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 age ≥ 65 who had a hip-containing computed tomography scan during care between 2005-2018, 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 bone mineral density 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 versus not-treated patients were calculated by logistic regression; adjustments included age, BMD T-score, a BMD-treatment interaction, body mass index, race/ethnicity, and seven baseline clinical risk factors. At two-year follow-up, 33.9% of the women (750/2211 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 versus 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 is 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 computed tomography (CT or CAT) scan as part of their medical care for any reason, we measured bone mineral density 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.

Bone mineral density in women newly diagnosed with breast cancer: a prospective cohort study.

Estrogen may have opposing effects on health, namely increasing the risk of breast cancer and improving bone health by increasing bone mineral density (BMD). The objective of this study was to compare dual-energy X-ray absorptiometry (DXA) BMD between women newly diagnosed with breast cancer and matched controls without breast cancer. Women newly diagnosed with breast cancer treated between April 2012 and October 2017 were prospectively enrolled. A control group was established of women with negative mammography or breast ultrasound, matched 1:1 by age, body mass index, parity, and the use of hormone replacement therapy. All those included had DXA BMD, and lab assessments at enrollment. Of 869 women with newly diagnosed breast cancer, 464 signed informed consent. Of the 344 who completed the study protocol, 284 were matched to controls. Overall, the mean age was 58 years. Compared to the control group, for the breast cancer group, the mean vitamin D level was lower (48.9 ± 19.0 vs. 53.8 ± 28.8 nmol/L, p = 0.022); and mean values were higher of total hip BMD (0.95 ± 0.14 vs. 0.92 ± 0.12 g/cm2, p = 0.002), T score (-0.38 ± 1.17 vs. -0.68 ± 0.98, p = 0.002), and Z score (0.32 ± 1.09 vs. 0.01 ± 0.88, p < 0.001). Among the women with breast cancer, no correlations were found of baseline BMD with tumor size or grade, nodal involvement, or breast cancer stage. We concluded that women with newly diagnosed breast cancer tend to have higher BMD than women with similar characteristics but without breast cancer. This implies that BMD might be considered a biomarker for breast cancer risk.

Bisphosphonate treatment and the risk of atypical femoral fracture among patients participating in a Fracture Liaison Service of a tertiary medical center.

Bisphosphonates are common treatment for osteoporosis. Among patients admitted with hip fracture, atypical femoral fractures (AFF) were more prevalent in those who were treated with Bisphosphonates for five or more years. Five years of Bisphosphonates treatment may signify an increased risk for AFF, though the absolute risk remains very low. PURPOSE: Atypical femoral fractures (AFF) are a rare complication of bisphosphonate (BP) treatment. We evaluated the correlation between BP exposure and AFF risk among hip fracture patients. METHODS: This retrospective nested case-control study included patients over age 50 years, operated for osteoporotic hip fracture between July 2014 and November 2018, who attended our Fracture Liaison Service. We classified fracture radiographs and compared demographic, clinical, biochemical, and drug purchase data between patients with AFF and those with typical osteoporotic hip fracture (controls). To correct for the younger age of patients with AFF, we matched each case (AFF) with three controls according to age ([Formula: see text] 1 year) and sex and performed a conditional logistic regression model. RESULTS: Of 989 patients, 31 (3%) had AFF. Patients with AFF were younger than those with inter-trochanteric fractures (mean ± SD: 72.3 ± 10.3 vs. 80.2 ± 9.6 years, p < 0.001). Following matching, the mean Charlson's Comorbidity Index (CCI) was lower in the AFF than in the control group (2.9 ± 3.7 vs. 4.7 ± 4.2; p = 0.030) and a higher proportion of them were treated with BP for 5 years or more (58.1 vs. 16.0%; p < 0.001). Among patients admitted with hip fracture who were treated with BP for 5 years or more, the odds ratio of this fracture being atypical was significantly higher compared with no BP treatment (21.7; 95% CI-4.1-113.9). CONCLUSIONS: Patients with AFF compared to typical hip fractures showed better baseline medical conditions irrespective of their younger age. Five years of BP treatment may be associated with an increased risk for AFF, though the absolute risk remains very low.

