Two regimens , each represented by one large trial , which showed limited evidence of efficacy in reducing the incidence of hip or other appendicular skeleton fractures were : 1 ) Oral Vitamin D when accompanied by calcium supplementation .
2 ) 1,25 dihydroxy Vitamin D ( calcitriol ) .
This appeared more effective than calcium in a direct comparison .
Hypercalcaemia and gastro-intestinal symptoms , reported in less than 5 % of participants , were slightly more common when Vitamin D analogues were taken .
However , the risk of death was marginally less .
REVIEW ER 'S CONCLUSIONS Uncertainty remains about the efficacy of regimens which include Vitamin D or its analogues in fracture prevention .
Particularly if co-supplementation of calcium is required , significant cost differences are likely to exist between regimens .
BACKGROUND Due to their known effects on bone metabolism , Vitamin D and related compounds have been proposed for the prevention of osteoporosis and fractures .
OBJECTIVES To determine the effects of supplementation with Vitamin D or a Vitamin D analogue in the prevention of fractures of the axial and appendicular skeleton in elderly men or women with involutional or post-menopausal osteoporosis .
The Association of Radiographically Detected Vertebral Fractures with Back Pain and Function: A Prospective Study
Radiographically detected vertebral fractures ( hereafter referred to as vertebral fractures ) are a hallmark of postmenopausal osteoporosis and an important end point in clinical trials of osteoporosis treatment . Women with vertebral fractures have low bone mass compared with women without these fractures and , independently of bone mass , have an increased risk for additional vertebral and other fractures [ 1 - 4 ] . Vertebral fractures are common : Five percent of 50-year-old white women and 25 % of 80-year-old women have had at least one vertebral fracture [ 5 ] . Surprisingly , however , the manner in which vertebral fractures affect health remains uncertain . Cross-sectional studies in community-derived sample s of older women have demonstrated only a modest association [ 6 - 8 ] or no association [ 9 - 11 ] between prevalent vertebral fractures and back pain or disability . Cross-sectional studies do not distinguish more recent fractures from older vertebral fractures and may fail to capture transient increases in pain or disability [ 12 ] , a limitation that may underestimate the clinical effect of these fractures [ 13 ] . Back pain is common among elderly women [ 14 ] , and frequent causes of back pain , such as degenerative disc disease , facet joint osteoarthritis , spinal stenosis , and scoliosis , may obscure the impact of vertebral fracture . Only about one third of new vertebral fractures come to medical attention [ 15 , 16 ] , suggesting that most vertebral fractures are asymptomatic . However , attitudes toward back pain in older women and access to health care may also play a role in determining whether vertebral fractures come to medical attention . We examined the effect of incident vertebral fractures on back pain and back-related functional limitations in a large community-based sample of elderly women who underwent serial spinal radiography and annual assessment s of back pain and disability over the same period . Methods Participants Study patients were participants in the Study of Osteoporotic Fractures , a cohort recruited from population -based listings in four U.S. metropolitan areas . Details of the design of this study are published elsewhere [ 17 ] .  Lateral spine radiographs were obtained for 9677 white women between the ages of 65 and 99 years ( median age , 70 years ) who underwent baseline examination between 1986 and 1988 . Repeated spinal radiographs suitable for morphometry were obtained for 7223 women ( 75 % of the original cohort ) at a follow-up clinic visit held an average of 3.7 years ( range , 1.3 to 5.1 years ) later . All participants gave informed consent . Vertebral Morphometry Lateral radiographs of the thoracic and lumbar spine were obtained in accordance with current guidelines [ 18 ] . Quantitative vertebral morphometry was performed using six-point digitization as described elsewhere [ 3 , 19 ] to calculate the anterior ( Ha ) , mid- ( Hm ) , and posterior ( Hp ) height for each vertebral body from T4 to L4 . A system of triage of radiographs , described elsewhere [ 3 , 20 ] , was used to reduce the number of radiographs requiring morphometric measurements . Briefly , trained technicians separated sets of radiographs into normal , uncertain , or probably fractured groups on the basis of a limited semiquantitative grading scheme that categorized women by the most abnormal vertebral level [ 20 ] . Uncertain grade s were further categorized by the study radiologist as normal or probably fractured . Morphometry was done on the radiograph pairs that were categorized as probably fractured ( 42 % ) . In a r and om sample of 503 women whose radiographs were triaged and then digitized , triage missed no incident fractures according to the study definition . Definition of Vertebral Fracture A vertebra was classified as having a prevalent fracture on the baseline radiograph if any of the following ratios were more than 3 SDs ( > 4 SDs for severe fractures ) below the normal mean for that vertebral level : ( Ha/Hp ) , ( Hm/Hp ) , or a combination of ( H/H [ ] 1 ) and ( Hai/Hai 1 ) [ 3 , 21 ] . A new ( incident ) fracture was identified if any of the three vertebral heights ( Ha , Hm , or Hp ) on follow-up radiographs decreased by 20 % or more and by at least 4 mm compared with the baseline height . Incident fractures identified by morphometry were review ed by a radiologist to exclude imaging artifacts or such conditions as osteophytosis and Scheuermann disease ; 7 % of vertebrae meeting the morphometric criteria for incident fracture were reclassified as not fractured . Incident Clinical Fractures We used previously described methods [ 22 ] to assess the occurrence of clinical fractures of any bone during follow-up . Women were considered to have a clinical vertebral fracture if they reported a new diagnosis of spinal fracture and a clinical radiology report confirmed that a vertebral fracture was present . Measurements of Pain , Disability , and Limited Activity We evaluated outcome measures by using a previously described question naire [ 7 , 23 ] that asked about back pain and back-related disability in the past 12 months and the number of days of limited activity due to back pain . The question naire was administered at baseline and at three annual follow-up contacts held before assessment of vertebral fractures . The third follow-up contact coincided with follow-up radiography . Back pain was assessed on scales of frequency ( 0 , never or rarely ; 1 , some of the time ; 2 , most of the time ; or 3 , all of the time ) and severity ( 0 , no pain ; 1 , mild pain ; 2 , moderate pain ; or 3 , severe pain ) . The two pain questions had high internal consistency ( Cronbach = 0.81 ) and were summed for a total score that could range from 0 to 6 . We defined clinical ly significant back pain as pain that was experienced most or all of the time or pain that was moderate or severe . Women without significant back pain at baseline were considered to have increased back pain if clinical ly significant pain had developed between any follow-up contacts . For women with clinical ly significant back pain at baseline , increased back pain was defined as an increase in total pain score of at least two points . Both types of increase had a similar association with incident fractures and thus were combined for a single outcome . Back-related disability was assessed with questions about the degree of difficulty ( 0 , no difficulty ; 1 , some difficulty ; 2 , much difficulty ; or 3 , unable to perform activity ) in six activities of daily living that involved the back ( bending down to pick up light-weight objects , lifting a 10-pound object from the floor , reaching for objects just above the head , putting on socks or stockings , getting in and out of an automobile , and st and ing for 2 hours ) . These measures were combined in a back-related disability score ranging from 0 to 18 . As reported elsewhere [ 7 ] , this scale has high internal consistency ( Cronbach = 0.82 ) and is highly correlated ( Spearman r = 0.73 ) with a more extensive instrument used to assess disability caused by low back pain [ 24 ] . We defined clinical ly significant disability as much difficulty or unable in one or more of the six activities . Women without significant disability at baseline were considered to have increased disability if clinical ly significant disability had developed between any follow-up contacts . For women with clinical ly significant disability at baseline , increased disability was defined as an increase in disability score of at least three points . Both types of increase had a similar association with incident fractures and thus were combined for a single outcome . We also asked participants if they had limited their activities because of back pain since the last contact ; if the answer was yes , we asked for the number of days they had stayed in bed and the number of days on which activity was limited ( not including days in bed ) because of back pain . Questions were adapted from previous surveys [ 25 , 26 ] . For all follow-up contacts , we summed the number of days of bed rest and , in a separate measure , the number of days of limited activity ; we then divided these numbers by the total years of follow-up to estimate the average number of affected days per year . Other Measurements The baseline question naire assessed potential confounding factors that may be associated with the risk for incident vertebral fracture and with back pain or disability  , including smoking ( current or past smoker ) ; inactivity , defined as walking less than one block daily ( yes or no ) ; a previous physician diagnosis of osteoporosis or spinal fracture ( yes or no ) ; current use of estrogen ( yes or no ) ; hip pain in the past 12 months ( yes or no ) ; and height at 25 years of age . At the baseline examination , we assessed height and weight and calculated body mass index ( kg/m2 ) . We assessed grip strength by using an isometric dynamometer ( Jamar Hydraulic H and Dynamometer , JA Preston , Jackson , Mississippi ) at baseline and at the follow-up examination and calculated change in grip strength between the two measurements . A r and om sample of 16 % of baseline spine radiographs was assessed for spinal disc degeneration by using previously published methods [ 27 ] . Statistical Analysis Unless otherwise indicated , analyses were done separately in groups stratified by the presence of one or more baseline prevalent vertebral fractures . Descriptive and bivariate associations were assessed by using the t-test for continuous variables and the chi-square test for dichotomous variables . The association between incident vertebral fractures and dichotomous outcomes ( increased back pain and increased back disability ) was analyzed with logistic regression techniques . We analyzed the association of incident vertebral fracture with days of bed rest and days of  limited activity per year by using Poisson regression . The distribution of days of bed rest ( mean SD , 0.44 5.15 ) and limited-activity days ( 16.3 53.7 ) indicate that considerable overdispersion is present . Poisson regression allowing for this overdispersion provides a good estimation and inferential scheme [
Two regimens , each represented by one large trial , which showed limited evidence of efficacy in reducing the incidence of hip or other appendicular skeleton fractures were : 1 ) Oral Vitamin D when accompanied by calcium supplementation .
2 ) 1,25 dihydroxy Vitamin D ( calcitriol ) .
This appeared more effective than calcium in a direct comparison .
Hypercalcaemia and gastro-intestinal symptoms , reported in less than 5 % of participants , were slightly more common when Vitamin D analogues were taken .
However , the risk of death was marginally less .
REVIEW ER 'S CONCLUSIONS Uncertainty remains about the efficacy of regimens which include Vitamin D or its analogues in fracture prevention .
Particularly if co-supplementation of calcium is required , significant cost differences are likely to exist between regimens .
BACKGROUND Due to their known effects on bone metabolism , Vitamin D and related compounds have been proposed for the prevention of osteoporosis and fractures .
OBJECTIVES To determine the effects of supplementation with Vitamin D or a Vitamin D analogue in the prevention of fractures of the axial and appendicular skeleton in elderly men or women with involutional or post-menopausal osteoporosis .