Atypical Femur Fracture Risk versus Fragility Fracture Prevention with Bisphosphonates.

BACKGROUND: Bisphosphonates are effective in reducing hip and osteoporotic fractures. However, concerns about atypical femur fractures have contributed to substantially decreased bisphosphonate use, and the incidence of hip fractures may be increasing. Important uncertainties remain regarding the association between atypical femur fractures and bisphosphonates and other risk factors. METHODS: We studied women 50 years of age or older who were receiving bisphosphonates and who were enrolled in the Kaiser Permanente Southern California health care system; women were followed from January 1, 2007, to November 30, 2017. The primary outcome was atypical femur fracture. Data on risk factors, including bisphosphonate use, were obtained from electronic health records. Fractures were radiographically adjudicated. Multivariable Cox models were used. The risk-benefit profile was modeled for 1 to 10 years of bisphosphonate use to compare associated atypical fractures with other fractures prevented. RESULTS: Among 196,129 women, 277 atypical femur fractures occurred. After multivariable adjustment, the risk of atypical fracture increased with longer duration of bisphosphonate use: the hazard ratio as compared with less than 3 months increased from 8.86 (95% confidence interval [CI], 2.79 to 28.20) for 3 years to less than 5 years to 43.51 (95% CI, 13.70 to 138.15) for 8 years or more. Other risk factors included race (hazard ratio for Asians vs. Whites, 4.84; 95% CI, 3.57 to 6.56), height, weight, and glucocorticoid use. Bisphosphonate discontinuation was associated with a rapid decrease in the risk of atypical fracture. Decreases in the risk of osteoporotic and hip fractures during 1 to 10 years of bisphosphonate use far outweighed the increased risk of atypical fracture among Whites but less so among Asians. After 3 years, 149 hip fractures were prevented and 2 bisphosphonate-associated atypical fractures occurred in Whites, as compared with 91 and 8, respectively, in Asians. CONCLUSIONS: The risk of atypical femur fracture increased with longer duration of bisphosphonate use and rapidly decreased after bisphosphonate discontinuation. Asians had a higher risk than Whites. The absolute risk of atypical femur fracture remained very low as compared with reductions in the risk of hip and other fractures with bisphosphonate treatment. (Funded by Kaiser Permanente and others.).

Outcomes post fragility fracture among members of an integrated healthcare organization.

This study highlights an unmet need in osteoporosis management, suggesting that beyond bone mineral density and fracture history, gender, fracture type, and age should be considered for fracture risk assessment. Following fragility fracture, men, patients with a spine or hip fracture, and those aged ≥ 65 have a higher disease burden. INTRODUCTION: The objective of this study was to characterize osteoporosis-related fracture incidence and identify predictors of subsequent fractures and mortality. METHODS: This retrospective cohort study, conducted within Kaiser Permanente Southern California, included patients aged ≥ 50 years with qualifying fractures from 1/1/2007 to 12/31/2016, identified from diagnosis/procedure codes. Rates for fracture incidence, mortality, and resource utilization in the year post-fracture are reported. Associations between index fracture types and demographic/clinical characteristics, and mortality, subsequent fracture, and rehospitalization outcomes were estimated. RESULTS: Of 63,755 eligible patients, 66.7% were ≥ 65 years and 69.1% female. Index fractures included nonhip/nonspine (64.4%), hip (25.3%), and spine (10.3%). Age-adjusted subsequent fracture rate/100 person-years was higher for those with an index spine (14.5) versus hip fracture (6.3). Hospitalization rate/100 person-years was highest for patients ≥ 65 (31.8) and for spine fractures (43.5). Men (vs women) had higher age-adjusted rates of hospitalization (19.4; 17.7), emergency room visits (73.8; 66.3), and use of rehabilitation services (31.7; 27.2). The 30-day age-adjusted mortality rate/100 person-years was 46.7, 32.4, and 15.5 for spine, hip, and nonspine/nonhip fractures. The 1-year age-adjusted mortality rate/100 person-years was 14.7 for spine and 15.6 for hip fractures. In multivariable analyses, spine and hip fractures (vs nonhip/nonspine fractures) were significant predictors of 1-year mortality, all-cause and osteoporosis-related hospitalization, and nursing home use (all P-values < 0.0001). CONCLUSION: Morbidity is high in the year following a fragility fracture and men, patients with a spine or hip fracture, and those aged ≥ 65 have a greater disease burden.

Sub-acute hyponatraemia more than chronic hyponatraemia is associated with serious falls and hip fractures.