Estimation of Long-Term Efficacy of Denosumab Treatment in Postmenopausal Women With Osteoporosis: A FRAX- and Virtual Twin-Based Post Hoc Analysis From the FREEDOM and FREEDOM Extension Trials.

The 3-year placebo-controlled FREEDOM (Fracture REduction Evaluation of Denosumab in Osteoporosis Every 6 Months) trial established the antifracture efficacy of denosumab in postmenopausal women with osteoporosis. The 7-year open-label extension demonstrated that denosumab treatment for up to 10 years was associated with low rates of adverse events and low fracture incidence. The extension lacked a long-term control group, thus limiting the ability to fully evaluate long-term efficacy. This analysis provides a quantitative estimate of the long-term antifracture efficacy of denosumab based on two approaches: comparison with FRAX®- (Fracture Risk Assessment Tool-) and virtual twin-estimated 10-year fracture rates. Subjects who were randomized to denosumab in the FREEDOM trial, continued into the Extension study, completed the 10-year visit, and missed ≤1 dose in the FREEDOM trial and ≤1 dose in the Extension (n = 1278) were included in the analysis. The 10-year observed cumulative incidence of major osteoporotic fracture (MOF) and hip fractures was compared with the 10-year fracture probability predicted at baseline by FRAX, a computer-based fracture risk algorithm, and with that estimated for a hypothetical cohort of 10-year placebo controls (virtual twins). The observed 10-year fracture incidence was lower than the 10-year probability predicted by FRAX for both MOF (10.75% [95% CI, 9.05 to 12.46] versus 15.63% [95% CI, 15.08 to 16.18], respectively), and hip fractures (1.17% [95% CI, 0.58 to 1.76] versus 5.62% [95% CI, 5.28 to 5.97], respectively). The observed fracture incidence was also lower than the fracture rate estimated in a hypothetical cohort of 10-year placebo controls for MOF (23.13% [95% CI, 17.76 to 28.87]; relative risk 0.49 [95% CI, 0.36 to 0.64]). These data support the long-term efficacy of denosumab in reducing MOF and hip fractures in postmenopausal women with osteoporosis. © 2020 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.

Favorable skeletal benefit/risk of long-term denosumab therapy: A virtual-twin analysis of fractures prevented relative to skeletal safety events observed.

Antiresorptive therapies reduce fracture risk; however, long-term bone turnover inhibition may raise concerns about rare, but serious, skeletal adverse events-atypical femoral fracture (AFF) and osteonecrosis of the jaw (ONJ). Denosumab, a fully human monoclonal antibody against RANKL, has demonstrated sustained low vertebral and nonvertebral fracture rates with low skeletal adverse event rates in the 3-year FREEDOM trial and its 7-year Extension (in which all subjects received open-label denosumab). In this analysis, we aimed to estimate fractures prevented relative to skeletal adverse events observed with 10 years of denosumab therapy. We modeled a hypothetical placebo group using the virtual-twin method, thereby allowing calculation of fractures prevented with denosumab treatment (relative to the virtual-placebo group) in the context of AFF or ONJ events observed in the long-term denosumab group. Estimated virtual-placebo and observed long-term denosumab exposure-adjusted fracture rates per 100,000 subject-years were calculated for fractures classified as clinical (3180 and 1777, respectively), major osteoporotic (2699 and 1525), vertebral (1879 and 901), and nonvertebral (2924 and 1528), and compared with observed AFF and ONJ in the long-term denosumab group (5 and 35 per 100,000 subject-years, respectively). The skeletal benefit/risk ratio (fractures prevented per adverse event observed) for clinical fractures was 281 (AFF) and 40 (ONJ). Based on this model, denosumab treatment for up to 10 years has a favorable skeletal benefit/risk profile when comparing fractures prevented per skeletal adverse event observed. Clinical trial registration: NCT00089791, NCT00523341.

Osteoporosis and Hip Fracture Risk From Routine Computed Tomography Scans: The Fracture, Osteoporosis, and CT Utilization Study (FOCUS).

