Pia Eiken

Some antihyperglycemic medications have been found to affect bone metabolism. We assessed the long-term effects of metformin compared with placebo on bone mineral density (BMD) and trabecular bone score (TBS) in patients with type 2 diabetes. Metformin had no significant effect on BMD in the spine and hip or TBS compared with a placebo.

Diabetes is associated with an increased risk of fracture, however, neither bone mineral density, falls, diabetes complications nor other risk factors can explain why. Among patients with diabetes, hyperglycaemia may have detrimental effects on bone, but also use of anti-diabetic treatment may have an impact on fracture risk. In this article we assess the relationship between diabetes, bone and fracture and the effects of hyperglycaemia and anti-diabetic treatment on bone. Furthermore, fracture preventive measures in patients with diabetes are evaluated.

Background Data from observational studies have suggested that thiazide diuretics protect against fractures. Few studies have investigated time frames from initiation of treatment to fracture occurrence. Objective To evaluate the time to spinal, hip, femur, wrist and upper extremity fracture occurrence before and after thiazide exposure. Methods A matched retrospective cohort study of patient information from national Danish patient databases was conducted. Patients with reimbursed prescriptions for noncompounded thiazide diuretics with potassium supplementation (Anatomical Therapeutic Chemical classification system code C03AB) between 1996 and 2011 were matched with nonexposed control subjects by date of birth and gender. Weekly odds ratios (ORs) of fracture occurrence and total incidence rates (IRs) and incidence rate ratios (IRRs) of fracture risk were calculated for the periods before treatment initiation, weeks 1–42 and weeks 43–780. Results A total of 1 602 141 ‘thiazide exposure periods’ (46 8271 individuals) and 1 530 233 ‘nonexposure periods’ (655 399 individuals) were included in the analysis. Thiazide use was associated with factors of increased de novo fracture risk. Weekly adjusted fracture risk between exposure and nonexposure was increased prior to commencing thiazide therapy, further increasing from weeks 1–42 weeks and then decreasing gradually from weeks 43–780. There was a decreasing trend in total age‐adjusted risk during these periods: IRR [95% confidence interval 1.44 [1.42; 1.47], 1.27 [1.24; 1.29] and 1.14 [1.11; 1.18], respectively. Prescription patterns showed several treatment breaks amongst thiazide users. Conclusions It appears that thiazides reduce the background risk of fracture that is increased prior to commencing therapy. Long duration and continuity of thiazide exposure seems to be important to obtain this protective effect on fracture risk, but we have found in this study that this approach is not always used in clinical practice.

Despite aggressive treatment of cardiovascular disease (CVD) risk factors individuals with type 2 diabetes (T2D) still have increased risk of cardiovascular morbidity and mortality. The primary aim of this study was to examine the cross-sectional association between total (25-hydroxy vitamin D (25(OH)D)) and risk of CVD in patients with T2D. Secondary objective was to examine the association between 25(OH)D and bone health. A Danish cohort of patients with T2D participating in a randomised clinical trial were analysed. In total 415 patients (68% men, age 60±9 years (mean±s.d.), duration of diabetes 12±6 years), including 294 patients (71%) treated with insulin. Carotid intima–media thickness (IMT) and arterial stiffness (carotid artery distensibility coefficient (DC) and Young's elastic modulus (YEM)) were measured by ultrasound scan as indicators of CVD. Bone health was assessed by bone mineral density and trabecular bone score measured by dual energy X-ray absorptiometry. In this cohort, 214 patients (52%) were vitamin D deficient (25(OH)D 0.3) or bone health (P>0.6) after adjustment for CVD risk factors. In conclusion, 25(OH)D status was not associated with carotid IMT, arterial stiffness or bone health in this cohort of patients with T2D. To explore these associations and the association with other biomarkers further, multicentre studies with large numbers of patients are required.

The association between hyponatremia and osteoporosis was evaluated in humans. A significant association was found between low sodium levels, lower bone mineralization in the hip, and with several common conditions. Hyponatremia could be used as a marker of osteoporosis and systemic disease.

