If you missed these Headline News Now items the first time around, AAOS Now gives you a second chance to review them. Headline News Now—the AAOS thrice-weekly, online update of news of interest to orthopaedic surgeons—brings you the latest on clinical, socioeconomic, and political issues, as well as important announcements from AAOS.

Common food dye may help reduce spinal cord injuries
According to a study published in the Proceedings of the National Academy of Sciences (July 28, 2009), systemic administration of the food dye Brilliant Blue G (BBG) may present a feasible approach for treating traumatic spinal cord injury (SCI). The neuroprotective effects of BBG were tested in a weight-drop model of thoracic SCI in rats. Administration of BBG 15 minutes after injury reduced spinal cord anatomic damage and improved motor recovery with no evident toxicity. Additionally, BBG treatment directly reduced local activation of astrocytes and microglia, as well as neutrophil infiltration, suggesting that BBG protected spinal cord neurons from purinergic excitotoxicity and reduced local inflammatory responses.

OI linked to collagen mutation
A study in Biophysical Journal (August 5, 2009) finds that osteogenesis imperfecta (OI) stems from a genetic mutation that creates a defective collagen molecule that repels, rather than attracts, other collagen molecules on a range of scales. The researchers used a hierarchy of full atomistic and mesoscale simulation to demonstrate that OI mutations severely compromise the mechanical properties of collagenous tissues at multiple scales, from single molecules to collagen fibrils. Mutations that led to the most severe OI phenotype correlated with the strongest effects, leading to weakened intermolecular adhesion, increased intermolecular spacing, reduced stiffness, as well as reduced failure strength of collagen fibrils.

SVT linked to likelihood of DVT
Superficial vein thrombosis (SVT) may be an indicator for deep vein thrombosis (DVT), according to an Austrian study published in the Archives of Dermatology (July 2009). Forty-six consecutive patients (32 women, 14 men) diagnosed with SVT between November 2006 and June 2007 underwent color-coded duplex sonography to confirm SVT and exclude or detect DVT. DVT was detected in 24 percent of patients who had SVT. DVT was usually asymptomatic and occurred in the same leg as SVT in 73 percent of the patients; it was found in the other leg in 9 percent of patients, and 18 percent of patients had DVT in both legs.

VCAM-1 predicts joint replacement risk?
A European study published in the Arthritis & Rheumatism (August 2009) finds that levels of soluble vascular cell adhesion molecule 1 (VCAM-1) may serve as an independent predictor of the risk of hip and knee joint replacement due to severe osteoarthritis (OA). Of 192 participants in the prospective Bruneck cohort study, 60 received hip or knee arthroscopy between 1990 and 2005. Researchers found that VCAM-1 level emerged as a significant predictor of the risk of joint replacement surgery, “equaling or even surpassing the effects of age.” Adding the VCAM-1 level to a risk model that already included age, sex, and body mass index resulted in more accurate risk classification of individual participants.

Zoledronic acid, fractures, and mortality
A study in the Journal of Bone and Mineral Research (JBMR) (July 2009) finds that annual infusions of zoledronic acid may reduce mortality after hip fracture in ways unrelated to simply preventing new fractures. Researchers analyzed the cases of 2,127 patients (1,065 on active treatment, 1,062 on placebo; mean age, 75 yrs.; 76 percent women) who were administered zoledronic acid or placebo within 90 days after surgical repair of an osteoporotic hip fracture and annually thereafter. They found a consistent reduction in overall clinical fractures and mortality among patients who received the first dose 2 weeks or later after surgical repair, as well as a reduction in clinical fracture subgroups such as vertebral, non-vertebral, and hip.

Teriparitide and bone healing
A study published online in JBMR finds that fracture repair time may be reduced through treatment with teriparatide, but the results should be interpreted with caution. Researchers conducted a prospective, randomized, double-blind study of 102 postmenopausal women (age 45-85 yrs.) who sustained a dorsally angulated distal radial fracture in need of closed reduction, but no surgery. Within 10 days of fracture, the patients were assigned to 8 weeks of once-daily injections of placebo (n=34), teriparatide 20 µg (n=34) or 40 µg (n=34). The estimated median time from fracture to first radiographic evidence of complete cortical bridging in three of four cortices was 9.1 weeks in the placebo group, 7.4 weeks for teriparatide 20, and 8.8 weeks for teriparatide 40. No significant difference in healing time was found between the teriparatide 40 versus placebo groups. In post hoc analyses, no significant difference in healing time was found between teriparatide 40 and teriparatide 20; the time to healing was shorter in the teriparatide 20 cohort than in the placebo group.