Methods now exist for analyzing previously taken clinical computed tomography (CT) scans to measure a dual-energy X-ray absorptiometry (DXA)-equivalent bone mineral density (BMD) at the hip and a finite element analysis-derived femoral strength. We assessed the efficacy of this "biomechanical CT" (BCT) approach for identifying patients at high risk of incident hip fracture in a large clinical setting. Using a case-cohort design sampled from 111,694 women and men aged 65 or older who had a prior hip CT scan, a DXA within 3 years of the CT, and no prior hip fracture, we compared those with subsequent hip fracture (n = 1959) with randomly selected sex-stratified controls (n = 1979) and analyzed their CT scans blinded to all other data. We found that the age-, race-, and body mass index (BMI)-adjusted hazard ratio (HR; per standard deviation) for femoral strength was significant before (women: HR = 2.8, 95% confidence interval [CI] 2.2-3.5; men: 2.8, 2.1-3.7) and after adjusting also for the (lowest) hip BMD T-score by BCT (women: 2.1, 1.4-3.2; men: 2.7, 1.6-4.6). The hazard ratio for the hip BMD T-score was similar between BCT and DXA for both sexes (women: 2.1, 1.8-2.5 BCT versus 2.1, 1.7-2.5 DXA; men: 2.8, 2.1-3.8 BCT versus 2.5, 2.0-3.2 DXA) and was higher than for the (lowest) spine/hip BMD T-score by DXA (women: 1.6, 1.4-1.9; men: 2.1, 1.6-2.7). Compared with the latter as a clinical-practice reference and using both femoral strength and the hip BMD T-score from BCT, sensitivity for predicting hip fracture was higher for BCT (women: 0.66 versus 0.59; men: 0.56 versus 0.48), with comparable respective specificity (women: 0.66 versus 0.67; men: 0.76 versus 0.78). We conclude that BCT analysis of previously acquired routine abdominal or pelvic CT scans is at least as effective as DXA testing for identifying patients at high risk of hip fracture. © 2018 American Society for Bone and Mineral Research.

Evaluation of a Multimodal, Direct-to-Patient Educational Intervention Targeting Barriers to Osteoporosis Care: A Randomized Clinical Trial.

Osteoporosis treatment rates are declining, even among those with past fractures. Novel, low-cost approaches are needed to improve osteoporosis care. We conducted a parallel group, controlled, randomized clinical trial evaluating a behavioral intervention for improving osteoporosis medication use. A total of 2684 women with self-reported fracture history after age 45 years not using osteoporosis therapy from US Global Longitudinal Study of Osteoporosis in Women (GLOW) sites were randomized 1:1 to receive a multimodal, tailored, direct-to-patient, video intervention versus usual care. The primary study outcome was self-report of osteoporosis medication use at 6 months. Other outcomes included calcium and vitamin D supplementation, bone mineral density (BMD) testing, readiness for behavioral change, and barriers to treatment. In intent-to-treat analyses, there were no significant differences between groups (intervention versus control) in osteoporosis medication use (11.7% versus 11.4%, p = 0.8), calcium supplementation (31.8% versus 32.6%, p = 0.7), vitamin D intake (41.3% versus 41.9%, p = 0.8), or BMD testing (61.8% versus 57.1%, p = 0.2). In the intervention group, fewer women were in the precontemplative stage of behavior change, more women reported seeing their primary care provider, had concerns regarding osteonecrosis of the jaw, and difficulty in taking/remembering to take osteoporosis medications. We found differences in BMD testing among the subgroup of women with no prior osteoporosis treatment, those who provided contact information, and those with no past BMD testing. In per protocol analyses, women with appreciable exposure to the online intervention (n = 257) were more likely to start nonbisphosphonates (odds ratio [OR] = 2.70; 95% confidence interval [CI] 1.26-5.79) compared with the usual care group. Although our intervention did not increase the use of osteoporosis therapy at 6 months, it increased nonbisphosphonate medication use and BMD testing in select subgroups, shifted participants' readiness for behavior change, and altered perceptions of barriers to osteoporosis treatment. Achieving changes in osteoporosis care using patient activation approaches alone is challenging. © 2018 American Society for Bone and Mineral Research.

