Symeon Tournis

Type 2 diabetes mellitus and fracture risk

Increased fracture risk, traditionally associated with type 1 diabetes, has lately been of great concern in patients with type 2 diabetes. A variable increase in fracture risk has been reported, ranging from 20% to 3-fold, depending on skeletal site, diabetes duration and study design. Longer disease duration, the presence of diabetic complications, inadequate glycemic control, insulin use and increased risk for falls are all reported to increase fracture risk. Patients with type 2 diabetes display a unique skeletal phenotype with either normal or more frequently increased, bone mineral density and impaired structural and geometric properties. Recently, alterations in bone material properties seem to be the predominant defect leading to increased bone fragility. Accumulation of advanced glycation end-products and changes in collagen cross-linking along with suppression of bone turnover seem to be significant factors impairing bone strength. FRAX score has been reported to underestimate fracture risk and lumbar spine BMD is inadequate in predicting vertebral fractures. Anti-diabetic medications, apart from thiazolidinediones, appear to be safe for the skeleton, although more data are needed. Optimal strategies to reduce skeletal fragility in type 2 diabetic patients are yet to be determined.

The use of bisphosphonates in women prior to or during pregnancy and lactation.

OBJECTIVE: The unique pharmacokinetics of bisphosphonates (BPs) in conjunction with their use by an increasing number of women at reproductive age has raised serious concerns about their safety during pregnancy and lactation. Bisphosphonates cross the placenta. Animal studies have shown adverse effects on both the fetus and the mother, mostly at doses much higher than those commonly used in humans. Protracted parturition, maternal mortality, embryolethality, severe general underdevelopment and marked skeletal retardation of the fetuses (increased amount of diaphyseal bone trabeculae, decreased diaphyseal length), small fetal weight and abnormal tooth growth have been observed. DESIGN: We conducted a thorough research of the literature in order to identify human studies concerning this issue. RESULTS: We identified a total of 78 cases involving fetuses whose mothers had been exposed to BPs before conception or during pregnancy, along with 7 cases of BPs exposure prior to or during lactation. The vast majority of mothers and infants did not demonstrate serious adverse effects. However, there were cases of shortened gestational age, low neonatal birth weight and transient hypocalcaemia of the newborns, while the very few reported cases of spontaneous abortions and congenital anomalies probably resulted from maternal underlying diseases and concomitant medication. CONCLUSION: The administration of bisphosphonates in pregnancy should be assessed in view of their potential hazardous effects on both mother and fetus. In cases of absolute or relative indications of BPs prior to pregnancy, close observation of the mother and the infant, especially during the first two weeks of life, is imperative for the successful outcome of pregnancy.

Effect of Rhythmic Gymnastics on Volumetric Bone Mineral Density and Bone Geometry in Premenarcheal Female Athletes and Controls

CONTEXT AND OBJECTIVE Weight-bearing exercise during growth exerts positive effects on the skeleton. Our objective was to test the hypothesis that long-term elite rhythmic gymnastics exerts positive effects on volumetric bone mineral density and geometry and to determine whether exercise-induced bone adaptation is associated with increased periosteal bone formation or medullary contraction using tibial peripheral quantitative computed tomography and bone turnover markers. DESIGN AND SETTING We conducted a cross-sectional study at a tertiary center. SUBJECTS We studied 26 elite premenarcheal female rhythmic gymnasts (RG) and 23 female controls, aged 9-13 yr. MAIN OUTCOME MEASURES We measured bone age, volumetric bone mineral density, bone mineral content (BMC), cortical thickness, cortical and trabecular area, and polar stress strength index (SSIp) by peripheral quantitative computed tomography of the left tibia proximal to the distal metaphysis (trabecular) at 14, 38 (cortical), and 66% (muscle mass) from the distal end and bone turnover markers. RESULTS The two groups were comparable according to height and chronological and bone age. After weight adjustment, cortical BMC, area, and thickness at 38% were significantly higher in RG (P < 0.005-0.001). Periosteal circumference, SSIp, and muscle area were higher in RG (P < 0.01-0.001). Muscle area was significantly associated with cortical BMC, area, and SSIp, whereas years of training showed positive association with cortical BMC, area, and thickness independent of chronological age. CONCLUSIONS RG in premenarcheal girls may induce positive adaptations on the skeleton, especially in cortical bone. Increased duration of exercise is associated with a positive response of bone geometry.

