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.).

Proceedings of the 2017 Santa Fe Bone Symposium: Insights and Emerging Concepts in the Management of Osteoporosis.

The 18th Annual Santa Fe Bone Symposium was held on August 4-5, 2017, in Santa Fe, New Mexico, USA. The symposium convenes health-care providers and clinical researchers to present and discuss clinical applications of recent advances in research of skeletal diseases. The program includes lectures, oral presentations by endocrinology fellows, case-based panel discussions, and breakout sessions on topics of interest, with emphasis on participation and interaction of all participants. Topics included the evaluation and treatment of adult survivors with pediatric bone diseases, risk assessment and management of atypical femur fractures, nonpharmacologic strategies in the care of osteoporosis, and skeletal effects of parathyroid hormone with opportunities for therapeutic intervention. Management of skeletal complications of rheumatic diseases was discussed. Insights into sequential and combined use of antiresorptive agents were presented. Individualization of patient treatment decisions when clinical practice guidelines may not be applicable was covered. Challenges and opportunities with osteoporosis drug development were discussed. There was an update on progress of Bone Health TeleECHO (Bone Health Extension for Community Healthcare Outcomes), a teleconferencing strategy for sharing knowledge and expanding capacity to deliver best-practice skeletal health care.

Evaluating Atypical Features of Femur Fractures: How Change in Radiological Criteria Influenced Incidence and Demography of Atypical Femur Fractures in a Community Setting.

Identification of atypical femoral fractures (AFFs) can be challenging. To assist in the radiological assessment, an American Society for Bone and Mineral Research (ASBMR) Task Force developed a case definition for AFFs in 2010, revising it in 2013. How the revised definition performs in a community setting compared with the 2010 definition is unknown. We applied the 2013 criteria to 372 femoral fractures that occurred between January 1, 1996, and June 30, 2009, employing two independent expert physician reviewers. We used radiographs that had been categorized in a previous study on the incidence of atypical fractures using 2010 ASMBR criteria (BEAK1). In this follow-up study (BEAK2), the same reviewers reviewed all previously identified femoral shaft fractures (FSFs) (n = 197) and distal femur fractures (n = 131) plus a 15% random sample of intertrochanteric fractures (n = 49). After initial review, agreement between the two reviewers ranged from 63% to 100% for specific features, and 84% of radiographs received the same overall classification. Fewer fractures met the 2013 compared with 2010 ASMBR case definition of AFFs (37 per 2013 criteria versus 74 per 2010 criteria). Forty-three radiographs (58%) categorized as AFFs according to 2010 criteria were no longer AFFs when 2013 criteria were applied, and an additional 12 non-atypical FSFs according to 2010 criteria were reclassified as AFFs according to 2013 criteria. The major cause of AFF reclassification was the change in the definition of transverse configuration. The modification of the comminution, non-traumatic, and periosteal/endosteal thickness criteria resulted in the reclassification of non-atypical FSFs to AFFs. Incidence rate of AFFs according to 2013 ASBMR criteria was lower overall during the 13 years of observation than when the 2010 ASBMR criteria were applied, although we saw a slight increase starting in 2000. As in BEAK1, we found that those with AFFs were younger, more often female, and had a higher exposure rate to bisphosphonates than those with non-atypical FSFs. As we continue to unravel the demographics of those who suffer from AFFs, our study adds information about how the change in criteria influences epidemiological work. © 2017 American Society for Bone and Mineral Research.

Lower Total Knee Arthroplasty Revision Risk Associated With Bisphosphonate Use, Even in Patients With Normal Bone Density.