A multi-modal intervention for Activating Patients at Risk for Osteoporosis (APROPOS): Rationale, design, and uptake of online study intervention material.

OBJECTIVE: To develop an innovative and effective educational intervention to inform patients about the need for osteoporosis treatment and to determine factors associated with its online uptake. METHODS: Postmenopausal women with a prior fracture and not currently using osteoporosis therapy were eligible to be included in the Activating Patients at Risk for OsteoPOroSis (APROPOS). Four nominal groups with a total of 18 racially/ethnically diverse women identified osteoporosis treatment barriers. We used the Information, Motivation, Behavior Skills conceptual model to develop a direct-to-patient intervention to mitigate potentially modifiable barriers to osteoporosis therapy. The intervention included videos tailored by participants' race/ethnicity and their survey responses: ranked barriers to osteoporosis treatment, deduced barriers to treatment, readiness to behavior change, and osteoporosis treatment history. Videos consisted of "storytelling" narratives, based on osteoporosis patient experiences and portrayed by actresses of patient-identified race/ethnicity. We also delivered personalized brief phone calls followed by an interactive voice-response phone messages aimed to promote uptake of the videos. RESULTS: To address the factors associated with online intervention uptake, we focused on participants assigned to the intervention arm (n = 1342). These participants were 92.9% Caucasian, with a mean (SD) age 74.9 (8.0) years and the majority (77.7%) had some college education. Preference for natural treatments was the barrier ranked #1 by most (n = 130; 27%), while concern about osteonecrosis of the jaw was the most frequently reported barrier (at any level; n = 322; 67%). Overall, 28.1% (n = 377) of participants in the intervention group accessed the videos online. After adjusting for relevant covariates, the participants who provided an email address had 6.07 (95% CI 4.53-8.14) higher adjusted odds of accessing their online videos compared to those who did not. CONCLUSION: We developed and implemented a novel tailored multi-modal intervention to improve initiation of osteoporosis therapy. An email address provided on the survey was the most important factor independently associated with accessing the intervention online. The design and uptake of this intervention may have implications for future studies in osteoporosis or other chronic diseases.

Increase in Fracture Risk Following Unintentional Weight Loss in Postmenopausal Women: The Global Longitudinal Study of Osteoporosis in Women.

Increased fracture risk has been associated with weight loss in postmenopausal women, but the time course over which this occurs has not been established. The aim of this study was to examine the effects of unintentional weight loss of ≥10 lb (4.5 kg) in postmenopausal women on fracture risk at multiple sites up to 5 years after weight loss. Using data from the Global Longitudinal Study of Osteoporosis in Women (GLOW), we analyzed the relationships between self-reported unintentional weight loss of ≥10 lb at baseline, year 2, or year 3 and incident clinical fracture in the years after weight loss. Complete data were available in 40,179 women (mean age ± SD 68 ± 8.3 years). Five-year cumulative fracture rate was estimated using the Kaplan-Meier method, and adjusted hazard ratios for weight loss as a time-varying covariate were calculated from Cox multiple regression models. Unintentional weight loss at baseline was associated with a significantly increased risk of fracture of the clavicle, wrist, spine, rib, hip, and pelvis for up to 5 years after weight loss. Adjusted hazard ratios showed a significant association between unintentional weight loss and fracture of the hip, spine, and clavicle within 1 year of weight loss, and these associations were still present at 5 years. These findings demonstrate increased fracture risk at several sites after unintentional weight loss in postmenopausal women. This increase is found as early as 1 year after weight loss, emphasizing the need for prompt fracture risk assessment and appropriate management to reduce fracture risk in this population. © 2016 American Society for Bone and Mineral Research.

ZNF687 Mutations in Severe Paget Disease of Bone Associated with Giant Cell Tumor.