Adipose Tissue Lipolysis Is Upregulated in Lean and Obese Men During Acute Resistance Exercise

OBJECTIVE—To investigate the effect of acute resistance exercise on adipose tissue triacylglycerol lipase activity (TGLA) in lean and obese men. RESEARCH DESIGN AND METHODS—Nine lean and eight obese men performed 30 min of circuit resistance exercise. Adipose tissue and blood were sampled during exercise for TGLA, metabolite, and hormone determinations. Respiratory exchange ratio (RER) was measured throughout exercise. RESULTS—Energy expenditure of exercise relative to body mass was higher in the lean and RER was higher in the obese men, suggesting lower fat oxidation. TGLA increased 18-fold at 5 min of exercise in the lean men and 16-fold at 10 min of exercise in the obese men. The delayed lipolytic activation in the obese men was reflected in serum nonesterified fatty acid and glycerol concentrations. Plasma insulin increased in the obese but did not change in the lean men. CONCLUSIONS—Resistance exercise upregulated adipose tissue lipolysis and enhanced energy expenditure in lean and obese men, with a delayed lipolytic activation in the obese men.

Intensity of Resistance Exercise Determines Adipokine and Resting Energy Expenditure Responses in Overweight Elderly Individuals

OBJECTIVE To evaluate the time course of leptin, adiponectin, and resting energy expenditure (REE) responses in overweight elderly males after acute resistance exercise protocols of various intensity configurations. RESEARCH DESIGN AND METHODS Forty inactive men (65–82 years) were randomly assigned to one of four groups (n = 10/group): control, low-intensity resistance exercise, moderate-intensity resistance exercise, and high-intensity resistance exercise. Exercise energy cost, REE, leptin, adiponectin, cortisol, insulin, lactate, glucose, nonesterified fatty acids (NEFAs), and glycerol were determined at baseline, immediately after exercise, and during a 72-h recovery period. RESULTS Exercise energy cost was lower in high-intensity than in low-intensity and moderate-intensity groups (221.6 ± 8.8 vs. 295.6 ± 10.7 and 281.6 ± 9.8 kcal, P < 0.001). Lactate, glucose, NEFAs, and glycerol concentrations increased (P < 0.001) after exercise and returned to baseline thereafter in all groups. REE increased (P < 0.001) in all groups at 12 h in an intensity-dependent manner (P < 0.05). REE reached baseline after 48 h in the low- and moderate-intensity groups and after 72 h in the high-intensity group. Cortisol peaked in all active groups after exercise (P < 0.001) and remained elevated (P < 0.001) for 12 h. After adjustment for plasma volume shifts, leptin remained unaltered. Adiponectin concentration increased after 12 h and remained elevated for 24 h only in the high-intensity group (P < 0.001). CONCLUSIONS Resistance exercise does not alter circulating leptin concentration but does increase REE and adiponectin in an intensity-dependent manner for as long as 48 and 24 h, respectively, in overweight elderly individuals. It appears that resistance exercise may represent an effective approach for weight management and metabolic control in overweight elderly individuals.

Intensive insulin treatment reduces transient ischaemic episodes during acute coronary events in diabetic patients.

