***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: CONTEXT Type 1 and type 2 diabetes mellitus are associated with an increased risk of fracture . OBJECTIVE The objective of the study was to compare the bone structure and density between type 1 and type 2 diabetes patients and to investigate fracture associations . DESIGN This was a cross-sectional study . SETTING AND PATIENTS Physician-diagnosed type 1 and type 2 diabetes patients were included from the outpatient clinics at two university hospitals participated in the study . MAIN OUTCOME MEASURES Bone density and structure were assessed by dual-energy x-ray absorptiometry and high-resolution peripheral quantitative computed tomography . Blood sample s were collected for bone turnover markers . Prevalent vertebral fractures were assessed by vertebral fracture assessment and x-ray , and incident fractures were collected from The Danish National Hospital Discharge Register . RESULTS Bone mineral density ( BMD ) was higher in type 2 than type 1 diabetes patients at the hip , femur , and spine ; however , only the hip differed in multivariate-adjusted models . Bone tissue stiffness at the tibia was increased in type 2 diabetes patients also in adjusted models . Sclerostin levels were inversely associated with fracture in type 1 diabetes patients . The patients with the highest tertile of sclerostin had an 81 % decreased risk of a fracture compared with the lowest tertile . CONCLUSIONS Type 1 and type 2 diabetes patients differ in BMD of the hip and tissue stiffness at the tibia . Sclerostin may be a marker independent of BMD to predict fractures in type 1 diabetes patients and thus potentially of clinical importance . Studies with longer follow-up are needed Abstract Many osteoporotics have comorbid diabetes mellitus ( DM ) , hypertension ( HT ) , and dyslipidemia ( DL ) . However , whether such comorbidities alter response to anti-osteoporotic treatment is unknown . We did post hoc analyses of combined data from three  risedronate Japanese phase III trials to determine whether the presence of DM , HT , or DL affects its efficacy and safety . Data from 885 subjects who received 48-week treatment with risedronate were collected and combined from the three phase III trials . They were divided into two groups by the presence or absence of comorbidities : DM ( n = 53 ) versus non-DM ( n = 832 ) ; HT ( n = 278 ) versus non-HT ( n = 607 ) ; and DL ( n = 292 ) versus non-DL ( n = 593 ) . Bone mineral density ( BMD ) , urinary type 1 collagen N-telopeptide ( uNTX ) , and serum bone-specific alkaline phosphatase ( BAP ) were measured at baseline and sequentially until 48 weeks . BMD or bone markers were not different between any of the two groups . Overall , BMD was increased by 5.52 % , and uNTX and BAP were decreased by 35.4 and 33.8 % , respectively . Some bone markers were slightly lower in DM and DL subjects , but the responses to risedronate were not significantly different . Statin users had lower uNTX and BAP , but showed no difference in the treatment response . All the other medications had no apparent effect . Adverse event incidence was marginally higher in DL compared with non-DL ( Relative risk 1.06 ; 95 % confidence interval 1.01–1.11 ) , but was not related to increase in any specific events . Risedronate shows consistent safety and efficacy in suppressing bone turnover and increasing BMD in osteoporosis patients with comorbid DM , HT , and /or DL CONTEXT Recent studies indicate that glucagon-like peptide (GLP)-1 regulates bone turnover , but the effects of GLP-1 receptor agonists ( GLP-1 RAs ) on bone in obese weight-reduced individuals are unknown . OBJECTIVE To investigate the role of GLP-1 RAs on bone formation and weight loss-induced bone mass reduction . DESIGN R and omized control study . SETTING Outpatient research hospital clinic . PARTICIPANTS Thirty-seven healthy obese women with body mass index of 34 ± 0.5 kg/m(2 ) and age 46 ± 2 years . INTERVENTION After a low-calorie-diet-induced 12 % weight loss , participants were r and omized to treatment with or without administration of the GLP-1 RA liraglutide ( 1.2 mg/d ) for 52 weeks . In case of weight gain , up to