Paget disease of bone (PDB) is a skeletal disorder characterized by focal abnormalities of bone remodeling, which result in enlarged and deformed bones in one or more regions of the skeleton. In some cases, the pagetic tissue undergoes neoplastic transformation, resulting in osteosarcoma and, less frequently, in giant cell tumor of bone (GCT). We performed whole-exome sequencing in a large family with 14 PDB-affected members, four of whom developed GCT at multiple pagetic skeletal sites, and we identified the c.2810C>G (p.Pro937Arg) missense mutation in the zinc finger protein 687 gene (ZNF687). The mutation precisely co-segregated with the clinical phenotype in all affected family members. The sequencing of seven unrelated individuals with GCT associated with PDB (GCT/PDB) identified the same mutation in all individuals, unravelling a founder effect. ZNF687 is highly expressed during osteoclastogenesis and osteoblastogenesis and is dramatically upregulated in the tumor tissue of individuals with GCT/PDB. Interestingly, our preliminary findings showed that ZNF687, indicated as a target gene of the NFkB transcription factor by ChIP-seq analysis, is also upregulated in the peripheral blood of PDB-affected individuals with (n = 5) or without (n = 6) mutations in SQSTM1, encouraging additional studies to investigate its potential role as a biomarker of PDB risk.

Development of a molecular test of Paget's disease of bone.

Depending on populations, 15 to 40% of patients have a familial form of Paget's disease of bone (PDB), which is transmitted in an autosomal-dominant mode of inheritance with incomplete penetrance. To date, only SQSTM1 gene mutations have been linked to the disease. Several single nucleotide polymorphisms (SNPs) have been associated with PDB in patient non-carriers of SQSTM1 mutations, but they have minor size effects. The current clinical practice guidelines still recommend to measure total serum alkaline phosphatase (sALP) for PDB screening. However, genetic or bone biomarkers alone may lack sensitivity to detect PDB. Thus, the objective of this study was to develop a molecular test of PDB, combining genetic and bone biomarkers, in order to detect PDB, which is frequently asymptomatic. We genotyped 35 SNPs previously associated with PDB in 305 patients, and 292 healthy controls. In addition, serum levels of 14 bone biomarkers were assayed in 51 patients and 151 healthy controls. Bivariate and multivariate logistic regression models with adjustment for age and sex were fitted to search for a combination of SNPs and/or bone biomarkers that could best detect PDB in patient non-carriers of SQSTM1 mutations. First, a combination of five genetic markers gave rise to the highest area under the ROC curve (AUC) with 95% confidence interval [95% CI] of 0.731 [0.688; 0.773], which allowed us to detect 81.5% of patients with PDB. Second, a combination of two bone biomarkers had an AUC of 0.822 [0.726; 0.918], and was present in 81.5% of patients with PDB. Then, the combination of the five genetic markers and the two bone biomarkers increased the AUC up to 0.892 [0.833; 0.951], and detected 88.5% of patients with PDB. These results suggested that an algorithm integrating first a screen for SQSTM1 gene mutations, followed by either a genetic markers combination or a combined genetic and biochemical markers test in patients non-carrier of any SQSTM1 mutation, may detect the PDB phenotype better than biomarkers already available in the clinical practice.

Association between gastrointestinal events and compliance with osteoporosis therapy.

PURPOSE: The aim of this study was to estimate the rate of gastrointestinal (GI) events, and association between GI events and compliance with osteoporosis therapy among osteoporotic women. METHODS: A retrospective cohort study using a large administrative claims database in the United States from 2001 through 2010 was conducted. We studied women ≥ 55 years old who were continuously enrolled in a health plan for at least 2 years, a baseline year before and a follow-up year after the date of the first prescription of oral bisphosphonate as the first oral osteoporosis treatment. Compliance with osteoporosis therapy was measured using the medication possession ratio (MPR), with compliance defined as MPR ≥ 0.8. Multivariate logistic regression was used to assess the association between occurrence of GI events and compliance with osteoporosis therapy after controlling for demographic and clinical characteristics. RESULTS: A sample consisting of 75,593 women taking at least one oral bisphosphonate with mean (SD) age of 64 (8) years was identified. A total of 21,142 (28%) patients experienced at least one GI event during the follow-up period. Only 31,306 (41%) patients were compliant with osteoporosis therapy. Patients who experienced GI events after initiation of oral bisphosphonates were 29% less likely to adhere to osteoporosis therapy as compared to patients who did not experience GI events (odds ratio [95% CI], 0.71 [0.69-0.74]; P < .001). CONCLUSIONS: Less than half of the patients were compliant with osteoporosis therapy within one year after initiating oral bisphosphonates, and the likelihood of compliance was significantly lower by 29% among women with GI events.

