Subsequent Nonvertebral Fractures Research Articles

Romosozumab in patients who experienced an on-study fracture: post hoc analyses of the FRAME and ARCH phase 3 trials

SummaryPost hoc analysis of FRAME and ARCH revealed that on-study nonvertebral and vertebral fractures by Month 12 were less common in women initially treated with romosozumab versus placebo or alendronate. Recurrent fracture risk was also lower in romosozumab‑treated patients, and there were no fracture‑related complications. Results support continuing romosozumab treatment post‑fracture.PurposePost hoc analysis evaluating efficacy and safety of romosozumab, administered in the immediate post‑fracture period, in the FRAME and ARCH phase 3 trials.MethodsIn FRAME (NCT01575834) and ARCH (NCT01631214), postmenopausal women with osteoporosis were randomized 1:1 to romosozumab 210 mg monthly or comparator (FRAME, placebo; ARCH, alendronate 70 mg weekly) for 12 months, followed by antiresorptive therapy (FRAME, denosumab; ARCH, alendronate). In patients who experienced on-study nonvertebral or new/worsening vertebral fracture by Month 12, we report the following: fracture and treatment‑emergent adverse event (TEAE) incidence through 36 months, bone mineral density changes (BMD), and romosozumab timing. Due to the sample sizes employed, meaningful statistical comparisons between treatments were not possible.ResultsIncidence of on-study nonvertebral and vertebral fractures by Month 12 was numerically lower in romosozumab- versus comparator-treated patients (FRAME, 1.6% and 0.5% versus 2.1% and 1.6%; ARCH, 3.4% and 3.3% versus 4.6% and 4.9%, respectively). In those who experienced on-study nonvertebral fracture by Month 12, recurrent nonvertebral and subsequent vertebral fracture incidences were numerically lower in patients initially treated with romosozumab versus comparator (FRAME, 3.6% [2/56] and 1.8% [1/56] versus 9.2% [7/76] and 3.9% [3/76]; ARCH, 10.0% [7/70] and 5.7% [4/70] versus 12.6% [12/95] and 8.4% [8/95], respectively). Among those with on-study vertebral fracture by Month 12, recurrent vertebral and subsequent nonvertebral fracture incidences were numerically lower with romosozumab versus comparator (FRAME, 0.0% [0/17] and 0.0% [0/17] versus 11.9% [7/59] and 8.5% [5/59]; ARCH, 9.0% [6/67] and 7.5% [5/67] versus 15.0% [15/100] and 16.0% [16/100], respectively). In patients with fracture by Month 12, no fracture‑related complications were reported in romosozumab-treated patients. BMD gains were numerically greater with romosozumab than comparators.ConclusionData suggest support for the efficacy and safety of continuing romosozumab treatment following fracture.Trial registrationsNCT01575834; NCT01631214.

Association of Osteoporosis Medication Use After Hip Fracture With Prevention of Subsequent Nonvertebral Fractures

Osteoporosis medication treatment is recommended after hip fracture, yet contemporary estimates of rates of initiation and clinical benefit in the patient population receiving routine care are not well documented. To report osteoporosis treatment initiation rates between January 1, 2004, and September 30, 2015, and to estimate the risk reduction in subsequent nonvertebral fractures associated with treatment initiation in patients with hip fracture. In this cohort study, data from a commercial insurance claims database from the United States were analyzed. Patients 50 years and older who had a hip fracture and were not receiving treatment with osteoporosis medications before their fracture were included. Prescription dispensing of an osteoporosis medication within 180 days of a hip fracture hospitalization. Each initiation episode was matched with 10 nonuse episodes on person-time after the index hip fracture event to preclude immortal time bias and followed up for the outcome of nonvertebral fracture until change in exposure or a censoring event. An instrumental variable analysis using 2-stage residual inclusion method was conducted using calendar year, specialist access, geographical variation in prescribing patterns, and hospital preference. Among 97 169 patients with a hip fracture identified, the mean (SD) age was 80.2 (10.8) years, and 64 164 (66.0%) were women. A continuous decline over the study years was observed in osteoporosis medication initiation rates from 9.8% (95% CI, 9.0%-10.6%) in 2004 to 3.3% (95% CI, 2.9%-3.8%) in 2015. In the effectiveness analyses, the hospital preference instrumental variable had a stronger association with treatment (pseudo R2 = 0.20) than the other 3 instrumental variables (specialist access: pseudo R2 = 0.04; calendar year: pseudo R2 = 0.05; and geographic variation: pseudo R2 = 0.07). Instrumental variable analysis with hospital preference suggested a rate difference of 4.2 events (95% CI, 1.1-7.3) per 100 person-years in subsequent fractures associated with osteoporosis treatment initiation compared with nonuse in an additive hazard model. Low rates of osteoporosis treatment initiation after a hip fracture in recent years were observed. Clinically meaningful reduction in subsequent nonvertebral fracture rates associated with treatment suggests that improving prescriber adherence to guidelines and patient adherence to prescribed regimens may result in notable public health benefit.