BACKGROUND: Falls and hip fractures among older people are associated with high morbidity and mortality. Hyponatraemia may be a risk for falls/hip fractures, but the effect of hyponatraemia duration is not well understood. AIMS: To evaluate individuals with periods of sub-acute and chronic hyponatraemia on subsequent risk for serious falls and/or hip fractures. METHODS: Retrospective cohort study in the period 1 January 1998 to 14 June 2016 within an integrated health system of individuals aged ≥55 years with ≥2 outpatient serum sodium measurements. Hyponatraemia was defined as sodium <135 mEq/L with sub-acute (<30 days) and chronic (≥30 days) analysed as a time-dependent exposure. Multivariable Cox proportional-hazards modelling was used to estimate hazard ratios (HR) for serious falls/hip fractures based on sodium category. RESULTS: Among 1 062 647 individuals totalling 9 762 305 sodium measurements, 96 096 serious falls/hip fracture events occurred. Incidence (per-1000-person-years) of serious falls/hip fractures were 11.5, 27.9 and 19.8 for normonatraemia, sub-acute and chronic hyponatraemia. Any hyponatraemia duration compared to normonatraemia had a serious falls/hip fractures HR (95%CI) of 1.18 (1.15, 1.22), with sub-acute and chronic hyponatraemia having HR of 1.38 (1.33, 1.42) and 0.91 (0.87, 0.95), respectively. Examined separately, the serious falls HR was 1.37 (1.32, 1.42) and 0.92 (0.88, 0.96) in sub-acute and chronic hyponatraemia, respectively. Hip fracture HR were 1.52 (1.42, 1.62) and 1.00 (0.92, 1.08) for sub-acute and chronic hyponatraemia, respectively, compared to normonatraemia. CONCLUSIONS: Our findings suggest that early/sub-acute hyponatraemia appears more vulnerable and associated with serious falls/hip fractures. Whether hyponatraemia is a marker of frailty or a modifiable risk factor for falls remains to be determined.

BIOCHEMICAL DYNAMICS OF UNTREATED PRIMARY HYPERPARATHYROIDISM: AN OBSERVATIONAL STUDY.

Objective: The natural biochemical history of untreated primary hyperparathyroidism (PHPT) is poorly understood. The purpose of this study was to determine the extent of biochemical fluctuations in patients with PHPT. Methods: Retrospective cohort study from January 1, 1995, to December 31, 2014. Serum calcium and parathyroid hormone (PTH) levels in patients with classic (Ca >10.5 mg/dL, PTH >65 pg/mL) and nonclassic (Ca >10.5 mg/dL, PTH 40 to 65 pg/mL) PHPT were followed longitudinally at 1, 2, and 5 years. Biochemical profiles in follow-up were ranked in descending biochemical severity as classic PHPT, nonclassic PHPT, normal calcium with elevated PTH (Ca <10.5 mg/dL, PTH >65 pg/mL), possible PHPT (Ca >10.5 mg/dL, PTH 21 to 40 pg/mL), or absent PHPT (Ca >10.5 mg/dL, PTH <21 pg/mL or Ca <10.5 mg/dL, PTH <65 pg/mL). Results: Of 10,598 patients, 1,570 were treated with parathyroidectomy (n = 1,433) or medications (n = 137), and 4,367 were censored due to study closure, disenrollment, or death. In the remaining 4,661 untreated patients with 5 years of follow-up, 235 (5.0%) progressed to a state of increased biochemical severity, whereas 972 (20.8%) remained the same, and 3,454 (74.1%) regressed to milder biochemical states. In 2,522 untreated patients with classic PHPT, patients most frequently transitioned to the normal calcium with elevated PTH group (n = 1,257, 49.8%). In 2,139 untreated patients with nonclassic PHPT, patients most frequently transitioned to the absent PHPT group (n = 1,354, 63.3%). Conclusion: PHPT is a biochemically dynamic disease with significant numbers of patients exhibiting both increases and decreases in biochemical severity. Abbreviations: IQR = interquartile range; KPSC = Kaiser Permanente Southern California; PHPT = primary hyperparathyroidism; PTH = parathyroid hormone; PTx = parathyroidectomy.

The Relationship of Parathyroidectomy and Bisphosphonates With Fracture Risk in Primary Hyperparathyroidism: An Observational Study.

