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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.


Orthopaedic Proceedings
Vol. 91-B, Issue SUPP_I | Pages 70 - 70
1 Mar 2009
Sonne-Holm S Jacobsen S Jensen T Hyldstrup L Rovsing H Rovsing H
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Background: The epidemiology of Schmorl nodes is based on post-mortem investigations. The proposed pathogenesis of the focal nodes is a bulging of the disc into the vertebral body depending of the degree of osteoporosis. Secondar peripheral osteophytes are formed at the annular insertion.

Study design: A cross sectional epidemiological study of 4151 participants of the Copenhagen Osteoarthritis Study in 1993 with a 13 years follow with the Roland-Morris (R-MQ) back pain questionnaire.

In 1993 standardized, lateral radiographs of the lumbar spine were recorded and the bone mineral density (BMD) was estimated by digital x-ray radiogrammetry of standardised hand x-rays.

Methods: Statistical correlations were made between Schmorl nodes and low back pain in 1993, the R-MQ score, BMD and the presence of osteophytes, disc degeneration and endplate sclerosis.

Results: There were 2610 women and 1538 men. At follow up 1190 women and 674 responded. In 196 cases one or more Schmorl nodes in the lumbar spine were found (women 3.7 %, men 6.5 %). A decreasing prevalence of Schmorl nodes by ages was found in both genders (p< 0.000). At the time of the radiographic examination participants with Schmorl nodes clamed of low back pain (p=0.003). The presence of nodes was without relation to osteophytosis, intervertebral disc degeneration or sclerosis of endplates (p> 0.14) in 1993. Neither was the R-MQ score at follow-up related to Schmorls nodes(p> 0.26). The presence of nodes was associated with higher BMD (mean 0.50 (SD 0.079) versus 0.53 (SD 0.081)(p=0.000), however the difference disappeared taking into account age at examination.

Conclusion: This large scaled epidemiological study cannot confirm the hitherto hold opinion of the implication of the Schmorls nodes. The nodes are not associated with radiological degeneration and osteoporosis neither are they a predictor of lower back pain later in life.


Orthopaedic Proceedings
Vol. 91-B, Issue SUPP_I | Pages 153 - 153
1 Mar 2009
Jacobsen S Jensen T Bach-Mortensen P Sonne-Holm S Hyldstrup L
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Background/Objective: Since estrogen receptors (ERα/ERβ) were identified in human chondrocytes, animal-and experimental studies have demonstrated the importance of continued estrogen production for the integrity of articular cartilage. However, human epidemiological support of the hypothesis has been inconclusive. The present study investigated the relationship between reduced bone mineral densities (BMD), as a surrogate parameter of endogenous estrogen status – assessed by digital x-ray radiogrammetry (DXR), and reduced minimum hip joint space width (JSW).

Methods: Standardised hand radiographs of the Copenhagen Osteoarthritis Study cohort of 3.913 adults (1.470M/2.443F) with a mean age of 60 years (range, 18–92), were analysed by the X-Posure digital software v. 2.0 (Sectra-Pronosco). The system is operator independent. From 1.200 individual measurements per radiograph mean BMD was calculated. Minimum hip joint JSW was assessed in standardized, pelvic radiographs.

Results: DXR-BMD decreased in both men and women after the age of 45 years, progressively more so in women. While minimum hip JSW in men remained relatively unaltered throughout life, a marked decline in female minimum hip JSW after 45 years was observed. We found moderate, but highly significant relationships between reduced BMD and reduced hip JSW in women (p < 0.001), adjusted for age and dysplastic joint incongruity.

Conclusion: We believe that the present study supports the hypothetical relationship between reduced estrogen levels and hip joint space width reduction in women.