Parathyroid Hormone-Related Changes of Bone Structure.

Parathyroid hormone (PTH) increases the release of serum calcium through osteoclasts, which leads to bone resorption. Primary, PTH stimulates osteoblasts leading to increase RANKL (receptor activator for nuclear factor kappa-B ligand) expression and thus differentiation of osteoclasts. In kidneys, PTH increases calcium and decrease phosphate reabsorption. In kidneys, PTH stimulates 1alpha-hydroxylase to synthesize active vitamin D. Primary hyperparathyroidism (PHPT) is characterized by skeletal or renal complications. Nowadays, the classical form of PHPT is less seen and asymptomatic or subclinical (oligo symptomatic) forms are more frequent. Previously, it was thought that cortical bone is preferably affected by PHPT and that predispose bones to fracture at sites with a higher amount of cortical bone. However, an increased risk of vertebral fractures has been found by most of the studies showing that also trabecular bone is affected. Bone Mass measurement (BMD) at all skeletal sites is advised, but another specific tool for fracture assessment is needed. Trabecular bone score (TBS), an indirect measure of trabecular bone, maybe a useful method to estimate fracture risk. TBS is associated with vertebral fractures in PHPT regardless of BMD, age, BMI and gender. Furthermore, there is an association between TBS and high resolution peripheral quantitative computed tomography (HR-pQCT) parameters in the trabecular and cortical compartment. However, studies considering the effect of PHPT treatment on TBS are more conflicting. Secondary hyperparathyroidism caused by vitamin D deficiency was associated with impaired bone microarchitecture in all age categories, as measured by TBS and Hr-pQCT with further improvement after treatment with vitamin D.

Fibroblast Growth Factor 23 and Klotho Are Associated With Trabecular Bone Score but Not Bone Mineral Density in the Early Stages of Chronic Kidney Disease: Results of the Cross-Sectional Study.

This study evaluates bone mineral density (BMD) and trabecular bone score (TBS) in relationship with new markers of chronic kidney disease (CKD), fibroblast growth factor 23 (FGF23), and klotho. The patients in this cross-sectional study were divided as follows: group A -patients in stages G1-3; group B -patients in stages G4 - 5 according to KDIGO. Plasma levels of soluble klotho and FGF23 were determined by ELISA. Bone mineral density (BMD) and trabecular bone score (TBS) were measured. 74 patients with CKD (mean age 68.8 years) were included in the study. Higher levels of FGF23 were observed in group B (N=15) compared to group A (N=59; p=0.001) were observed. FGF23 was higher in group A compared to group B. Significant difference in TBS within the first 3 stages of CKD was observed (mean TBS in G1=1.375 vs. G2=1.340 vs. G3a=1.24; p<0.05) and negative correlation of FGF23 and TBS (R=-0.33; p=0.05) and positive correlation between klotho and TBS (R=0.419; p=0.04) was observed. This study confirmed that FGF23 and klotho are associated with TBS, but TBS reflects a decrease in kidney function only in the first 3 stages of CKD. Thus, FGF23 and klotho together with TBS are promising markers of early trabecular bone impairment in CKD.

Prediction of Vertebral Fractures by Trabecular Bone Score in Patients With Ankylosing Spondylitis.

Ankylosing spondylarthritis (AS) is associated falsely increased lumbar spine bone mineral density (BMD). New tool for discrimination of subjects at fracture risk is needed. Vertebral fracture (VF) prediction of routine methods for osteoporosis assessment, BMD and trabecular bone score (TBS), in patients with AS. Cross-sectional study of all AS patients regularly followed at the rheumatology outpatient clinics of two centers. All subjects undergone BMD measurement at lumbar spine (LS), total hip (TH) and femoral neck (FN) using Hologic® Horizon device. TBS at L1-4 in all subjects by TBS InSight® software were assessed. Vertebral fracture assessment (VFA) was performed using the lateral spine imaging IVA™ and graded using Genant semi-quantitative approach. 119 AS subjects (90 males/29 females), mean age 47.6 years were included in the study. In 20 patients 34 VFs were detected, from whom 7 patients had multiple fractures. Subjects with VF were older and had lower FN BMD, TBS in comparison to non-VF subjects. No differences in LS BMD, FN BMD or BASDAI between groups were observed. Among patients with VF only 3 had T-score less than -2.5 but 7 has TBS less than 1.23 which means highly degraded microarchitecture. AS patients with VF have lower TBS and FN BMD in comparison to non-VF subjects. In addition, TBS was able to detect 20 % more VFs than BMD. Therefore, TBS seems promising in VF discrimination among patients with AS.