BACKGROUND: The comparative effectiveness of surgical and medical treatments on fracture risk in primary hyperparathyroidism (PHPT) is unknown. OBJECTIVE: To measure the relationship of parathyroidectomy and bisphosphonates with skeletal outcomes in patients with PHPT. DESIGN: Retrospective cohort study. SETTING: An integrated health care delivery system. PARTICIPANTS: All enrollees with biochemically confirmed PHPT from 1995 to 2010. MEASUREMENTS: Bone mineral density (BMD) changes and fracture rate. RESULTS: In 2013 patients with serial bone density examinations, total hip BMD increased transiently in women with parathyroidectomy (4.2% at <2 years) and bisphosphonates (3.6% at <2 years) and declined progressively in both women and men without these treatments (-6.6% and -7.6%, respectively, at >8 years). In 6272 patients followed for fracture, the absolute risk for hip fracture at 10 years was 20.4 events per 1000 patients who had parathyroidectomy and 85.5 events per 1000 patients treated with bisphosphonates compared with 55.9 events per 1000 patients without these treatments. The risk for any fracture at 10 years was 156.8 events per 1000 patients who had parathyroidectomy and 302.5 events per 1000 patients treated with bisphosphonates compared with 206.1 events per 1000 patients without these treatments. In analyses stratified by baseline BMD status, parathyroidectomy was associated with reduced fracture risk in both osteopenic and osteoporotic patients, whereas bisphosphonates were associated with increased fracture risk in these patients. Parathyroidectomy was associated with fracture risk reduction in patients regardless of whether they satisfied criteria from consensus guidelines for surgery. LIMITATION: Retrospective study design and nonrandom treatment assignment. CONCLUSION: Parathyroidectomy was associated with reduced fracture risk, and bisphosphonate treatment was not superior to observation. PRIMARY FUNDING SOURCE: National Institute on Aging.

The effect of osteoporosis management on proximal humeral fracture.

HYPOTHESIS AND BACKGROUND: Proximal humeral fractures comprise 10% of fractures in the Medicare population. The effect, if any, of treating osteoporosis to prevent these fractures has not been determined. The primary objective is to determine the effectiveness of a systematic osteoporosis screening and treatment program on the hazard of developing a fracture over the treatment period. The secondary aim is to determine demographic risk factors. METHODS: This is a retrospective cohort study in a health care organization serving 3.3 million members. Individuals selected for dual-energy x-ray absorptiometry screening were (1) women aged 65 years or older; (2) men aged 70 years or older; and (3) individuals aged 50 years or older who have a history of fragility fracture, use glucocorticoids, have a parental history of hip fracture, have rheumatoid arthritis, use alcohol at a high rate, or are cigarette smokers. Treatment consisted primarily of pharmacologic intervention with bisphosphonates. RESULTS: Individuals diagnosed with osteoporosis had a hazard ratio of 7.43 for sustaining a fracture over the study period. Patients screened with dual-energy x-ray absorptiometry had a hazard ratio of 0.17 whereas those treated medically had a hazard ratio of 0.55 versus untreated controls. Risk factors that significantly increased the risk of a fracture developing included age, female gender, white race, diabetes mellitus, and history of a distal radius fracture. DISCUSSION AND CONCLUSION: Over the study period, screening and treatment for osteoporosis significantly decreased the hazard ratio for proximal humeral fracture. This information broadens the impact of such programs because current best practices are primarily based on prevention of spine and hip fractures.

Fertility and pregnancy outcomes in primary hyperparathyroidism: Observations from a large insured population.

CONTEXT: Primary hyperparathyroidism (PHPT) has initially been implicated in adverse maternal and neonatal outcomes, while subsequent population studies have failed to show an association. OBJECTIVE: To compare maternal, pregnancy, and neonatal outcomes in patients with and without PHPT. DESIGN: Retrospective matched-cohort study (2005-2020). SETTING: An integrated healthcare delivery system in Southern California. PATIENTS: Women aged 18-44 years were included. Patients with biochemical diagnosis of PHPT were matched 1:3 with eucalcemic controls (non-PHPT). MAIN OUTCOME MEASURES: Achievement of pregnancy, pregnancy outcomes (including rates of abortion, maternal complications), and neonatal outcomes (including hypocalcemia, need for intensive care). RESULTS: The cohort comprised 386 women with PHPT and 1158 age-matched controls. Pregnancy rates between PHPT and control groups were similar (10.6% vs 12.8%). The adjusted rate ratio of pregnancy was 0.89 (95% CI: 0.64-1.24) (PHPT vs non-PHPT). Twenty-nine pregnancies occurred in women with co-existing PHPT and 191 pregnancies occurred in controls, resulting in 23 (79.3%) and 168 (88.0%) live births, respectively (p=0.023). Neonatal outcomes were similar. Live birth rates were similar (86.4%, 80%, 79.2%) for those undergoing parathyroidectomy prior (n=22), during (n=5), or after pregnancy/never (n=24). Among patients who underwent parathyroidectomy during pregnancy, no spontaneous abortions occurred in women entering pregnancy with peak calcium <11.5 mg/dL [2.9 mmol/L]. CONCLUSIONS: We observed no difference in pregnancy rates between women with or without PHPT. Performing parathyroidectomy before pregnancy or during the second trimester appears to be a safe and successful strategy, and adherence to this strategy may be most critical for patients with higher calcium levels (≥11.5 mg/dL [2.9 mmol/L]).