Determinants of short term fracture risk in patients with a recent history of low-trauma non-vertebral fracture

Low-trauma fractures tend to cluster in time, and subsequent fractures have a role in increased morbidity and mortality in osteoporotic patients. The aim of this study was to identify the risk factors of short-term subsequent non-vertebral fracture (NVF).Patients were included from the Fracture Liaison Service (FLS) which provides assessment for osteoporosis to all in-hospital patients admitted for a low-trauma NVF in the Orthopaedics department. Location and date of occurrence of previous fractures, risk factors for osteoporosis and falls were collected. Bone mineral density was measured at the lumbar spine and total hip; presence of vertebral fractures was evaluated using vertebral fracture assessment (VFA).Nine hundred and fifty patients were included (84% women; 75±12years), with a mean T-score at the femoral neck of −2.3±1.0. Four hundred and sixty eight (49%) patients were in the FLS because of a hip fracture. Using multivariable analysis, the risk of being in the FLS with a previous fracture ≤3years before was associated with: history of fall in the year before the admission (OR=2.75, CI 95% 1.55–4.93), history of severe low-trauma NVF (OR=2.54; CI 95% 1.45–4.52), and BMI lower than 20kg/m2 (OR=2.45, CI 95% 1.25–4.87); age older than 78years-old was protective to the risk of re-fracture (OR=0.44, CI 95% 0.24–0.80).Some risk factors (age, history of fall and of previous severe non-vertebral fracture) can help in the selection of patients at high risk of refracture, who should receive the highest priority for a treatment.

Fracture Liaison Service: Impact on Subsequent Nonvertebral Fracture Incidence and Mortality

A fracture liaison service model of care is widely recommended and applied, but data on its effectiveness are scarce. Therefore, the risk of subsequent nonvertebral fractures and mortality within two years after a nonvertebral fracture was analyzed in patients who presented to a hospital with a fracture liaison service and a hospital without a fracture liaison service. In 2005 to 2006, all consecutive patients with an age of fifty years or older presenting with a nonvertebral fracture were included. In the group that presented to a hospital without a fracture liaison service (the no-FLS group), only standard fracture care procedures were followed to address proper fracture-healing. In the group that presented to a hospital with a fracture liaison service (the FLS group), dual x-ray absorptiometry scans and laboratory testing were performed, and if applicable, patients were treated according to the Dutch guideline for osteoporosis. The risk for subsequent nonvertebral fracture and mortality were analyzed using multivariable Cox regression models with adjustments for age, sex, and baseline fracture location. In total, 1412 patients presented to the fracture liaison service (73.2% were women, and the mean age was 71.1 years), and 1910 underwent standard fracture care (69.8% were women, and the mean age was 69.5 years). After adjustment for age, sex, and baseline fracture location, patients who attended the fracture liaison service had a significantly lower mortality risk (hazard ratio: 0.65; 95% confidence interval [CI]: 0.53 to 0.79) over two years of follow-up. The subsequent nonvertebral fracture risk was also significantly lower in the patients in the FLS group, but this effect was time-dependent, with a hazard ratio of 0.84 (95% CI: 0.64 to 1.10) at twelve months and 0.44 (95% CI: 0.25 to 0.79) at twenty-four months. Patients seen at the fracture liaison service had a significantly lower mortality and subsequently a lower risk of nonvertebral fracture than those not seen at the fracture liaison service, with a reduction of 35% and 56%, respectively, over two years of follow-up. A fracture liaison service appears to be a successful approach to reduce the number of subsequent fractures and premature mortality in this cohort of patients.

SAT0373 The role of the combination of bone and fall related risk factors on short-term subsequent fracture risk

BackgroundBone- and fall-related risk factors contribute to subsequent NVF risk and mortalityObjectivesWe analysed whether a combination of bone-related and fall-related risk factors (RFs) in patients with a recent non-vertebral fracture...

