Alliances of the gut and bone axis.

Gut hormones secreted from enteroendocrine cells following nutrient ingestion modulate metabolic processes including glucose homeostasis and food intake, and several of these gut hormones are involved in the regulation of the energy demanding process of bone remodelling. Here, we review the gut hormones considered or known to be involved in the gut-bone crosstalk and their role in orchestrating adaptions of bone formation and resorption as demonstrated in cellular and physiological experiments and clinical trials. Understanding the physiology and pathophysiology of the gut-bone axis may identify adverse effects of investigational drugs aimed to treat metabolic diseases such as type 2 diabetes and obesity and new therapeutic candidates for the treatment of bone diseases.

The Antiresorptive Effect of GIP, But Not GLP-2, Is Preserved in Patients With Hypoparathyroidism-A Randomized Crossover Study.

Glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-2 (GLP-2) are gut hormones secreted postprandially. In healthy humans, both hormones decrease bone resorption accompanied by a rapid reduction in parathyroid hormone (PTH). The aim of this study was to investigate whether the changes in bone turnover after meal intake and after GIP- and GLP-2 injections, respectively, are mediated via a reduction in PTH secretion. This was tested in female patients with hypoparathyroidism given a standardized liquid mixed-meal test (n = 7) followed by a peptide injection test (n = 4) using a randomized crossover design. We observed that the meal- and GIP- but not the GLP-2-induced changes in bone turnover markers were preserved in the patients with hypoparathyroidism. To understand the underlying mechanisms, we examined the expression of the GIP receptor (GIPR) and the GLP-2 receptor (GLP-2R) in human osteoblasts and osteoclasts as well as in parathyroid tissue. The GIPR was expressed in both human osteoclasts and osteoblasts, whereas the GLP-2R was absent or only weakly expressed in osteoclasts. Furthermore, both GIPR and GLP-2R were expressed in parathyroid tissue. Our findings suggest that the GIP-induced effect on bone turnover may be mediated directly via GIPR expressed in osteoblasts and osteoclasts and that this may occur independent of PTH. In contrast, the effect of GLP-2 on bone turnover seems to depend on changes in PTH and may be mediated through GLP-2R in the parathyroid gland. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Non-parathyroid hypercalcemia associated with paraffin oil injection in 12 younger male bodybuilders: a case series.

INTRODUCTION: Injection of paraffin oil to augment muscles size is a troubling phenomenon known to cause a foreign body reaction with formation of granulomas. In a few case reports, long-term side effects have been reported in terms of hypercalcemia and renal failure. METHODS: We identified a case series of 12 male bodybuilders presenting with non-parathyroid hypercalcemia who previously had injected paraffin oil to increase muscles size. RESULTS: At admission, all patients had moderate-to-severe hypercalcemia with suppressed PTH levels and impaired renal function. Calcitriol levels were within the normal range or slightly elevated. Follow-up measurements showed marked hypercalciuria with nearly normal levels of bone turnover markers. A correlation was found between levels of peptidyl dipeptidase and calcitriol (R = 0.812, P = 0.050). Treatment with antiresorptive agents seemed less effective than glucocorticoids, which resulted in a significantly lowering of ionized calcium levels and improved renal function, although no patients were cured by this treatment. Immunosuppression with azathioprine or mycophenolate may have a glucocorticoid-saving effect. One patient had surgery with removal of affected muscle tissue, without any apparent effect on plasma calcium levels. CONCLUSION: The hypercalcemia and associated hypercalciuria seems to be due to an intestinal hyperabsorption of calcium. It remains to be elucidated, whether an increased calcitriol synthesis within granulomas is the only (main) mechanism by which intestinal calcium absorption is increased. Glucocorticoids seem most appropriate as the first choice for treatment. Bodybuilders should be warned against use of intramuscular oil injections (and other substances), as this may have severe adverse health consequences.

Symptoms and syndromes of bodily distress: an exploratory study of 978 internal medical, neurological, and primary care patients.

