***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: BACKGROUND Pediatric osteoporosis is uncommon but can result in painful and debilitating insufficiency fractures . Treatment options for osteoporosis in children are few . Bisphosphonate therapy for children has not been approved by the Food and Drug Administration ( FDA ) in the United States , but its use in that population has been increasing . R and omized controlled studies have not been done because of the small subject pool and the difficulty in r and omizing a child with an insufficiency fracture to a placebo arm of a study . This retrospective case-control study of a population of children with primarily neuromuscular disease was done to review changes in bone mineral density as reflected by dual x-ray absorptiometry ( DXA ) scanning . METHODS Medical records and DXA scans were screened to identify children with low bone density who had been treated with alendronate as well as similar control subjects with low bone density for their age who had not received alendronate .  Medication acquisition was confirmed by refill records , and cumulative exposure was calculated . Interval DXA scans were review ed to correlate bone mineral density change in grams per square centimeter as well as the percent change and percent change over time for both alendronate-treated and control subjects . RESULTS Twenty-eight alendronate-treated subjects and thirty control subjects met the inclusion criteria . No significant improvement in bone mineral density was seen in the alendronate-treated subjects as compared with the control subjects . Some patients in both groups exhibited marked improvement , with improvement of > 31 % seen only in the alendronate-treated subjects . CONCLUSIONS Alendronate does not reliably improve bone density in children and young adults with primarily neuromuscular disease and without osteogenesis imperfecta . Individual patients treated with bisphosphonates must be carefully followed to ensure medication compliance and appropriate response OBJECTIVE To evaluate feasibility and utility of the soleus H-reflex and tibialis anterior flexor reflex ( FR ) in identifying spinal cord neuronal response to intrathecal baclofen ( ITB ) in children with severe spastic cerebral palsy . METHODS During a r and omized , double-blind , placebo-controlled dose-escalation test treatment , maximum H amplitude/maximum M amplitude ( H/M ratio ) and FR parameters were bilaterally recorded at baseline and 2 - 3 h after intrathecal bolus administration of placebo and increasing doses of baclofen until both an improvement in the individual treatment goal ( s ) and a one-point reduction on the Ashworth scale were observed . RESULTS Electrophysiological data of 14 children were studied . The H-reflex was feasible in 13 children , the FR threshold area in 9 and the FR , elicited with supramaximal stimulation , in only one child . After ITB , the H/M ratio significantly decreased ( left : 0.67+/-0.47 to 0.15+/-0.18 , P=0.005 ; right : 0.55+/-0.32 to 0.14+/-0.19 , P=0.002 ) without placebo effect . FR threshold area after ITB , only decreased significantly in children not taking oral baclofen ( left : 146+/-53 to 41+/-54 mV ms , P=0.000 ; right : 156+/-80 to 66+/-48 mV ms , P=0.002 ) . CONCLUSIONS This is the first r and omized , double-blind , placebo-controlled dose-escalation study in spastic children demonstrating the soleus H-reflex to be a feasible and objective measure to quantify the decreasing motoneuron excitability in response to ITB bolus administration . Only in children not taking oral baclofen , FR threshold area can also be used as an objective outcome measure , yet feasibility is limited . SIGNIFICANCE We suggest introducing the H-reflex as the electrophysiological gold st and ard for the evaluation of the effect of ITB in spastic children BACKGROUND Severe osteogenesis imperfecta ( OI ) is a disorder characterized by osteopenia , frequent fractures , progressive deformity , loss of mobility , and chronic bone pain . There has been no effective therapy for the disorder until recently . The main objective of this study was to determine the efficacy and safety of pamidronate in improving bone mineralization and reducing fracture incidence in osteogenesis imperfecta . METHODS Intravenous pamidronate was administered to 64 children ( from 21 months to 10 years old ) with severe OI , in a 1 mg/kg single daily dose for 3 sequential days at 