The role of the combination of bone and fall related risk factors on short-term subsequent fracture risk and mortality

BackgroundWe analysed whether a combination of bone- and fall-related risk factors (RFs) in addition to a recent non-vertebral fracture (NVF) contributed to subsequent NVF risk and mortality during 2-years in patients who were offered fall and fracture prevention according to Dutch fracture- and fall-prevention guidelines.Methods834 consecutive patients aged ≥50 years with a recent NVF who were included. We compared subgroups of patients according to the presence of bone RFs and/or fall RFs (group 1: only bone RFs; group 2: combination of bone and fall RFs; group 3: only fall RFs; group 4: no additional RFs). Univariable and multivariable Cox regression analyses were performed adjusted for age, sex and baseline fracture location (major or minor).Results57 (6.8%) had a subsequent NVF and 29 (3.5%) died within 2-years. Univariable Cox regression analysis showed that patients with the combination of bone and fall RFs had a 99% higher risk in subsequent fracture risk compared to all others (Hazard Ratio (HR) 1.99; 95% Confidence Interval (CI) 1.18-3.36) Multivariable analyses this was borderline not significant (HR 1.70; 95% CI: 0.99-2.93). No significant differences in mortality were found between the groups.ConclusionEvaluation of fall RFs contributes to identifying patients with bone RFs at highest immediate risk of subsequent NVF in spite of guideline-based treatment. It should be further studied whether earlier and immediate prevention following a NVF can decrease fracture risk in patients with a combination of bone and fall RFs.

Impact of guideline implementation by a fracture nurse on subsequent fractures and mortality in patients presenting with non-vertebral fractures

Introduction Systematic implementation of guidelines in patients presenting with a fracture increases identification of patients at high risk for subsequent fractures and contributes to a decreased fracture risk. Its effect on prevention of subsequent fractures and on mortality has not been documented. The aim of this study was to determine the impact of the implementation of specific guidelines on the risk of subsequent fractures and mortality in patients presenting with a non-vertebral fracture (NVF). Patients and methods Before-after impact analysis in consecutive patients older than 50 years who were admitted to the hospital with a NVF during 2 periods: pre-intervention group ( n = 1,920, enrolled in 1999-2001) and intervention group ( n = 1,335, enrolled in 2004-2006). The intervention consisted of a dedicated fracture nurse who systematically offered fracture risk evaluation and treatment according to available guidelines. The 2-year absolute risk (AR) and hazard ratio's (HR, with 95% confidence interval (CI)) of subsequent NVFs and mortality were analysed between both groups after adjustment for age, sex and baseline fracture location by multivariable Cox regression and by intention-to-treat. Results The AR of subsequent fracture was 9.9% before and 6.7% after intervention, indicating a decrease of 35% in the risk of subsequent fracture (HR 0.65; CI: 0.51-0.84, after adjustment for age, sex and baseline fracture location) and 17.9% and 11.6%, respectively, for subsequent mortality, indicating a decrease of 33% in the risk of subsequent mortality (HR: 0.67; CI: 0.55-0.81, after adjustment for age, sex and baseline fracture location). Conclusions Systematic implementation of guidelines for fracture prevention by a dedicated fracture nurse immediately after a NVF is associated with a significant reduction of the 2-year risk of subsequent NVF and mortality.

Prevalence and costs of osteoporotic patients with subsequent non-vertebral fractures in the US

This study assesses prevalence of subsequent fractures during the year after incident osteoporosis-related non-vertebral fractures among privately insured and Medicare populations and compares costs between patients with and without subsequent fractures. Many non-vertebral fracture patients incur subsequent fractures, and those who do are significantly more costly during the year after incident fracture. To estimate the prevalence of subsequent osteoporosis-related non-vertebral (NV) fractures during the year following an incident NV fracture and compare costs between NV fracture patients with and without subsequent fractures. Using insurance claims data (1999-2006), privately-insured (ages 18-64years) and Medicare (ages 65+ years) patients with ≥1 subsequent osteoporosis-related NV fracture within a year of an incident osteoporosis-related NV fracture were matched to controls with incident NV fractures but no subsequent fractures. Subsequent fractures were identified as any claim for an NV fracture occurring >3months after the incident NV fracture (>6months were required for fractures occurring at the same site as the incident fracture). The study assessed prevalence of subsequent fractures and compared costs (from the payer's perspective) between patients with and without subsequent fractures over the year following an incident NV fracture. Among privately insured NV fracture patients, 14.1% had any subsequent NV fractures, 1.6% had subsequent hip fractures, and 13.0% had subsequent non-vertebral, non-hip (NVNH) fractures, while 22.6% of Medicare NV fracture patients had subsequent NV fractures, 9.4% had subsequent hip fractures, and 15.5% had subsequent NVNH fractures. Mean excess health care costs per privately insured subsequent fracture patient were $9,789 ($19,072 vs. $9,914, p < 0.01), while excess medical costs per Medicare subsequent fracture patient were $12,527 ($31,904 vs. $19,377, p < 0.01). NV fracture patients are at substantial risk for subsequent NV fractures within 1year, and patients who incur subsequent fractures are significantly more costly than those who do not during the year following an incident fracture.