Gastrointestinal events and association with initiation of treatment for osteoporosis.

BACKGROUND: Preexisting gastrointestinal (GI) events may deter the use of pharmacologic treatment in patients diagnosed with osteoporosis (OP). The objective of this study was to examine the association between preexisting GI events and OP pharmacotherapy initiation among women diagnosed with OP. METHODS: The study utilized claims data from a large US managed care database to identify women aged ≥55 years with a diagnosis code for OP (index date) during 2002-2009. Patients with a claim for pharmacologic OP treatment in the 12-month pre-index period (baseline) were excluded. OP treatment initiation in the post-index period was defined as a claim for bisphosphonates (alendronate, ibandronate, risedronate, zoledronic acid), calcitonin, raloxifene, or teriparatide. During the post-index period (up to 12 months), GI events were identified before treatment initiation. A time-dependent Cox regression model was used to investigate the likelihood of initiating any OP treatment. Among patients initiating OP treatment, a discrete choice model was utilized to assess the relationship between post-index GI events and likelihood of initiating with a bisphosphonate versus a non-bisphosphonate. RESULTS: In total, 65,344 patients (mean age 66 years) were included; 23.7% had a GI event post diagnosis and before treatment initiation. Post-index GI events were associated with a 75% lower likelihood of any treatment initiation (hazard ratio 0.25; 95% confidence interval 0.24-0.26). Among treated patients (n=23,311), those with post-index GI events were 39% less likely to receive a bisphosphonate versus a non-bisphosphonate (odds ratio 0.61; 95% confidence interval 0.54-0.68). CONCLUSION: GI events after OP diagnosis were associated with a decreased likelihood of OP treatment initiation and an increased likelihood of treatment initiation with a non-bisphosphonate versus a bisphosphonate.

Undertreatment of osteoporosis and the role of gastrointestinal events among elderly osteoporotic women with Medicare Part D drug coverage.

OBJECTIVES: To examine the rate of osteoporosis (OP) undertreatment and the association between gastrointestinal (GI) events and OP treatment initiation among elderly osteoporotic women with Medicare Part D drug coverage. METHODS: This retrospective cohort study utilized a 20% random sample of Medicare beneficiaries. Included were women ≥66 years old with Medicare Part D drug coverage, newly diagnosed with OP in 2007-2008 (first diagnosis date as the index date), and with no prior OP treatment. GI event was defined as a diagnosis or procedure for a GI condition between OP diagnosis and treatment initiation or at the end of a 12-month follow-up, whichever occurred first. OP treatment initiation was defined as the use of any bisphosphonate (BIS) or non-BIS within 1 year postindex. Logistic regression, adjusted for patient characteristics, was used to model the association between 1) GI events and OP treatment initiation (treated versus nontreated); and 2) GI events and type of initial therapy (BIS versus non-BIS) among treated patients only. RESULTS: A total of 126,188 women met the inclusion criteria: 72.1% did not receive OP medication within 1 year of diagnosis and 27.9% had GI events. Patients with a GI event were 75.7% less likely to start OP treatment (odds ratio [OR]=0.243; P<0.001); among treated patients, patients with a GI event had 11.3% lower odds of starting with BIS versus non-BIS (OR=0.887; P<0.001). CONCLUSION: Among elderly women newly diagnosed with OP, only 28% initiated OP treatment. GI events were associated with a higher likelihood of not being treated and, among treated patients, a lower likelihood of being treated with BIS versus non-BIS.

Gastrointestinal Events Among Patients Initiating Osteoporosis Therapy: A Retrospective Administrative Claims Database Analysis.