Osteoporosis treatment prevents hip fracture similarly in both sexes: the FOCUS observational study.

Randomized trials have not been performed, and may never be, to determine if osteoporosis treatment prevents hip fracture in men. Addressing that evidence gap, we analyzed data from an observational study of new hip fractures in a large integrated healthcare system to compare the reduction in hip fractures associated with standard-of-care osteoporosis treatment in men versus women. Sampling from 271,389 patients aged ≥ 65 who had a hip-containing CT scan during care between 2005 and 2018, we selected all who subsequently had a first hip fracture (cases) after the CT scan (start of observation) and a sex-matched equal number of randomly selected patients. From those, we analyzed all who tested positive for osteoporosis (DXA-equivalent hip BMD T-score ≤ -2.5, measured from the CT scan using VirtuOst). We defined "treated" as at least six months of any osteoporosis medication by prescription fill data during follow-up; "not-treated" was no prescription fill. Sex-specific odds ratios of hip fracture for treated vs not-treated patients were calculated by logistic regression; adjustments included age, BMD T-score, BMD-treatment interaction, BMD, race/ethnicity, and seven baseline clinical risk factors. At two-year follow-up, 33.9% of the women (750/2,211 patients) and 24.0% of the men (175/728 patients) were treated primarily with alendronate; 51.3% and 66.3%, respectively, were not-treated; and 721 and 269, respectively, had a first hip fracture since the CT scan. Odds ratio of hip fracture for treated vs not-treated was 0.26 (95% confidence interval: 0.21-0.33) for women and 0.21 (0.13-0.34) for men; the ratio of these odds ratios (men:women) was 0.81 (0.47-1.37), indicating no significant sex effect. Various sensitivity and stratified analyses confirmed these trends, including results at five-year follow-up. Given these results and considering the relevant literature, we conclude that osteoporosis treatment prevents hip fracture similarly in both sexes.

Much evidence suggests that osteoporosis treatment should prevent hip fracture similarly in both sexes. However, because of their expense, randomized clinical trials to demonstrate that definitively have not been performed and may never be. As a result, osteoporosis testing and treatment are not as widely adopted for men as it is for women. Addressing that evidence gap, we analyzed data from over 250,000 patients in the Kaiser Permanente healthcare system in Southern California. Sampling a subset of all patients over a 13-year period who had had a CT (CAT) scan as part of their medical care for any reason, we measured BMD from the CT scans to identify all patients who had osteoporosis at the hip and then used data from the electronic health records to determine statistically the risk of a future hip fracture for those who were treated for osteoporosis versus those who were not treated. We found that the reduction in risk of hip fracture associated with treatment did not differ between the sexes. These results demonstrate that treating osteoporosis in patients at high risk of hip fracture should reduce the risk of hip fracture similarly in both sexes.

Associations between childhood obesity and upper and lower extremity injuries.

OBJECTIVES: To estimate the overall and age-specific associations between obesity and extremity musculoskeletal injuries and pain in children. METHODS: This cross-sectional study used information from electronic medical records of 913178 patients aged 2-19 years enrolled in an integrated health plan in the period 2007-2009. Children were classified as underweight, normal weight, overweight, or moderately/extremely obese and, using multivariable logistic regression methods, the associations between weight class and diagnosis of upper or lower extremity fractures, sprains, dislocations and pain were calculated. RESULTS: Overweight (OR 1.18, 95% CI 1.15 to 1.20), moderately obese (OR 1.24, 95% CI 1.20 to 1.27) and extremely obese (OR 1.34, 95% CI 1.30 to 1.39) children had statistically significantly higher odds of lower extremity injuries/pain compared to normal weight, adjusted for sex, age, race/ethnicity and insurance status. Age-stratified analyses yielded similar results. No consistent association was observed between body mass index and injuries/pain of the upper extremities. CONCLUSIONS: Greater body mass index is associated with increased odds of lower extremity injuries and pain issues. Because the benefits of physical activity may still outweigh the risk of injury, attention should be paid to injury prevention strategies for these children at greater risk for lower extremity injuries.