BACKGROUND: Bisphosphonates (BPs) are associated with lower total knee arthroplasty (TKA) revision risk, but the effect of bone mineral density has not been evaluated. METHODS: A cohort of 34,116 primary TKA patients was evaluated with revision surgery and periprosthetic fractures as end points. BP usage was the exposure of interest. Bone quality (normal, osteopenia, and osteoporosis) and patient age (<65 vs ≥65 years) were evaluated as effect modifiers of risk estimates. RESULTS: Of the patients, 19.6% were BP users. In BP users, 0.5% underwent an aseptic revision; and 0.6%, a periprosthetic fracture. In non-BP users, 1.6% underwent aseptic revision; and 0.1%, a periprosthetic fracture. CONCLUSION: Bisphosphonate use was associated with lower risk of revision in all bone quality categories in those older than 65 years. The risk of periprosthetic fractures was higher for patients on BP.

Association of Bisphosphonate Use and Risk of Revision After THA: Outcomes From a US Total Joint Replacement Registry.

BACKGROUND: Total hip arthroplasty (THA) is often performed in patients who are older and may take bisphosphonates to treat a variety of conditions, most commonly osteoporosis. However, the clinical effects of bisphosphonate use on patients who have undergone THA are not well described. QUESTIONS/PURPOSES: (1) Is bisphosphonate use in patients with osteoarthritis undergoing primary THA associated with a change in the risk of all-cause revision, aseptic revision, or periprosthetic fracture compared with patients not treated with bisphosphonates? (2) Does the risk of bisphosphonate use and revision and periprosthetic fracture vary by patient bone mineral density and age? METHODS: A retrospective cohort study of 12,878 THA recipients for the diagnosis of osteoarthritis was conducted; 17.8% of patients were bisphosphonate users. Data sources for this study included a joint replacement registry (93% voluntary participation) and electronic health records and an osteoporosis screening database with complete capture of cases as part of the Kaiser Permanente integrated healthcare system. The endpoints for this study were revision surgery for any cause, aseptic revision, and periprosthetic fracture. The exposure of interest was bisphosphonate use; patients were considered users if prescriptions were continuously refilled for a period equal to or longer than 6 months. Bone quality (based on dual-energy x-ray absorptiometery ordered based on the National Osteoporosis Foundation's clinical guidelines taken within 5 years of the THA) and patient age (< 65 versus ≥ 65 years) were evaluated as effect modifiers. Patient, surgeon, and hospital factors were evaluated as confounders. Cox proportional hazards models were used. Hazard ratios (HRs) and 95% confidence intervals (CIs) were determined. RESULTS: Age- and sex-adjusted risks of all-cause (HR, 0.50; 95% CI, 0.33-0.74; p < 0.001) and aseptic revision (HR, 0.53; 95% CI, 0.34-0.81; p = 0.004) was lower in bisphosphonate users than in nonusers. The adjusted risk of periprosthetic fractures in patients on bisphosphonates was higher than in patients not on bisphosphonates (HR, 1.92; 95% CI, 1.13-3.27; p = 0.016). Lower risks of all-cause revision and aseptic revision were observed in patients with osteopenia (HR, 0.49; 95% CI, 0.29-0.84; and HR, 0.53; 95% CI, 0.29-0.99, respectively) and osteoporosis (HR, 0.22; 95% CI, 0.08-0.62; and HR, 0.33; 95% CI, 0.11-0.99, respectively). CONCLUSIONS: Patients considered bisphosphonate users who underwent THA had a lower risk for revision surgery. Bisphosphonate use was associated with a higher risk of periprosthetic fractures in younger patients with normal bone quantity. Evaluation of bone quality and bisphosphonate use for the diagnosis of osteoporosis is encouraged in patients with osteoarthritis who are candidates for primary THA. Further research is required to determine the optimal duration of therapy because long-term bisphosphonate use has been associated with atypical femur fractures. LEVEL OF EVIDENCE: Level III, therapeutic study.

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.

Osteoporosis management program decreases incidence of hip fracture in patients with prostate cancer receiving androgen deprivation therapy.

