***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 
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    Input: Context Primary hyperparathyroidism is treated with surgery or medication , and not enough is known about which treatment is preferred . Contribution The research ers studied what happened to several thous and patients with primary hyperparathyroidism . Compared with follow-up alone , surgery was associated with fewer hip fractures and fewer fractures of any type , regardless of whether patients met guideline criteria for surgery . Bisphosphonates were associated with increases in bone mineral density but not with fewer fractures . Caution This observational study could not establish cause and effect . Implication Most patients managed in the community who meet guideline criteria do not have surgery . This practice should be reassessed . Primary hyperparathyroidism ( PHPT ) is a common endocrine disorder , affecting 1 in 400 women and 1 in 1200 men in the United States ( 1 ) . Untreated PHPT leads to loss of bone mineral density ( BMD ) over time ( 2 ) , raising concern about the development of osteoporosis and associated elevated fracture risk ( 3 , 4 ) . Surgery , the only definitive treatment for PHPT ( 5 , 6 ) , yields prompt and sustained improvements in BMD ( 79 ) and may reduce fracture risk ( 3 , 1012 ) . Bisphosphonates  improve BMD in patients with PHPT in the short term to an extent that is similar to improvements seen after surgery ( 1317 ) . However , no reductions in fracture risk have been reported with these medications ( 18 ) . Using a large population -based cohort , we examined BMD changes and fracture rates among patients with PHPT managed with parathyroidectomy , bisphosphonates , or observation .  Methods Study Setting The study population included all active enrollees in Kaiser Permanente Southern California , an integrated health care delivery system serving approximately 3.5 million subscribers . The membership closely mirrors the population of the greater Los Angeles metropolitan area demographically and socioeconomically ( 1 ) . Because most members receive employer-based insurance benefits , outmigration rates are low , with two thirds of subscribers maintaining membership for at least 5 years . This remains true among enrollees who are eligible for Medicare . Participants The Kaiser Permanente Southern California Laboratory Management System was queried to identify patients with a biochemical diagnosis of PHPT from 1 January 1995 through 31 December 2010 . We have previously published fracture data on a subset of these patients ( 10 , 11 ) . We included patients with classic PHPT , as defined by hypercalcemia ( serum total calcium level > 2.63 mmol/L [ > 10.5 mg/dL ] ) and parathyroid hormone ( PTH ) excess ( PTH level > 65 ng/L ) . We excluded patients who were members for less than 6 months , those younger than 20 years , and those with secondary ( renal ) hyperparathyroidism ( serum creatinine level > 221.0 mol/L [ > 2.5 mg/dL ] ) . Any patient with 2 or more tests for immunosuppressant levels was considered a likely kidney transplant recipient with possible tertiary hyperparathyroidism and was excluded . Given the adverse effects of some breast cancer treatments on BMD ( 19 ) , we excluded patients with a history of breast cancer . Those who initiated bisphosphonate treatment before the date of study inclusion and those treated with an incomplete course of bisphosphonates ( duration < 1 year ) were also excluded . Treatments Patients who had parathyroidectomy were identified using International Classification of Diseases , Ninth Revision ( ICD-9 ) , procedure codes 06.8 , 06.81 , and 06.89 and Current Procedural Terminology codes 60500 and 60502 . Bisphosphonate treatment was ascertained by querying the pharmacy data base for prescriptions for alendronate , pamidronate , risedronate , ib and ronate , and zoledronate . The duration of bisphosphonate use was defined as the time between the first and last dispensation date s. Patients who received both medical and surgical treatment were assigned to the initial treatment group and were then censored on receipt of the second treatment . Bone Densitometry The BMD of the total hip and lumbar spine ( L2 , L3 , and L4 ) was measured using dual-energy x-ray absorptiometry through 31 December 2012 . Measurements were obtained using Hologic and Lunar ( GE Healthcare ) densitometers . The distal nondominant forearm was not routinely assessed . Fracture Outcomes Fractures were categorized into hip and nonhip fractures by using ICD-9 diagnostic codes ( Appendix Table 1 ) . Multiple encounters