Introduction: Recent studies show an association between hyponatremia and osteoporosis. We have previously reported a case of severe male osteoporosis due to chronic syndrome of inappropriate secretion of antidiuretic hormone (SIADH). Here, we provide a follow-up on this case after cure of the condition that further supports the causal relationship. The Case: A 38-year-old man had been diagnosed with severe osteoporosis most likely due to chronic SIADH. The SIADH was believed to be idiopathic. A magnetic resonance imaging scan, however, revealed a tumor in the sinus, and biopsies showed an esthesioneuroblastoma, immunohistochemically positive for antidiuretic hormone (ADH). After the tumor was removed, ADH and sodium levels normalized. A dual-energy x-ray absorptiometry scan performed 7 months after the patient's last surgery showed a significant spontaneous improvement in bone mineral density in the lumbar vertebrae. Conclusion: This case provides evidence for a causal relationship between SIADH and chronic hyponatremia and impaired bone metabolism that can lead to severe secondary osteoporosis. The effect on bone metabolism is at least partially reversible.

Fractures after the age of 50 are frequently observed in Denmark, and many of these may be osteoporotic. This study examined the incidence of all and subsequent fractures in a 10-year period from 2001 to 2011. The incidence of subsequent fractures was high, especially following hip fracture.

Background. The aim of this study was to investigate IL-6 and 25-hydroxyvitamin D (25-OH D) associations with muscle size and muscle function in dialysis patients. Methods. Patients were included in a 16-week control period followed by 16 weeks of high-intensity resistance training thrice weekly. IL-6 and 25-OH D were analysed after an over-night fast. Muscle fibre size was analysed in biopsies from m. vastus lateralis. Muscle power was tested using a Leg Extensor Power Rig. Results. Patients () with IL-6 6.49pg/ml (median) were older and had decreased muscle power and a reduced protein intake () compared with patients with IL-6 < 6.49pg/ml. IL-6 was not associated with muscle fibre size. Vitamin D deficiency (25-OH D < 50nmol/l) was present in 51% of the patients and not associated with muscle power. IL-6 remained unchanged during the training period, whilst muscle power increased by 2023% (). Conclusion. Elevated IL-6 values were associated with decreased muscle power but not with decreased muscle fibre size. Half of the patients were suffering from vitamin D deficiency, which was not associated with muscle power. IL-6 was unchanged by high-intensity resistance training in dialysis patients in this study.

Context: Food ingestion decreases bone resorption, and glucose-dependent insulinotropic polypeptide (GIP) may mediate this effect. Mice overexpressing GIP have increased osteoblast activity and are rescued from age-related bone loss, whereas GIPR knockout mice have decreased cortical bone mass and compromised bone quality. Carriers of the functional variant GIPR Glu354Gln (rs1800437) have higher plasma glucose 2 hours after glucose ingestion, suggesting that the variant encoding GIPR 354Gln decreases the effect of GIP. Objective: The objective of the study was to investigate the effect of GIPR Glu354Gln on bone mineral density (BMD) and fracture risk. Design: This was a prospective, comprehensive, cohort study (number NCT00252408). Participants: A total of 1686 perimenopausal women were included. Main Outcome Measures: Dual-energy X-ray absorptiometry was performed at baseline and after 10 years. Incident fractures were recorded during the follow-up and were obtained from the Danish National Patient Registry, giving a total follow-up time of a minimum 16 years. Results: After 10 years, women with the minor frequency C allele of rs1800437 (354Gln) had significantly lower BMD at the femoral neck compared with carriers of the major G-allele (CC: 0.755 ± 0.015 g/cm² vs CG: 747 ± 0.005 g/cm²; GG: 0.766 ± 0.004 g/cm², P < .001). Correspondingly, total hip BMD was significantly lower among C allele carriers (CC: 0.881 ± 0.016 g/cm²; CG: 0.884 ± 0.005 g/cm²; and GG: 0.906 ± 0.004 g/cm², P < .001). Finally, women homozygous for the variant C allele had an increased risk (hazard ratio 1.6, confidence interval 1.0–2.6, P < .05) of nonvertebral fractures. Conclusion: This study demonstrates an association between a functional GIPR polymorphism Glu354Gln (rs1800437) and BMD and fracture risk. These findings further establish GIP to be involved in the regulation of bone density.