OBJECTIVE: To evaluate the incidence of hip fracture in men with prostate cancer receiving androgen deprivation therapy (ADT). MATERIALS AND METHODS: One of the detrimental side effects of ADT for prostate cancer is osteoporosis. Through an osteoporosis prevention program implemented in our healthcare system, the patients at risk undergo dual x-ray absorptiometry scans and receive treatment if the T-score indicates bone loss. We evaluated the incidence of hip fracture in men with prostate cancer who were receiving ADT through a retrospective, cohort study conducted within a managed care organization. The participants were all men newly diagnosed with prostate cancer from January 2003 to December 2007 receiving leuprolide injections. Patients who had had a dual x-ray absorptiometry scan beginning 3 months before the index date through the end of study were included in the intervention group; all others were included in the comparison group. The main outcome of interest was a hip fracture occurring after the index date, excluding cancer pathologic fractures, traumatic fractures, and fractures associated with epilepsy. RESULTS: A total of 1071 patients were in the intervention group, and 411 were in the comparison group. In the intervention group, 18 hip fractures occurred compared with 17 in the comparison group. The incidence rate of hip fractures per 1000 person-years was 5.1 (95% confidence interval 3.0-8.0) in the intervention group and 18.1 (95% confidence interval 10.5-29.0) in the comparison group. CONCLUSION: The incidence rate of hip fracture in this population was reduced >70% with enrollment in an osteoporosis management system, avoiding this morbid complication of ADT.

Incidence of atypical nontraumatic diaphyseal fractures of the femur.

Bisphosphonates reduce the rate of osteoporotic fractures in clinical trials and community practice. "Atypical" nontraumatic fractures of the diaphyseal (subtrochanteric or shaft) part of the femur have been observed in patients taking bisphosphonates. We calculated the incidence of these fractures within a defined population and examined the incidence rates according to duration of bisphosphonate use. We identified all femur fractures from January 1, 2007 until December 31, 2011 in 1,835,116 patients older than 45 years who were enrolled in the Healthy Bones Program at Kaiser Southern California, an integrated health care provider. Potential atypical fractures were identified by diagnostic or procedure codes and adjudicated by examination of radiographs. Bisphosphonate exposure was derived from internal pharmacy records. The results showed that 142 patients had atypical fractures; of these, 128 had bisphosphonate exposure. There was no significant correlation between duration of use (5.5 ± 3.4 years) and age (69.3 ± 8.6 years) or bone density (T-score -2.1 ± 1.0). There were 188,814 patients who had used bisphosphonates. The age-adjusted incidence rates for an atypical fracture were 1.78/100,000/year (95% confidence interval [CI], 1.5-2.0) with exposure from 0.1 to 1.9 years, and increased to 113.1/100,000/year (95% CI, 69.3-156.8) with exposure from 8 to 9.9 years. We conclude that the incidence of atypical fractures of the femur increases with longer duration of bisphosphonate use. The rate is much lower than the expected rate of devastating hip fractures in elderly osteoporotic patients. Patients at risk for osteoporotic fractures should not be discouraged from initiating bisphosphonates, because clinical trials have documented that these medicines can substantially reduce the incidence of typical hip fractures. The increased risk of atypical fractures should be taken into consideration when continuing bisphosphonates beyond 5 years.

Risk of fractures requiring hospitalization after an initial prescription for zolpidem, alprazolam, lorazepam, or diazepam in older adults.