OBJECTIVE: Physical complaints not attributable to verifiable, conventionally defined diseases, i.e., medically unexplained or functional somatic symptoms, are prevalent in all medical settings, but their classification is contested as numerous overlapping diagnoses and syndrome labels have been introduced. This study aims to determine whether functional somatic symptoms cluster into distinct syndromes and diagnostic entities. METHODS: The 978 consecutively admitted patients from a neurological department (n = 120), a medical department (n = 157), and from primary care (n = 701) were interviewed using the Schedules for Clinical Assessment in Neuropsychiatry (SCAN) diagnostic instrument. RESULTS: Patients complained of a median of five functional somatic symptoms; women of six, men of four (p < .0001). No single symptoms stood out as distinctive for patients with multiple symptoms. Principal component factor analysis identified a cardiopulmonary including autonomic (CP), a musculoskeletal (MS), and a gastrointestinal (GI) symptom group explaining 36.9% of the variance. Latent class analysis showed that the symptom groups are likely to materialize in the same patients, suggesting that they are different manifestations of a common latent phenomenon. Inclusion of a group of five additional general, unspecific symptoms in latent class analysis allowed construction of clinical diagnostic criteria for 'bodily distress disorder' dividing patients into three classes: nonbodily distress (n = 589), modest bodily distress (n = 329, prevalence 25.3%, men 20.4%, women 25.6%), and severe bodily distress (n = 60, prevalence 3.3%, men 1.2%, women 4.8%). CONCLUSION: The study suggests that bodily distress disorder as defined here may unite many of the functional somatic syndromes and some somatoform disorder diagnoses. Bodily distress may be triggered by stress rather than being distinct diseases of noncerebral pathology.

Systematic genetic screening in a prospective group of Danish patients with pheochromocytoma.

Recent guidelines recommend consideration of genetic screening in all newly diagnosed patients with pheochromocytoma. Patients diagnosed with pheochromocytoma in the Region of Southern Denmark during 2006-2013 without previously recognized monogenetic etiology were offered genetic screening for mutations in the VHL, RET, SDHB, SDHC, and SDHD genes. A total of 41 patients were included, and genetic data were available in 35. In four of the 35 patients, a pathogenic variant was identified prior to the diagnosis of pheochromocytoma (von Hippel-Lindau disease, n=2; neurofibromatosis type 1, n=2). The patients carrying a genetic mutation were all younger than 45 years at time of diagnosis of pheochromocytoma, two patients presented with bilateral tumors, and one patient had a positive family history of pheochromocytoma. Genetic screening of the remaining 31 patients did not identify any mutations. The sporadic cases had a median age of 58 years (range 33-80 years). Three of 31 sporadic cases (ages 60, 69, and 76 years at time of diagnosis) presented with bilateral adrenal tumors, one patient had multiple adrenal tumors in both adrenal glands, and no patients had a positive family history of pheochromocytoma. Of the 31 patients, 24 (68.6%) were diagnosed with pheochromocytoma due to evaluation of an adrenal incidentaloma. In conclusion, monogenetic etiology was identified in four of 35 (11.4%) patients diagnosed with pheochromocytoma.

Optical coherence tomography plaque characterization in a patient with ST segment elevation myocardial infarction after cocaine intake.

A 28-year old man presented to the Emergency Department with malaise after cocaine intake. After arrival he developed retrosternal chest pain and the electrocardiogram showed ST segment elevations in V1-V2 and ST segment depressions in V5-V6. An acute coronary angiogram revealed a focal non-occlusive lesion with thrombus in the left anterior descending artery. Supplementary optical coherence tomography (OCT) detected plaque erosion with adherent thrombus to be the responsible underlying pathophysiological mechanism. The patient received an effective antithrombotic regimen. Repeat angiogram with additional OCT one month later documented thrombus resolution and complete restoration of the previously eroded coronary vascular surface area.

Mental illness and health care use: a study among new neurological patients.

We investigated 198 new neurological patients to learn if mental illness had an impact on nonpsychiatric health care use. Mental illness was assessed in a two-phase design, including the Schedules for Clinical Assessment in Neuropsychiatry (SCAN), providing ICD-10 diagnoses and two brief rating scales: the Symptom Check List (SCL-8) for anxiety and depression and the Whiteley-7 for somatization. The patients' use of health care was studied 5-10 years before and 18 months after the psychiatric assessment, using data from national patient registers. Mental illness was linked to data on health care use through weighted logistic regression. ICD-10 psychiatric disorders increased the risk of subsequent high use of nonpsychiatric hospital admissions - somatoform disorders with more than five times (OR=5.6; 95% CI=1.6-20.1) and anxiety/depression with almost four times (OR=3.7; 95% CI=1.1-12.0). There was also a trend, though less marked, linking mental illness to previous hospital use. Use of primary care was also markedly increased by mental disorders, however, only in patients entering the study as inpatients. In conclusion, neurological patients are at risk of being high users of health care if they have a mental illness, somatoform disorders being the most powerful risk factor. The results are consistent with the findings among internal medical patients.