The Long-Term Effects of Growth Hormone Replacement on Bone Mineral Density and Trabecular Bone Score: Results of the 10-Year Prospective Follow-up.

There are only few studies concerning about long-term effect of growth hormone (GH) replacement therapy on bone mineral density and bone microstructure. To assess effect of GH replacement therapy on bone mineral density (BMD) and trabecular bone score (TBS) in adult GH deficient (AGHD) subjects over period of 10 years. From 2005 to 2018, a prospective study of AGHD patients was conducted in national referral center for treatment of GHD. All patients received subcutaneous recombinant human GH in an IGF 1-normalizing regimen once a day. Lumbar spine (L-spine) and total hip (TH) BMD using Hologic densitometers were measured at baseline and every two years during treatment with rhGH. TBS was derived from L1-L4 DXA using iNsight® software (Medimaps, France) at each time point. Periods of measurement were baseline, year 2; 4; 6; 8 and 10. In total, 63 patients (38 males, 25 females, mean age 25.1±16 years) were included in the study. After 10 years of GH treatment, IGF-1 significantly increased (~35 %), with greatest increase at year 2. During 10-year follow-up, L-spine BMD increased approximately of 7 % (NS). TH BMD increase of 11 % during follow-up (p=0.0003). The greatest increment of BMD was achieved at year 6 on both sites, L-spine (+6 %) and TH BMD (+13 %) (p<0.05). There was no significant change of TBS during whole follow-up. In this study, sustaining positive effect of GH replacement therapy on bone density in subjects with adult GH deficiency over 10 years of follow-up was observed. The study did not show effect on TBS, as indirect measure of trabecular bone microarchitecture.

Parathyroid Hormone-Related Changes of Bone Structure.

Parathyroid hormone (PTH) increases the release of serum calcium through osteoclasts, which leads to bone resorption. Primary, PTH stimulates osteoblasts leading to increase RANKL (receptor activator for nuclear factor kappa-B ligand) expression and thus differentiation of osteoclasts. In kidneys, PTH increases calcium and decrease phosphate reabsorption. In kidneys, PTH stimulates 1alpha-hydroxylase to synthesize active vitamin D. Primary hyperparathyroidism (PHPT) is characterized by skeletal or renal complications. Nowadays, the classical form of PHPT is less seen and asymptomatic or subclinical (oligo symptomatic) forms are more frequent. Previously, it was thought that cortical bone is preferably affected by PHPT and that predispose bones to fracture at sites with a higher amount of cortical bone. However, an increased risk of vertebral fractures has been found by most of the studies showing that also trabecular bone is affected. Bone Mass measurement (BMD) at all skeletal sites is advised, but another specific tool for fracture assessment is needed. Trabecular bone score (TBS), an indirect measure of trabecular bone, maybe a useful method to estimate fracture risk. TBS is associated with vertebral fractures in PHPT regardless of BMD, age, BMI and gender. Furthermore, there is an association between TBS and high resolution peripheral quantitative computed tomography (HR-pQCT) parameters in the trabecular and cortical compartment. However, studies considering the effect of PHPT treatment on TBS are more conflicting. Secondary hyperparathyroidism caused by vitamin D deficiency was associated with impaired bone microarchitecture in all age categories, as measured by TBS and Hr-pQCT with further improvement after treatment with vitamin D.

Fibroblast Growth Factor 23 and Klotho Are Associated With Trabecular Bone Score but Not Bone Mineral Density in the Early Stages of Chronic Kidney Disease: Results of the Cross-Sectional Study.