two meals per day could be replaced with a low-calorie-diet product to maintain the weight loss . MAIN OUTCOME MEASURES Total , pelvic , and arm-leg bone mineral content ( BMC ) and bone markers [ C-terminal telopeptide of type 1 collagen ( CTX-1 ) and N-terminal propeptide of type 1 procollagen ( P1NP ) ] were investigated before and after weight loss and after 52-week weight maintenance . Primary endpoints were changes in BMC and bone markers after 52-week weight maintenance with or without GLP-1 RA treatment . RESULTS Total , pelvic , and arm-leg BMC decreased during weight maintenance in the control group ( P < .0001 ) , but not significantly in the liraglutide group . Thus , total and arm-leg BMC loss was four times greater in the control group compared to the liraglutide group ( estimated difference , 27 g ; 95 % confidence interval , 5 - 48 ; P = .01 ) , although the 12 % weight loss was maintained in both groups . In the liraglutide group , the bone formation marker P1NP increased by 16 % ( 7 ± 3 μg/L ) vs a 2 % ( -1 ± 4 μg/L ) decrease in the control group ( P < .05 ) . The bone resorption marker CTX-1 collagen did not change during the weight loss maintenance phase . CONCLUSIONS Treatment with a long-acting GLP-1 RA  increased bone formation by 16 % and prevented bone loss after weight loss obtained through a low-calorie diet , supporting its role as a safe weight-lowering agent Bone density , bone turnover and fracture susceptibility were evaluated in 1,132 r and omly recruited women , all 75 years old . Seventy-four of the women had diabetes , while 1,058 women did not .  Areal bone mineral density ( aBMD ) of the hip and lumbar spine was investigated by dual energy X-ray absorptiometry ( DXA ) , and bone mass of the calcaneus was measured by ultrasound . Urinary deoxypyridinoline/creatinine ( U-DPD/Crea ) and serum C-terminal cross-linked telopeptide of type 1 collagen ( S-CTX ) were assessed as markers of bone resorption . Serum bone-specific alkaline phosphatase ( S-bone ALP ) and serum osteocalcin ( S-OC ) were assessed as markers of bone formation . Also , serum 25(OH ) vitamin D and serum parathyroid hormone ( S-PTH ) were assessed . Fracture susceptibility was evaluated retrospectively and prospect ively for up to 6.5 years . In diabetic women , the aBMD of the femoral neck was 11 % higher ( p < 0.001 ) , and BMD of the lumbar spine was 8 % higher ( p = 0.002 ) than in non-diabetic women . There was no difference in bone mass by ultrasound of the calcaneus . Women with diabetes had higher BMD of the femoral neck ( p < 0.001 ) and lumbar spine ( p = 0.03 ) also after correction for differences in body weight . In diabetic women , U-DPD/Crea , S-CTX , and S-OC were decreased when compared with non-diabetic women ( p = 0.001 or less ) . After correction for covariance of body weight and plasma creatinine , S-CTX ( p < 0.001 ) and S-OC ( p < 0.001 ) were still lower in the diabetic women . Diabetic patients had hypovitaminosis D ( p = 0.008 ) , a difference explained by differences in time spent outdoors and body weight . S-PTH did not differ between the groups . Women with diabetes had no more lifetime fractures ( 52 % ) than women without diabetic disease ( 57 % ) , ( p = 0.31 ) . This study shows that elderly women with diabetes and without severe renal insufficiency have high bone mass and low bone turnover . The high bone mass and low bone turnover is not likely to have a strong influence on fracture susceptibility The diurnal variation in bone resorption markers is poorly understood and may contain essential information about regulation of bone resorption . To explore the acute regulation of bone resorption we studied bone turnover in 14 postmenopausal women during a r and omized , crossover , 24 h study of oral glucose tolerance test ( OGTT ) , normal diet , or fasting .  