Improving osteoarthritis diagnosis
A Danish study published online in Arthritis Research & Therapy finds that the use of biochemical and magnetic resonance imaging (MRI)-based biomarkers may improve the diagnosis and prognosis of knee osteoarthritis. The research team examined 159 patients (287 knees) at baseline and after 21 months, quantifying both biochemical (urinary collagen type II C-telopeptide fragment, CTX-II) and MRI-based (cartilage volume, thickness, area, roughness, homogeneity, and curvature in the medial tibio-femoral compartment) markers. They found that cartilage roughness had the highest diagnostic accuracy among individual markers for distinguishing patients with radiographic osteoarthritis from healthy controls and that homogeneity was the best marker for predicting longitudinal radiographic progression. The aggregate cartilage longevity marker (combining CTX-II, volume, area, thickness, congruity, roughness, and homogeneity) was superior to the individual biochemical and MRI markers.

Mortality and hip, vertebral fractures
A study published online in the Canadian Medical Association Journal finds that vertebral and hip fractures may be associated with an increased risk of death. The authors conducted a 5-year observational cohort study of 7,753 randomly selected Canadians (2,187 men and 5,566 women) aged 50 years and older. Overall, about one in four individuals who sustained a hip fracture died within 5 years; the risk of dying within 5 years of sustaining a vertebral fracture was one in six.

Effectiveness of vertebroplasty
The New England Journal of Medicine (NEJM) (Aug. 6, 2009) reports on a pair of multicenter trials (United States and Australia) that examine the effectiveness of vertebroplasty in reducing pain and pain-related disability in patients with osteoporotic vertebral fractures. Both studies found little difference in pain and pain-related disability, regardless of whether the patients were treated with vertebroplasty or placebo. In the U.S. trial, researchers randomly assigned 131 patients with one to three painful osteoporotic vertebral compression fractures to undergo either vertebroplasty or a simulated procedure without cement. After intervention, both groups had immediate improvement in disability and pain scores, with a trend toward a higher rate of clinically meaningful improvement in pain in the vertebroplasty group. At 1 month, however, no significant difference was found between the groups.

The Australian study was a randomized, double-blind trial of 71 patients who had one or two unhealed, painful osteoporotic vertebral fractures of less than 12 months’ duration and were randomly assigned to undergo vertebroplasty or a sham procedure. At 3 months follow-up, the mean reductions in pain scores were 2.6 in the vertebroplasty group and 1.9 in the control group. Both groups saw similar improvement with respect to pain at night and at rest, physical functioning, quality of life, and perceived improvement.

Reducing bleeding after joint replacement
Administration of apixaban thromboprophylaxis after major joint replacement was associated with lower rates of clinically relevant bleeding compared to enoxaparin in a study published in the NEJM (Aug. 6, 2009). The authors conducted a double-blind, double-dummy study of 3,195 patients randomly assigned to receive 2.5 mg of apixaban orally twice daily (n=1,599) or 30 mg of enoxaparin subcutaneously every 12 hours (n=1,596). Both medications were started 12 to 24 hours after surgery and continued for 10 to 14 days. Although the rates of primary efficacy outcome were similar—9.0 percent with apixaban as compared with 8.8 percent with enoxaparin, the composite incidence of major bleeding and clinically relevant non-major bleeding was 2.9 percent with apixaban and 4.3 percent with enoxaparin (P=0.03).

Limb-sparing surgery or amputation?
A study published in Cancer (Sept. 15, 2009) finds that limb salvage surgery may not offer a better functional outcome and health-related quality of life for young people with bone and soft tissue sarcomas of the lower limb. A review of published papers on limb-sparing surgery that also measured patient’s functional health and quality of life found that, while limb-sparing surgery is generally as effective as amputation in removing cancer, it is also associated with more complications. Differences in disability between patients whose limb was amputated and those who underwent limb-sparing surgery are smaller than expected, and no significant differences are found in psychological health and quality of life between patients who underwent amputations and those who had limb-sparing surgery.

Perspective on comparative effectiveness data
An article in the NEJM (Aug. 12, 2009) examines the issue of incorporating comparative-effectiveness information into U.S. Food and Drug Administration labeling of pharmaceuticals and medical devices. FDA requires developers of new treatments to demonstrate that they are safe and effective to receive approval for market entry, but the agency demands proof of superiority to existing products only when it is patently unethical to withhold active treatment from study patients. Therefore, many new drugs are approved on the basis of demonstrated superiority to placebo. Placebo-controlled trials that are not supplemented by active-comparator trials leave providers, patients, and payors without guidance on a new product’s advantages or disadvantages compared to existing products. The authors argue that an evidence gap exists and continues to grow with each placebo-controlled trial, enabling developers to market their products as the next generation of advances and differentiating them in terms of features that bear little relation to disease outcomes. The current regulatory climate thus favors the creation of products that differ minimally from existing therapies.

The cost of osteoporosis-related fractures
A study from the federal Agency for Health Quality and Research (AHRQ) finds that the hospitalization rate for patients admitted with osteoporotic-linked fractures increased by 55 percent between 1996 and 2005. Of the more than 1 million hospitalizations in 2006 that had a diagnosis of osteoporosis, more than one-quarter also involved a fracture. Osteoporotic fractures cost hospitals $2.4 billion in 2006.