Risk of subsequent fracture and mortality within 5 years after a non-vertebral fracture

SummaryThe absolute 5-year risk of subsequent non-vertebral fractures (NVFs) in 1,921 patients presenting with a NVF was 17.6% and of mortality was 32.3%. These risks were highest within the first year, indicating the need to study which reversible factors can be targeted to immediately minimise subsequent fracture risk and mortality.IntroductionNVFs are the most frequent clinical fractures in patients presenting at the emergency unit because of a clinical fracture. The aim of the study was to determine the 5-year absolute risk (AR) of subsequent NVF and mortality in patients at the time they present with a NVF.MethodsBetween 1999 and 2001, 1,921 consecutive patients 50+ years from a level 1 trauma centre were included. All NVFs were confirmed on radiograph reports, and mortality was checked in the national obituary database. Available potential risk factors for a subsequent NVF and mortality (age, sex and baseline fracture location: major—hip, pelvis, multiple ribs, proximal tibia/humerus and distal femur; minor—all others) were expressed as hazard ratios (HR) with 95% confidence intervals (CI) using multivariable Cox regression analysis.ResultsThe AR for a subsequent NVF was 17.6% and was related to age (HR per decade, 1.44; 95%CI, 1.29–1.60). The AR for mortality was 32.3% and was related to age (HR per decade, 2.59; 95%CI, 2.37–2.84), male sex (HR, 1.74; 95%CI, 1.44–2.10), major fracture at baseline (HR, 5.56; 95%CI, 3.48–8.88; not constant over time) and subsequent fracture (HR, 1.65; 95%CI, 1.33–2.05). The highest risks were found within the first year (NVFs, 6.4%; mortality, 12.2%) and were related to age and, in addition, to baseline fracture location for mortality.ConclusionsWithin 5 years after an initial NVF, nearly one in five patients sustained a subsequent NVF and one in three died. One third of subsequent NVFs and mortality occurred within 1 year, indicating the need to study which reversible factors can be targeted to immediately prevent subsequent fractures and mortality.

Positive impact of compliance to strontium ranelate on the risk of nonvertebral osteoporotic fractures

Adherence is now one of the major issues in the management of osteoporosis. This paper relates the relationship existing between adherence to strontium ranelate and the risk of subsequent nonvertebral fracture among postmenopausal women with osteoporosis. The aim of this study is to investigate compliance to strontium ranelate (SR) therapy and the impact of compliance on the risk of nonvertebral fractures among women with osteoporosis. This study was a post-hoc analysis of pooled data from two international, phase III, randomized, placebo-controlled, double-blind studies (the Spinal Osteoporosis Therapeutic Intervention and Treatment Of Peripheral Osteoporosis). A nested case-control study was performed in the strontium ranelate-treated population. Compliance was quantified using the medication possession ratio (MPR). Two hundred eighty-five nonvertebral fracture cases (hip fx n = 70; major nonvertebral fx n = 213) were identified and matched to 1,425 controls. The mean MPR was 86.8% for controls and 82.6% for cases (p < 0.001). Women who were compliant to SR had a 38% reduction in all nonvertebral fractures compared with those who were not (OR = 0.62; 95%CI[0.47-0.81; p < 0.001). Considering hip fractures only, the risk was reduced by 50% for compliant patients compared to noncompliant patients (OR = 0.50; 95%CI[0.28-0.88]; p < 0.05). Our analyses emphasize the importance of good compliance to treatment in order to reduce the risk of osteoporotic fractures. In particular, there was a greater reduction in the risk of nonvertebral and hip fractures with increase compliance.

Acute and long-term increase in fracture risk after hospitalization for vertebral fracture.