This study evaluates bone mineral density (BMD) and trabecular bone score (TBS) in relationship with new markers of chronic kidney disease (CKD), fibroblast growth factor 23 (FGF23), and klotho. The patients in this cross-sectional study were divided as follows: group A -patients in stages G1-3; group B -patients in stages G4 - 5 according to KDIGO. Plasma levels of soluble klotho and FGF23 were determined by ELISA. Bone mineral density (BMD) and trabecular bone score (TBS) were measured. 74 patients with CKD (mean age 68.8 years) were included in the study. Higher levels of FGF23 were observed in group B (N=15) compared to group A (N=59; p=0.001) were observed. FGF23 was higher in group A compared to group B. Significant difference in TBS within the first 3 stages of CKD was observed (mean TBS in G1=1.375 vs. G2=1.340 vs. G3a=1.24; p<0.05) and negative correlation of FGF23 and TBS (R=-0.33; p=0.05) and positive correlation between klotho and TBS (R=0.419; p=0.04) was observed. This study confirmed that FGF23 and klotho are associated with TBS, but TBS reflects a decrease in kidney function only in the first 3 stages of CKD. Thus, FGF23 and klotho together with TBS are promising markers of early trabecular bone impairment in CKD.

Prediction of Vertebral Fractures by Trabecular Bone Score in Patients With Ankylosing Spondylitis.

Ankylosing spondylarthritis (AS) is associated falsely increased lumbar spine bone mineral density (BMD). New tool for discrimination of subjects at fracture risk is needed. Vertebral fracture (VF) prediction of routine methods for osteoporosis assessment, BMD and trabecular bone score (TBS), in patients with AS. Cross-sectional study of all AS patients regularly followed at the rheumatology outpatient clinics of two centers. All subjects undergone BMD measurement at lumbar spine (LS), total hip (TH) and femoral neck (FN) using Hologic® Horizon device. TBS at L1-4 in all subjects by TBS InSight® software were assessed. Vertebral fracture assessment (VFA) was performed using the lateral spine imaging IVA™ and graded using Genant semi-quantitative approach. 119 AS subjects (90 males/29 females), mean age 47.6 years were included in the study. In 20 patients 34 VFs were detected, from whom 7 patients had multiple fractures. Subjects with VF were older and had lower FN BMD, TBS in comparison to non-VF subjects. No differences in LS BMD, FN BMD or BASDAI between groups were observed. Among patients with VF only 3 had T-score less than -2.5 but 7 has TBS less than 1.23 which means highly degraded microarchitecture. AS patients with VF have lower TBS and FN BMD in comparison to non-VF subjects. In addition, TBS was able to detect 20 % more VFs than BMD. Therefore, TBS seems promising in VF discrimination among patients with AS.

The Long-Term Effects of Growth Hormone Replacement on Bone Mineral Density and Trabecular Bone Score: Results of the 10-Year Prospective Follow-up.

There are only few studies concerning about long-term effect of growth hormone (GH) replacement therapy on bone mineral density and bone microstructure. To assess effect of GH replacement therapy on bone mineral density (BMD) and trabecular bone score (TBS) in adult GH deficient (AGHD) subjects over period of 10 years. From 2005 to 2018, a prospective study of AGHD patients was conducted in national referral center for treatment of GHD. All patients received subcutaneous recombinant human GH in an IGF 1-normalizing regimen once a day. Lumbar spine (L-spine) and total hip (TH) BMD using Hologic densitometers were measured at baseline and every two years during treatment with rhGH. TBS was derived from L1-L4 DXA using iNsight® software (Medimaps, France) at each time point. Periods of measurement were baseline, year 2; 4; 6; 8 and 10. In total, 63 patients (38 males, 25 females, mean age 25.1±16 years) were included in the study. After 10 years of GH treatment, IGF-1 significantly increased (~35 %), with greatest increase at year 2. During 10-year follow-up, L-spine BMD increased approximately of 7 % (NS). TH BMD increase of 11 % during follow-up (p=0.0003). The greatest increment of BMD was achieved at year 6 on both sites, L-spine (+6 %) and TH BMD (+13 %) (p<0.05). There was no significant change of TBS during whole follow-up. In this study, sustaining positive effect of GH replacement therapy on bone density in subjects with adult GH deficiency over 10 years of follow-up was observed. The study did not show effect on TBS, as indirect measure of trabecular bone microarchitecture.

