***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: ALX 111 [ parathyroid hormone ( 1 - 84 ) - NPS Allelix , recombinant human parathyroid hormone , rhPTH ( 1 - 84 ) , PREOS ] is a full-length , recombinant human parathyroid hormone . It has potential as an anti-osteoporotic agent , due to its properties as a bone formation stimulant . This profile has been selected from R&D Insight , a pharmaceutical intelligence data base produced by Adis International Ltd. It has been recommended that ALX 111 should be given for 1 to 2 years and may be given in combination with an antiresorptive agent , such as estrogen or a bisphosphonate . In December 1999 , Allelix Biopharmaceuticals merged with NPS Pharmaceuticals . This combined company is operating as NPS Pharmaceuticals in the US and as NPS Allelix in Canada . The merger has enabled a phase III study of ALX 111 to begin in the US , Europe and South America . NPS harmaceuticals has signed an agreement with Bio-Imaging Technologies , which will provide all image h and ling and analysis for this trial . Until 1994 , Allelix Biopharmaceuticals and Glaxo in Canada were involved in a joint venture to investigate the efficacy of ALX 111 in osteoporosis . Allelix was subsequently , until September 1998 , collaborating with Astra of Sweden in developing ALX 111 . Astra had acquired exclusive worldwide rights to ALX 111 and was responsible for development of the agent . However , Astra returned all rights to ALX 111 to Allelix as a result of its merger with Zeneca to form AstraZeneca . In December 1999 , Allelix Biopharmaceuticals merged with NPS Pharmaceuticals . This combined company is operating as NPS Pharmaceuticals in the US and as NPS Allelix in Canada . The merger has enabled a phase III study of ALX 111 to begin in the US , Europe and South America . The phase III trial of ALX 111 for the treatment of osteoporosis has completed patient enrolment , and phase II trials have been completed in Canada and the Netherl and s. The 18-month , phase III , multicentre , placebo-controlled trial ( Treatment of Osteoporosis with Parathyroid Hormone ; TOP ) has been design ed to assess the bone-building and fracture-reducing potential of the drug , and over 2600 postmenopausal women with osteoporosis who have not received previous drug therapy for osteoporosis have been enrolled . Treatment will be completed in September 2003 , but more than 75 % of patients enrolled in the TOP study have chosen to enrol in an Open Label Extension Study ( OLES ) , which allows for a total treatment period of up to 24 months . NPS Pharmaceuticals has signed an agreement with Bio-Imaging Technologies , which will provide all image h and ling and analysis for this trial . In September 2002 , NPS Pharmaceuticals announced that it has met its patient enrolment target ( n > 150 ) for its POWER ( PTH for Osteoporotic Women on Estrogen Replacement ) study ; a 24-month phase III trial initiated in Europe in November 2001 . In this trial , women with osteoporosis receive SC injections of ALX 111 or placebo , in combination with their existing hormone replacement therapies , to test the bone building potential of the drug . In addition to the POWER study , a clinical trial sponsored by the National Institutes of Health ( NIH ) is being conducted to evaluate the potential of ALX 111 to build bone in combination with another osteoporosis medication . The ' PaTH ' study ( PTH/alendronate ) is design ed to assess the effect of various combinations and sequential uses of ALX 111 and Merck 's Fosamax , a drug for slowing the loss of bone due to osteoporosis . The PaTH study , initiated in May 2000 and scheduled to conclude in September 2003 , involved 238 patients with postmenopausal osteoporosis . It is thought that alendronic acid and ALX 111 , when administered in combination , may act in an additive manner to treat osteoporosis because they act in different ways ; alendronic acid acts to inhibit resorption and ALX 111 speeds up bone formation and resorption , with a net increase in formation . Results of this study are still being analysed but preliminary results appear to be positive . The effect of ALX 111 on bone cell cultures underare still being analysed but preliminary results appear to be positive . The effect of ALX 111 on bone cell cultures under conditions of microgravity was tested in orbit on the Space Shuttle Columbia , which was launched on 16 January 2003 but did not survive re-entry . This study was one in a series of studies known as ' OSTEO ' and had been prepared by research ers from NPS Pharmaceuticals using Millenium Biologix ' OSTEO Mini-Lab System . Under space flight conditions , astronauts experience a loss in bone density at a rate up to ten times faster than that of earth-bound patients with osteoporosis , and it was hoped that this study would indicate the mechanism of action of ALX 111 at cellular and genetic levels . The results of these studies were represented by the sample s of human bone cells , which were lost during the re-entry tragedy Parathyroid hormone ( PTH ) increases trabecular but may decrease cortical bone mass during treatment of postmenopausal osteoporosis . In a 2-year trial , PTH , with or without sequential calcitonin ( CT ) , was given to 29 osteoporotic women ( mean age 67 + /- 7 years ) , in 3-month cycles [ 28 days hPTH(1 - 34 ) , 50 microg/day , + /-42 days CT , 75 units/day , 20 days " free " ] . Over 2 years , lumbar spine bone mineral density measurements increased an average of 10 % . Paired iliac crest biopsies were obtained 28 days and 2 years after starting the trial . The addition of CT made no difference to changes seen with cyclical PTH alone . Thus , the histomorphometric analyses for all 29 treated patients were compared with a separate group of biopsies from untreated osteoporotic control patients ( n = 15 ) . No significant increments in total bone volume or trabecular architecture were seen over 2 years of cyclical PTH treatment , although the light microscopic appearance of bone was normal . At the level of the bone remodeling unit , a twofold increase in total trabecular erosion surface over the control measurements was observed within the first 28 days of PTH treatment ( 10 + /- 5 vs. 5 + /- 3 % trabecular surface , p < 0.01 ) , which was sustained over 2 years . Trabecular bone formation rates ( surface referent ) were 11 + /- 7 microm(3)/microm(2)/year in control patients and threefold higher in treated patients both acutely ( 31 + /- 31 microm(3)/microm(2)/year , p < 0.01 ) and after 2 years ( 33 + /- 43 microm(3)/microm(2)/year , p < 0 . 