Thyroid function in hidradenitis suppurativa: a population-based cross-sectional study from Denmark.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic inflammatory disease. Numerous studies have associated HS with obesity, and recently with metabolic syndrome (MetS). Both obesity and MetS are linked with metabolic changes. Thyroid hormones play a central role in metabolism and exert pleiotropic effects on adipogenesis and the basal metabolism of lipids and glucose. We hypothesized that patients with HS have an altered or dysfunctional metabolism expressed as thyroid function. AIM: To investigate thyroid function in individuals with HS compared with healthy controls (HCs). METHODS: We conducted a retrospective comparative cross-sectional study using blood samples and questionnaire-based self-reported information to assess thyroid function. RESULTS: Our study comprised 430 patients in a population-based HS group, and 20 780 HCs. The age/sex-adjusted analysis showed a significantly lower level (P < 0.001) of thyroid-stimulating hormone (TSH) and a significantly higher level (P < 0.0001) of total triiodothyronine (tT3) for the HS compared with the HC group. The age/sex-adjusted analysis also showed a significant association between clinical hyperthyroidism and HS (an OR = 1.91, 95% CI 1.19-3.07; P = 0.02). When this analysis was adjusted further for the potential confounders of body mass index, smoking and oral contraception, the results remained significant. CONCLUSION: This study suggests that HS is associated with hyperthyroidism. Hyperthyroidism may indicate an altered or dysfunctional metabolism.

Danish, national cross-sectional observational study on the prevalence of prior major osteoporotic fractures in adults presenting with hip fracture-limitations and scope for fracture liaison services in prevention of hip fracture.

Fracture liaison services prevent hip fractures by identifying other osteoporotic fractures that generally debut at a younger age. However, this study showed that a minority of hip fracture patients are already known to the health services through having had prior osteoporotic fractures. Identification of vertebral fractures in particular is lacking. INTRODUCTION: The purpose of this study was to examine the prevalence of prior major osteoporotic fractures (MOF) in the prior 10 years preceding hip fracture in order to provide information about the potential for prevention of hip fractures by fracture liaison services (FLS). METHODS: We included all patients aged 50+ with surgically treated hip fracture in one calendar year (N = 8158) in the Danish Hospital Discharge Register. Prior fractures were identified using the same data source. A prior hip fracture was only included as a prior fracture if occurring more than 6 months before the present fracture. RESULTS: A total of 28% of hip fracture patients (32% of women and 19% of men) had at least one recognized MOF in the preceding 10 years. Forearm and humerus fractures constituted > 70% of prior MOF. In both genders, vertebral fractures only represented a small percentage (2.6%) of previously recognized MOF. Men were less likely than women to have experienced a prior MOF, chiefly due to fewer forearm and humerus fractures. CONCLUSION: The majority of hip fractures-and in particular hip fractures in men-occur without a previously treated MOF that could have resulted in early detection and treatment of osteoporosis. With current treatment modalities, a maximum of one in six hip fractures in Denmark can be prevented through FLS initiatives. Identification of patients with vertebral fractures for assessment and treatment is therefore critical for successful prevention of hip fractures using this strategy.

Vitamin D status and measurements of markers of bone metabolism in patients with small intestinal resection.

BACKGROUND AND AIMS: Vitamin D deficiency is common in patients with small intestinal resection and may lead to secondary hypersecretion of parathyroid hormone (PTH), which in turn may result in increased bone turnover rate and loss of bone mineral. The aims of this study were to investigate the prevalence of vitamin D deficiency, as assessed by low serum concentrations of 25-hydroxyvitamin D (25(OH)D) in patients with small intestinal resection and to explore the relation of 25(OH)D to PTH, markers of bone turnover rate, and bone mineral density (BMD) in these patients. PATIENTS: Forty two patients with small intestinal resection, a faecal energy excretion of more than 2.0 MJ/day, and a mean length of the remaining small intestine of 199 cm were included. Diagnoses were Crohn's disease (n=35) and other (n=7). METHODS: 25(OH)D was analysed by radioimmunoassay and bone turnover rate was assessed by measurement of serum osteocalcin, serum alkaline phosphatase, urine pyridinoline, and urine deoxypyridinoline. BMD was measured by dual energy x ray absorptiometry. RESULTS: Mean 25(OH)D concentration was 13.4 (SD 9.7) ng/ml, which was significantly below the reference mean of 26.4 (SD 13.2) ng/ml (p<0.001). Vitamin D deficiency (25(OH)D concentration

Short-term administration of glucagon-like peptide-2. Effects on bone mineral density and markers of bone turnover in short-bowel patients with no colon.