Pathophysiology of growth hormone secretion disorders and their impact on bone microstructure as measured by trabecular bone score.

This article is focused on endocrine-mediated osteoporosis caused by growth hormone (GH) disorders; adult GH deficiency and acromegaly. GH and insulin like growth factor-1 (IGF-1) stimulate linear bone growth through complex hormonal interactions and activates epiphyseal prechondrocytes. GH, via receptor activator of nuclear factor-kappaB (RANK), its ligand (RANK-L), and the osteoprotegerin system, stimulates production of osteoprotegerin and its accumulation in bone matrix. Malfunction of this mechanism, could lead to specific bone impairment. However, the primary problem of bone disease in GH secretion disorders is the primary prevention of osteoporotic fractures, so it is important to determine bone quality that better reflects the patient's actual predisposition to fracture. A method estimating bone quality from lumbar spine dual X-ray absorptiometry (DXA) scans is trabecular bone score (TBS). TBS in addition to bone mineral density (BMD) is a promising predictor of the osteoporotic fracture risk in women with postmenopausal osteopenia. In acromegaly TBS better defines risk of fracture because BMD is normal or even increased. TBS helps to monitor the effect of growth hormone therapy. Despite these findings, TBS should not be used alone, but a comprehensive consideration of all fracture risk factors, BMD and bone turnover markers is necessary.

Good long-term glycemic compensation is associated with better trabecular bone score in postmenopausal women with type 2 diabetes.

Osteoporosis is an increasingly widespread disease, as well as diabetes mellitus. It is now accepted that osteoporotic fractures are a serious co-morbidity and complication of diabetes. Despite of good bone mineral density in Type 2 Diabetes (T2DM) patients is the fracture risk elevated. It is due to reduced bone quality. To determine the effect of glycemic compensation on bone density and trabecular bone score (TBS) in T2DM. We analyzed a cohort of 105 postmenopausal women with T2DM. For all patients, central bone density (spinal and lumbar spine) was tested by DXA methodology, glycemic control parameters were assessed, and anthropometric parameters were measured. Bone quality was analyzed using TBS software. The results were statistically processed. Good glycemic compensation with glycated hemoglobin (A1c) value <7.0 % DCCT did not lead to BMD changes in patients with T2DM. However, patients with HbA1c <7 % DCCT had significantly better TBS (1.254±0.148 vs. 1.166±0.094, p=0.01). There was a negative correlation between TBS and glycated hemoglobin (r= -0,112, p<0.05) with glycemic fasting (r= -0.117, p<0.05). The optimal effect on TBS is achieved when all three markers of glycemic compensation (glycated hemoglobin, fasting plasma glucose and postprandial glycemia) are in optimal range. By using ROC curves glycated hemoglobin has the most significant effect on TBS. Optimal glycemic compensation, evaluated by glycated hemoglobin, does not lead to changes in BMD but has a beneficial effect on TBS in T2DM. Good glycemic control is required also for reduction of the risk of osteoporosis and osteoporotic fractures.

Prevalence and risk factors for drug-induced liver injury among patients with rheumatic diseases treated with biological therapy: a single-center experience.

Drug-induced liver injury (DILI) is a common event in patients with rheumatic diseases (RD) on biological therapy (BT). We aimed at evaluating the prevalence and pattern of DILI. Consecutive RD patients treated with BT were followed for 6 months. ALT and ALP >the upper limit normal (ULN) and 3xULN injury Grade 2. 582 liver function tests (LFTs) in 199 patients were evaluated, median age 53y, 59.3 % females, RA in 108, AS 49, and PsA 42 patients. ALT Grade 1 elevation was observed in 25.6 %, transient in 18.6 %, persisting in 7 %, Grade 2 in 1.5 %, ALP Grade 1 in 3.5 %, transient in 2 %, persisting in 1.5 %. We report no case of ALP Grade 2 or Hy´s law (ALT>3xULN, bilirubin>2xULN). Patients with persisting ALT elevation had higher BMI (28.23 vs. 25.74, p=0.016), lower DAS28 (2.22 vs. 5.28, p=0.046). ALT Grade 1 injury was more frequent with solo tocilizumab compared with other agents (27.5 % vs. 13.6 %, p=0.01). DILI was frequent, in 18.6 % transient, in 7 % persisting, Grade 2 in 1.5 %, led to treatment alteration in 0.5 %, with higher prevalence on solo tocilizumab therapy. We report no new safety signals for BT in RD.