OBJECTIVES: To determine whether zolpidem is a safer alternative to benzodiazepines. DESIGN: Retrospective cohort study. SETTING: Community based. PARTICIPANTS: Health maintenance organization members with an initial prescription for zolpidem (n = 43,343), alprazolam (n = 103,790), lorazepam (n = 150,858), or diazepam (n = 93,618). MEASUREMENTS: Zolpidem and benzodiazepine prescriptions were identified from pharmacy databases. Rates of nonvertebral fractures and hip fractures requiring hospitalization were compared before and after an initial prescription for each treatment, adjusting for confounders using doubly robust estimation. RESULTS: In patients aged 65 and older, the rates of nonvertebral fractures and dislocations were similar in the pre- treatment intervals. The rate ratios (RRs) for the 90-day posttreatment interval relative to the pretreatment interval were 2.55 (95% confidence interval (CI) = 1.78-3.65; P < .001) for zolpidem, 1.14 (95% CI = 0.80-1.64; P = .42) for alprazolam, 1.53 (95% CI = 1.23-1.91; P < .001) for lorazepam, and 1.97 (95% CI = 1.22-3.18; P = .01) for diazepam. The ratio of RRs (RRR)-the RR in the posttreatment period adjusted for the corresponding RR in the pretreatment period-were 2.23 (95% CI = 1.36-3.66; P = .006) for zolpidem relative to alprazolam, 1.68 (95% CI = 1.12-2.53; P = .02) for zolpidem relative to lorazepam, and 1.29 (95% CI = 0.72-2.30; P = .32) for zolpidem relative to diazepam. The RRs decreased with time from the initial prescription (trend P < .001), as would be expected if the association is causal. CONCLUSION: In older adults, the risk of injury with zolpidem exceeded that with alprazolam and lorazepam and was similar to that with diazepam. If the associations are causal, then the high incidence of these fractures implies that these treatment induce a substantial number of fractures and consequential costs. Further study of the association is imperative.

Hip fracture in postmenopausal women after cessation of hormone therapy: results from a prospective study in a large health management organization.

OBJECTIVE: Millions of women in the United States and across the globe abruptly discontinued postmenopausal hormone therapy (HT) after the initial Women's Health Initiative trial publication. Few data describing the effects of HT cessation on hip fracture incidence in the general population are available. We evaluated the impact of HT cessation on hip fracture incidence in a large cohort from the Southern California Kaiser Permanente health management organization. METHODS: In this longitudinal observational study, 80,955 postmenopausal women using HT as of July 2002 were followed up through December 2008. Data on HT use after July 2002, antiosteoporotic medication use, and occurrence of hip fracture were collected from the electronic medical record system. Bone mineral density (BMD) was assessed in 54,209 women once during the study period using the dual-energy x-ray absorptiometry scan. RESULTS: After 6.5 years of follow-up, age- and race-adjusted Cox proportional hazard models showed that women who discontinued HT were at 55% greater risk of hip fracture compared with those who continued using HT (hazard ratio, 1.55; 95% CI, 1.36-1.77). Hip fracture risk increased as early as 2 years after cessation of HT (hazard ratio, 1.52; 95% CI, 1.26-1.84), and the risk incrementally increased with longer duration of cessation (P for trend < 0.0001). Longer duration of HT cessation was linearly correlated with lower BMD (ß estimate [SE]) = -0.13 [0.003] T-score SD unit per year of HT cessation; P < 0.0001). CONCLUSIONS: Women who discontinued postmenopausal HT had significantly increased risk of hip fracture and lower BMD compared with women who continued taking HT. The protective association of HT with hip fracture disappeared within 2 years of cessation of HT. These results have public health implications with regard to morbidity and mortality from hip fracture.

Outcomes of an osteoporosis disease-management program managed by nurse practitioners.

PURPOSE: To detail the outcomes of an osteoporosis disease-management program where nurse practitioners (NPs) have taken a leadership role in screening, diagnosing, and treating patients at risk for osteoporosis. DATA SOURCES: An electronic medical record (EMR) was used to collect demographic, pharmacy, dual x-ray absorptiometry (DXA) scan, and fracture data from a population of over 625,000 patients with one or more risk factors for osteoporosis. Monthly reports were generated and distributed to the NPs to assist them in identifying patients that required screening or treatment. CONCLUSIONS: Over a 6-year period there was a 263% increase in the number of screening DXA scans done each year, a 153% increase in the number of patients on anti-osteoporosis medications each year, and a 38.1% decrease in the expected hip fracture rate. IMPLICATIONS FOR PRACTICE: NPs play an important leadership role in managing osteoporosis within a large health maintenance organization. The screening and interventions used can be applied by any NP in any practice setting on an individual basis to reduce hip fracture rates in the United States.