The aims of this study were to determine the magnitude of the increase in risk of further fracture following hospitalization for vertebral fracture, and in particular to determine the time course of this risk. The records of the Swedish Patient Register were examined from 1987 to 1994 to identify all patients who were admitted to hospital for thoracic or lumbar vertebral fractures. Vertebral fractures were characterized as due to high- or low-energy trauma. Patients were followed for subsequent hospitalizations for hip fracture, and for all fractures combined. A Poisson model was used to determine the absolute risk of subsequent nonvertebral fracture and compared with that of the general population. We analyzed 13.4 million hospital admissions from which 28,869 individuals with vertebral fracture were identified, of which 60% were associated with low-energy trauma. There was a marked increase in subsequent incidence of hip and all fractures within the first year following hospitalization for vertebral fracture in both men and women. Thereafter, fracture incidence declined toward, but did not attain, baseline risk. Increased risks were particularly marked in the young. The increase in fracture risk was more marked following low-energy vertebral fracture than in the case of high-energy trauma. We conclude that the high incidence of new fractures within a year of hospitalization for vertebral fractures, irrespective of the degree of trauma involved, indicates that such patients should be preferentially targeted for treatment. It is speculated that short courses of treatment at the time of first vertebral fracture could provide important therapeutic dividends.

Effects of a short-term vitamin D and calcium supplementation on body sway and secondary hyperparathyroidism in elderly women.

Long-term vitamin D and calcium supplementation is effective in reducing nonvertebral fractures in elderly people. Increased bone fragility caused by secondary hyperparathyroidism (sHPT) and impaired balance are known risk factors for hip fractures. The hypothesis is that short-term therapy with calcium and vitamin D may improve body sway as well as sHPT more effectively than calcium monotherapy. The effects of 8 weeks of supplementation with vitamin D (cholecalciferol) and calcium on body sway and biochemical measures of bone metabolism were measured. The sample consisted of 148 women (mean [+/-SD] age, 74 +/- 1 years) with a 25-hydroxycholecalciferol level below 50 nmol/liter. They received either 1200 mg of calcium plus 800 IU of vitamin D or 1200 mg of calcium per day. We measured intact parathyroid hormone (PTH), markers of bone turnover, and body sway before and after treatment. Falls and fractures among the participants were followed over a 1-year period. Compared with calcium mono, supplementation with vitamin D and calcium resulted in an increase in serum 25-hydroxyvitamin D of 72% (p < 0.0001), a decrease in the serum PTH of 18% ( p = 0.0432), and a decrease in body sway of 9% (p = 0.0435). The mean number of falls per subject during a 1-year follow-up period was 0.45 for the calcium mono group and 0.24 for the calcium and vitamin D group (p = 0.0346). Short-term supplementation with vitamin D and calcium improves sHPT and body sway and therefore may prevent falls and subsequent nonvertebral fractures in elderly women.

Association of race and other potential risk factors with nonvertebral fractures in community-dwelling elderly women.

This study determined potential associations of sociodemographic, lifestyle, health, and drug use factors known to affect bone metabolism with incident nonvertebral fractures. The baseline sample consisted of 2,590 female, nonproxy subjects from the Duke Established Populations for Epidemiologic Studies of the Elderly, which focuses on five adjacent counties in the Piedmont area of North Carolina. Information about potential risk factors was collected during a baseline in-home interview during 1986-1987. Subsequent nonvertebral fractures were reported at follow-up interviews during the annual follow-up periods (1988-1993). The authors used multivariate analyses in which weighted data were adjusted for sampling design. After controlling for other potential confounding sociodemographic, lifestyle, health, and drug use factors, they found that African American race (adjusted odds ratio (OR) = 0.43, 95% confidence interval (CI) 0.31-0.58), age (adjusted OR = 1.04, 95% CI 1.01-1.06), alcohol consumption (adjusted OR = 1.61, 95% CI 1.01-2.57), being underweight (adjusted OR = 1.63, 95% CI 1.13-2.34), cognitive impairment (adjusted OR = 1.67, 95% CI 1.12-2.48), impaired mobility (adjusted OR = 1.15, 95% CI 1.03-1.29), and phenytoin use (adjusted OR = 2.93, 95% CI 1.04-8.30) were associated with first fracture occurrence. Similar findings were observed for nonhip, nonvertebral fractures. African Americans were less likely than Whites to have nonvertebral fractures, and these differences were not related to lifestyle or health factors examined in this study.