in a given patient for the same diagnostic code were considered a single fracture . Patients were followed for fracture until 31 December 2012 . Appendix Table 1 . Fracture Categories * Consensus Guidelines for Parathyroid Surgery To assess the potential influence of adherence to practice guidelines on fracture risk , we performed stratified analyses using the criteria described in the consensus guidelines for the management of asymptomatic PHPT ( 20 ) . These guidelines have undergone several iterations over time ; we decided to use the 2002 guidelines ( 21 ) because they are broadly representative of the study period yet sufficiently similar to current guidelines to permit generalization of our findings to modern practice . Because we excluded patients with significant chronic kidney disease as part of our study design , we applied the 4 remaining guideline criteria : serum calcium level greater than 2.88 mmol/L ( > 11.5 mg/dL ) , 24-hour urinary calcium level greater than 400 mg , T-score less than 2.5 at any site , and age younger than 50 years . A patient was considered to have satisfied guideline criteria if they met 1 or more criteria at any time before death , disenrollment , fracture , or the end of the study period . Statistical Analysis BMD Changes in BMD were studied over 4 discrete periods : 0 to 2 years , 2 to 5 years , 5 to 8 years , and beyond 8 years , as defined by the interval between BMD examinations . Baseline BMD was recorded within 2 years of the index date of biochemical diagnosis . Follow-up BMD data were compared with baseline values by using linear regression , controlling for age , race/ethnicity , and Charlson Comorbidity Index score . The Charlson score has recently been found to predict fracture risk in elderly patients and those with chronic comorbidities ( 22 , 23 ) . Treatment groups were assigned according to whether parathyroidectomy , bisphosphonate treatment , or no treatment had occurred before the date of the follow-up BMD examination . Fractures To account for variability in treatment duration , a time-dependent Cox proportional hazards model was applied to estimate fracture risk ( 24 ) . On the basis of the estimated regression coefficients and cumulative baseline hazards from the time-dependent Cox models , we estimated the absolute risk for fracture at 1 , 2 , 5 , and 10 years after baseline for each of the treatment scenarios . For each treatment , the absolute risk was calculated as the average of estimated risks for individual patients who were still at risk at each time point ( 25 , 26 ) . Covariates included age , race/ethnicity , and comorbidity score . The 95 % CIs for the absolute risk and their between-group differences were obtained using a nonparametric bootstrap with 200 replications . In a secondary analysis , we also applied a marginal structural model to adjust for possible bias in estimated treatment effects caused by nonr and om treatment assignment and time-dependent biochemical confounders that are influenced by treatment , namely calcium and PTH levels . Treatment effects were estimated using the inverse probability of treatment weighting ( IPTW ) technique and weighted pooled logistic regression treating each person-year as an observation ( 2730 ) . All analyses were done using SAS Enterprise Guide 5.1 ( SAS Institute ) . Further details are provided in the Appendix . Estimation of Residual Confounding Residual confounding after application of the marginal structural model was assessed using falsification end points ( 31 , 32 ) . A composite falsification end point , defined as at least 1 emergency department admission or inpatient hospitalization for heart failure ( ICD-9 code 428.xx ) , syncope ( 780.2 ) , pneumonia ( 486.xx ) , or urinary tract infection ( 599.0 ) was created . These events , which are unlikely to be causally related to treatment assignment , were chosen as possible surrogate markers for frailty or high fall risk . We also used sensitivity analysis to determine whether the observed differences in fracture rate could be fully explained by an unmeasured confounder ( Appendix ) ( 33 ) . Ethics The study was approved by the institutional review boards of the University of California , Los Angeles , and Kaiser Permanente Southern California . Role of the Funding Source The study was funded by the National Institute on Aging , which had no role in the design , conduct , or analysis of the study or the decision to su bmi t the manuscript for publication . Results Patient Characteristics The study cohort comprised 6272 patients with PHPT ( Table 1 and Figure 1 ) , most of whom were female ( 71 % ) , were