Clinical Outcomes of Telehealth in Patients With Coronary Artery Disease and Heart Failure During the COVID-19 Pandemic.

The COVID-19 pandemic necessitated a rapid adoption of telehealth (TH); however, its safety in subspecialty clinical practice remains uncertain. To assess the clinical outcomes associated with TH use in patients with coronary artery disease and/or heart failure during the initial phase of the COVID-19 pandemic, eligible adult patients who saw cardiologists from March 1, 2020, to August 31, 2020 (TH period) were identified. Patients were divided into two 3-month subcohorts (TH1, TH2) and compared with corresponding 2019 prepandemic subcohorts. The primary outcome was cardiovascular (CV) events within 3 months after index visits. Secondary analysis was CV events in patients aged ≥75 years within 3-month follow-up associated with TH use. Multivariable logistic regression was used to evaluate the association between TH use and CV outcomes. The study cohort included 6,485 TH and 7,557 prepandemic patients. The mean age was 70 years, with 40% of patients aged ≥75 years and 35% women. TH visits accounted for 0% of visits during the prepandemic period, compared with 68% during the TH period. Telephone visits comprised ≥92% of all TH encounters. Compared with the prepandemic period, patients seen during the TH period had fewer overall CV events (adjusted odds ratio 0.78, 95% confidence interval 0.67 to 0.90). Patients aged ≥75 years had similar findings (adjusted odds ratio 0.70, 95% confidence interval 0.55 to 0.89). Additional analysis of CV outcome events within 6 months after index visits showed similar findings. In conclusion, TH largely by way of telephone encounters can be safely incorporated into the ambulatory cardiology practice regardless of age.

Long-term effects of primary hyperparathyroidism and parathyroidectomy on kidney function.

IMPORTANCE: Limited evidence supports kidney dysfunction as an indication for parathyroidectomy in asymptomatic primary hyperparathyroidism (PHPT). OBJECTIVE: To investigate the natural history of kidney function in PHPT and whether parathyroidectomy alters renal outcomes. DESIGN: Matched control study. SETTING: A vertically integrated health care system serving 4.6 million patients in Southern California. PARTICIPANTS: 6058 subjects with PHPT and 16 388 matched controls, studied from 2000 to 2016. EXPOSURES: Biochemically confirmed PHPT with varying serum calcium levels. MAIN OUTCOMES: Estimated glomerular filtration rate (eGFR) trajectories were compared over 10 years, with cases subdivided by severity of hypercalcemia: serum calcium 2.62-2.74 mmol/L (10.5-11 mg/dL), 2.75-2.87 (11.1-11.5), 2.88-2.99 (11.6-12), and >2.99 (>12). Interrupted time series analysis was conducted among propensity-score-matched PHPT patients with and without parathyroidectomy to compare eGFR trajectories postoperatively. RESULTS: Modest rates of eGFR decline were observed in PHPT patients with serum calcium 2.62-2.74 mmol/L (−1.0 mL/min/1.73 m2/year) and 2.75-2.87 mmol/L (−1.1 mL/min/1.73 m2/year), comprising 56% and 28% of cases, respectively. Compared with the control rate of −1.0 mL/min/1.73 m2/year, accelerated rates of eGFR decline were observed in patients with serum calcium 2.88-2.99 mmol/L (−1.5 mL/min/1.73 m2/year, P < .001) and >2.99 mmol/L (−2.1 mL/min/1.73 m2/year, P < .001), comprising 9% and 7% of cases, respectively. In the propensity score­matched population, patients with serum calcium >2.87 mmol/L exhibited mitigation of eGFR decline after parathyroidectomy (−2.0 [95% CI: −2.6 to −1.5] to −0.9 [95% CI: −1.5 to 0.4] mL/min/1.73 m2/year). CONCLUSIONS AND RELEVANCE: Compared with matched controls, accelerated eGFR decline was observed in the minority of PHPT patients with serum calcium >2.87 mmol/L (11.5 mg/dL). Parathyroidectomy was associated with mitigation of eGFR decline in patients with serum calcium >2.87 mmol/L.

Increased risks of vertebral fracture and reoperation in primary spinal fusion patients who test positive for osteoporosis by Biomechanical Computed Tomography analysis.