Impact of smoking cigarette on the mRNA expression of cytokines in mucosa of inflammatory bowel disease.

It is well known that smoking is the risk factor in the development and clinical course of Crohn s disease (CD), but on the other hand, smoking is a protective factor against ulcerative colitis (UC). The pathways that are influenced by smoking in CD and UC are poorly understood. The aim of our study was to analyse the influence of smoking on the mRNA expression of cytokines in mucosa in patients with CD and UC. We performed a cross-sectional study. The cohort consisted of 86 IBD patients (48 CD patients and 38 UC patients) and took place at the IBD Centre at the University Hospital Bratislava-Ruzinov. We took the demographic and clinical data of each patient, including information about their smoking habits. We performed a colonoscopy on each patient and took biopsies from both inflamed and non-inflamed sigma (CD, UC) and terminal ileum (CD). mRNA was extracted from mucosal biopsy samples for each cytokine and was normalized to a housekeeping gene (GAPDH). Finally, we compared the mRNA expression of target cytokines in the mucosa of smokers and non-smokers in IBD patients. Smokers with Crohn s disease have a significantly higher mRNA expression of pro-inflammatory cytokine TNF ? (p=0.003) in inflamed mucosa in sigma compared with non-smokers. In smokers with ulcerative colitis, we observed significantly higher mRNA expression of anti-inflammatory cytokine IL 10 (p=0.022) in non-inflamed mucosa of sigma. Similarly, smokers with UC have a significantly decreased mRNA expression of cytokine TLR 2 (p=0.024) and CCR1 (p=0.049) in non-inflamed mucosa of sigma. Based on our results, smoking has a positive influence on cessation and the clinical course of UC due to the stimulation of anti-inflammatory cytokine IL 10 in mucosa. On the other hand, smokers with CD have a higher expression of pro-inflammatory cytokine TNF ?, which could be associated with a worsening of the disease and response to therapy.

Influence of vitamin D on the expression of mRNA of cytokines in the mucosa of inflammatory bowel disease patients.

The aim of this study was to analyze the influence of 25(OH)VD serum concentration on the expression of mRNA cytokines (IL-6, IL-8, IL-12, IL-17, IL-23, TNFα, CCR1, CCR2, CCR5, CCR9, CCL5, TLR2, TLR4, TLR5, CD207 ,CD206, FoxP3) in mucosa of IBD patients. The cohort consisted of 86 IBD patients (48 CD and 38 UC) followed at the IBD center of University Hospital Bratislava-Ruzinov. We performed colonoscopy in each patient and took biopsies from mucosa of sigma and terminal ileum. Serum concentration of 25(OH)VD was assessed at the time of colonoscopy. mRNA was extracted from mucosal biopsy samples for each cytokine. Then we analyzed the correlation between VD and the expression of mRNA of cytokines from biopsies samples.  In CD we observed a significant positive correlation of serum concentration 25(OH)VD and the expression mRNA level of IL-6. There was also trend towards significant positive correlation of the expression mRNA of TNFα, IL-10, IL-23, TLR 2 in inflamed mucosa of terminal ileum as well as the expression mRNA of CCR5 and CCR1 in non-inflamed mucosa from terminal ileum. We also found a trend towards positive correlation between 25(OH)VD and the expression mRNA of IL-23, TLR4, CD 207, CCR1, CCR5 and CD 206 in non-inflamed mucosa of sigma in UC.VD significantly correlated with the levels of expression of several inflammatory cytokines including TNFα in colonic mucosa of patients with IBD (Tab. 4, Fig. 3, Ref. 31).