Whereas fasting counteracted variation in bone resorption , as measured by serum C-telopeptide fragments of collagen type 1 degradation ( s-CTx ) , OGTT and normal diet induced a 50 % reduction ( p < 0.001 ) over 2 h. For OGTT , s-CTx reverted to baseline levels after 6 h , and for normal diet s-CTx remained suppressed during the afternoon and returned to baseline overnight . Repeated OGTT at 8:00 A.M. and 8:00 P.M. in nine postmenopausal women demonstrated that identical reductions in s-CTx could be obtained at both timepoints with an intermediate return to baseline between tests . A 2 h r and omized , crossover study of OGTT and fasting in 23 men and premenopausal women similarly revealed a 50 % decrease in s-CTx . A r and omized , crossover 2 h study of insulin tolerance test compared with fasting in six men and premenopausal women demonstrated a 20%-30 % decrease in s-CTx ( p < 0.01 - 0.05 ) . Nine hour follow-up of ten healthy individuals during a crossover experiment of OGTT , protein , and fat intake revealed a comparable 50 % reduction in s-CTx , but distinct profiles of serum glucose and serum insulin . Bone resorption was reduced by intake of food , glucose , fat , and protein and counteracted by fasting , and this seems to have been be independent of age and gender . Both exogenous and endogenous insulin stimulation tests induced a reduction in bone resorption , but this was only partial when compared with the reduction observed during food intake OBJECTIVES Our objectives were to evaluate the effect of rosiglitazone on bone metabolism and to assess the association between changes in bone turnover parameters and plasma cytokine levels in postmenopausal diabetic women . DESIGN This was a 12-wk open-label r and omized-controlled trial . PATIENTS OR OTHER PARTICIPANTS A total of 56 obese postmenopausal women with newly diagnosed diabetes and 26 nondiabetic healthy controls matched for age and body mass index were included in the study . INTERVENTIONS The subjects were instructed to follow a weight-maintenance diet . Half were r and omly assigned to receive rosiglitazone 4 mg/d , and the other half remained on diet alone . MAIN OUTCOME MEASURES Before and after the interventions , metabolic bone markers and serum cytokine levels were assessed . RESULTS Serum total alkaline phosphatase ( ALP ) and bone-specific ALP levels were statistically significantly lower 12 wk after initiation of rosiglitazone treatment . There were no statistically significant changes in osteocalcin levels among the three groups or in deoxypyridinoline levels in the rosiglitazone group . At the end of 12 wk , all patients had statistically significantly decreased IL-1beta and TNF-alpha levels compared with baseline . Changes in bone-specific ALP levels showed a moderate negative correlation with the changes in the TNF-alpha levels after rosiglitazone treatment and after diet in the diabetic control group . CONCLUSIONS Rosiglitazone use is associated with reduced bone formation at earlier stages in postmenopausal diabetic women . The cytokine-lowering effects of rosiglitazone and lifestyle changes could reverse the early inhibitory effect of rosiglitazone therapy on bone formation . Further studies will clarify the long-term effects of rosiglitazone therapy on bone loss and fracture CONTEXT Fractures are a major health burden in elderly institutionalized persons . Type 2 diabetes mellitus ( DM ) has a high prevalence in nursing home patients and has been associated with positive effects on bone mass in younger , community-dwelling elderly . OBJECTIVE The objective of this study was to investigate whether type 2 DM affects bone mass , bone turnover , or prospect i ve fracture rates in frail , elderly women living in nursing homes . DESIGN , SETTING , AND PARTICIPANTS This study was a prospect i ve cohort of 583 patients with type 2 DM and 1081 control ( CTR ) individuals above age 70 recruited from 95 nursing homes in Austria . Patients were enrolled and followed up by mobile study teams . MAIN OUTCOME MEASURES We performed  quantitative bone ultrasound measurements  at the calcaneus , radius , and proximal third phalanx , measurements of quadriceps strength , and biochemical parameters of mineral met 
    Output:
    
Markers of both bone formation and bone resorption are decreased in patients with diabetes .
This suggests that diabetes mellitus is a state of low bone turnover , which in turn may lead to more fragile bone .
Altered levels of sclerostin and osteoprotegerin may be responsible for this