BACKGROUND CONTEXT: While osteoporosis is a risk factor for adverse outcomes in spinal fusion patients, diagnosing osteoporosis reliably in this population has been challenging due to degenerative changes and spinal deformities. Addressing that challenge, biomechanical computed tomography analysis (BCT) is a CT-based diagnostic test for osteoporosis that measures both bone mineral density and bone strength (using finite element analysis) at the spine; CT scans taken for spinal evaluation or previous care can be repurposed for the analysis. PURPOSE: Assess the effectiveness of BCT for preoperatively identifying spinal fusion patients with osteoporosis who are at high risk of reoperation or vertebral fracture. STUDY DESIGN: Observational cohort study in a multi-center integrated managed care system using existing data from patient medical records and imaging archives. PATIENT SAMPLE: We studied a randomly sampled subset of all adult patients who had any type of primary thoracic (T4 or below) or lumbar fusion between 2005 and 2018. For inclusion, patients with accessible study data needed a preop CT scan without intravenous contrast that contained images (before any instrumentation) of the upper instrumented vertebral level. OUTCOME MEASURES: Reoperation for any reason (primary outcome) or a newly documented vertebral fracture (secondary outcome) occurring up to 5 years after the primary surgery. METHODS: All study data were extracted using available coded information and CT scans from the medical records. BCT was performed at a centralized lab blinded to the clinical outcomes; patients could test positive for osteoporosis based on either low values of bone strength (vertebral strength ≤ 4,500 N women or 6,500 N men) and/or bone mineral density (vertebral trabecular bone mineral density ≤ 80 mg/cm3 both sexes). Cox proportional hazard ratios were adjusted by age, presence of obesity, and whether the fusion was long (four or more levels fused) or short (3 or fewer levels fused); Kaplan-Meier survival was compared by the log rank test. This project was funded by NIH (R44AR064613) and all physician co-authors and author 1 received salary support from their respective departments. Author 6 is employed by, and author 1 has equity in and consults for, the company that provides the BCT test; the other authors declare no conflicts of interest. RESULTS: For the 469 patients analyzed (298 women, 171 men), median follow-up time was 44.4 months, 11.1% had a reoperation (median time 14.5 months), and 7.7% had a vertebral fracture (median time 2.0 months). Overall, 25.8% of patients tested positive for osteoporosis and no patients under age 50 tested positive. Compared to patients without osteoporosis, those testing positive were at almost five-fold higher risk for vertebral fracture (adjusted hazard ratio 4.7, 95% confidence interval = 2.2-9.7; p<.0001 Kaplan-Meier survival). Of those positive-testing patients, those who tested positive concurrently for low values of both bone strength and bone mineral density (12.6% of patients overall) were at almost four-fold higher risk for reoperation (3.7, 1.9-7.2; Kaplan-Meier survival p<.0001); the remaining positive-testing patients (those who tested positive for low values of either bone strength or bone mineral density but not both) were not at significantly higher risk for reoperation (1.6, 0.7-3.7) but were for vertebral fracture (4.3, 1.9-10.2). For both clinical outcomes, risk remained high for patients who underwent short or long fusion. CONCLUSION: In a real-world clinical setting, BCT was effective in identifying primary spinal fusion patients aged 50 or older with osteoporosis who were at elevated risks of reoperation and vertebral fracture.

Dexamethasone Suppression Testing in a Contemporary Cohort with Adrenal Incidentalomas in Two U.S. Integrated Healthcare Systems.

Autonomous cortisol secretion (ACS) from an adrenal adenoma can increase the risk for comorbidities and mortality. The dexamethasone suppression test (DST) is the standard method to diagnose ACS. A multi-site, retrospective cohort of adults with diagnosed adrenal tumors was used to understand patient characteristics associated with DST completion and ACS. Time to DST completion was defined using the lab value and result date; follow-up time was from the adrenal adenoma diagnosis to the time of completion or censoring. ACS was defined by a DST > 1.8 µg/dL (50 nmol/L). The Cox proportional hazards regression model assessed associations between DST completion and patient characteristics. In patients completing a DST, a logistic regression model evaluated relationships between elevated ACS and covariates. We included 24,259 adults, with a mean age of 63.1 years, 48.1% obese, and 28.7% with a Charlson comorbidity index ≥ 4. Approximately 7% (n = 1768) completed a DST with a completion rate of 2.36 (95% CI 2.35, 2.37) per 100 person-years. Fully adjusted models reported that male sex and an increased Charlson comorbidity index were associated with a lower likelihood of DST completion. Current or former smoking status and an increased Charlson comorbidity index had higher odds of a DST > 1.8 µg/dL. In conclusion, clinical policies are needed to improve DST completion and the management of adrenal adenomas.

