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Orthopaedic Proceedings
Vol. 102-B, Issue SUPP_7 | Pages 32 - 32
1 Jul 2020
Colgan SM Schemitsch EH Adachi J Burke N Hume M Brown J McErlain D
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Fragility fractures associated with osteoporosis (OP) reduce quality of life, increase risk for subsequent fractures, and are a major economic burden. In 2010, Osteoporosis Canada produced clinical practice guidelines on the management of OP patients at risk for fractures (Papaioannou et al. CMAJ 2010). We describe the real-world incidence of primary and subsequent fragility fractures in elderly Canadians in Ontario, Canada in a timespan (2011–2017) following guideline introduction.

This retrospective observational study used de-identified health services administrative data generated from the publicly funded healthcare system in Ontario, Canada from the Institute for Clinical Evaluative Sciences. The study population included individuals ≥66 years of age who were hospitalized with a primary (i.e. index) fragility fracture (identified using ICD-10 codes from hospital admissions, emergency and ambulatory care) occurring between January 1, 2011 and March 31, 2015. All relevant anatomical sites for fragility fractures were examined, including (but not limited to): hip, vertebral, humerus, wrist, radius and ulna, pelvis, and femur. OP treatment in the year prior to fracture and subsequent fracture information were collected until March 31, 2017. Patients with previous fragility fractures over five years prior to the index fracture, and those fractures associated with trauma codes, were excluded.

115,776 patients with an index fracture were included in the analysis. Mean (standard deviation) age at index fracture was 80.4 (8.3) years. In the year prior to index fracture, 32,772 (28.3%) patients received OP treatment. The incidence of index fractures per 1,000 persons (95% confidence interval) from 2011–2015 ranged from 15.16 (14.98–15.35) to 16.32 (16.14–16.51). Of all examined index fracture types, hip fractures occurred in the greatest proportion (27.3%) of patients (Table). The proportion of patients incurring a second fracture of any type ranged from 13.4% (tibia, fibula, knee, or foot index fracture) to 23% (vertebral index fracture). Hip fractures were the most common subsequent fracture type and the proportion of subsequent hip fractures was highest in patients with an index hip fracture (Table). The median (interquartile range [IQR]) time to second fracture ranged from 436 (69–939) days (radius and ulna index fracture) to 640 (297–1,023) days (tibia, fibula, knee, or foot index fracture). The median (IQR) time from second to third fracture ranged from 237 (75–535) days (pelvis index fracture) to 384 (113–608) days (femur index fracture).

This real-world study found that elderly patients in Ontario, Canada incurring a primary fragility fracture from 2011–2015 were at risk for future fractures occurring over shorter periods of time with each subsequent fracture. These observations are consistent with previous reports of imminent fracture risk and the fragility fracture cascade in OP patients (Balasubramanian et al. ASBMR 2016, Toth et al. WCO-IOF-ESCEO 2018). Overall, these data suggest that in elderly patients with an index fragility fracture at any site (with the exception of the radius or ulna), the most likely subsequent fracture will occur at the hip in less than 2 years.


Orthopaedic Proceedings
Vol. 92-B, Issue SUPP_II | Pages 332 - 332
1 May 2010
Nordsletten L Lyles K Colon-Emeric C Magaziner J Adachi J Pieper C Hyldstrup L Eriksen EF Boonen S
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Fracture prevention has so far been studied in patients included on the basis of low bone density, and not after a fracture. In this study the inclusion criteria was a new hip fracture irrespective of bone density. An international, multicenter, randomized, double-blind, placebo-controlled, parallel-group trial (HORIZON-RFT) studied whether the bisphosphonate, zoledronic acid (ZOL) 5 mg, reduced subsequent clinical fractures in men and women ≥50 yrs after a hip fracture.

Methods: Patients with hip fracture were included. They received daily vitamin D3 and calcium supplements. Of 2127 randomized, 2111 were treated with once-yearly IV infusions of ZOL 5 mg (n=1054) or placebo (PBO; n=1057) and followed until 211 experienced new clinical fractures (the primary efficacy endpoint).

Results: Baseline characteristics were similar. Median age was 76 yrs (range, 50–98); 76% were women. Clinical fractures occurred in 92 ZOL and 139 PBO patients. 2-year cumulative event rates were 8.59% and 13.88%, respectively (Kaplan-Meier); relative risk reduction was 35% (HR=0.65; 95% CI: 0.50–0.84; P=.0012). ZOL reduced risk for clinical vertebral and nonvertebral fractures vs. PBO by 46% (HR=0.54; 95% CI: 0.32–0.92; P=.0210) and 27% (HR=0.73; 95% CI: 0.55–0.98; P=.0338), respectively. ZOL reduced risk of hip fractures by 30% vs. PBO (HR=0.70; 95% CI: 0.41–1.19; P=NS). AEs and SAEs were comparable between groups. There were no significant differences in cardiovascular parameters or long-term renal function. No cases of ONJ were reported. Death occurred in 9.58% of ZOL patients vs 13.34% PBO, a 28% lower mortality risk (HR=0.72; 95% CI: 0.56–0.93, P=.0117).

Conclusions: Subjects with a new hip fracture treated with annual IV ZOL infusions experienced significantly fewer clinical fractures vs. placebo. ZOL was well tolerated with a favorable safety profile. This is the first trial demonstrating a mortality benefit for an antiresorptive agent.