Use of complementary therapy among internal medical inpatients. Prevalence, costs and association with mental disorders and physical diseases.

OBJECTIVES: The aims of this study were to determine the prevalence of complementary therapy/medicine (CT) use among internal medical inpatients. Furthermore, to examine the association between the use of CT and (a) mental disorders, (b) physical diseases, and (c) use of health care. METHODS: A total of 294 consecutive medical inpatients were interviewed about their use of CT. A stratified subsample of 157 people was assessed for current mental disorders, using an extensive, standardized, semistructured interview (Schedules for Clinical Assessment in Neuropsychiatry version 2.1 [SCAN]). Health care use was assessed by use of national patient registers. RESULTS: There were 22.5% CT utilizers. More females than males used CT (P=.033). CT utilization was not associated with age, mental disorders, life-threatening or chronic physical diseases or with use of health care services. CONCLUSIONS: The use of CT is common among medical inpatients. More research is needed to understand why a significant proportion of patients seeks CT.

The prevalence of somatoform disorders among internal medical inpatients.

OBJECTIVE: To find the prevalence of somatoform disorders (SDs) among internal medical inpatients and to study the comorbidity with other psychiatric disorders. METHODS: Of 392 eligible consecutive medical inpatients, 294 (75%) accepted to participate and, using a two-phase design, were assessed for ICD and DSM-IV somatoform diagnoses and for ICD-10 psychiatric diagnoses. RESULTS: A total of 18.1% (95% CI: 12.8-24.9%) of the patients fulfilled the diagnostic criteria for an ICD-10 disorder, and 20.2% (95% CI:14.7-27.2% ) for a DSM-IV SD. The prevalence of specified disorders revealed marked differences between the two diagnostic systems, e.g., concerning somatisation disorder (SD), which was more prevalent in the ICD-10 (5%) than in the DSM-IV (1.5%) equivalent. Quite the contrary was found in undifferentiated SD (0.7% in ICD-10 and 10% in DSM-IV). According to ICD-10 criteria, 3.5% had hypochondriasis, 2.6% a dissociative disorder, 3.2% a somatoform autonomic dysfunction, 1.5% had neurasthenia or persistent somatoform pain disorder, and 5% had an SD, unspecified. SDs were more prevalent among younger females. Thirty-six percent of the patients with SDs also had another psychiatric disorder, 11% a depression, and 25% an anxiety disorder. The physicians detected about 1/3 of the cases. CONCLUSION: Somatoform disorders were prevalent among internal medical inpatients especially among younger women.

Detecting mental disorders in general hospitals by the SCL-8 scale.

OBJECTIVE: The objective of this study is to validate the eight-item dichotomised version of the Symptoms Check List (SCL-8d) as a screening tool for psychiatric disorders. METHODS: The study population included 198 consecutive new neurological inpatients and outpatients and 294 consecutive internal medical inpatients, aged 18 or older. All patients received the SCL-8d questionnaire, and a stratified subsample was interviewed using the Schedules for Clinical Assessment in Neuropsychiatry (SCAN) interview. We tested the external SCL-8d validity using the SCAN interview as gold standard. The test was performed based on weighted data to correct for the skewness introduced by stratification. RESULTS: The diagnostic performance of the SCL-8d was excellent in the internal medical setting but not quite as good in the neurological sample. It performed better among the older compared with the younger patients, whereas the scale was not affected by gender. In the combined sample at the cut point 0/1, the sensitivity (SE) of the SCL-8d was 0.73 (confidence interval [CI](95%): 0.60-0.82), the specificity (SP) 0.61 (CI(95%): 0.53-0.68) and the positive predictive value (PPV) 0.42 (CI(95%): 0.34-0.50), using any International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) psychiatric disorder, excluding somatoform and substance abuse disorders, as gold standard. The risk of a patient having a mental disorder (except phobia, substance abuse or somatoform disorder) was less than 6% in case of a negative screening test. In patients with a current depressive disorder, 87.1% (27/31) were screening positive, and all except 1 (93.0%) of the 14 patients with a modest to severe depression scored 1 or higher on the SCL-8d. All 17 patients with an anxiety disorder, excluding phobias, were screening positive. CONCLUSION: The study suggests that the SCL-8d is a valid, brief screening tool for use in nonpsychiatric medical settings, especially to detect emotional psychiatric disorders (EPDs).