PURPOSE: Our purpose was to characterize the occurrence of gastrointestinal (GI) events among women on oral bisphosphonate therapy. METHODS: This was a retrospective cohort study that used a United States (US) claims database. The study period was from January 1, 2000, to December 31, 2011. The index date was the date of the first oral bisphosphonate (alendronate, ibandronate, or risedronate) prescription and occurred between January 1, 2001, and December 31, 2010. The pre- and post-index periods were the 1-year periods before and after the index date, respectively. The analysis included women with osteoporosis aged ≥55 years at the index date who were naive to all osteoporosis treatments before the index date and were continuously enrolled in the health plan for at least 1 year before and 1 year after the index date. Patients with a diagnosis of malignant neoplasm during the pre- or post-index periods or a diagnosis of Paget disease anytime in the claims history were excluded. The occurrence of GI events (defined as esophagitis; gastroesophageal reflux disease; ulcer, stricture, perforation, or hemorrhage of the esophagus; gastric, duodenal, or peptic ulcer; acute gastritis; duodenitis; GI hemorrhage; nausea/vomiting; or dysphagia) was assessed during the pre-index period and at 3, 6, and 12 months in the post-index period. The rate of GI events was defined as the percentage of patients having at least 1 GI event in each analysis period (ie, pre-index and post-index periods). GI events in the post-index period were also stratified by the presence of GI events in the pre-index period. FINDINGS: A total of 75,593 women were included in the analysis. The average age at the index date was 64.4 years. Gastroprotective agents were used by 17.9% of patients. Approximately one fourth of patients (26.6%; n = 20,073) had ≥1 GI events in the pre-index period. Approximately the same proportion of patients (28.0%; n = 21,142) experienced GI events in the post-index period. The cumulative rate of GI events during the post-index period was higher among patients who had GI events in the pre-index period (51.2%) than among patients without a GI event in the pre-index period (19.6%). IMPLICATIONS: Among women with osteoporosis enrolled in a US commercial plan, GI events were common regardless of bisphosphonate use. Approximately one fourth of US women on bisphosphonate therapy experienced GI events within the year after initiation of therapy, and one half of US women with a previous GI event had another event while taking bisphosphonates.

Cost and consequences of noncompliance with osteoporosis treatment among women initiating therapy.

OBJECTIVE: The objective was to evaluate compliance with osteoporosis (OP) treatments and determine the fracture and healthcare burden associated with noncompliance. METHODS: This retrospective analysis of a US claims database identified women initiating an OP medication from 1 January 2002 to 30 June 2009. Patients were ≥55 years and had ≥1 pharmacy claim for a bisphosphonate or non-bisphosphonate (raloxifene, calcitonin, teriparatide); the index date was the first pharmacy claim. There were three study periods: baseline (12 months pre-index); compliance period (0-12 months post-index); and follow-up period (12-24 months post-index). Medication possession ratio (MPR) was calculated during the compliance period to differentiate two cohorts: compliant (MPR ≥ 80%) and noncompliant (MPR < 80%). Outcomes during follow-up were modeled by logistic regression (presence of fracture), Poisson regression (healthcare utilization incidence rate) and gamma regression (healthcare costs), all adjusted for patient demographic and clinical characteristics. RESULTS: Overall, 685,505 women initiating OP therapy were identified and 57,913 (8.4%) met the inclusion criteria: only 23,430 (40.5%) were compliant and 34,483 (59.5%) were noncompliant. Mean age was 64 years. Noncompliance was associated with a 20% higher risk of any fracture (odds ratio: 1.20, 95% CI = 1.07-1.35), a higher incidence rate ratio (IRR) for inpatient utilization (IRR: 1.26, 95% CI = 1.19-1.34) and a lower rate of outpatient utilization (IRR: 0.97, 95% CI = 0.95-0.98). Noncompliant patients had 13% higher medical costs (cost ratio: 1.13, 95% CI = 1.06-1.21) than compliant patients. LIMITATIONS: Inclusion in this study required 36 months of continuous healthcare coverage. Thus, the results are primarily applicable to a stable, managed care population and may not be generalizable to other populations. CONCLUSION: Noncompliance with OP therapy was associated with a higher risk of fracture, higher all-cause medical costs and a higher frequency of inpatient service utilization. Additional research is needed to identify barriers to compliance with OP therapy.