title: The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials Incidence of Anticonvulsant Osteomalacia and Effect of Vitamin D: Controlled Therapeutic Trial Effect of high-dosage cholecalciferol and extended physiotherapy on complications after hip fracture: a randomized controlled trial. Influence of vitamin D administration on bone ultrasound measurements in patients on anticonvulsant therapy. Prevention of bone loss and vertebral fractures in patients with chronic epilepsy--antiepileptic drug and osteoporosis prevention trial. Early predisposition to osteomalacia in Indian adults on phenytoin or valproate monotherapy and effective prophylaxis by simultaneous supplementation with calcium and 25-hydroxy vitamin D at recommended daily allowance dosage: a prospective study.
abstract: Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more The bone mineral content ( B.M.C. ) in both forearms ( related to total body calcium ) was measured by photon absorptiometry for a controlled therapeutic trial in a representative sample of epileptic out patients , comprising 226 patients treated with one or two major anticonvulsant drugs ( phenytoin , phenobarbitone , primidone ) .  Initially the mean B.M.C. value for all epileptic patients was 87 % of normal . During treatment with 2,000 international units of vitamin D2 daily for three months an average B.M.C. increase of 4 % was found , whereas the B.M.C. values remained unchanged in the placebo group and in the control groups . The incidence of hypocalcaemia and raised serum alkaline phosphatase was 12 % and 43 % respectively . The biochemical indices of osteomalacia were related to B.M.C. These results indicate that epileptic patients should be closely supervised for the occurrence of anticonvulsant osteomalacia , and , possibly , receive prophylactic treatment with vitamin BACKGROUND Care of elderly patients after hip fracture is not well established . METHODS We enrolled 173 patients with acute hip fracture who were 65 years or older ( 79.2 % women ; mean age , 84 years ; 77.4 % living at home ) . Using a factorial design , we r and omly allocated patients to extended physiotherapy ( PT ) ( supervised 60 min/d during acute care plus an unsupervised home program ) vs st and ard PT ( supervised 30 min/d during acute care plus no home program ; single-blinded ) , and to cholecalciferol therapy , 2000 vs 800 IU/d ( double-blinded ) . Primary outcome was rate of falls ; secondary outcome was rate of hospital readmissions during the 12-month follow-up . All analyses included 173 individuals and used multivariate Poisson regression analyses . RESULTS At baseline , 50.9 % of participants had 25-hydroxyvitamin D levels of less than 12 ng/mL and 97.7 % of less than 30 ng/mL. We documented 212 falls and 74 hospital readmissions . Because this was a factorial design trial , all analyses tested the main effect of each treatment while controlling for the other in 173 participants . Extended vs st and ard PT reduced the rate of falls by 25 % ( 95 % confidence interval [ CI ] , -44 % to -1 % ) . Cholecalciferol treatment , 2000 vs 800 IU/d , did not reduce falls ( 28 % ; 95 % CI , -4 % to 68 % ) , but reduced the rate of hospital readmissions by 39 % ( 95 % CI , -62 % to -1 % ) . CONCLUSIONS Extended PT was successful in reducing falls but not hospital readmissions , whereas cholecalciferol treatment , 2000 IU/d , was successful in reducing hospital readmission but not falls . Thus , the 2 strategies may be useful together because they address 2 different and important complications after hip fracture BACKGROUND The objective of the study was to evaluate bone mass status ( as measured by bone ultrasound ) in patients on anticonvulsant therapy  , and the influence that Vitamin D administration exerts over it . MATERIAL S AND METHODS We measured and compared the basal serum levels of 25(OH)D3 , parathyroid hormone ( PTH ) , and phalangeal bone ultrasound ( Ad-SOS ) , in 30 adult patients who were taking anticonvulsant drugs , with a control group of similar age and sex . We then gave the patients a large oral dose of 3 mg ( 120.000 UI ) of 25(OH)D3 , and repeated the measurements after one month . RESULTS Basal 25(OH)D3 and Ad-SOS values were significantly lower , and PTH values significantly higher ( P < 0.0001 in all ) , in the patient group . The low Ad-SOS values for the patients were independent of the treatment , but directly related to basal 25(OH)D3 levels ( r = 0.45 , P<0.01 ) . There was a negative association between PTH and 25(OH)D3 ( r = -0.64 , P<0.0001 ) , and no correlation between PTH y Ad-SOS ( r = -0.20 , p NS ) . After ingestion of the large dose of the vitamin D , the patient group registered a significant ( P<0.0001 ) increase in 25(OH)D3 levels , their Ad-SOS values increased ( P<0.0001 ) nearly to the mean basal value of the control group , and PTH decreased significantly ( P<0.0001 ) . CONCLUSIONS These findings justify the need to assure adequate vitamin D intake in patients being treated with anticonvulsants , independently of the treatment , age , sex , and activity status , in order to prevent osteomalacia PURPOSE To evaluate whether use of a bisphosphonate ( risedronate ) in addition to calcium and vitamin D in male veterans with epilepsy who were taking antiepileptic drugs ( AEDs ) long term can prevent the loss of bone mass ( BMD , bone mineral density ) associated with AED use compared to patients who were treated with a placebo plus calcium and vitamin D. As a secondary end point we studied the incidence of new morphometric vertebral and nonvertebral fractures . METHODS Antiepileptic drug and osteoporosis prevention trial ( ADOPT ) was design ed as a prospect i ve 2-year double-blind , r and omized placebo controlled study involving 80 male veterans with epilepsy who were being treated with AEDs such as phenytoin , phenobarbital , sodium valproate , or carbamazepine for a minimum of 2 years . All enrolled participants received calcium and vitamin D supplementation , and were r and omized to risedronate or matching placebo .  