4-month intervals , over 24 - 48 months duration . Clinical status , biochemical characteristics including bone turnover markers , bone mineral density of the lumbar spine and femoral neck , and radiological changes were assessed regularly during treatment . RESULTS The number of fractures decreased from a median of 8 ( range 4 - 11 ) to 0 fractures/year ( range 0 - 4 ) ( p < 0.05 ) . After 16 months of treatment , there was significant improvement in bone mineral density ( BMD-DEXA ) z-score of the lumbar spine from a median of -5.90 ( range -7.01 to -4.76 ) to -2.70 ( range -4.46 to -1.98 ) ( p < 0.001 ) . Serum alkaline phosphatase ( ALP ) ( bone formation marker ) decreased from a median of 731.0 U/l ( range 438 - 998 U/l ) to 183 U/l ( range 95 - 286 U/l ) ( p < 0.001 ) , implying a significant reduction in bone turnover and resorption and increase in bone mineralization . There was no improvement in growth velocity or height SDS . Mobility and ambulation improved in all but five children ( all five had taken the drug for less than 2.5 years ) . There was a significant relief of chronic pain and fatigue but no adverse effects in all children using the drug . CONCLUSION Cyclic pamidronate administration is effective in improving bone mineralization and reducing fracture incidence in childhood osteogenesis imperfecta Over the past 20 years , orally administered biphosphonates have been used extensively in the management of a number of common skeletal disorders of different etiology . Recently , in clinical practice , in a number of cases in whom oral therapy is insufficient or contraindicated , intravenous administration of pamidronate presents an alternative therapeutic option . In order to investigate the clinical and radiological effects of cyclic intravenous pamidronate administration in children with osteogenesis imperfecta , a prospect i ve open study of pamidronate treatment was undertaken in a cohort of eight bed-bounded ( 3.6 - 13.8 years ) patients with severe osteoporosis and vertebral deformities .  Pamidronate was administered at a dose of 0.5 mg/kg/ day for three days . Tri-monthly cyclic intravenous infusions were performed over-one year . Bone density , verebral corpus heights , estimated volumetric bone density and biochemical measurements were analyzed . Side effects of the therapy were determined via question naire . Significant reductions in the number of bone fractures and pain were observed in all patients . Ambulation scores were significantly altered and seven of eight patients became independent . Serum alkaline phosphatase levels decreased significantly . Lumbar X-ray and densitometry showed a striking improvement by the end of the treatment period . Even spaced dense lines corresponding to infusion periods were observed on roentgenograms of the radio-ulnar region . Pubertal progression and growth velocity were not affected inversely during therapy . Although we did not observe any severe side effect , one patient 's blood urea nitrogen level was altered slightly . In conclusion , one year cyclical pamidronate treatment seems to be effective and safe in improving bone mineralization and in reducing fracture incidence in severe osteoporosis BACKGROUND The current study investigated the efficacy , safety , tolerability , and compliance of a transdermal buprenorphine delivery system for the management of chronic cancer pain in the pediatric population . PROCEDURE Sixteen pediatric patients with moderate to severe cancer-related pain not satisfactorily controlled with previous non-opioid therapies were enrolled .  Transdermal buprenorphine was administered following a 72 hour schedule and rescue medication ( tramadol ) was allowed for breakthrough pain . Pain intensity was assessed using the Wong-Baker faces pain rating scale ( WBS ) and other parameters related to the global quality of life were evaluated . Children 's evaluations of efficacy , compliance , and tolerability were recorded using numerical scales . Adverse events were monitored during the study and the medications needed to control opioid-related nausea and constipation were recorded . RESULTS Eleven patients ( 68.75 % ) responded to transdermal buprenorphine after 2 weeks of treatment . Pain intensity measured with WBS decreased from 6.25 at baseline to 1.38 at Day + 60 ( P < 0.001 ) . All outcome measures of global quality of life ( quality of sleep , alimentation , play and activity , speech , and crying ) significantly improved over the 60-day study period . Children 's evaluations of compliance and tolerability of the drug were always positive over the entire period of treatment . No severe adverse events were recorded . Opioid-related nausea was well controlled with medication on request , and the need for laxative therapy was greater at the end of the second month of treatment . CONCLUSIONS Transdermal buprenorphine was found to represent an efficient , safe and well tolerated approach to the management of children 's chronic cancer pain OBJECTIVE . Sedating critically ill patients often involves prolonged opioid infusions causing opioid tolerance . Naloxone has been hypothesized to limit opioid tolerance by decreasing adenylate cyclase/cyclic adenosine monophosphate activation . The study purpose was to investigate the effect of low-dose naloxone on the maximum cumulative daily fentanyl dose in critically ill children . METHODS . We conducted a double-blinded , r and omized , placebo-control trial from December 2002 through July 2004 in a university PICU . We enrolled 82 children age 1 day to 18 years requiring mechanical ventilation and fentanyl infusions anticipated to last for > 4 days were eligible for enrollment . Those receiving additional oral analgesia or sedation , having a history of drug dependence or withdrawal , or having significant neurologic , renal , or hepatic disease were excluded . In addition to fentanyl infusions , patients received low-dose naloxone or placebo infusions . Medications were adjusted using the Modified Motor Activity Assessment Scale . Withdrawal was monitored using the Modified Narcotic Withdrawal Scale . Intervention was a low-dose naloxone infusion ( 0.25 μg/kg per hour ) and the main outcome variable was the maximum cumulative daily fentanyl dose ( micrograms per kilogram per day ) . RESULTS . There was no difference in the maximum cumulative daily fentanyl dose between patients treated with naloxone ( N = 37 ) or those receiving placebo ( N = 35 ) . Adjustment for the starting fentanyl dose also failed to reveal group differences . Total fentanyl dose received throughout the study in the naloxone group ( 360 μg/kg ) versus placebo ( 223 μg/kg ) was not statistically different . Placebo patients trended toward fewer rescue midazolam boluses ( 10.7 vs 17.8 ) , lower total midazolam dose ( 11.6 mg/kg vs 23.9 mg/kg ) , and fewer rescue fentanyl boluses ( 18.5 vs 23.9 ) . CONCLUSIONS . We conclude that administration of low-dose naloxone ( 0.25 μg/kg per hour ) does not decrease fentanyl requirements in critically ill , mechanically ventilated children CONTEXT Information on the use of oral bisphosphonate agents to treat pediatric osteogenesis imperfecta ( OI ) is limited . OBJECTIVE The objective of the investigation was to study the efficacy and safety of daily oral alendronate ( ALN ) in children with OI . DESIGN AND PARTICIPANTS We conducted a multicenter , double-blind , r and omized , placebo-controlled study . One hundred thirty-nine children ( aged 4 - 19 yr ) with type I , III , or IV OI were r and omized to either placebo ( n = 30 ) or ALN ( n = 109 ) for 2 yr . ALN doses were 5 mg/d in children less than 40 kg and 10 mg/d for those 40 kg and greater . MAIN OUTCOME MEASURES Spine areal bone mineral density ( BMD ) z-score , urinary N-telopeptide of collagen type I , extremity fracture incidence , vertebral area , iliac cortical width , bone pain , physical activity , and safety parameters were measured . RESULTS ALN  increased spine areal BMD by 51 % vs. a 12 % increase with placebo ( P < 0.001 ) ; the mean spine areal BMD z-score increased significantly from -4.6 to -3.3 ( P < 0.001 ) with ALN , whereas the change in the placebo group ( from -4.6 to -4.5 ) was insignificant . Urinary N-telopeptide of collagen type I decreased by 62 % in the ALN-treated group , compared with 32 % with placebo ( P < 0.001 ) . Long-bone fracture incidence , average midline vertebral 
    Output:
    
The adverse events in the BoNT-A trials mostly involved those who received the intervention drug and involved seizures .
Gastrointestinal problems were the most frequent adverse event in those who received alendronate .
The trial investigating pamidronate found no evidence of a difference in pain compared to the control group .
Based on current data this systematic review is unable to determine the effects of pharmacological interventions for pain for CYP with LLCs .