Speckle tracking can detect subclinical myocardial dysfunction in rheumatoid arthritis patients.

INTRODUCTION: Patients with rheumatoid arthritis (RA) have shorter life expectancy and their risk of cardiovascular death is more than 50 % higher than the rest of the population. Early myocardial dysfunction in RA patients may be detectable sooner using speckle­tracking echocardiography. METHOD: Cross-sectional study enrolled 55 patients with RA (mean age 44.1 years) without known cardiovascular disease and 31 healthy controls. All subjects underwent a standard echocardiographic examination: indexed left ventricular mass, left ventricle ejection fraction, isovolumic contraction and relaxation times (IVCT and IVRT), mitral valve inflow curve (E/A), septal mitral annular motion (e'), and E/e' ratio as well as the speckle tracking assessment of left ventricle longitudinal, radial and circular strain and strain rate. RESULTS: In standard echocardiographic examination RA patients exhibited higher indexed left ventricle mass (96.36±20.90 g/m2 vs 95.84±21.86 %, p=0.013), lower ejection fraction (64.84±3.87 % vs 67.10±3.87 %, p=0.011) and prolonged IVCT (61.51±9.30 ms vs 53.71±8.95 ms, p=0.001). Diastolic dysfunction was demonstrated by prolonged IVRT (81.62±9.56 ms vs 74.58±12.02 ms, p=0.007) as well as by higher E/e' ratio (8.21±1.76 vs 7.21±1.52, p=0.009). Speckle­tracking method detected lower global longitudinal epicardial strain (-19.51 % vs -21.46 %, p=0.049). Radial, circular, and transversal strains and strain rates were same in both groups. Global longitudinal epicardial strain correlated with IVCT and IVRT, disease duration, and markers of myocardial damage NTproBNP. CONCLUSIONS: Standard echocardiographic assessment of myocardial function is examiner- and angle-dependent method with considerable limitations for evaluation of minimal subclinical changes. Speckle-tracking echocardiography significantly revealed incipient myocardial dysfunction in RA patients without overt cardiovascular diseases. This correlates with clinical RA characteristics and markers of cardiac damage (Tab. 4, Ref. 48).

Genetics of neuroendocrine factors in rheumatoid arthritis.

Inadequate production of cortisol related to inflammation and decrease in adrenal androgen production are hallmarks of hypothalamic-pituitary-adrenal (HPA)-related endocrine findings in rheumatoid arthritis (RA). In particular, lower dehydroepiandrosterone sulfate (DHEAS) levels were consistently found in a subset of premenopausal RA females. Recently, several new gene variants have been identified in association with serum DHEAS concentrations, such as in SULT2A1 and HHEX genes. These DHEAS-related genes and other variants involved in HPA regulation may play a role in the adrenal androgen deficiency in RA. The aim of our study was to review involvement of genetic mechanisms of HPA regulation, with focus on adrenal androgens, in the context of RA pathophysiology. Although, effects of the DHEAS-related gene variants appear to be relatively small compared to other well-known factors such as age, complex interactions between DHEAS-associated genotypes and adrenal androgen hypofunction phenotype may exist in RA. Further studies analyzing specific neuroendocrine phenotype/genotype in RA are needed.

Impact of the growth hormone replacement on bone status in growth hormone deficient adults.