BACKGROUND: Glucagon-like peptide 2 (GLP-2) is a newly discovered intestinotrophic hormone. We have recently reported that a 5-week GLP-2 treatment improved the intestinal absorptive capacity of short-bowel patients with no colon. Additionally, GLP-2 treatment was associated with changes in body composition that included a significant increase in total body bone mass. This article describes the effect of GLP-2 on spinal and hip bone mineral density (BMD) and biochemical markers of bone turnover in these patients. METHODS: In an open-labelled pilot study, eight short-bowel patients (3M, 5F; mean age 49 years) with small-bowel resection and no colon received 400 microg s.c. of GLP-2 twice daily for 5 weeks. Four received home parenteral nutrition (mean length of residual jejunum 83 cm) and 4 did not (mean length of ileum resected 106 cm). The outcome measures were the mean percent change from baseline in spinal and hip BMD measured by dual-energy X-ray absorptiometry, changes in four biochemical markers of bone-turnover, PTH, 25-hydroxy vitamin-D, and the intestinal absorption of calcium. RESULTS: Mean +/- s(x) (SEM) percent changes in spinal and hip BMD were 1.1+/-0.4% (P < 0.05) and 1.9+/-0.8% (P = 0.06), respectively. The intestinal calcium absorption increased by 2.7% (P = 0.87). Serum ionized calcium increased in 5/8 patients with a concomitant decrease in serum PTH values. Three of the four markers of bone turnover decreased. CONCLUSION: A 5-week GLP-2 administration significantly increased spinal BMD in short-bowel patients with no colon. The mechanism by which GLP-2 affects bone metabolism remains unclear, but may be related to an increased mineralization of bone resulting from an improved intestinal calcium absorption.

Comparison of quantitative ultrasound and dual X-ray absorptiometry in estrogen-treated early postmenopausal women.

Identifying individuals at risk of developing osteoporosis is important in order to initiate early treatment. Many new techniques have been proposed as alternatives for DXA-scanning. Some of these alternatives certainly have advantages, but none have so far been demonstrated to predict fractures better, or even to identify individuals at risk of osteoporosis as well as with the standard method. In this study, comprising a group of women from the Danish Osteoporosis Prevention Study, we wished to investigate whether a technique based on quantitative ultrasound (QUS) could identify individuals with low BMC/BMD as measured by dual X-ray absorptiometry (DXA). Furthermore, we wished to test whether the method could detect differences between untreated individuals and those treated with hormone replacement therapy. We found that QUS could detect differences between the treated and untreated groups, but it was unable to identify women with low BMD, although it might be able to identify persons not at risk of osteoporosis. Low QUS values should be followed by a regular DXA measurement to confirm the presence of osteoporosis.

Alendronate increases lumbar spine bone mineral density in patients with Crohn's disease.

BACKGROUND & AIMS: Low bone mineral density (BMD) is a common complication of Crohn's disease and may lead to increased morbidity and mortality because of fractures. We investigated the effect of treatment with the bisphosphonate alendronate on bone mass and markers of bone remodeling in patients with Crohn's disease. METHODS: A 12-month double-blind, randomized, placebo-controlled trial examined the effect of a 10-mg daily dose of alendronate. Thirty-two patients with a bone mass T score of -1 of the hip or lumbar spine were studied. The main outcome measure was the difference in the mean percent change in BMD of the lumbar spine measured by dual-energy x-ray absorptiometry. Secondary outcome measures included changes in BMD of the hip and total body and biochemical markers of bone turnover (S-osteocalcin, urine pyridinoline, and urine deoxypyridinoline excretion). RESULTS: Mean (+/-SEM) BMD of the lumbar spine showed an increase of 4.6% +/- 1.2% in the alendronate group compared with a decrease of 0.9% +/- 1.0% in patients receiving placebo (P < 0.01). BMD of the hip increased by 3.3% +/- 1.5% in the alendronate group compared with a smaller increase of 0.7% +/- 1.1% in the placebo group (P = 0.08). Biochemical markers of bone turnover decreased significantly in the alendronate group (P < 0.001). Alendronate was well tolerated, and there was no difference in adverse events among treatment groups. CONCLUSIONS: Treatment with alendronate, 10 mg daily, significantly increased BMD in patients with Crohn's disease and was safe and well tolerated.

Thyroid hormone treatment aiming at reduced, but not suppressed, serum thyroid-stimulating hormone levels in nontoxic goitre: effects on bone metabolism amongst premenopausal women.