A brief diagnostic screening instrument for mental disturbances in general medical wards.

OBJECTIVE: Mental illness is prevalent among general hospital ward patients but often goes unrecognised. The aim of this study was to validate the SCL-8d as a brief questionnaire for mental disturbances for use in general hospitals. METHODS: The study included 2040 patients, 18 years or older, consecutively admitted to 11 general internal medicine wards in seven European countries. All patients were screened on admission by means of the SCL-8d questionnaire. The psychometric performance (i.e., the internal validity) of the SCL-8d scale was tested using modern item response theory (IRT) in the form of the Rasch model. RESULTS: Differences between sample characteristics were considerable. Even so, the SCL-8d scale showed a remarkable, statistically significant fit in terms of internal homogeneity (P>.01) in all individual settings, except in Spain and Germany where the item "Everything is an effort" had to be excluded to obtain a fit. When pooling data from all centres, an excellent statistical significance of fit (P>.05) was obtained by exclusion of the "Effort" item. The scale was homogeneous as to gender (P>.05), but not age as it performed better among young patients than among patients older than 60 years (P<.01). In these two patient groups both internal and external homogeneity (gender, median age) was achieved. The SCL-8d sum score showed a marked correlation with current and previous treatment for mental illness. CONCLUSION: Apart from the "Effort" item ranking differently on the latent severity dimension as to age, the SCL-8d seems very robust from a psychometric point of view. Besides being short, the SCL-8d scale contains only emotional symptoms. It would therefore seem to be an excellent diagnostic tool for use in medical settings.

Follow-up on mental illness in medical inpatients: health care use and self-rated health and physical fitness.

Consecutively admitted internal medical inpatients (N=294) who were psychiatrically assessed with the Schedules for Clinical Assessment in Neuropsychiatry in a two-phase design were followed up in a review of public files on their use of medical care over 18 months. Self-rated outcome was assessed from health and fitness ratings at admission and after 1 year. ICD-10 mental disorders had a statistically significant impact on the risk (odds ratio) of high use (above the 80th percentile) of primary care, as did ICD-10 anxiety/depression, and worry about illness (as assessed by the Whiteley-7 Scale). The authors found a less-than-significant tendency for mental illness to influence the use of inpatient admissions and self-rated outcome.

Use of health services, mental illness, and self-rated disability and health in medical inpatients.

OBJECTIVE: The primary objective of this study was to investigate if among medical inpatients their health service use was associated with 1) presence and type of mental disorders, 2) emotional distress and somatization, 3) self-rated physical disability and health. METHOD: Health service use (number of admissions to nonpsychiatric departments and reimbursement of primary care services) as well as psychological distress (SCL-8D) and somatization (Whiteley-7) was assessed for 294 consecutive medical inpatients. Patients rated their own health and physical functioning, and medical consultants assessed them for chronic and life-threatening diseases. A subsample of 157 patients was assessed for ICD-10 psychiatric diagnoses by means of an extensive semistructured interview (SCAN). RESULTS: High use (above 80th percentile) of inpatient admissions was statistically significantly associated to mental disorders (adjusted OR = 3.6 [95%CI, 1.3-9.7]), to anxiety and/or depression, somatoform disorders, chronic and life-threatening physical disease, severe (self-rated) physical disability, and SCL-8 and Whiteley-7 scores. High use of primary care was statistically significantly associated to mental disorders (OR = 3.4 [95%CI, 1.5-8.0]), to anxiety and/or depression, somatoform disorders, moderate or severe (self-rated) physical disability, fair, poor or very poor (self-rated) health, and the Whiteley-7 score. The SCL-8D score was significant in men only. CONCLUSION: Mentally disordered medical inpatients use health care more heavily than patients without, also after adjustment for medical disease severity. Use is closely associated to the Whiteley-7 and the SCL-8D.