OBJECTIVES This study tested the impact of intensive metabolic treatment with insulin on transient myocardial ischaemia detected with continuous 12-lead ST-segment monitoring during non-ST segment elevation acute coronary syndromes in type 2 diabetic patients. METHODS AND RESULTS The study included 57 type 2 diabetic patients with non-ST segment elevation acute coronary syndromes.Twenty-eight patients randomized to conventional treatment plus intensive insulin therapy (group A) and twenty-nine to conventional therapy only (group B). Group A patients received insulin by infusion for 48 hours according to a predefined protocol aiming to maintain normoglycaemia. Group B patients received standard coronary care unit treatment. The ST-segment monitoring was performed for 48 hours in the coronary care unit. The two groups were comparable in terms of medical history, clinical and biochemical data. Three patients from both groups were excluded from the analysis because there was objective evidence for evolution in persistent ST-segment elevation acute myocardial infarction. Six patients (24%) from group A vs. twelve from group B (46.2%) had evidence of transient ischaemia (p = 0.098). Group A patients showed significantly lower values in the mean number [group A vs. group B: 0.4 +/- 0.8 vs. 2 +/- 3.1, p < 0.01] and total duration of ST-episodes [group A vs. group B: 2.4 +/- 5.1 vs. 21.2 +/- 31 min, p < 0.01]. Multivariate analysis revealed that the mean plasma glucose during the study period was a powerful predictor of the presence (b:0.377,p < 0.01), the number (b:0.523,p < 0.001) and the total duration (b: 0.686, p < 0.001) of ST-episodes, respectively. CONCLUSIONS; Intensive insulin treatment considerably decreases the number and the total duration of ST-episodes in type 2 diabetic patients suffering from non-ST segment elevation acute coronary syndromes.Objectives — This study tested the impact of intensive metabolic treatment with insulin on transient myocardial ischaemia detected with continuous 12-lead ST-segment monitoring during non-ST segment elevation acute coronary syndromes in type 2 diabetic patients. Methods and results — The study included 57 type 2 diabetic patients with non-ST segment elevation acute coronary syndromes.Twenty-eight patients randomized to conventional treatment plus intensive insulin therapy (group A) and twenty-nine to conventional therapy only (group B). Group A patients received insulin by infusion for 48 hours according to a predefined protocol aiming to maintain normoglycaemia. Group B patients received standard coronary care unit treatment. The ST-segment monitoring was performed for 48 hours in the coronary care unit.The two groups were comparable in terms of medical history, clinical and biochemical data. Three patients from both groups were excluded from the analysis because there was objective evidence for evolution in persistent ST-segment elevation acute myocardial infarction. Six patients (24%) from group A vs. twelve from group B (46.2%) had evidence of transient ischaemia (p=0.098). Group A patients showed significantly lower values in the mean number [group A vs. group B: 0.4 ± 0.8 vs. 2 ± 3.1, p<0.01] and total duration of ST-episodes [group A vs. group B: 2.4 ± 5.1 vs. 21.2 ± 31 min, p<0.01]. Multivariate analysis revealed that the mean plasma glucose during the study period was a powerful predictor of the presence (b: 0.377, p<0.01), the number (b: 0.523, p<0.001) and the total duration (b: 0.686, p<0.001) of ST-episodes, respectively. Conclusions — Intensive insulin treatment considerably decreases the number and the total duration of ST-episodes in type 2 diabetic patients suffering from non-ST segment elevation acute coronary syndromes.

Volumetric bone mineral density and bone geometry assessed by peripheral quantitative computed tomography in women with differentiated thyroid cancer under TSH suppression

TSH suppression therapy in patients with differentiated thyroid cancer (DTC) has been associated with adverse effects on areal bone mineral density (aBMD) only in postmenopausal women. The purpose of study was to examine the effect of TSH suppression therapy on skeletal integrity using peripheral quantitative computed tomography (pQCT) at the radius and tibia in pre‐ and postmenopausal women with DTC and controls.

Sequential treatment with teriparatide and strontium ranelate in a postmenopausal woman with atypical femoral fractures after long-term bisphosphonate administration.