OBJECTIVES: To study the effects of six months' treatment with either T4 or T3, aiming at reduced but not totally suppressed serum TSH levels, as measured by a third generation TSH assay, on biochemical bone turnover parameters as well as bone mass in patients with nontoxic goitre. DESIGN: Prospective randomized study with a matched control group, not blinded. SETTING: Two University Hospital Clinics in Copenhagen. SUBJECTS AND INTERVENTION: Twenty-four consecutive premenopausal women with moderate sized nontoxic goitre. Fourteen patients randomized to T4 or T3 treatment for six months with monthly titration of the dose, aiming at TSH values between 0.005 and 0.2 mUL(-1). Ten controls. MAIN OUTCOME MEASURES: Serum parathyroid hormone (PTH), serum procollagen I C-terminal propeptide (PICP), serum alkaline phosphatase, serum osteocalcin, u-pyridinoline, u-deoxypyridinoline, u-hydroxyproline. Bone mass (BMD) at the lumbar spine and at both femoral necks. RESULTS: Serum TSH was generally kept within the desired interval. There was no difference in any marker of bone metabolism between the effects of T4 and T3. Consequently, these groups were combined in order to evaluate the effect of thyroid hormones on the bone and mineral metabolism. Thyroid hormone treatment resulted in increased levels of serum ionized calcium (Ca) (P=0.02), serum alkaline phosphatase (P=0.007), serum-PICP (P=0.003), serum osteocalcin (P=0.02) and urinary excretion of deoxypridinoline (P=0.03) compared to untreated controls. Bone mass did not change. CONCLUSION: Six months treatment with either T4 or T3 of premenopausal women with nontoxic goitre, aiming at reduced but not totally suppressed TSH values, resulted in biochemical signs of increased bone turnover, whereas bone mass remained unaltered. No differences were found between the effects of T4 or T3 treatment.

Assessment of different markers of bone resorption in postmenopausal osteoporotic women treated with pamidronate.

The aim of this study was to evaluate the different bone resorption markers, total pyridinoline (Pyr) and total deoxypyridinoline (Dpyr), assessed by a HPLC method, free Dpyr, assessed by a new immunoassay, and urinary excretion of hydroxyproline (OH-proline), in postmenopausal osteoporotic women during long-term treatment with pamidronate. A total of 60 postmenopausal women with previous distal forearm fracture were included in this 12-month placebo-controlled and double-blind study, where intermittent oral pamidronate, 75 or 150 mg, or placebo were given daily for 4 weeks, every 16 weeks. After 1 week a significant reduction in urinary excretion of total Dpyr was observed in the group treated with 150 mg pamidronate compared to the placebo (p < 0.01) and to the 75-mg group (p < 0.001). A maximal 50.4% decrease in total Dpyr, (p < 0.0001 compared to the placebo group, p < 0.01 compared to the 75-mg group), was observed after 3 weeks of treatment with 150 mg pamidronate, and this decrease persisted to week 52. After 4 weeks of treatment with 150 mg pamidronate the maximal decrease in free Dpyr was only 26.5%, which persisted during 12 months of treatment. Decreases in urinary excretion of total Pyr and OH-proline were less than the decreases in total Dpyr. The correlation between total Dpyr (HPLC method) and free Dpyr (Pyrilinks-D assay) at baseline was r = 0.91. Total Dpyr assessed by the HPLC method reflects the pamidronate-induced decrease in bone resorption, and the changes in this resorption marker were more pronounced than changes in free Dpyr, total Pyr and OH-proline. In this study free Dpyr analysis was less suitable for reflecting bone resorption during bisphosphonate therapy.

A single measurement of biochemical markers of bone turnover has limited utility in the individual person.

Biochemical markers of bone turnover are used to estimate the rate of bone loss in the individual osteoporotic patient. During recent years it has become increasingly clear that the biological variability of biochemical bone markers has to be taken into consideration in the evaluation of their usefulness in the clinical setting. Eleven premenopausal, 8 perimenopausal and 11 postmenopausal healthy women were included. We assessed the analytical and the biological components of variation for a number of resorptive and formative bone markers: u-hydroxyproline, u-pyridinoline, and u-deoxypyridinoline together with u-calcium and u-creatinine, s-total alkaline phosphatases and s-osteocalcin. Blood and urine samples were collected five times with 7-day intervals. Urinary parameters were expressed as outputs and corrected for creatinine in fasting night urines and second void fasting morning urines. The absolute values differed with a tendency towards increasing values in the postmenopausal women, but the biological variations in relation to menopausal status were not different. The biological variability was much higher for the urinary resorptive markers than for the formative markers in the blood. The critical difference expressing the difference needed between two serial results from the same person to be significant at a 5% level was 15% for s-alkaline phosphatases, 18% for s-osteocalcin, and lowest in the second void fasting morning urines with values of 28% and 34% for u-pyridinoline/creatinine and u-deoxypyridinoline/creatinine, and 50% and 112% for u-hydroxyproline/creatinine and u-calcium/creatinine, respectively. The index of individuality, denoting the individual variation divided by the variation between subjects, was in the range from 0.19 for s-alkaline phosphatases to 1.23 for u-hydroxyproline/minute in second void fasting morning urine making the use of conventional reference intervals difficult. Low indices, however, indicate high test performance and offer the possibility of stratification of persons within a range. The number of samples required to determine the true individual mean value +/- 5% for the single person, ranged from 5 for s-total alkaline phosphatases, 6 for s-osteocalcin, 23 for u-deoxypyridinoline/creatinine in the fasting morning urine to over two hundred for u-calcium analytes. It is concluded that, due to high biological variation, a single measurement of biochemical markers of bone turnover is of limited utility in the individual person. We recommend that routine clinical use of biochemical markers should be restricted until further evidence justifies it.