white ( 56 % ) , were older than 59 years ( 64 % ) , and had no comorbid conditions ( 55 % ) . Baseline BMD measurements revealed normal BMD in 11 % of participants , osteopenia in 36 % , and osteoporosis in 53 % . The prevalence of osteoporosis was greatest in the bisphosphonate group . When covariate balance was assessed using the IPTW method ( Appendix Table 2 ) , adequate adjustment for differences in patient characteristics was achieved when the observation and parathyroidectomy groups were compared . All covariates except baseline BMD status were balanced between the observation and bisphosphonate groups , necessitating fracture risk analyses stratified by baseline BMD status . Table 1 . Patient Characteristics , by Initial Treatment Group Figure 1 . Study flow diagram . BMD = bone mineral density ;  PHPT  = primary hyperparathyroidism ; PTH = parathyroid hormone . Appendix Table 2 . Unadjusted and Adjusted Covariates With Inverse Probability of Treatment Weighting * Treatments Observation was the most common form of management ( 55 % ) , with the Objective : To determine whether surgical volume influences the cause of operative failures after  parathyroidectomy for hyperparathyroidism . Summary and Background Data : The surgical success rate for hyperparathyroidism from high-volume centers exceeds 95 % , but some patients have unsuccessful parathyroidectomies . Although operative failure can be due to hyperfunctioning parathyroid gl and s in ectopic locations , less experienced surgeons may be more likely to miss an abnormal parathyroid in normal anatomic locations , which we describe as “ preventable operative failure . ” Methods : We used 2 prospect i ve data bases containing over 2000 consecutive patients who underwent parathyroidectomy .  We identified 159 patients with persistent/recurrent hyperparathyroidism subsequently cured with additional surgery . The initially failed operations were classified as being performed at high- ( > 50 cases/yr ) or low-volume ( < 50 cases/yr ) hospitals . Hospital volume was obtained from a Wisconsin state data base of 89 hospitals , which reported 6336 parathyroid operations during the same decade . Results : Patients who initially failed their operation performed at the high- or low-volume centers were similar with regard to age , laboratory values , gender , and parathyroid weights . Despite a higher incidence of multigl and disease ( which increases the likelihood of operative failure ) in the high-volume group , patients in the low-volume group were more likely to have a missed parathyroid gl and in a normal anatomic location ( 89 % vs. 13 % , P < 0.0001 ) , and thus a higher proportion of preventable operative failures . Conclusions : Surgical volume influences the failure pattern after  parathyroidectomy for hyperparathyroidism . Preventable operative failures are more common in low-volume centers BACKGROUND There is an ongoing controversy regarding how to take care of patients with mild primary hyperparathyroidism ( PHPT ) and how to grade their disease activity in terms of bone parameters . This prospect i ve and r and omized study was undertaken to evaluate skeletal effects of delayed surgical treatment in such patients . METHODS Fifty patients with mild PHPT ( serum calcium , 2.55 to 2.95 mmol/L ; 10.2 to 11.8 mg/dL ) were r and omized to parathyroidectomy either at diagnosis or 1 year later . Hip and spine bone mineral density ( BMD , determined by dual energy x-ray absorptiometry ) , bone alkaline phosphatase in serum , osteocalcin and beta-CrossLaps in plasma , and calcium in urine were measured in all patients at inclusion in the study and 1 and 2 years later . RESULTS The skeletal effects of mild PHPT varied with anatomy and time of exposure . Parathyroidectomy decreased all biochemical bone markers ( P < .0001 ) and increased lumbar spine BMD ( P < .05 ) equally in both groups , even in patients without overt osteoporosis , whereas hip BMD was increased ( P < .05 ) in the early intervention group only . CONCLUSION Prolonged exposure to mild and seemingly stable PHPT is a risk factor for hip fractures , which adds to other reasons for surgical treatment of this condition without delay regardless of serum calcium levels Parathyroidectomy is the definitive therapy for patients with symptomatic primary hyperparathyroidism . However , the role of surgery in mild asymptomatic primary hyper 
    Output:
    
Patients with mild PHPT without indications for surgery experience a limited number of adverse consequences during short-term follow-up limiting our ability to estimate the benefit of surgery during this timeframe .