INTRODUCTION: Growth hormone deficiency (GHD) is associated with reduced bone mineral density (BMD). GH replacement has positive effect on BMD but the magnitude of this effect and its mechanism are debated. OBJECTIVES: The objectives of this study was first, to assess the effect of GH replacement on BMD, and second, to evaluate the effect of GH treatment on bone turnover and microarchitecture and to assess the factors influencing the effect of the therapy on BMD. PATIENTS AND METHODS: Adult GHD (AO-GHD) and childhood onset GHD (CO-GHD) patients treated with GH using IGF-I normalization GH replacement regimen were prospectively followed during 2 years. Lumbar spine (L1-L4) and total femur BMD by Hologic discovery, in the subset of patients also bone turnover markers; osteocalcin and carboxy-terminal collagen crosslinks (CTx) were assessed at baseline and at months 3, 6, 12 and 24, respectively. The trabecular bone score (TBS) derived from lumbar spine DXA by the iNsight® software was assessed in a subset of study population at baseline and months 12 and 24. RESULTS: In total, 147 GHD patients (age 35.1 years, 84 males/63 females, 43 of childhood onset GHD/104 AO-GHD) were included. BMD of lumbar spine and femur increased significantly during the treatment (14% and 7% increase at 2 years, respectively; p<0.0001). Bone markers increased during the first 12 months of treatment with subsequent decrease of CTx. At month 24, significant increase in TBS was observed (4%, p=0.02). BMD increase was significantly higher in males (15% increase in males vs. 10% in females, p=0.037) and childhood onset GHD (CO-GHD) patients (13% increase in CO-GHD, p=0.004). CONCLUSION: GH supplementation leads to an increase of BMD with corresponding changes in bone turnover markers and changes in microarchitecture as assessed by trabecular bone score. Positive effect of GH on bone status is more pronounced in males and CO-GHD adults.

Effect of growth hormone on bone status in growth hormone-deficient adults.

BACKGROUND: Growth hormone deficiency (GHD) is associated with reduced bone mineral content and increased risk of osteoporotic fractures. Reduced peak bone mass might explain the low bone mineral density (BMD) among patients with childhood onset GHD (CO-GHD) whilst the cause of osteopenia in adult-onset GHD (AO-GHD) is not fully understood. OBJECTIVES: Prospective multicentric study to asses bone status in GHD adults after two years of recombinant growth hormone replacement treatment. METHODS: In 94 GHD adults (49 men; Ø 34.5 yrs) we have measured BMD and bone markers (CTX, osteocalcin) during two years of rhGH treatment (at baseline, after 3 and 6 months, and after 1 and 2 years). Patients were adequately substituted for GHD and other pituitary deficiencies. RESULTS: We have observed an increase in BMD-lumbar spine: n=42, 0.8155 →0.9418 g/cm2, p<0.0001; femoral neck n=41; 0.8468 →0.9031; p= 0.0004; BMD-whole body 1.0179 →1.0774; p=0.0003. We have compared gender difference: BMD-L-spine by 15.8 % in men (n=21) and by 5.6 % in women (n=19) (p= 0.008); BMD-femoral neck increased by 11.03 % in men and by about 3.0 % in women (p=0.032). In women, the initial decrease in BMD was recorded after 3 months. CO-GHD adults yielded a higher increase in BMD -L-spine (16.6 %, p=0.022). A correlation exists between IGF-I levels and BMD in lumbar spine (1st year: R=0.348, p=0.026; 2nd year: R= 0.33, p=0.0081) and between IGF-I and osteocalcin (1st year: R=0.383; p=0.0038). CONCLUSION: Two-year therapy with recombinant human growth hormone improved bone status. IGF-I appears to be a good indicator of rhGH effect on bone (Tab. 3, Fig. 9, Ref. 36). Text in PDF www.elis.sk.

The prevalence and risk factors for osteoporosis in patients with inflammatory bowel disease.

AIM: Osteoporosis is a known chronic complication of inflammatory bowel diseases (IBD). The aim of our study was to describe the prevalence of reduced bone mineral density (BMD) in IBD patients and to identify crucial risk factors for osteoporosis. METHODS: The cohort consisted of 76 IBD patients, 40 with Crohn's disease (CD) and 36 with ulcerative colitis (UC). Clinical characteristics of every patient were recorded, i.e. age, sex, duration of the disease, clinical behavior, location of disease according to Montreal classification, surgeries, steroid medication, sIBDQ, and smoking habits. We examined the serum 25-hydroxyl vitamin D3 (25-OHD3) in each patient. The BMD was determined by dual-energy X-ray absorptiometry (DXA) at the lumbar spine and femoral neck. RESULTS: Osteoporosis was documented in 10 IBD patients (13.2 %), while osteopenia in 35 of them (46.1 %). Patients with CD have significantly lower femoral Z score than patients with UC. Femoral Z score was strongly associated with disease duration, and in CD patients suffering from stricturing form, with ileic or ileocolic location and history of proctocolectomy or total colectomy. Patients with osteoporosis had a significantly lower level of 25-OHD3 than patients with normal BMD. CONCLUSION: Patients with long disease duration and those suffering from stricturing form of CD with ileic/ileocolic location and history of proctocolectomy/total colectomy are at higher risk of developing osteoporosis than other IBD patients. The high proportion of osteopenia/osteoporosis in our study underlines the importance of BMD measurement in all IBD patients as a base for initiating the appropriate treatment (Tab. 1, Fig. 3, Ref. 63).