05 ) . The activation frequency of trabecular remodeling was threefold higher than controls through 2 years of treatment ( p < 0.05 ) . The mean wall thickness of completed osteons after 2 years of treatment was significantly larger than controls ( 28 + /- 7 vs. 22 + /- 5 microm , p < 0.01 ) , suggesting a positive remodeling balance , as well as the histomorphometric evidence of increased bone turnover and the increased resorption surfaces . Over 2 years of cyclical PTH therapy , cortical thickness remained significantly higher than controls ( 680 + /- 202 vs 552 + /- 218 microm , p < 0.05 ) , without significant changes in cortical porosity . Thus , the histomorphometric changes during cyclical PTH therapy in patients with severe osteoporosis are consistent with increased trabecular bone turnover and a positive remodeling balance , with no evidence for detrimental changes in cortical bone Parathyroid hormone ( PTH ) has been proposed as a skeletal activator for cyclical protocol s of treatment for osteoporosis ; among several potential drugs that might serve to depress the subsequent phase of osteoclastic bone resorption , calcitonin is the most selective . Twenty patients aged 50 - 78 years were enrolled in a study of their biochemical responses during a 14-day activation cycle with synthetic hPTH 1 - 38 , given as a subcutaneous injection of 400 IU/day ; half the patients were r and omly allocated to receive a subsequent 56-day depressor cycle with calcitonin in a dose of 100 U/day , while the remainder received no further treatment . All patients received an initial 24-h intravenous infusion of hPTH 1 - 38 ( 0.5 U/kg/h ) to evaluate the PTH-dependent renal synthesis of 1,25(OH)2D . Serum calcium increased from 2.20 + /- 0.07 mmol/l to 2.56 + /- 0.16 ( P less than 0.005 ) during PTH infusion , but was not significantly different from baseline during intermittent treatment . Baseline concentrations of serum 1,25(OH)2D were 22.8 + /- 8.2 pg/ml , increased to 52.2 + /- 25.1 ( P less than 0.005 ) during infusion and remained significantly higher than baseline after 14 days intermittent therapy ( 33.1 + /- 19.4 , P less than 0.05 ) . Gastrointestinal absorption of 45Ca , as represented by alpha ( peak fractional absorption/h ) , increased from 0.397 + /- 0.173 to 0.552 + /- 0.210 ( P less than 0.01 ) during hPTH 1 - 38 therapy and was moderately correlated with the increment in serum 1,25(OH)2D levels ( r = 0.5 , P less than 0.03 ) . Daily calcium excretion was significantly increased above baseline during hPTH 1 - 38 therapy , but there were no correlations between changes in urinary calcium , alpha or serum 1,25(OH)2D levels . Baseline fasting urinary excretion of OH-proline increased during hPTH 1 - 38 treatment from 30.5 + /- 13.9 mol/mmol creatinine to 43.4 + /- 17.5 immediately after hPTH 1 - 38 infusion ( P less than 0.025 ) , and mean excretion was persistently higher than baseline during intermittent treatment ; the increased urine calcium and OH-proline excretion are consistent with PTH-induced activation of bone resorption . Serum alkaline phosphatase and osteocalcin levels increased significantly during a 90-day period of observation after the hPTH 1 - 38 cycle , which is consistent with increased osteoblast activity in association with coupled bone formation . ( ABSTRACT TRUNCATED AT 400 WORDS Abstract Daily treatment with hPTH ( 1–34 ) is associated with a significant increase in bone formation which results in large gains in lumbar spine bone mass . However , bone formation is known to occur on trabecular , endocortical and periosteal surfaces . The purpose of this study was to determine whether daily treatment with hPTH ( 1–34 ) for 1 year was associated with a change in vertebral cross-sectional area , or vertebral size , as measured by serial quantitative computed tomography scans . Fifty-one postmenopausal women treated chronically with both glucocorticoids and hormone replacement therapy ( HRT ) were r and omized to either daily hPTH ( 1–34 )  for 1 year and HRT or to a control group treated with only HRT .  Measurements of bone density of the spine were obtained every 6 months by dual-energy X-ray absorptiometry ( DXA ) and annually by QCT of the L1 and L2 vertebrae . Vertebral cross-sectional area ( VCSA ) was obtained from the QCT scans . In addition , we estimated the vertebral compressive strength ( VSFOM , g2/cm4 = trabecular BMD2 × VCSA ) . After 1 year of hPTH ( 1–34 )  treatment , VCSA increased 4.8 % ( p < 0.001 ) , and 1 year after treatment was discontinued VCSA was still 2.6 % higher than the baseline value ( p < 0.05 ) . The control group had no change in VCSA . In addition , estimated vertebral compressive strength increased more than 200 % over baseline levels in the hPTH ( 1–34 ) treatment group and no change was observed in the control group . In summary , daily treatment with hPTH ( 1–34 ) for 1 year increased vertebral size as measured by VCSA and this increase was maintained after hPTH ( 1–34 ) was discontinued . Since vertebral fracture risk is related to both bone size and bone mass , we cautiously speculate that the increase in vertebral size associated with hPTH ( 1–34 ) treatment is at least partially responsible for increased vertebral bone strength and reduction of fracture risk associated with this therapy in postmenopausal osteoporosis In a recent study of women with 
    Output:
    
When teriparatide is intermittently administered in low doses , it reduces the incidence of vertebral fractures ( 67 % ) and non-vertebral fractures ( 38 % ) and increases bone mineral density in the lumbar column and femur .