Fracture Risk and Association With TDF Use Among People With HIV in Large Integrated Health Systems.

BACKGROUND: Greater decline in bone health among people with HIV (PWH) has been documented but fracture risk and the impact of specific antiretroviral therapy (ART) regimens remain unclear. SETTING: Retrospective analyses of electronic health record data from 3 US integrated health care systems. METHODS: Fracture incidence was compared between PWH aged 40 years or older without prior fracture and demographically matched people without HIV (PWoH), stratified by age, sex, and race/ethnicity. Multivariable Cox proportional hazards models were used to estimate fracture risk associated with HIV infection. The association of tenofovir disoproxil fumarate (TDF) use and fracture risk was evaluated in a subset of PWH initiating ART. RESULTS: Incidence of fracture was higher in PWH [13.6/1000 person-years, 95% confidence interval (CI): 13.0 to 14.3, n = 24,308] compared with PWoH (9.5, 95% CI: 9.4 to 9.7, n = 247,313). Compared with PWoH, the adjusted hazard ratio (aHR) for fracture among PWH was 1.24 (95% CI: 1.18 to 1.31). The association between HIV infection and fracture risk increased with age, with the lowest aHR (1.17, 95% CI: 1.10 to 1.25) among those aged 40-49 years and the highest aHR (1.89, 95% CI: 1.30 to 2.76) among those aged 70 years or older. Among PWH initiating ART (n = 6504), TDF was not associated with significant increase in fracture risk compared with non-TDF regimens (aHR: 1.18, 95% CI: 0.89 to 1.58). CONCLUSIONS: Among people aged 40 years or older, HIV infection is associated with increased risk of fractures. Bone health screening from the age of 40 years may be beneficial for PWH. Large cohort studies with longer follow-up are needed to evaluate TDF effect and the potential benefit of early screening.

Distal radius fracture risk reduction with a comprehensive osteoporosis management program.

PURPOSE: To study risk factors associated with osteoporotic distal radius fractures and evaluate the effectiveness of the screening and treatment components of a comprehensive osteoporosis program. METHODS: We retrospectively identified a cohort of patients aged 60 years or older from a large health maintenance organization. For the period 2002 to 2008, information on age, race, sex, diabetes status, osteoporosis diagnosis, osteoporosis screening activity, medications dispensed, and fracture events, including distal radius, proximal humerus, and hip fractures were recorded. We compared demographic and clinical characteristics for patients with and without distal radius fractures. We estimated multivariable estimates of the associations between pharmacologic treatment, and osteoporosis screening and distal radius fracture risk using Cox proportional hazards methods, and adjusted them for age, sex, race, diabetes status, and prior history of hip or proximal humerus fractures. RESULTS: Overall, 1.7% of the cohort (n = 8,658) of the study population (N = 524,612) sustained a new distal radius fracture during 2002 to 2008. In the multivariable model, we found that patients who received pharmacological intervention were 48% less likely to sustain a distal radius fracture. Similarly, patients who were screened for osteoporosis were 83% less likely to sustain a distal radius fracture. Patients with osteoporosis were 8.9 times more likely to have a distal radius fracture than patients without osteoporosis. White subjects had a 1.6 times higher risk of distal radius fracture than non-whites, and women had a 3.8 times higher risk than men. CONCLUSIONS: White race, female sex, and a diagnosis of osteoporosis are high risks for distal radius fracture. Screening for and pharmacologic management of osteoporosis using a multidisciplinary team approach in a comprehensive osteoporosis management program resulted in a statistically significant decrease in the risk of distal radius fracture. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic III.

Bisphosphonates and the risk of atypical femur fractures.

