteoclasts that are responsible for the coupling to normal bone formation. Thus, we suggest that acidification is essential for normal bone remodeling and that attenuated acidification leads to uncoupling with decreased bone resorption and unaffected bone formation.

Resumption of methimazole after 131I therapy of hyperthyroid diseases: effect on thyroid function and volume evaluated by a randomized clinical trial.

OBJECTIVE: Retrospective studies have indicated that anti-thyroid drugs (ATD) might possess a radioprotective effect, leading to a higher rate of recurrence of hyperthyroidism after iodine-131 ((131)I) therapy. DESIGN: A randomized clinical trial was performed to clarify whether resumption of methimazole after (131)I influences the final outcome of this treatment. METHODS: We assigned 149 patients with Graves' disease or a toxic nodular goitre to groups either to resume (+ATD) or not to resume (-ATD) methimazole 7 days after (131)I. Before (131)I therapy, all patients were rendered euthyroid by methimazole, which was discontinued 4 days before the (131)I therapy. RESULTS: During the follow-up period of 12 Months, 13 patients developed hypothyroidism, 42 were euthyroid, and 18 had recurrence of hyperthyroidism in the +ATD group; the respective numbers in the -ATD group were 16, 42 and 18 (P=0.88). At 3 weeks after (131)I therapy, the serum free-thyroxine index was slightly decreased (by 5.7%; 95% confidence interval (CI) -15.5 to 5.4%) in the +ATD group, in contrast to an increase of 35.9% (95% CI 18.8 to 55.5%) in the -ATD group (P<0.001 between groups). In the subgroup that remained euthyroid during follow-up, thyroid Volume reduction, assessed by ultrasonography, was smaller in the +ATD group [38.7% (95% CI 33.3 to 44.1%)] than in the -ATD group [48.6% (95% CI: 41.5-55.6%)] (P<0.05). CONCLUSION: No radioprotective effect could be demonstrated, with regard to final thyroid function, for the resumpton of methimazole 7 days after (131)I therapy. Although resumption of methimazole slightly reduced the magnitude of shrinkage of the goitre obtained by (131)I, the prevention of a temporary thyrotoxicosis in the early period after radiation favours this regimen.