***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: UNLABELLED An 18-month r and omized double-blind study was conducted in postmenopausal women with osteoporosis to compare the effects of once-daily teriparatide 20 microg with alendronate 10 mg on bone histomorphometry . Biopsies were obtained from 42 patients .  Indices of bone formation were significantly higher after 6 or 18 months of teriparatide compared with alendronate treatment . INTRODUCTION Alendronate and teriparatide increased BMD , assessed by DXA , by different mechanisms of action , supported by changes in biochemical markers of bone turnover . The purpose of this cross-sectional study was to explore the differential effects of these two osteoporosis treatments at the bone tissue level by examining bone histomorphometric parameters of bone turnover after either 6 or 18 months of treatment . MATERIAL S AND METHODS Patients were a cohort from a r and omized parallel double-blind study conducted to compare the effects of once-daily teriparatide 20 microg and alendronate 10 mg in postmenopausal women with osteoporosis . Transiliac crest bone biopsies were obtained after tetracycline double labeling from 42 patients treated for 6 months ( n = 23 ) or 18 months ( n = 14 ) ; 5 additional patients were biopsied from contralateral sides at 6 and 18 months . Biopsy specimens adequate for quantitative analysis were analyzed by 2D histomorphometry from 17 patients at 6 months ( teriparatide , n = 8 ; alendronate , n = 9 ) and 15 patients at 18 months ( teriparatide , n = 8 ; alendronate , n = 7 ) . Data were analyzed by two- sample tests . RESULTS Histomorphometric indices of bone formation were significantly and markedly greater in the teriparatide group than in the alendronate group at 6 and 18 months , whereas indices of bone resorption were only significantly greater in the teriparatide group than in the alendronate group at 6 months . Bone formation and activation frequency were significantly lower at 18 months compared with 6 months in the teriparatide group , returning to levels comparable with untreated postmenopausal women . In the teriparatide group , the peak in histomorphometric bone formation indices coincided with peak levels for N-terminal propeptide of type I collagen , a biochemical marker of bone formation . The degree of mineralization was lower at 18 months than at 6 months with treatment in both groups but was not different between groups . CONCLUSIONS These results confirm the opposite mechanisms of action of teriparatide and alendronate on bone remodeling and confirm the bone formation effect of teriparatide BACKGROUND Alendronate , an oral bisphosphonate , is available for the treatment of osteoporosis in a 70-mg once-weekly and a 10-mg once-daily formulation . OBJECTIVES This study aim ed to determine patient preference for once-weekly versus once-daily dosing with alendronate , and to determine which treatment regimen the patients believed was more convenient and would be easier to comply with for a long period . METHODS This was a multicenter , r and omized , open-label , preference study in which postmenopausal women with osteoporosis were enrolled to receive 9 weeks of treatment in crossover fashion ( 4 weeks with each study regimen separated by a 1-week washout period ) . The study regimens included once-weekly alendronate 70 mg and once-daily alendronate 10 mg . The primary and secondary end points were assessed with a question naire completed by the patient . Adverse events ( AEs ) were recorded to assess patient tolerability of the study medications . RESULTS A total of 324 patients met the eligibility requirements ; 288 were r and omized to treatment , 287 ( mean age , 64.8 years ) received treatment , 272 completed the question naire , and 266 completed the study . Of the patients who completed the question naire , 235 patients preferred the 70-mg once-weekly dosing regimen compared with the 10-mg once-daily regimen ( 86.4 % vs 9.2 % ; P < 0.001 ) . Most patients also believed that once-weekly dosing was more convenient than once-daily dosing ( 89.0 % vs 7.7 % ; P < 0.001 ) and would allow them to achieve better long-term compliance ( 87.5 % vs 8.5 % ; P < 0.001 ) . Clinical AEs were reported in 30.7 % of patients treated with once-weekly alendronate and 30 % of patients treated with once-daily alendronate , with no significant differences between treatments . CONCLUSION When once-weekly alendronate 70 mg was compared with once-daily alendronate 10 mg in this study , 70-mg once-weekly alendronate was the preferred dosing regimen Osteoporotic fractures remain a major public health problem for their correlated morbidity and mortality . The primary aim of therapy must be the prevention of the first fragility fracture and avoiding subsequent fractures in patients who already have an existing fracture . There are evidence s from r and omized controlled trials ( RCTs ) about the efficacy of antiresorptives , such as bisphosphonates in reducing the risk of fracture , but none of these agents completely abolish the fracture risk . The reduction of RRR by different therapies in RCTs is relatively constant but it is important to note that the proportion of inadequate-responders ( i.e. : patients fracturing despite adequate pharmacological treatment ) is increasing with the severity of the disease : the higher the risk of fracture the higher the proportion of inadequate-responders . Thus , the proportion of non responders across different trials is directly related to the fracture incidence observed in the control group of RCTs which is the most proximate indicator of osteoporosis severity . Teriparatide ( TPTD ) demonstrate a real increases of both trabecular and cortical bone volume , which are associated with a true reduction of fracture risk , as many RCTs confirm . The beneficial effect of introducing a treatment with antiresorptives after the treatment course with TPTD has been clearly demonstrated with the prevention of the reabsorption of the new bone tissue built during TPTD therapy and rapidly lowers cortical porosity , which leads to further increases in BMD . For these results , the introduction of an anti-resorptive after the treatment course with TPTD is strongly recommended and taken into account . In Italy TPTD is fully reimbursed in patients incurring in a new vertebral or hip fracture while on chronic treatment with antiresorptive or in naive patients with 3 or more vertebral or hip fractures . In conclusion , since patients with severe osteoporosis are at very high risk of new fractures with worsening of