Total body , bilateral proximal femora , and anteroposterior ( AP ) lumbar spine BMDs in addition to morphometric lateral vertebral assessment s ( LVAs ) were evaluated by a dual energy x-ray absorptiometry ( DXA ) instrument . Comparisons of BMDs were made between baseline , 1 year , and after 2 years of enrollment in the study . The incidence of new vertebral and nonvertebral fractures was secondary end point . KEY FINDINGS Of the 80 patients initially enrolled in the study , 53 patients completed the study . Baseline characteristics of the two groups were similar . At the end of the study , in the placebo plus calcium and vitamin D group , we observed a significant improvement in BMD at any of the evaluated sites when compared to their baseline scans in 69 % ( 18/26 ) of the participants . In the risedronate plus calcium and vitamin D group , we observed significant improvement of BMDs in 70 % ( 19/27 ) of the participants . At the end of the study , the risedronate group experienced a significant increase of BMD at the lumbar spine L1 - 4 ( 1.267 - 1.332 g/cm(2 ) ) , which was significantly larger than that seen in the placebo group ) ( 1.229 g/cm(2 ) vs. 1.245 g/cm(2 ) ; p = 0.0066).There were nonsignificant differences between the two groups regarding changes of total body BMD or at the proximal bilateral femora . Five new vertebral fractures and one nonvertebral fracture were observed only in the placebo group . SIGNIFICANCE Calcium and vitamin D supplementation or calcium and vitamin D supplementation in addition to risedronate improved BMD in more than 69 % of male veterans with epilepsy who were taking AEDs . In the group receiving risedronate plus calcium and vitamin D there was a significant improvement of BMD at the lumbar spine as compared to the placebo group , which also received calcium and vitamin D. The use of risedronate plus calcium and vitamin D prevented the incidence of new vertebral fractures and one nonvertebral fracture in this cohort BACKGROUND Long-term therapy with antiepileptic drugs ( AED ) may be associated with increased total serum alkaline phosphatase ( ALP ) levels and reduced serum calcium , inorganic phosphorous , and vitamin D levels . These adverse biochemical alterations have an adverse effect on bone health . OBJECTIVE To determine ( a ) onset of derangements in serum total ALP and its isoenzymes ( liver , bone ) , calcium and 25-hydroxy vitamin D ( 25-OHD ) concentrations after initiation of treatment with phenytoin or valproic acid monotherapy  and ( b ) the effect of simultaneous supplementation with calcium and 25-OHD at recommended daily allowance ( RDA ) dosage , on these biochemical parameters . MATERIAL S AND METHODS Study was a prospect i ve , case-controlled study in adults . Serum biochemical parameters were estimated at baseline , 30 , 60 , and 90 days of starting AED treatment in the study subjects : Groups -- A ( only calcium supplementation ) and Group B ( both calcium and 25-OHD supplementation ) . STATISTICAL ANALYSIS Mean+/-SD , and students ' paired t test ( between groups A and B ) unpaired students ' t test ( drug-wise ) . RESULTS At 60 days of AED therapy Group A showed a significant increase in serum total ALP ( 78.83+/-11.04 to 101.75 + /- 9.56 IU/l ) ( P < 0.001 ) , ALP-liver isoenzyme , ( 41.97+/- 10.81 to 68.83 + /-7.81 IU/L ) ( P < 0.001 ) , significant decrease in calcium ( 9.30 + /- 0.36 to 8.80 + /- 0.38 mg% ) ( P < 0.001 ) , ALP-bone isoenyzme ( 36.84 + /- 5.01 to 32.92 + /- 6.46 IU/L ) ( P < 0.001 ) , and a significant decrease in 25-OHD ( 25.19 + /- 5.98 to 19.76 + /- 5.35 ng/ml ) ( P < 0.001 ) at 90 days . In contrast Group B , at 60 days , showed a significant decrease in serum total ALP ( 81.92 + /- 19.63 to 54.77 . + /- 11.53 IU/L ) ( P < 0.0001 ) , ALP-liver isoenzyme ( 48.01 . + /- 13.53 to 28.12 . + /- 5.88 IU/L ) ( P < 0.0001 ) , significant increase in calcium ( ( 9.24 + /- 0.31 to 9.93 + /- 0.26 mg% ) ( P < 0.001 ) and ALP-bone isoenzyme levels ( 33.93 + /- 12.2 to 26.25 + /- 8.23 IU/L ) . In Group B , 25-OHD levels showed a significant increase at 90 days ( 24.36 + /- 3.42 to 31.53 + /- 327 ng/ml ) ( P < 0.0001 ) . CONCLUSION Biochemical derangements in calcium metabolism involving the bone are seen by 60 days after starting AED monotherapy , indicating predisposition to development of osteomalacia in these patients . This is preventable by simultaneous oral supplementation with calcium and 25-OHD
target: All 6 studies that investigated bone mineralization had significant findings ; however , due to varying method ologies , the impact of vitamin D on bone mineralization was inconclusive .
  SIGNIFICANCE Vitamin D does appear to have some benefit to bone health in adults with epilepsy , and therefore supplementation could potentially be a requisite to using some AEDs .
background: OBJECTIVE Several antiepileptic drugs ( AEDs ) have been associated with a detrimental effect on bone health through a reduction in serum vitamin D. Subsequently , several studies have investigated the effect of vitamin D supplementation in persons with epilepsy being treated with AEDs .
  The present systematic review of published literature was conducted to determine the effect of vitamin D intervention on bone health in adults with epilepsy .