Breaking Barriers: Studying Fracture Healing in the BONES Program.

SUMMARY: The Bioventus Observational Noninterventional EXOGEN Studies (BONES) Program includes 3 concurrent studies designed to estimate the incidence of fracture nonunions in patients treated with the EXOGEN Ultrasound Bone Healing System compared with those receiving standard fracture care. This article outlines the design and methodology within the fifth metatarsal fracture study; similar approaches are taken in the second and third BONES Program studies, which examine nonunions of the tibia and scaphoid. The BONES Program is an external comparator design and incorporates several unique, fit-for-purpose components to strengthen the approach and allow it to be submitted to the US Food and Drug Administration (FDA) to be considered for a label expansion. BONES consisted of 2 cohorts: (1) EXOGEN-treated patients recruited into a patient registry and (2) comparator patients from a large administrative health claims database. The study used International Classification of Diseases, Tenth Revision, nonunion diagnosis codes reported by the treating clinician for the primary outcome measure. Many data sources (medical and billing records, patient-reported health data, usage data from the device itself, and commercial product complaint system) were used on the registry side, alongside insurance claims data to source the external comparator cohort, to achieve broader understanding of factors predisposing patients to the development of nonunions. In step with the FDA's increasing acceptance of real-world evidence for use in regulatory decision making and coupled with the infeasibility of a randomized clinical trial in this setting, the innovative study design of the BONES Program allowed for both an evaluation of the effect of EXOGEN in mitigating nonunions in a real-world setting and an assessment of the patient experience with EXOGEN treatment.

NASHA hyaluronic acid for the treatment of shoulder osteoarthritis: a prospective, single-arm clinical trial.

Background: Osteoarthritis of the shoulder or glenohumeral joint is a painful condition that can be debilitating. Intra-articular injection with hyaluronic acid should be considered for patients not responding adequately to physical therapy or anti-inflammatory medication. Methods: This was a single-arm, open-label, prospective study of a single intra-articular injection of NASHA (non-animal hyaluronic acid) in patients with symptomatic glenohumeral osteoarthritis. Patients were followed up for 26 weeks post-treatment, during which time rescue medication with acetaminophen was permissible. The study objective was to demonstrate that a single injection of NASHA is well tolerated with an over-6-month 25% reduction in shoulder pain on movement, assessed using a 100-mm visual analog scale. Results: Forty-one patients were enrolled, all of whom received study treatment. The mean decrease in shoulder pain on movement score over the 6-month study period was -20.1 mm (95% CI: -25.2, -15.0 mm), corresponding to a mean reduction of 29.5% (22.0, 37.0%). Statistically significant improvements were also observed in shoulder pain at night and patient global assessment. There was no clear change over time in the percentage of patients using rescue medication and mean weekly doses were below 3500 mg. Seventeen patients (41.5%) experienced adverse events, all of which were mild or moderate. Two adverse events (both shoulder pain) were deemed related to study treatment. Conclusion: This study provides preliminary evidence that a single injection of NASHA may be efficacious over 6 months and well tolerated in patients with symptomatic glenohumeral osteoarthritis. Larger studies are needed for confirmation.

Nonanimal Hyaluronic Acid for the Treatment of Ankle Osteoarthritis: AProspective, Single-Arm Cohort Study.

Ankle osteoarthritis (OA) can cause disabling symptoms, and some patients prefer to be treated with minimally invasive procedures. Nonanimal hyaluronic acid (NASHA) is a cross-linked hyaluronic acid product that has a prolonged intra-articular residence time. The authors report the first study of NASHA for the treatment of ankle OA. Thirty-seven patients with Kellgren-Lawrence grade II or III ankle OA received an intra-articular injection of NASHA (1 mL). Outcomes included visual analogue scale (VAS) scores for pain and disability. At baseline, the mean VAS pain score was 50.1 ± 14.5mm. During the 26-week follow-up period, the least squares (LS) mean change from baseline in the ankle OA VAS pain score was -20.5mm (95% confidence interval [CI] -25.5 to -15.6 mm), an LS mean percentage reduction of 40.0% (95% CI 30.2% to 49.9%). The LS mean change from baseline in the VAS disability score during 26 weeks was -19.2mm (95% CI -24.8 to -13.6 mm), a percentage reduction of 34% (95% CI 22.3% to 45.7%). Five participants experienced a total of 7 adverse events considered to be related to study treatment (injection site pain, n = 3; injection site joint pain, n = 3; plantar fasciitis, n = 1). This study shows promise for viscosupplementation with NASHA in the treatment of ankle OA. A single injection was associated with clinically meaningful reductions in pain and disability during a 26-week period and, in general, was well tolerated.