Vitamin D deficiency - a possible link between osteoporosis and metabolic syndrome.

OBJECTIVES: The aim of our study was to evaluate the relationship between bone mineral density (examined by DXA - dual energy x-ray absorptiometry), vitamin D3 levels and the signs of metabolic syndrome. METHODS: We examined 55 subjects (37 women, 18 men, age median 67.8 years) with no history of osteoporosis, suffering from metabolic syndrome (defined as abdominal obesity and more than 2 of other components - arterial hypertension, dyslipidemia and diabetes mellitus or impaired glucose tolerance, according to IDF, 2006). RESULTS: Osteoporosis (T-score less than - 2.5) was found in 32.7 % (15 women and 3 men) and osteopenia (T-score between - 1.5 and - 2.5) in 29 % (13 women and 3 men) of patients. We observed a negative correlation between BMI and fat percentage (examined by DXA) and vitamin D3 levels. Low concentration of vitamin D3 was found in 90 % of patients with median 19.36 ug/l (64 % measured in winter, 36 % in summer, no relationship between vitamin D3 levels and season). We also observed a negative correlation between the low concentration of vitamin D3 and presence of diabetes mellitus as a part of metabolic syndrome. CONCLUSION: The link between osteoporosis and metabolic syndrome could influence the therapeutic approach in both disorders and vitamin D supplementation may play an important role in prevention of these severe conditions (Tab. 5, Fig. 1, Ref. 29).

Effect of long-term oral anticoagulant therapy on bone mineral density and bone turnover markers: a prospective 12 month study.

INTRODUCTION: Vitamin K-dependent posttranslational modification of glutamate to gamma-carboxyglutamate is a biochemical feature of the vertebrate blood-clotting cascade. This conversion activates clotting factors and bone proteins, including osteocalcin, a widely accepted marker of osteoblastic activity. Vitamin K antagonists, such as warfarin, inhibit this process. OBJECTIVE: This study was aimed at evaluating the effect of warfarin treatment on BMD and bone turnover markers and determining the relationship between BMD and bone turnover markers. PATIENTS AND METHODS: Fifty-four warfarin users and 62 age- and sex-matched healthy controls were enrolled in 1-year prospective study. Bone mineral density, bone turnover markers, 25-hydroxyvitamin D, serum and urinary calcium measurements were done at baseline and after 12 months of warfarin treatment. RESULTS: No differences were observed between warfarin-treated and control groups in Ca-S, Ca-dU, ALP-S, 25-OHD and BMD after 12 months.The concentrations of serum CTx (306.48 +/- 29 ng/l) and osteocalcin (16.54 +/- 1.06 ig/l) were significantly lower (p < 0.001 and p < 0.05 respectively) after 12 month in warfarin-treated group compared to control group (403.29 +/- 24.7 ng/l and 22.88 +/- 1.33 ig/l). A significant increase in serum and urinary Ca values (p < 0.05) was observed in patients with oral anticoagulant therapy after 12 month compared to baseline levels. Biochemical markers of bone metabolism did not correlate with BMD in either group. CONCLUSION: The long-term use of coumarin was not associated with decreased bone mineral density in our study, but the significantly lower OC and CTx serum levels in coumarin-treated patients suggest that vitamin K has an influence on bone turnover (Tab. 3, Fig. 2, Ref. 29). Full Text in free PDF www.bmj.sk.