quality of life and life expectancy , antiresorptives represent a sub-optimal treatment in these patients , werehas , since TPTD demonstrated real and substantial improvements in bone mass and reduction of fracture risk independently of initial risk , TPTD represents the only therapeutic option able to reverse at least in part this disabling disease Context Many postmenopausal women have osteopenia but not osteoporosis or fracture history . Information about the cost-effectiveness of treating such women with alendronate should guide clinical recommendations . Contribution The investigators estimate that the costs of treating postmenopausal women with osteopenia ( femoral neck T-scores > 2.5 ) for 5 years with alendronate  range from $ 70000 to $ 332000 per quality -adjusted life-year . Caution s Unless the cost of alendronate decreases or new data show that alendronate reduces fracture risk more than is currently thought , treatment of osteopenia with alendronate costs more than Americans are typically willing to pay for health care interventions . The Editors Osteoporosis is associated with an increased risk for fractures , which , in turn , is associated with clinical ly significant morbidity . The broad consensus is that patients who present with fractures should be treated for osteoporosis ( 1 - 5 ) . In the absence of fractures , however , the indications for antiresorptive drug therapy are controversial . Many agree that patients with osteoporosis who meet the World Health Organization criteria ( bone mineral density [ BMD ] > 2.5 SDs less than the young healthy mean or a T-score 2.5 [ 6 ] ) should be treated ( 1 - 5 ) . However , many fractures among postmenopausal women occur in those with T-scores better than 2.5 because more women have scores in this range than in the osteoporotic range ( 7 , 8) . While some do not recommend treating osteopenic postmenopausal women who do not have a history of clinical fracture ( 1 , 2 ) , guidelines published by the National Osteoporosis Foundation ( 3 ) and the American College of Obstetrics and Gynecology ( 4 ) recommend drug therapy for postmenopausal women who lack additional fracture risk factors at a T-score of 2.0 or less and for those with 1 or more additional fracture risk factors at a T-score of 1.5 or less . Miller and colleagues ( 9 ) suggested that a treatment T-score threshold of 1.8 may be reasonable for postmenopausal women even without additional fracture risk factors . As public health policy , however , such intervention makes sense only if the costs and risks of treatment are outweighed by a reduction in the ultimate cost and disability attributable to osteoporotic fractures . This is particularly relevant for osteopenia , since many postmenopausal women have low bone mass ( 10 ) , and the societal direct medical cost of pharmacologic therapy for women with osteopenia would therefore be enormous . The cost-effectiveness of drug therapy may be particularly problematic in younger , early postmenopausal women , who , even if osteopenic , are not expected to be at high risk for fracture ( 11 ) . We aim ed to estimate the lifetime health benefits and costs of alendronate therapy to prevent fracture in postmenopausal women with osteopenia . Our analysis used the societal perspective . Methods We constructed a Markov cost-utility model that contained 8 health states and compared 5 years of treatment with alendronate ( 1 of the most commonly prescribed antiresorptive agents ) with no drug therapy for women 55 to 75 years of age with varying levels of BMD T-scores ( 1.5 to 2.4 ) . The health states we used were no fracture , post-distal forearm fracture , post- clinical vertebral fracture ( that is , clinical ly evident at onset ) , post-radiographic vertebral fracture ( that is , not clinical ly evident at onset ) , post-hip fracture , post-other fractures ( that is , fracture of the proximal forearm , humerus , scapula , clavicle , sternum , ribs , pelvis , distal femur , patella , tibia , or proximal fibula ) , post-hip and vertebral fracture , and death . Women in the no fracture state can develop a distal forearm , hip , clinical vertebral , radiographic vertebral , or other fracture , at which time transition to that post-fracture state occurs . We assigned the direct and indirect costs of that fracture as transition costs . We modeled the disutility associated with these fractures as a lower value of a quality -adjusted life-year ( QALY ) associated with that fracture state . We assigned long-term care costs beyond the first year after hip fracture as a cost per year in the post-hip and vertebral fracture or post-hip fracture state . Individuals are eligible ( at risk ) to move to a different state once every 6 months . We assumed a discount rate of 3 % for both costs and health benefits and a drug adherence rate of 100 % . For the base-case analyses , we ran the model with 9 different combinations of starting age ( 55 , 65 , and 75 years ) and femoral neck T-score ( 1.5 , 2.0 , and 2.4 ) until age 105 years , using Monte Carlo simulations with 40000 trials each , by using Data Pro HealthCare software ( TreeAge Software , Inc. , Williamstown , Massachusetts ) . Probabilities of Fractures We developed the risks for each type of fracture as a function of age from comprehensive population -based , age-specific data for women from the Rochester Epidemiology Project ( 12 ) . This data base captures almost all health care utilization within Olmsted County , Minnesota ( 13 ) . Since an estimated 35 % of all vertebral fractures in Olmsted County were clinical ly evident at onset ( 14 ) , we set the incidence rate of radiographic ( but clinical ly inapparent ) vertebral fracture at 1.86 times that of clinical vertebral fracture . The rates for other fractures are the sum of incidences of the specific fracture types ( 12 ) . We plotted fracture rates against the midpoint of each associated age range , and we determined a best-fitting power curve for each fracture as a continuous function of age . We adjusted each fracture risk function for bone density by using the method of De Laet and colleagues ( 15 , 16 ) , and we programmed the risk functions to change with increasing age and decreasing BMD for each stage of the Markov model . Relative Risk for Fracture during Drug Therapy The Fracture Intervention Trial ( FIT ) ( 17 ) of alendronate versus placebo enrolled many participants with osteopenia ( femoral neck T-score , 1.6 
    Output:
    
Conclusion : Teriparatide may be superior to alendronate for increasing lumbar spine BMD in postmenopausal osteoporosis .