Intraindividual variability in bone markers in the urine.

The biological variability of urinary bone resorption markers was measured in 30 healthy and 20 postmenopausal osteoporotic women. The second spot urines were collected at weekly intervals for 5 weeks and urinary pyridinium crosslinks, hydroxyproline, calcium and Ntx were evaluated. Results are discussed in relation to analytical variability, critical difference values and index of individuality. In conclusion monitoring and classifying bone turnover in groups of persons are well established, but the routine use of urinary biochemical bone markers in the individual patient is of limited use.

[Adverse effects of selective serotonin uptake inhibitors. Hyponatremia caused by Schwartz-Bartter syndrome]. / Bivirkninger ved behandling med selektive serotoningenoptagelseshaemmere. Hyponotrioemi på grund af Schwartz-Bartters syndrom.

This report describes three cases of hyponatraemia/syndrome of inappropriate secretion of antidiuretic hormone. The cases are most likely caused by treatment/intoxication with three different selective serotonin reuptake inhibitors: Fluoxetine, paroxetine and citalopram. All three patients were elderly women (75-83 years). Serum sodium values returned to normal or near normal after discontinuation of the drug and concomitant fluid restriction. Hyponatraemia has previously been described as an adverse effect to fluoxetine and paroxetine, but not to citalopram.

Procollagen type I N-terminal propeptide (PINP) as an indicator of type I collagen metabolism: ELISA development, reference interval, and hypovitaminosis D induced hyperparathyroidism.

A sandwich enzyme-linked immunosorbent assay (ELISA) for quantification of the N-terminal propeptide of human procollagen type I (PINP) utilizing purified alpha 1-chain specific rabbit antibodies is described. The ELISA measured the content of the alpha 1-chain of PINP independent of the molecular form of the molecule. A parallelism was found between amniotic fluid (calibrator), normal and patient serum, and purified PINP (alpha 1), as well as the high and low molecular weight forms of PINP (alpha 1). The concentration of PINP in the calibrator (second trimester amniotic fluid) was determined to 25 micrograms/mL and the detection limit was 62 pg/mL measured in amniotic fluid, and 41 pg/mL measured in serum. The interassay coefficients of variation were 4.6% (low control) and 5.3% (high control), and the corresponding intraassay parameters were 2.9% and 4.9%. Recovery studies revealed an accuracy between 93% and 105%. The normal range (n = 57) for PINP was 56 ng/mL (median) the 10th and 90th centiles being 30 and 82 ng/mL, respectively. Patients with hyperparathyroidism due to hypovitaminosis D had median serum level of 168 ng/mL with a 10th centile of 44 ng/mL and a 90th centile of 450 ng/mL, these values being significantly different from the normal range (p < 0.001). The PINP-ELISA was superior to commercially available assays for PICP and osteocalcin in separation between healthy controls and patients with osteomalaci.

Recent progress in the prevention of osteoporosis. To screen or not to screen?

Screening can be defined as: "Early detection of an asymptomatic condition which might develop to a symptomatic disease if not detected and treated". The purpose of a screening programme for osteoporosis is to identify individuals at risk and consequently to intervene in order to prevent future fractures. The principles of a screening test were outlined by William and Jungner in a WHO publication from 1968 (1). The 10 principles are still valid.

Inter-relations between the calcium set-points of Parfitt and Brown in primary hyperparathyroidism: a sequential citrate and calcium clamp study.