Bisphosphonates are effective in reducing hip and other fractures. However, concerns about atypical femur fractures (AFFs) have contributed to substantially decreased bisphosphonate use, and hip fracture rates may be increasing. Despite this impact, important uncertainties remain regarding AFF risks including the association between bisphosphonate use and other risk factors such as BMD, age, weight, and race. To address this evidence gap, a cohort study of 196,129 women ≥50 years of age in the Southern California Kaiser Permanente HMO women (with ≥1 bisphosphonate prescription) were studied; the primary outcome was radiographically-adjudicated AFF between 2007 and 2017. Risk factors including bisphosphonate use and race were obtained from electronic health records. Multivariable Cox models were used for analysis. Benefit-risk was modeled for 1-10 years of bisphosphonates to compare fractures prevented vs. AFFs associated. Among 196,129 women, 277 (0.1%) sustained AFFs. After multivariable adjustment, AFF risk increased with longer bisphosphonate duration: hazard ratio (HR) increased from HR = 8.9 (95%CI: 2.8,28) for 3-5 years to HR = 43.5 (13.7138.1) for >8 years. Hip BMD, surprisingly, was not associated with AFF risk. Other risk factors included Asian ancestry (HR = 4.8 (3.6, 6.6)), short stature, overweight, and glucocorticoid use. Bisphosphonate discontinuation was associated with rapid decrease in AFF risk. Decreases in osteoporotic and hip fractures risk during 1-10 years of bisphosphonates far outweighed the increase AFF risk in Caucasians, but less so in Asians. In Caucasians, after 3 years 149 hip fractures were prevented with 2 AFFs associated compared to 91 and 8 in Asians. The evidence for several potential mechanisms is summarized with femoral geometry being the most likely to explain AFF risk differences between Asians and Caucasians. The results from this new study add to the evidence base for AFF risk factors and will help inform clinical decision-making for individual patients about initiation and duration of bisphosphonate therapy and drug holidays.

Creating a Safety Net Process to Improve Colon Cancer Diagnosis in Patients With Rectal Bleeding.

Background Failure to follow up on patients with rectal bleeding is common and may result in a delay in diagnosis of colorectal cancer or in missing high-risk adenomas. The authors' purpose was to create an electronic patient safety net for those diagnosed with rectal bleeding but who did not have colonoscopy to ensure proper detection of colonic abnormalities, including colon cancer. Methods In an integrated health delivery system serving < 4.6 million patients in Southern California, from 2014 to 2019, the authors electronically identified patients with rectal bleeding aged 45 to 80 years but with no recently documented colonoscopy. These cases were reviewed by a gastroenterologist to determine if colonoscopy was appropriate. The physician looked for known documentation as to the cause of rectal bleeding and verified no contraindications to the procedure; if indicated, testing was offered. Results Using the authors' safety net program, 1430 patients with rectal bleeding who needed and completed a colonoscopy were identified. Of those patients, 7.5% had an advanced adenoma or cancer, with a total of 20 cancers, and 34% had findings that warranted more frequent colonoscopy. Conclusions The authors designed a safety net system that was able to capture information on patients with rectal bleeding who had not had a colonoscopy and detected in 34% colonic pathology that would have otherwise gone undetected. The program did not require many resources to implement and had the ability to potentially prevent harm from reaching patients whose rectal bleeding did not get prompt workup. Other health systems and practices should consider implementing a similar system.

Injury hospitalization as a marker for emergency medical services use in elderly patients.

BACKGROUND: The elderly utilize emergency medical services (EMS) at a higher rate than younger patients, yet little is known about the influence of injury on subsequent EMS utilization and costs. OBJECTIVE: To assess injury hospitalization as a potential marker for subsequent EMS utilization and costs by Medicare patients. METHODS: This observational study analyzed a retrospective cohort of all Medicare patients (> or = 67 years old) with an International Classification of Diseases, Ninth Revision (ICD-9) injury diagnosis admitted to 125 Oregon and Washington hospitals during 2001 and 2002 who survived to hospital discharge. The numbers of EMS transports and the total EMS costs were compared one year before and one year following the index hospitalization. RESULTS: There were 30,655 injured elders in our cohort. Their median ICD-9-based injury severity score was 0.97, with 4.1% meeting a definition of serious injury and 37% having hip fractures. The mean (range) numbers of EMS transports before and after the injury were 0.5 (0-45) and 0.9 (0-56), for an unadjusted incidence rate ratio (IRR) of 1.7 (95% confidence interval [CI] 1.7-1.8). The increase in EMS utilization following an injury hospitalization was even greater after adjusting for risk period and other model predictors (IRR 2.4, 95% CI 2.3-2.5). Annual mean EMS costs rose 74% following the injury hospitalization, from $211 to $367 per person. The greatest increase was in nonemergent EMS use, accounting for 67% of the increase in the number of uses. Institutionalization in a skilled nursing or rehabilitation facility either before or after injury was strongly associated with the need for EMS care. CONCLUSION: An injury hospitalization in the elderly serves as a sentinel marker for an abrupt increase in EMS utilization and costs, even after accounting for confounders.