OBJECTIVE: Despite the existence of numerous case series, no evidenced-based medical management for atypical fractures associated with bisphosphonate (BP) treatment has been established. DESIGN: We report the outcome of teriparatide (TRP) administration followed by strontium ranelate (SR) in a woman with a complete and an incomplete contralateral atypical fracture of the femoral diaphysis (AFF) associated with BP treatment. The spontaneous complete AFF was managed with intramedullary nailing, discontinuation of BP and initiation TRP. RESULTS: Eleven months later, she suffered a contralateral incomplete AFF. At the completion of the TRP treatment, she had only slight discomfort in the femur with the incomplete AFF. BMD testing revealed increase of 7.61% at the lumbar spine (LS) and 0.8% at the hip. Following TRP, 1-year SR treatment resulted in further BMD increase of 9.2% at the LS and 1.4% in the hip, while she does not report any pain. Bone markers remain within the normal range. CONCLUSION: Our case indicates that sequential therapy with TRP and SR in cases of AFF might be a rational treatment option. However, there is a need for additional information concerning the effect of TRP and SR, given alone or sequentially, in these patients in order to incorporate these drugs into the management of AFF.

Bone Quality Assessment as Measured by Trabecular Bone Score in Patients With End-Stage Renal Disease on Dialysis

Patients with end-stage renal disease (ESRD) on maintenance hemodialysis (HD) exhibit osteoporosis and increased fracture risk. Dual-energy X-ray absorptiometry scan measurements and calculation of fracture risk assessment toll score underestimate fracture risk in these patients and do not estimate bone quality. Trabecular bone score (TBS) has been recently proposed as an indirect measure of bone microarchitecture. In this study, we investigated alterations of bone quality in patients with ESRD on HD, using TBS. Fifty patients with ESRD on HD, with a mean age 62 years, and 52 healthy individuals matched for age, body mass index, and gender, were enrolled. All participants had a bone mineral density (BMD) measurement by dual-energy X-ray absorptiometry scan at the lumbar spine, femoral neck, total hip, and 1/3 radius. TBS was evaluated using TBS iNsight. Serum fetuin-A and plasma fibroblast growth factor-23 (FGF-23) (C-terminal) were also measured. Patients on dialysis had significantly lower BMD values at all skeletal sites measured. Plasma FGF-23 levels significantly increased and serum fetuin-Α significantly decreased in patients on dialysis compared with controls. TBS was significantly reduced in patients on dialysis compared with controls (1.11 ± 0.16 vs 1.30 ± 0.13, p < 0.001, respectively) independently of age; BMD; duration of dialysis; and serum levels of alkaline phosphatase, 25-OH-vitamin D, parathyroid hormone, fetuin-A, or plasma FGF-23. Patients on HD who were diagnosed with an osteoporotic vertebral fracture had numerically lower TBS values, albeit without reaching statistical significance, compared with patients on dialysis without a fracture (1.044 ± 0.151 vs 1.124 ± 0.173, respectively, p = 0.079). Bone microarchitecture, as assessed by TBS, is significantly altered in ESRD on patients on HD independently of BMD values and metabolic changes that reflect chronic kidney disease-mineral and bone disorder.

Effects of teriparatide retreatment in a patient with β‐thalassemia major

Bone disease is a frequent complication of β‐thalassemia major (β‐ΤΜ) and its etiology is multifactorial. Marrow expansion, chronic hypoxia, endocrine complications, and iron overload caused chiefly by chronic transfusion treatment are significant factors affecting skeletal health. Bone disease is prevalent even among patients on regular transfusions and adequate iron chelation. The life expectancy of patients with β‐thalassemia has increased during the past decade and so, nowadays, patients with thalassemia‐associated bone disease (TBD) often require long‐term management. There are limited data concerning their pharmacologic treatment. Bisphosphonates represent the most widely studied agents in such patients and there are no published studies about the effects of anabolic treatment. Retreatment with teriparatide has only occasionally been studied in patients with osteoporosis.