The objective of the present study was to compare the calcium set-points of E. M. Brown and A. M. Parfitt obtained by sequential citrate and calcium clamp in patients with primary hyperparathyroidism and healthy controls. Twenty-six patients with primary hyperparathyroidism were investigated and compared to 22 healthy volunteers. All participants were investigated by sequential calcium lowering and raising comprising the following four phases: Phase (1) blood ionized calcium lowering of about 0.20 mmol l-1; phase (2) steady-state (relative) hypocalcaemia of blood ionized calcium 0.20 mmol l-1 below baseline; phase (3) blood ionized calcium is raised to about 0.20 mmol l-1 above baseline; and phase (4) (relative) hypercalcaemia of blood ionized calcium 0.20 mmol l-1 above baseline. Serum parathyroid hormone (1-84) was measured by an immunoradiometric assay. Blood ionized calcium was measured by a calcium selective electrode. We found the calcium set-points of Parfitt to be 1.42 mmol l-1 (SD 0.12, n = 52) vs. 1.25 mmol l-1 (SD 0.04, n = 44) in patients and controls, respectively (P < 0.001). The calcium set-points of Brown were 1.32 mmol l-1 (SD 0.10, n = 26) vs. 1.13 mmol l-1 (SD 0.04, n = 22), respectively (P < 0.001). By comparing the calcium set-points of Parfitt and Brown, a strikingly good correlation was observed, in patients (r = 0.91, P < 0.001) and in controls (r = 0.85, P < 0.001). We demonstrate in this paper in vivo that Brown's and Parfitt's calcium set-points are raised in primary hyperparathyroidism and return to normal following parathyroidectomy.(ABSTRACT TRUNCATED AT 250 WORDS)

Progressive escape from parathyroid suppression: a common phenomenon in primary hyperparathyroidism (a calcium clamp study).

OBJECTIVE: Induced aggravation of hypercalcaemia in vivo and in vitro causes partial suppression of parathyroid hormone (PTH) secretion in primary hyperparathyroidism (PHP). Furthermore, one in-vitro study also demonstrates progressive escape from such action. The aim of the present in-vivo study was to examine whether escape from suppression is a common feature of PHP. DESIGN: A rapid increment in blood ionized calcium (B-Ca2+) to 0.25-0.30 mmol/l above individual baselines was achieved by intravenous calcium infusions. This induced or aggravated hypercalcaemia was kept constant for 2 hours (controls) or 4 hours (patients). PATIENTS AND CONTROLS: The study of PHP comprised 19 patients (18 females and one male) aged 39-85 years (geometric mean 66). For comparison we included the results obtained in a control group of 24 healthy subjects (11 women and 13 men) aged 20-68 years (geometric mean 32). MEASUREMENTS: The individual levels of B-Ca2+ were controlled by frequent bedside measurements of B-Ca2+. The changes in serum intact parathyroid hormone (S-PTH(1-84)) were registered. RESULTS: After 30 minutes of calcium infusion average concentrations of S-PTH(1-84) had decreased from 7.9 (6.7-9.4) pmol/l in PHP and 2.5 (2.1-2.9) pmol/l in controls to their respective nadir values of 2.9 (2.1-4.1) pmol/l and 0.6 (0.5-0.8) pmol/l. While S-PTH(1-84) remained suppressed at a stable level for 120 minutes in controls, in PHP it started to escape progressively after 30 minutes to a level of 4.2 (3.0-5.8) pmol/l (P < 0.001). Linear regression analysis of the individual S-PTH(1-84) observations in PHP, from 30 to 240 minutes of study, revealed that five patients did not escape (group A) while the remainder 14 patients escaped progressively (group B). Within group B, seven patients escaped significantly after 120 minutes, 10 after 180 minutes and 14 after 240 minutes. Although comparable respecting B-Ca2+ before and during calcium infusion, group A and B presented different S-PTH(1-84) curves. Thus, at times zero, 30, 120 and 240 minutes their respective average concentrations of S-PTH(1-84) measured 9.9 (9.1-10.9) vs 7.3 (5.9-9.0) (P < 0.02), 4.6 (3.7-5.7) vs 2.5 (1.6-3.9) (P < 0.01), 5.0 (3.9-6.5) vs 3.0 (1.9-4.8) (P < 0.05) and 5.2 (3.6-7.4) vs 3.9 (2.6-6.0) (NS) pmol/l. CONCLUSIONS: We hypothesize that two different mechanisms are involved in the parathyroid response to the calcium clamp, an initial and fast inhibition of PTH release, while the subsequent course depends on the balance between the intra-glandular secretion rate of PTH and the intra-glandular capacity for PTH degradation. The escape from parathyroid suppression during a sustained stable increment in B-Ca2+ suggests that the basal secretion over-rides degradation in a majority of the patients with PHP.